The Effectiveness of Systemp.desensitizer in the treatment of dentine hypersensitivity.
This study reports the effectiveness of Systemp.desensitizer (Ivoclar Vivadent, Schaan, Liechtenstein), when used both with and without an acid-etch step, in the treatment of patients with dentine hypersensitivity in UK dental practices. Ten general dental practitioners (GDPs) were selected from two practice-based research groups. The GDPs were each requested to use Systemp.desensitizer in the treatment of at least ten patients who presented with pain due to dentine hypersensitivity. Systemp.desensitizer was applied to the sensitive dentine area in strict accordance with the manufacturer's handling instructions, except that the patients were divided into two groups. For the first, group NE, the procedure was to isolate the tooth, gently blot it dry with cotton wool pellets, rub Systemp.desensitizer into the tooth for 20 seconds, then gently air-dry it. For the second, group E, the procedure was identical except that after isolation, the treatment area was etched for 15 seconds with 35% phosphoric acid. Patients were asked to complete a pro forma using a 10 cm visual analogue scale designed to provide details of the extent of their pain before treatment, 24 hours post-treatment, one week post-treatment, one month post-treatment, and three months post-treatment. The zero end of the scale was marked 'no pain' and the 10 cm end was marked 'extreme pain'. The percentage change in the patients' perception of their pain, relative to pretreatment, was calculated using repeated measures analysis and suitable follow-up confidence intervals for the mean changes in perceived pain. Comparisons were then made between the treatment groups NE and E. Ninety-one patients completed the first pro forma and 77 completed all the pro formas. Overall, there was a significant reduction in pain at each of the time points after treatment but the pattern of pain reduction across the two groups was different. In general, the non-etched group (group NE) saw an 'immediate' reduction in pain which was then fairly consistent across the longer term, whilst, in general, the etched group (group E) saw less reduction in pain 24 hours after treatment, and then further reduction in pain at both one week and one month after treatment. Thus the non-etched group experienced an early reduction whilst the etched group took longer to perceive a reduction in pain; however, there were no statistically significant differences between the reductions in pain scores between the two groups at any of the time points after treatment. It is concluded that Systemp.desensitizer was effective in reducing pain from dentine hypersensitivity in the patients treated, and this finding was unaffected by whether or not the tooth was acid-etched prior to application of the reagent.


Diagnostic accuracy of diabetic retinopathy grading by an artificial intelligence-enabled algorithm compared with a human standard for wide-field true-colour confocal scanning and standard digital retinal images.
Photographic diabetic retinopathy screening requires labour-intensive grading of retinal images by humans. Automated retinal image analysis software (ARIAS) could provide an alternative to human grading. We compare the performance of an ARIAS using true-colour, wide-field confocal scanning images and standard fundus images in the English National Diabetic Eye Screening Programme (NDESP) against human grading. Cross-sectional study with consecutive recruitment of patients attending annual diabetic eye screening. Imaging with mydriasis was performed (two-field protocol) with the EIDON platform (CenterVue, Padua, Italy) and standard NDESP cameras. Human grading was carried out according to NDESP protocol. Images were processed by EyeArt V.2.1.0 (Eyenuk Inc, Woodland Hills, California). The reference standard for analysis was the human grade of standard NDESP images. We included 1257 patients. Sensitivity estimates for retinopathy grades were: EIDON images; 92.27% (95% CI: 88.43% to 94.69%) for any retinopathy, 99% (95% CI: 95.35% to 100%) for vision-threatening retinopathy and 100% (95% CI: 61% to 100%) for proliferative retinopathy. For NDESP images: 92.26% (95% CI: 88.37% to 94.69%) for any retinopathy, 100% (95% CI: 99.53% to 100%) for vision-threatening retinopathy and 100% (95% CI: 61% to 100%) for proliferative retinopathy. One case of vision-threatening retinopathy (R1M1) was missed by the EyeArt when analysing the EIDON images, but identified by the human graders. The EyeArt identified all cases of vision-threatening retinopathy in the standard images. EyeArt identified diabetic retinopathy in EIDON images with similar sensitivity to standard images in a large-scale screening programme, exceeding the sensitivity threshold recommended for a screening test. Further work to optimise the identification of 'no retinopathy' and to understand the differential lesion detection in the two imaging systems would enhance the use of these two innovative technologies in a diabetic retinopathy screening setting.


[+]-Huperzine A treatment protects against N-methyl-D-aspartate-induced seizure/status epilepticus in rats.
The toxicity of organophosphorous (OP) nerve agents is attributed to their irreversible inhibition of acetylcholinesterase (AChE), which leads to excessive accumulation of acetylcholine (ACh) and is followed by the release of excitatory amino acids (EAA). EAAs sustain seizure activity and induce neuropathology due to over-stimulation of N-methyl-d-aspartate (NMDA) receptors. Huperzine A (Hup A), a blood-brain barrier permeable selective reversible inhibitor of AChE, has been shown to reduce EAA-induced cell death by interfering with glutamate receptor-gated ion channels in primary neuronal cultures. Although [-]-Hup A, the natural isomer, inhibits AChE approximately 38-fold more potently than [+]-Hup A, both [-]- and [+]-Hup A block the NMDA channel similarly. Here, we evaluated the protective efficacy of [+]-Hup A for NMDA-induced seizure in a rat model. Rats implanted with radiotelemetry probes to record electroencephalography (EEG), electrocardiography (ECG), body temperature, and physical activity were administered various doses of [+]-Hup A (intramuscularly) and treated with 20 microg/kg NMDA (intracerebroventricular) 20-30 min later. For post-exposure, rats were treated with [+]-Hup A (3 mg/kg, intramuscularly) 1 min after NMDA (20 microg/kg). Our data showed that pre- and post-exposure, [+]-Hup A (3 mg/kg) protects animals against NMDA-induced seizures. Also, NMDA-administered animals showed increased survival following [+]-Hup A treatment. [+]-Hup A has no visible effect on EEG, heart-rate, body temperature, or physical activity, indicating a reduced risk of side effects, toxicity, or associated pathology. Our results suggest that [+]-Hup A protects against seizure and status epilepticus (SE) by blocking NMDA-induced excitotoxicity in vivo. We propose that [+]-Hup A, or a unique combination of [+]- and [-]-Hup A, may prove to be effective for pre- and post-exposure treatment of lethal doses of OP-induced neurotoxicity.


[Biochemical abnormality of mutant TDP-43 protein].
Dominant mutations in the TDP-43 gene are causative for familial ALS, however, the relationship between mutant protein biochemical phenotypes and disease course and their significance to disease pathomechanism are unclarified. We found that longer half-lives of mutant proteins correlated with accelerated disease onset. Increased stability of TDP-43 protein was also observed in ALS/FTLD linked mutations in RNA recognition motif of TDP-43. Based on our findings, we established a cell model in which chronic stabilization of wild-type TDP-43 protein provoked cytotoxicity and recapitulated pathogenic protein cleavage and insolubility to the detergent sarkosyl, TDP-43 properties that have been observed in the lesions of sporadic ALS. Moreover, these cells expressing stabilized TDP-43 showed proteasomal impairment and dysregulation of their own mRNA levels. These results suggest that chronically increased stability of mutant or wild-type TDP-43 proteins results in a gain of toxicity through abnormal proteostasis.


How important is donor age in liver transplantation?
The age of liver donors has been increasing in the past several years because of a donor shortage. In the United States, 33% of donors are age 50 years or older, as are more than 50% in some European countries. The impact of donor age on liver transplantation (LT) has been analyzed in several studies with contradictory conclusions. Nevertheless, recent analyses of the largest databases demonstrate that having an older donor is a risk factor for graft failure. Donor age is included as a risk factor in the more relevant graft survival scores, such as the Donor Risk Index, donor age and Model for End-stage Liver Disease, Survival Outcomes Following Liver Transplantation, and the Balance of Risk. The use of old donors is related to an increased rate of biliary complications and hepatitis C virus-related graft failure. Although liver function does not seem to be significantly affected by age, the incidence of several liver diseases increases with age, and the capacity of the liver to manage or overcome liver diseases or external injuries decreases. In this paper, the importance of age in LT outcomes, the role of donor age as a risk factor, and the influence of aging on liver regeneration are reviewed.


Differentiation of lactococci by rRNA gene restriction analysis.
Strains of the subspecies of Lactococcus lactis could be differentiated by rRNA gene restriction fragment length polymorphisms (RFLP). 16S rRNA-specific oligonucleotide as well as polynucleotide DNA probes were used for the detection of restriction fragments. In addition, a site-specific probe was designed for the intergenic spacer region of 23S and 5S rRNA genes. For all lactococcal strains the putative presence of six rRNA operons was confirmed. A non-radioactive hybridization assay was used based on hybrid detection by chemiluminescence. Specific patterns were found for any of the strains investigated. Subspecies-specific restriction fragments could be identified in addition to the strain-specific patterns.


New 1,2,4-oxadiazole/pyrrolidine hybrids as topoisomerase IV and DNA gyrase inhibitors with promising antibacterial activity.
A series of hybridized pyrrolidine compounds with a 1,2,4-oxadiazole moiety were synthesized to develop effective molecules against the enzymes DNA gyrase and topoisomerase IV (Topo IV). Compounds 8-20 were developed based on a previously disclosed series of compounds from our lab, but with small structural modifications in the hopes of increasing the compounds' biological activity. In comparison to novobiocin, with IC50 = 170 nM, the findings of the DNA gyrase inhibitory assay revealed that compounds 16 and 17 were the most potent of all synthesized derivatives, with IC50 values of 180 and 210 nM, respectively. Compound 17 had the strongest inhibitory effect against Escherichia coli Topo IV of all the synthesized compounds, with an IC50 value of 13 µM, which was comparable to novobiocin (IC50 = 11 µM). Therefore, hybrids 16 and 17 appeared to be potential dual-target inhibitors. In the minimal inhibitory concentration (MIC) assays, compound 17 outperformed ciprofloxacin against E. coli, with an MIC of 55 ng/ml, compared to 60 ng/ml for ciprofloxacin. Finally, the docking study, along with the in vitro experiments, supports our promising approach to effectively develop potent leads for further optimization as dual DNA gyrase and Topo IV inhibitors.


Social relationships and physiological function: the effects of recalling social relationships on cardiovascular reactivity.
The mechanisms by which social relationships exert their influence on mental and physical health outcomes deserve greater attention. Although many studies assess the influence of actual social interactions on cardiovascular reactivity, we hypothesized that cognitive and behavioral processes (e.g., recalling and discussing relationships) may be important factors responsible for the health effects of social relationships. We had men and women recall and speak about specific relationships that differed in their underlying positive and negative substrates. Results revealed that gender moderated the hypothesized pattern of responses, with women showing consistently greater cardiovascular reactivity to the speaking task, particularly when speaking about negative relationships, compared to men. This study is discussed in light of recent research on gender differences in relationship outcomes as well as the potential importance of delineating the cognitive representations and processes that influence reactions to one's social environment.


The epidemiology of blood pressure in young Mexican adults.
The distribution of blood pressure and associated factors (height, weight, body mass index, age, social class) was assessed in young Mexican adults, with a cross-sectional study of 657 male and female students enrolled at the University of Mexico, aged from 19 to 25 years. Significantly higher blood pressure levels were observed in males than in females. Borderline hypertension was found in 20.7% of the study subjects. Of all anthropometric factors, age and social class, weight was determined by stepwise regression analysis as the best predictor for blood pressure when using a linear model. However, when a quadratic model was used, a 'U' relationship and a significant variation between blood pressure and social class was detected. This relationship was magnified when blood pressure was categorized into borderline hypertension and normotensives. These findings suggest the hypothesis that hypertension has a non-linear association with social class in environments that are undergoing an intermediate step of modernization and economic transition such as is occurring in Latin American countries today.


Higher MLCT lifetime of carbene iron(II) complexes by chelate ring expansion.
Combining strong σ-donating N-heterocyclic carbene ligands and π-accepting pyridine ligands with a high octahedricity in rigid iron(ii) complexes increases the 3MLCT lifetime from 0.15 ps in the prototypical [Fe(tpy)2]2+ complex to 9.2 ps in [Fe(dpmi)2]2+12+. The tripodal CNN ligand dpmi (di(pyridine-2-yl)(3-methylimidazol-2-yl)methane) forms six-membered chelate rings with the iron(ii) centre leading to close to 90° bite angles and enhanced iron-ligand orbital overlap.


Antibiotic Resistance and Virulence Phenotypes of Recent Bacterial Strains Isolated from Urinary Tract Infections in Elderly Patients with Prostatic Disease.
Acute bacterial prostatitis is one of the frequent complications of urinary tract infection (UTI). From the approximately 10% of men having prostatitis, 7% experience a bacterial prostatitis. The purpose of this study was to investigate the prevalence of uropathogens associated with UTIs in older patients with benign prostatic hyperplasia and to assess their susceptibility to commonly prescribed antibiotics as well as the relationships between microbial virulence and resistance features. Uropathogenic Escherichia coli was found to be the most frequent bacterial strain isolated from patients with benign prostatic hyperplasia, followed by Enterococcus spp., Enterobacter spp., Klebsiella spp., Proteus spp., Pseudomonas aeruginosa, and Serratia marcescens. Increased resistance rates to tetracyclines, quinolones, and sulfonamides were registered. Besides their resistance profiles, the uropathogenic isolates produced various virulence factors with possible implications in the pathogenesis process. The great majority of the uropathogenic isolates revealed a high capacity to adhere to HEp-2 cell monolayer in vitro, mostly exhibiting a localized adherence pattern. Differences in the repertoire of soluble virulence factors that can affect bacterial growth and persistence within the urinary tract were detected. The Gram-negative strains produced pore-forming toxins-such as hemolysins, lecithinases, and lipases-proteases, siderophore-like molecules resulted from the esculin hydrolysis and amylases, while Enterococcus sp. strains were positive only for caseinase and esculin hydrolase. Our study demonstrates that necessity of investigating the etiology and local resistance patterns of uropathogenic organisms, which is crucial for determining appropriate empirical antibiotic treatment in elderly patients with UTI, while establishing correlations between resistance and virulence profiles could provide valuable input about the clinical evolution and recurrence rates of UTI.


Phytochemical and comparative antibacterial studies on the crude ethanol and aqueous extracts of the leaves of Lecaniodiscus cupanoides Planch (Sapindaceae).
Phytochemical investigation was carried out on the leaves of Lecaniodiscus cupanoides Planch (Sapindaceae). The diameter of the zones of inhibition of the 90% ethanol and aqueous extracts of the leaves were compared in order to determine the relative activity of the extracts against the tested microorganisms and also to verify its claimed ethnomedicinal use in the treatment of microbial infections. Phytochemical tests were carried out employing standard procedures. The antimicrobial activity of the extract was tested against standard strains and clinical isolates of some aerobic bacteria using the agar well diffusion method. Commercial antibiotics were used as positive reference standards to determine the sensitivity of the strains. The minimum inhibitory concentration (MIC) values were also determined using the agar well diffusion method. Preliminary phytochemical studies revealed the presence of flavonoids, tannins, saponins and cardiac glycosides as the chemical classes of compounds present in the crude extract. The extracts showed inhibitory activity against clinical isolates of Bacillus subtilis. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa Staphylococcus aureus and a standard strain of Staphylococcus aureus (NCTC 10788). The ethanol extract was more active than the aqueous extract against all the microorganisms tested, except against the clinical isolates of Staphylococcus aureus. The MIC values ranged from 2.5 to 6.25 mg/mL for all the organisms tested. The results showed that the ethanol extract was more potent than the aqueous extract. The broad spectrum of activity displayed by the extracts would appear to provide the scientific basis for the use of the leaves of Lecaniodicus cupanoides for dressing of boils, burns and cuts in ethnomedicine.


Substance disorder among 100 American Indian versus 200 other patients.
The purpose of this study was to examine the demographic and clinical characteristics among American Indian (AI) patients and other patients with Psychoactive Substance Use Disorders (PSUD). The study was conducted at a university-based, alcohol-drug program in the Upper Midwest. One hundred AI patients presenting sequentially with PSUD were contrasted with 200 other patients (selected at random from 620 patients) presenting at the same clinical facility during the same period with PSUD. Data included demographic characteristics, current DSM-III-R PSUD diagnoses, previous treatment for PSUD, and family history of PSUD. Findings indicated several special aspects of PSUD among AI patients, which have implications for program planning and treatment evaluation.


Scoliosis in spinal muscular atrophy: review of 63 cases.
We reviewed the incidence and severity of scoliosis in 37 patients with the intermediate type and 26 with the mild type of spinal muscular atrophy. In the intermediate type, scoliosis has an early onset and rapid progression before puberty, and a spinal fusion will be needed in virtually all cases. This rapid progression occurred despite routine use of a spinal brace. Hip dislocation was frequently present but, in most cases, was secondary to the pelvic tilt and did not contribute to the scoliosis. In the mild type, the scoliosis was more variable. In the 30% of patients who had scoliosis, progression was rapid during puberty but only in those who had lost ambulation. Of the four children with the intermediate type and the seven with the mild type who walked in light-weight orthoses, progression of scoliosis was slow, except in those who had lost ambulation. The ultimate effect of walking in orthoses is difficult to assess because of small numbers, but it seems to slow or at least delay progressive scoliosis.


Pituitary Gonadotropin Gene Expression During Induced Onset of Postsmolt Maturation in Male Atlantic Salmon: In Vivo and Tissue Culture Studies.
Precocious male maturation causes reduced welfare and increased production costs in Atlantic salmon (Salmo salar) aquaculture. The pituitary produces and releases follicle-stimulating hormone (Fsh), the gonadotropin triggering puberty in male salmonids. However, little is known about how Fsh production is regulated in Atlantic salmon. We examined, in vivo and ex vivo, transcriptional changes of gonadotropin-related genes accompanying the initial steps of testis maturation, in pituitaries of males exposed to photoperiod and temperature conditions promoting maturation (constant light and 16°C). Pituitary fshb, lhb and gnrhr2bba transcripts increased in vivo in maturing males (gonado-somatic index > 0.1%). RNA sequencing (RNAseq) analysis using pituitaries from genetically similar males carrying the same genetic predisposition to mature, but differing by responding or not responding to stimulatory environmental conditions, revealed 144 differentially expressed genes, ~2/3rds being up-regulated in responders, including fshb and other pituitary hormones, steroid-related and other puberty-associated transcripts. Functional enrichment analyses confirmed gene involvement in hormone/steroid production and gonad development. In ex vivo studies, whole pituitaries were exposed to a selection of hormones and growth factors. Gonadotropin-releasing hormone (Gnrh), 17β-estradiol (E2) and 11-ketotestosterone (11-KT) up-regulated gnrhr2bba and lhb, while fshb was up-regulated by Gnrh but down-regulated by 11-KT in pituitaries from immature males. Also pituitaries from maturing males responded to Gnrh and sex steroids by increased gnrhr2bba and lhb transcript levels, but fshb expression remained unchanged. Growth factors (inhibin A, activin A and insulin-like growth factor 1) did not change gnrhr2bba, lhb or fshb transcript levels in pituitaries either from immature or maturing males. Additional pituitary ex vivo studies on candidates identified by RNAseq showed that these transcripts were preferentially regulated by Gnrh and sex steroids, but not by growth factors, and that Gnrh/sex steroids were less effective when incubating pituitaries from maturing males. Our results suggest that a yet to be characterized mechanism up-regulating fshb expression in the salmon pituitary is activated in response to stimulatory environmental conditions prior to morphological signs of testis maturation, and that the transcriptional program associated with this mechanism becomes unresponsive or less responsive to most stimulators ex vivo once males had entered pubertal developmental in vivo.


Age-specific prevalence of hepatitis A antibody in Thai children.
Age-specific prevalence of anti-HAV was determined for 3 groups of children whose mean ages were 12.6, 20.7 and 52.5 months. There were 41, 43 and 99 children in the respective age groups. All children were healthy, from middle to low socioeconomic families in Bangkok and vicinity. None of the children in the two younger age groups had anti-HAV antibody while 2 of 99 children in the oldest age group did. One of them resided in central Bangkok (Amphoe Dusit) and the other in Nonthaburi Province. The overall prevalence of anti-HAV in children under 5 years old was 1.1%. This demonstrates that hepatitis A transmission rates in Bangkok are very low when compared to ten years ago when prevalence rates were as high as 50-65%. From this study hepatitis A vaccine is recommended for 4-5 years old children in Bangkok. We need more epidemiologic data concerning hepatitis A transmission in Thailand before we can consider hepatitis A immunization for the whole country.


Instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis.
To assess the diversified effects of mechanical instability, excessive mechanical loading on subchondral bone remodeling. And to investigate the underlying cartilage degeneration and osteoarthritis (OA) progression in ipsilateral and contralateral knees, given that OA progression always affects joints bilaterally. Anterior cruciate ligament transection (ACLT) of the left knee was used to induce OA in C57/B6 mice for 1, 3 and 6 months. Both left (ipsilateral) and right (contralateral) knees underwent micro-computerized tomography (micro-CT) scan and morphological analysis. The subchondral bone metabolism analysis by immunostaining of tartrate-resistant acid phosphatase (TRAP) and Osterix. Behavioral analyses including von Frey test and CatWalk gait analysis were also performed. Western blot analysis was performed to assess the signaling pathways involved in OA progression. Analyses showed that various changes in ipsilateral and contralateral knees lead to OA progression. Articular cartilage was rapidly destroyed on the ipsilateral side but was only gradually destroyed on the contralateral side. Micro-CT data showed a rapid decrease with a subsequent partial recovery of bone volume in the late stage on the ipsilateral side, while a gradual condensation of bone density was seen on the contralateral side. Immunostaining showed increased osteoclastic and osteoblastic activity in the early stage on the ipsilateral side, but only slight osteoblastic changes on the contralateral side. Behavioral analyses including von Frey and gait analysis showed that contralateral knees compensate ipsilateral mechanical loading, but also that this mechanism failed to work in the late stage. Diversified mechanical loading properties lead to OA progression through different mechanisms of subchondral bone remodeling. Acute ACLT led to OA through bone density reduction, while the contralateral side developed OA gradually due to subchondral bone sclerosis.


Real-time LightCycler PCR for detection and discrimination of Bordetella pertussis and Bordetella parapertussis.
Real-time PCR assays based on the LightCycler technology were developed for individual (simplex PCR) and simultaneous (duplex PCR) detection and discrimination of Bordetella pertussis and Bordetella parapertussis in clinical samples. The assays were evaluated with 113 specimens from patients with and without symptoms of pertussis. Results were compared to those from conventional culture and TaqMan real-time PCR. The analytical sensitivity ranged from 0.1 to 10 CFU for B. pertussis and B. parapertussis, and intra- and interassay variations were less than 7%. Results were available within 2 h. With the simplex format, 21 of 100 samples from patients with clinical symptoms of pertussis were positive for B. pertussis and/or B. parapertussis. With the duplex format, 18 of 100 samples were positive. LightCycler PCR increased the diagnostic sensitivity over that of culture by 2.0-fold (duplex PCR) (P = 0.08) to 2.3-fold (simplex PCR) (P = 0.02). Our data suggest that duplex PCR in this format showed good analytical sensitivity but lost some sensitivity on clinical samples compared with the simplex format.


Measuring Well-Being of Migrant Gig Workers: Exampled as Hangzhou City in China.
The consistent innovations and applications of information technology drive the vigorous development of the gig economy, and generate gig workers such as food delivery workers and couriers, and make a great contribution to stabilizing employment and increasing income. Gig workers, mostly made up of migrants, and suffer from job and status difficulties. Research on the well-being of migrant gig workers can reveal the practical problems and provide suggestions for narrowing the wealth gap to promote social fairness and justice. Taking Hangzhou city in China as an example, this paper explores the well-being of food delivery workers, couriers, and online car-hailing drivers as representatives of migrant gig workers. Firstly, the relevant data are acquired through the questionnaire. Secondly, the characteristics of this group are analyzed through descriptive analysis, namely: most of them are migrant workers aged between 20 and 39 with low occupation satisfaction due to insufficient social security coverage and limited well-being, despite relatively high income. Based on the analysis of differences in demographic variables and structural equation modeling, the factors affecting the well-being of migrant gig workers are studied, which mainly are occupation satisfaction, social interaction, and social security. The results show that occupation satisfaction is positively affected by family characteristics, social interaction, and social security. In addition, family characteristics and social security positively impact social interaction, but the former has no significant effect on well-being. Finally, this paper enriches the research on the well-being of specific migrant gig workers and gives policy suggestions for enhancing the well-being of migrant gig workers in Hangzhou city from the perspective of optimizing the mechanism, pilot construction, and platform provision.


Biodegradation of the acetanilide herbicides alachlor, metolachlor, and propachlor.
Alachlor, metolachlor, and propachlor are detoxified in biological systems by the formation of glutathione-acetanilide conjugates. This conjugation is mediated by glutathione-S-transferase, which is present in microorganisms, plants, and mammals. Other organic sulfides and inorganic sulfide also react through a nucleophilic attack on the 2-chloro group of acetanilide herbicides, but the products are only partially characterized. Sorption in soils and sediments is an important factor controlling the migration and bioavailability of these herbicides, while microbial degradation is the most important factor in determining their overall fate in the environment. The biodegradation of alachlor and metolachlor is proposed to be only partial and primarily cometabolic, and the ring cleavage seems to be slow or insignificant. Propachlor biodegradation has been reported to proceed to substantial (> 50%) mineralization of the ring structure. Reductive dechlorination may be one of the initial breakdown mechanisms under anaerobic conditions. Aerobic and anaerobic transformation products vary in their polarity and therefore in soil binding coefficient. A catabolic pathway for chloroacetanilide herbicides has not been presented in the literature because of the lack of mineralization data under defined cultural conditions.


[Case report of prosthetic treatment for defected jaw with enucleation of the right maxillary sinus tumor].
The patient is a 71-year-old woman who had undergone a gingivectomy due to a gingival carcinoma of right maxillary sinus and a denture was made for the defected jaw. During three years and six months, |3 serves as the guidance tooth had suffered from various symptoms, from the detachment of the neighboring tooth to the use of an OP anchor followed by a partial fracture of the cuspid root. However, |3 has not been removed in accordance to the patient's request. In addition, a relining provided indirectly to the denture, it is still maintained and used for mastication, pronunciation and swallowing functions without difficulty. This is a case that a denture was made for the defected jaw. However, it is important ot take measures in the future, as the remaining tooth is not expected to be preserved for long.


Histologic evaluation of the effects of intrasulcular toothbrushing on human sulcular epithelium.
Nineteen young adult Caucasian males had an average Gingival Index Score of 0.47. Each was asked to demonstrate his present method of toothbrushing: thirteen used the scrub method, and six combined the scrub and roll methods. Control gingival tissue specimens were taken from the mandibular left first bicuspid or first molar regions, and the area was allowed to heal for 40 days. Following complete healing, intrasulcular brushing was used in the mandibular left posterior segment, for 30 seconds daily for a period of 40 days. The brushing was done by the investigator on 28 days and by the subjects on 12 days. The average Gingival Index Score following intrasulcular brushing was 0.25. A gingival specimen was taken from the experimental area of the mandibular left second bicuspid region. Histological findings in control specimens from 13 subjects showed parakeratinization for varying distances in the sulcus epithelium apical to the gingival crest. In six specimens a complete absence of sulcus keratinization was observed. The average Inflammatory Index Score was 1.21. Following intrasculcular brushing, 18 specimens showed a parakeratin layer apical to the gingival crest; in 14, it extended the entire length of the coronal sulcular epithelium or apparent clinical sulcus, whereas in four more it extended well beyond the gingival crest into the sulcus. In the six subjects whose control specimens showed an absence of keratin apical to the gingival crest, parakeratinization of part or all of the clinical sulcus was found following intrasulcular brushing. The average Inflammatory Index Score was 1.015. A moderately intense acute inflammatory reaction was observed within the attachment epithelium in three subjects. Possible therapeutic benefits and hazards of intrasulcular brushing are discussed.


Molecular functions and biological roles of hepatitis B virus x protein.
Chronic infection of hepatitis B virus (HBV) is one of the major causes of hepatocellular carcinoma (HCC) in the world. Hepatitis B virus X protein (HBx) has been long suspected to be involved in hepatocarcinogenesis, although its oncogenic role remains controversial. HBx is a multifunctional regulator that modulates transcription, signal transduction, cell cycle progress, protein degradation pathways, apoptosis, and genetic stability by directly or indirectly interacting with host factors. This review focuses on the biological roles of HBx in HBV replication and cellular transformation in terms of the molecular functions of HBx. Using the transient HBV replication assay, ectopically expressed HBx could stimulate HBV transcription and replication with the X-defective replicon to the level of those with the wild one. The transcription coactivation is mainly contributing to the stimulatory role of HBx on HBV replication although the other functions may affect HBV replication. Effect of HBx on cellular transformation remains controversial and was never addressed with human primary or immortal cells. Using the human immortalized primary cells, HBx was found to retain the ability to overcome active oncogene RAS-induced senescence that requires full-length HBx. At least two functions of HBx, the coactivation function and the ability to overcome oncogene-induced senescence, may be cooperatively involved in HBV-related hepatocarcinogenesis.


Self-repaired Process of a Traumatized Maxillary Central Incisor with Pulp Infarct after Horizontal Root Fracture Monitored by Laser Doppler Flowmetry Combined with Tissue Oxygen Monitor.
Achieving a precise diagnosis of the pulp status of traumatized teeth is difficult. The time to interfere through endodontic treatment for these teeth is greatly dependent on the doctor's experience. A 24-year-old male patient suffered a traumatic injury to tooth #9 that resulted in an apical root horizontal fracture 3 days before he came to the hospital. The injured tooth showed no response to pulp sensitivity testing at the first visit and was discolored 1 week later. Tooth #9 was immobilized to its adjacent teeth for 4 weeks by a composite splint. The patient was asked to make regular follow-up appointments for 72 weeks. The changes in the pulp microcirculation of tooth #9 after the injury were recorded using laser Doppler flowmetry (LDF) and a tissue oxygen monitor (OXY). The LDF was used to directly measure the pulpal blood flow, and the OXY was used to detect the tissue oxygen saturation and total hemoglobin at each appointment. Tooth #9 survived a period of pulp infarct that started at week 4 and showed complete revascularization within 10 weeks. The color of the tooth returned to normal after revascularization. The tooth responded to sensitivity testing at week 58, and radiographic examinations confirmed its hard tissue was healing. Without other clinical signs besides tooth discoloration and an absence of response to pulp sensitivity testing, the complete self-repair of pulp can be expected in teeth with pulp infarct after a horizontal root fracture, and more than 1 year of follow-up is recommended. The use of LDF combined with OXY monitoring has great value in the timely and precise reflection of changes in pulp status after dental trauma.


[Effects and clinical significance of virus load on red blood cell parameters in different stage of hepatitis B].
To evaluate the effect of the viral load on the red blood cell parameters in chronic hepatitis B patients and its clinical significance. In the study, 373 chronic hepatitis B patients were recruited, including 123 alanine transaminase (ALT) normal patients (ALT<40 U/L),128 ALT greater than or equal to the upper limit of normal, and less than 2 times higher than the upper limit of normal patients(40 U/L ≤ALT<80 U/L), and 122 ALT greater than or equal to 2 times higher than the upper limit of normal patients (ALT≥80 U/L). The blood routine parameters were measured by automatic blood cell counter. The liver function parameters were measured by automatic biochemical analyzer, the hepatitis B virus loads were measured by quantitative PCR analyzer and the results were analyzed by covariance analysis. In the ALT normal chronic hepatitis B patients group, the viral load had minor effects on the red blood cell parameters.But in the ALT abnormal chronic hepatitis B patients group, the viral load had a significant effect on the red blood cell parameters, and the effect was most manifest in the ALT≥ double upper limit of normal group. The specific performance was that with the viral load increasing, the red blood cell [low copies group (4.10±0.67)×10(12)/L,medium copies group (3.92±0.69)×10(12)/L,high copies group (3.54±0.90) ×10(12)/L], the hemoglobin[low copies group (129.66±21.12 ) g/L, medium copies group (126.23±23.38) g/L, high copies group (112.98±27.77) g/L], the hematocrit (low copies group 37.66±5.68, medium copies group 37.03±6.03, high copies group 33.34±8.15) decreased(P=0.006,0.007,0.010),the mean corpuscular volume [low copies group (92.17±6.53) fL, medium copies group (94.85±7.95) fL, high copies group (101.63±11.33) fL], the mean corpuscular hemoglobin [low copies group (31.70±2.22) pg, medium copies group (33.11±3.62) pg, high copies group (34.65±3.13) pg], the mean corpuscular hemoglobin concentration [low copies group (344.28±17.17) g/L, medium copies group (351.33±16.90) g/L, high copies group (358.12±15.67) g/L], and the red blood cell distribution width-standard deviation [low copies group (52.49±9.04) fL, medium copies group (56.96±7.19) fL, high copies group (61.23 ±7.23) fL] increased(P=0.000,0.000,0.002,0.000). Observing the effect of the viral load on the red blood cell parameters in chronic hepatitis B patients can reflect the effect of hepatitis B virus on the immune response and liver function in the different pathological stages, providing theoretical support for the clinical antiviral treatment.


Demonstration of interleukin-1 beta transcripts in acute myeloblastic leukemic cells by in situ hybridization.
The cells from some patients with acute myeloblastic leukemia will secrete autostimulatory cytokines in tissue culture without the addition of stimulators such as phorbol 12-myristate 13-acetate. Production of interleukin-1 beta (IL-1 beta), for example, has been observed in up to 50% of cases. In order to investigate the nature of the cell secreting IL-1 beta in AML, we used an antisense RNA probe to detect specific IL-1 beta transcripts in individual leukemic cells by in situ hybridization. In fresh, uncultured cells, IL-1 beta transcripts were observed in 1-40% of undifferentiated leukemic blast cells in 17 of 19 cases. In situ hybridization was at least as sensitive as Northern blot analysis in detecting IL-1 beta transcripts. No correlation of IL-1 beta transcript expression with FAB classification was observed. Normal blood and bone marrow mononuclear cells did not contain cells expressing IL-1 beta transcripts. These results support the concept that the regulation of cytokine genes in AML cells is aberrant.


Serum neurofilament light chains in progressive multiple sclerosis patients treated with repeated cycles of high-dose intravenous steroids.
Background and objectives: In progressive multiple sclerosis (MS) patients, CNS inflammation trapped behind a closed blood brain barrier drives continuous neuroaxonal degeneration, thus leading to deterioration of neurological function. Therapeutics in progressive MS are limited. High-dose intravenous glucocorticosteroids (HDCS) can cross the blood-brain barrier and may reduce inflammation within the CNS. However, the treatment efficacy of HDCS in progressive MS remains controversial. Serum neurofilament light chains (sNfL) are an established biomarker of neuroaxonal degeneration and are used to monitor treatment responses. We aimed to investigate whether repeated cycles of intravenous HDCS reduce the level of sNfL in progressive MS patients. Methods: We performed a monocentric observational study of 25 patients recruited during ongoing clinical routine care who were treated with repeated cycles of intravenous HDCS as long-term therapy for their progressive MS. sNfL were measured in 103 repeated blood samples (median time interval from baseline 28 weeks, range 2-55 weeks) with the Single Molecular Array (SiMoA) technology. The Expanded Disability Status Score (EDSS) was documented at baseline and follow-up. Results: The median age of patients was 55 years (range 46-77 years) with a median disease duration of 26 years (range 11-42 years). sNfL baseline levels at study inclusion were significantly higher in progressive MS patients compared to age-matched healthy controls (median 16.7 pg/ml vs 11.5 pg/ml, p=0.002). sNfL levels showed a positive correlation with patient age (r=0.2, p=0.003). The majority of patients (72%, 16/23) showed reduced sNfL levels ≥20 weeks after HDCS compared to baseline (median 13.3 pg/ml, p=0.03). sNfL levels correlated negatively with the time interval from baseline HDCS therapy (r=-0.2, p=0.03). This association was also evident after correction for treatment with disease-modifying drugs (adjusted R2=0.10, p=0.001). The EDSS remained stable (median 6.5) within a median treatment duration of 26 weeks (range 13-51 weeks). Conclusion: Although larger studies are needed to confirm our findings, we were able to demonstrate that HDCS treatment reduces sNfL levels and therefore may slow down neuroaxonal damage in a subgroup of patients with progressive MS. Moreover, a stable EDSS was observed during therapy. Findings suggest that HDCS may be beneficial for the treatment of progressive MS.


Characterization of the immunodeficiency of RIIIS/J mice: immune response to polysaccharide antigens.
RIIIS/J mice lack an autosomal dominant gene(s) that influences the magnitude of the antibody response to several polysaccharide antigens of bacterial origin. Low responsiveness is demonstrable whether polysaccharide is administered as a T-helper-cell-independent or -dependent antigen conjugated to an immunogenic carrier; however, RIIIS/J mice make good anti-hapten antibody responses to haptenated polysaccharides. The low antibody responses of RIIIS/J mice to type III pneumococcal polysaccharide do not appear to be the results of an imbalance in the activity of regulatory T lymphocytes. Compared with other strains of mice, RIIIS/J mice elicit low antibody responses to lipopolysaccharide (LPS). They do not develop a cyclic primary or secondary antibody response to Escherichia coli O113 LPS; the latter is not due to a lack of mitogenic response to E. coli O113 LPS. They also produce auto-anti-idiotypic antibody after being immunized with trinitrophenyl-Ficoll.


Number of knee and ankle injuries is associated with poor physical but not mental health.
The knee and ankle are among the most commonly injured joints in the body. Long-term strength and neuromuscular control deficits are common following these injuries, yielding lifelong disability and poor quality of life. However, it is unknown how the number of injuries sustained influences quality of life. Determine the association between the number of ankle or knee injuries sustained and physical and mental quality of life. A total of 806 ankle-injured (age:45.2 ± 15.3 yrs; body mass index [BMI]:28.6 ± 7.4 kg/m2), 658 knee-injured (age:49.3 ± 16.1 yrs; BMI:28.4 ± 7.4 kg/m2), and 996 uninjured (age:43.4 ± 16.1 yrs; BMI:26.9 ± 6.5 kg/m2) adults completed the SF-8 survey to determine the physical (PCS) and mental (MCS) contributions to quality of life. Respondents were categorized by injury history (ankle, knee, none) and number of injuries (0, 1, 2, or 3 or more [3+]) to the same joint. Backward linear regression models were used to determine the association between quality of life, age, and injury history separately for SF-8 PCS and MCS, as well as ankle versus knee injury. Reporting 1, 2, or 3+ ankle injuries along with age predicted SF-8 PCS (P < 0.001). Further, 1 or 2 ankle injuries and age (P < 0.001) predicted SF-8 MCS. Reporting 1, 2, or 3+ knee injuries along with age significantly predicted SF-8 PCS (P < 0.001). Age, but not knee injury history, significantly predicted SF-8 MCS (P < 0.001). Current age and history of sustaining at least one injury negatively impact physical quality of life following either a knee or ankle injury. However, mental quality of life was predicted most consistently by age. Efforts to reduce injuries should be employed to improve quality of life, but more research is needed to determine what other factors contribute to quality of life across the lifespan.


Assessing chronic pain in cognitively impaired elderly adults.
Too often, assessment of pain in the cognitively impaired population is not conducted as well as it could be. Pain assessment in impaired elderly patients is a complicated clinical challenge. Notwithstanding, the prevalence of pain among elderly patients is often high and often carries the risk of serious complications and decreased quality of life. The authors identify selected behaviors that demonstrate the presence of pain in cognitively impaired persons. Nurses must be aware of these behavioral indicators and their value in assessing for and treating pain in this special population.


Trajectories of loneliness and objective social isolation and associations between persistent loneliness and self-reported personal recovery in a cohort of secondary mental health service users in the UK.
Loneliness is a frequent and distressing experience among people with mental health problems. However, few longitudinal studies have so far investigated the trajectories of loneliness and objective social isolation, and the extent to which both issues may impact mental health outcomes among mental health service users. Therefore, this study aims to describe the trajectories of loneliness and objective social isolation and their associations with self-rated personal recovery among people leaving crisis resolution teams (CRTs). A total of 224 participants receiving care from CRTs (recruited for a large multi-site randomised controlled trial) were included in this longitudinal cohort study. They completed the eight-item University of California at Los Angeles Loneliness Scale (ULS-8), Lubben-Social Network Scale (LNSN-6), and the Questionnaire about the Process of Recovery (QPR) (primary outcome) at baseline, 4- and 18-month follow-up, as well as baseline sociodemographic and clinical variables. We compared groups who were persistently lonely (at all time points), intermittently lonely (at one or two time points) and never lonely. After adjusting for all potential confounders and baseline predictive variables, persistent severe loneliness was associated with worse personal recovery at 18-month follow-up compared with the never lonely (reference group) (coef. = - 12.8, 95% CI -11.8, - 3.8, p < .001), as was being intermittently lonely (coef. = - 7.8, 95% CI -18.8, - 6.8, p < .001). The persistently objectively social isolated group (coef. = - 9.8, 95% CI -15.7, - 3.8, p = .001) also had poorer self-rated recovery at 18-month follow-up than those who were not socially isolated at any timepoint (i.e., reference category). Results suggest that both persistent loneliness and objective social isolation are associated with poorer self-rated recovery following a crisis, compatible with a causal relationship. These findings suggest a potential role for interventions aimed at alleviating loneliness and objective social isolation in improving recovery outcomes for people with mental health symptoms. Increased awareness of both issues among health practitioners is also warranted.


[Fecunditiy and reproductive activity of Argas (A.) reflexus (Fabricius, 1794) (Acari: Ixodida: Argasidae) under laboratory conditions].
Fecundity and reproductive activity of 179 females of Argas (A.) reflexus in laboratory conditions, i.e. at temperature 23 +/- 1 degree C and 75% of relative humidity were observed. Under these conditions reproduction activity of females fed in spring lasted since March till August. However, most of females (63.0-91.8%) laid eggs in June and July. Disturbances in egg-laying process of Argas (A.) reflexus females fed in abnormal time, i.e., in autumn and kept in laboratory conditions, were stated. These females were active since December till July (maximum activity was observed in February-34.3% and March-40.0%). Pre-oviposition and oviposition periods were observed in this study, too.


[Video-guided TUR].
Video-TUR has become a very important new technique in urology, causing far less discomfort than conventional techniques for the surgeon. A mini-chip camera (Olympus OTVS-2) is attached to the lens system of a continuous-flow resectoscope (Olympus). A television monitor (Sony PVM 1442) provides reliable guidance for the cutting loop when resection is necessary for the treatment of benign hypertrophy or carcinoma of the prostate or carcinoma of the bladder. To maintain a good intravesical flow system, which is very important for a clear field of view, a suprapubic cystostomy should be placed. The surgeon sits in a comfortable position with both eyes on the screen so that eye-strain, back pain and mental stress can be reduced. The excellent depth perception is due to a 50-times enlargement by the camera, so that tissue-orientated TUR is possible. Even when it is not possible to place the patient in an optimal position, because of scrotal hernia or coxarthrosis, TUR can still easily be performed. In 120 transurethral prostate resections and 30 transurethral bladder tumour resections, the video technique has proved comfortable for the surgeon and safe for the patient. Video-TUR has been helpful in the presentation of this technique in urologic teaching. TUR of the prostate has been freed from much of its mystique, since the procedure can be watched while it is in progress. The video technique has opened up a new epoch in endourology, whose importance cannot yet be realized.


Polyoxomolybdate-Calix[4]arene Hybrid: A Catalyst for Sulfoxidation Reactions with Hydrogen Peroxide.
An easily accessible polyoxomolybdate-calix[4]arene hybrid 1 has been synthesized and applied as a heterogeneous catalyst in the sulfoxidation of thioethers to sulfoxides and to sulfones under strictly stoichiometric amounts of 30% H2O2 in CH3CN as the solvent. This study represents the first promising example of successful employment of calixarenes-polyoxometalate (POM) hybrid materials in the area of catalytic oxidations.


Identifying the drivers of abundance and size of the invasive ctenophore Mnemiopsis leidyi in Northwestern Mediterranean lagoons.
Acknowledged as among the worst invasive marine species, Mnemiopsis leidyi has spread through European Seas since the mid-1980's. Here we report a bimonthly survey conducted in 2010-11 in three lagoons (Bages-Sigean, Thau and Berre) and at two adjacent coastal stations (Sète and SOMLIT-Marseille) along the French Mediterranean coast. M. leidyi was present only in Berre and Bages-Sigean with maximum abundances observed in late summer. M. leidyi adults were present year round in Berre with the largest organisms (∼6 cm) observed in April. In Bages-Sigean, they occurred in sufficient abundance to be recorded by fishermen between August and November. Multiple linear regressions highlighted that abundance in both lagoons was mainly influenced by direct effects of salinity and chlorophyll-a, and temperature to a lesser extent. While M. leidyi has not yet been recorded in Thau, the lagoon is continually monitored to detect the potential establishment of M. leidyi.


Sexual function and satisfaction in men after laser treatment for penile carcinoma.
We evaluate sexual function, sexual satisfaction and cosmetic results after laser treatment of penile carcinoma. A total of 67 patients were treated at our clinic for penile cancer using combined carbon dioxide and neodymium:YAG lasers from 1986 to 2000. At the time of this study 58 men, with a mean age of 64 years were alive, of whom 46 (79%) agreed to participate in a structured face-to-face interview addressing sexual function, sexual satisfaction and cosmetic results. The length of time that had elapsed since treatment ranged from 6 months to 15 years (median 3 years). Of 40 patients (87%) who had been sexually active before treatment 30 (75%) had resumed activities at the time of the interview. Unaltered erectile function after treatment was reported by 33 patients (72%), 10 patients (22%) reported decreased function and 3 (6%) reported improved function. Of the 46 patients 23 (50%) were satisfied/very satisfied with their sexual life. After treatment only 3 of 30 (10%) of the evaluable men had dyspareunia. The cosmetic results were considered satisfying/very satisfying by 36 (78%) men. Laser treatment of localized penile carcinoma preserves the penis and generally provides satisfactory sexual function and cosmetic results.


Evaluation of the health hazards involved in house-spraying with DDT.
The dermal and respiratory exposure of workers during house-spraying operations has been measured to find out the main factors affecting the exposure, and to develop effective, acceptable protective measures and clothing. Dermal exposure was found to be much greater than respiratory exposure. The major factors affecting exposure with a single concentration of formulation appeared to be spray-pump pressure, height of area being sprayed, and absorbency of surface. Temperature, type of formulation, and nozzle size had little or no effect on exposure. A plastic cape, a hard hat with a plastic visor, and rubberized gauntlet gloves gave a fully clothed man almost complete protection from dermal and respiratory exposure. A tropical helmet equipped with a plastic-netting veil is proposed for field testing. This equipment gave good protection of the shoulders, back, and chest and excellent protection of the face and neck.


Expanding our borders: Cultural Diversity and Ethnic Minority Psychology's special issue on immigration.
Introduces the current special issue of the journal, Cultural Diversity and Ethnic Minority Psychology. This special issue focuses on the topic of immigration and highlights the important within group differences often overlooked when immigrants are conceptualized as a homogeneous group. The articles in this journal consider a variety of microsystems, such as educational settings, ethnic and gay communities, and communities with anti-immigration laws.


Structural similarity between the flagellar type III ATPase FliI and F1-ATPase subunits.
Construction of the bacterial flagellum in the cell exterior proceeds at its distal end by highly ordered self-assembly of many different component proteins, which are selectively exported through the central channel of the growing flagellum by the flagellar type III export apparatus. FliI is the ATPase of the export apparatus that drives the export process. Here we report the 2.4 A resolution crystal structure of FliI in the ADP-bound form. FliI consists of three domains, and the whole structure shows extensive similarities to the alpha and beta subunits of F0F1-ATPsynthase, a rotary motor that drives the chemical reaction of ATP synthesis. A hexamer model of FliI has been constructed based on the F1-ATPase structure composed of the alpha3beta3gamma subunits. Although the regions that differ in conformation between FliI and the F1-alpha/beta subunits are all located on the outer surface of the hexamer ring, the main chain structures at the subunit interface and those surrounding the central channel of the ring are well conserved. These results imply an evolutionary relation between the flagellum and F0F1-ATPsynthase and a similarity in the mechanism between FliI and F1-ATPase despite the apparently different functions of these proteins.


Consequences of Pathogen Lists: Why Some Diseases May Continue to Plague Us.
The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to specific goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that address what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular focus on what products we need to have.


Coulomb Bound States of Strongly Interacting Photons.
We show that two photons coupled to Rydberg states via electromagnetically induced transparency can interact via an effective Coulomb potential. This interaction gives rise to a continuum of two-body bound states. Within the continuum, metastable bound states are distinguished in analogy with quasibound states tunneling through a potential barrier. We find multiple branches of metastable bound states whose energy spectrum is governed by the Coulomb potential, thus obtaining a photonic analogue of the hydrogen atom. Under certain conditions, the wave function resembles that of a diatomic molecule in which the two polaritons are separated by a finite "bond length." These states propagate with a negative group velocity in the medium, allowing for a simple preparation and detection scheme, before they slowly decay to pairs of bound Rydberg atoms.


Spontaneous symmetry breaking in a quenched ferromagnetic spinor Bose-Einstein condensate.
A central goal in condensed matter and modern atomic physics is the exploration of quantum phases of matter--in particular, how the universal characteristics of zero-temperature quantum phase transitions differ from those established for thermal phase transitions at non-zero temperature. Compared to conventional condensed matter systems, atomic gases provide a unique opportunity to explore quantum dynamics far from equilibrium. For example, gaseous spinor Bose-Einstein condensates (whose atoms have non-zero internal angular momentum) are quantum fluids that simultaneously realize superfluidity and magnetism, both of which are associated with symmetry breaking. Here we explore spontaneous symmetry breaking in 87Rb spinor condensates, rapidly quenched across a quantum phase transition to a ferromagnetic state. We observe the formation of spin textures, ferromagnetic domains and domain walls, and demonstrate phase-sensitive in situ detection of spin vortices. The latter are topological defects resulting from the symmetry breaking, containing non-zero spin current but no net mass current.


A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis.
Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and Bacillus anthracis-specific, monoclonal antibody (mAb) (i.e., Raxibacumab and obiltoxaximab). In this study, we investigated the activity of immunomodulators, which potentiate inflammatory responses through innate immune receptors. The rationale for the use of innate immune receptor agonists as adjunctive immunomodulators for infectious diseases is based on the concept that augmentation of host defense should promote the antimicrobial mechanism of the host. Our aim was to explore the anti-B. anthracis effector function of Toll-like receptor (TLR) agonists using a mouse model. Amongst the six TLR ligands tested, Pam3CSK4 (TLR1/2 ligand) was the best at protecting mice from lethal challenge of B. anthracis. We then evaluated the activity of a novel TLR2 ligand, DA-98-WW07. DA-98-WW07 demonstrated enhanced protection in B. anthracis infected mice. The surviving mice that received DA-98-WW07 when re-challenged with B. anthracis 20 days post the first infection showed increased survival rate. Moreover, ciprofloxacin, when treated in adjunct with a suboptimal concentration of DA-98-WW07 demonstrated augmented activity in protecting mice from B. anthracis infection. Taken together, we report the prophylactic treatment potential of DA-98-WW07 for anthrax and the utility of immunomodulators in combination with an antibiotic to treat infections caused by the B. anthracis bacterium.


Management of a Periodontal Pocket Using a Removable Orthodontic Appliance and Nonsurgical Periodontal Therapy.
Purpose. As documented in the literature, bony defects can be managed by an orthodontic approach. Methods. This case report describes the treatment of a bony defect caused by orthodontic malposition through phase I periodontal therapy and a simple removable orthodontic appliance used for the first time in a 20-year-old girl. Results. The periodontal pocket was reduced from 8 mm to 3 mm shortly after treatment. Conclusion. This case report concludes that orthodontic therapy can be used successfully in treatment of bony defects caused by mesially tilted molars.


Data Sources Regarding the Nonmedical Use of Pharmaceutical Opioids in the United States.
Recent increases in the nonmedical use of pharmaceutical opioids and the adverse outcomes associated with them have stimulated a large amount of research and data collection on this public health problem. Systematic organization of the available data sources is needed to facilitate ongoing research, analysis, and evaluation. This work offers a systematic categorization of data sources regarding the nonmedical use of pharmaceutical opioids in the United States. A list of keywords regarding the nonmedical use of pharmaceutical opioids was used to conduct systematic searches in PubMed®. Filtration of search results generated 92 peer-reviewed academic articles, published between January 1995 and April 2012, as well as a number of primary data sources. Lists of topics were developed independently by two researchers which were later compared and consolidated. All sources were then categorized according to their relevance to each of these topics and according to their capacity for geographical and longitudinal trend analysis. Tables cataloging data sources can be used to identify data relevant to specific topics in diversion, nonmedical use, and adverse outcomes associated with pharmaceutical opioids, and they illustrate global trends in data coverage, identifying several topics that have minimal data. A network diagram illustrates global trends in data coverage, showing variation among sources in the number of topics they cover, as well as variation among topics in the number of sources that cover them. The categorization of data sources is hoped to facilitate ongoing research, analysis, and evaluation of this public health problem by serving as a guide for researchers, policy makers, and others who seek data regarding the nonmedical use of pharmaceutical opioids in the United States.


Role of different brain structures in the behavioural expression of WIN 55,212-2 withdrawal in mice.
We have evaluated several responses induced by the cannabinoid agonist WIN 55,212-2 related to its addictive properties, including rewarding effects and the development of physical dependence in mice. Moreover, we have studied the specific involvement of several brain regions with high density of CB1 cannabinoid receptors, such as striatum, hippocampus, amygdala and cerebellum, in the behavioural expression of SR 141716A-precipitated WIN 55,212-2 withdrawal. The systemic administration of the CB1 receptor antagonist SR 141716A (10 mg kg(-1), s.c.) precipitated behavioural signs of withdrawal in mice chronically treated with WIN 55,212-2 (1 and 2 mg kg(-1), intraperitoneal (i.p.)), revealing the development of physical dependence. The microinjection of SR 141716A (1.5 and 3 micrograms) into the cerebellum induced severe manifestations of abstinence in mice dependent on WIN 55,212-2 (1 mg kg(-1), i.p.). Out of 10 signs evaluated, seven were statistically significant: wet dog shakes, body tremor, paw tremor, piloerection, mastication, genital licks and sniffing. When the cannabinoid antagonist was administered into the hippocampus and the amygdala, a moderate but significant withdrawal syndrome was also observed. However, no signs of abstinence were induced when SR 141716A was microinjected into the striatum. WIN 55,212-2 produced rewarding effects in the place-conditioning paradigm in mice pre-exposed to a priming injection of the drug. These results show a reliable behavioural model to reveal rewarding effects and physical dependence induced by the repeated administration of WIN 55,212-2 in mice. The cerebellum and to a lesser extent the hippocampus and the amygdala participate in the behavioural expression of cannabinoid withdrawal.


Fluorodeoxyglucose positron emission tomography may aid the diagnosis of aggressive primary prostate cancer: A case series study.
Recent evidence has shown that positive results may be observed for fluorodeoxyglucose-positron emission tomography (FDG-PET) in undifferentiated, biologically aggressive and metastatic tumors. The present study describes a case series of six patients with normal prostate-specific antigen (PSA) serum levels who underwent FDG-PET due to other causes. Positive PET results were observed at the prostate and the patients were subsequently diagnosed with high-risk prostate cancer. Clinical, anamnestic, laboratory and instrumental data were collected from six asymptomatic patients with total serum PSA levels of <4 ng/ml who had undergone FDG-PET due to other causes. The FDG-PET and prostate biopsy were positive for prostate cancer. All the patients were treated with radical intent. The median age was 66 years (range, 52-72 years), the median total PSA value was 2.4 ng/ml (range, 1.5-3.9 ng/ml) and the body mass index was 26.4 (range, 21.8-30.2). Three of the six patients underwent FDG-PET due to a clinical suspicion of multiple myeloma, while three patients were examined for other oncological diseases. The pathological analysis at the prostate biopsy revealed three patients with a Gleason score of 6, two with a score of 7 (4+3) and one with a score of 8 (4+4). Five of the six patients were treated by radical prostatectomy and one by radiotherapy. The pathological analysis revealed one patient of pT2a stage, three of pT2c and one of pT3b. No patients demonstrated lymph node invasion. The definitive Gleason score was 3+3 in one patient, 4+3 in one patient, 4+4 in two patients and 5+3 in one patient. Following a median follow-up time of six months (range, 1-12 months), five of the six patients underwent FDG-PET again, which revealed negative results. At the end of this study, these patients were alive without evidence of disease. By contrast, one patient demonstrated positive FDG-PET results. In conclusion, FDG-PET has been used to characterize prostate cancers in patients with apparently normal PSA levels.


MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk.
We sought to examine the association between MC1R variants and the risk of melanoma and breast cancer in Polish population. We also determined the prevalence of compound heterozygous carriers of MC1R and CDKN2A (A148T) variants. We examined 500 unselected melanoma cases, 511 consecutive invasive breast cancer patients, 800 newborns, 421 healthy adults matched for sex and age with the melanoma cases and 511 healthy women matched for sex and age with the breast cancer cases. A statistically significant association of all 4 MC1R variants with the melanoma risk was found. For the R151C variant p value was 0.000008 and odds ratio 2.9; for the V60L variant p value was 0.007 and OR 1.78; for the R160C p was 0.006 and OR 1.76; for the R163Q p was 0.015 and odds ratio 2.1. None of the compound heterozygotes were significantly over-represented among any of the melanoma cases, the highest OR (4.2) observed in patients harbouring the A148T variant in CDKN2A and the R151C variant in MC1R. Positive association was found between carrying any of the MC1R variants and (i) increased occurrence of melanoma among I degree relatives of the carriers; (ii) increased occurrence of melanoma on UV-non-exposed skin areas. We also observed a tendency of increased risk of multiple melanomas among carriers of MC1R variants. The haplotype analysis demonstrates that MC1R variants do not co-occur in cis, compound carriers have both alleles affected. We found no association with the MC1R variants and breast cancer risk. In conclusion, the results of this population-based study show herein that MC1R variants are associated with increased melanoma risk in the Polish population. The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T.


On the origins of strain inhomogeneity in amorphous materials.
Strain is a crucial measure of materials deformation for evaluating and predicting the mechanical response, strength, and fracture. The spatial resolution attainable by the modern real and reciprocal space techniques continues to improve, alongside the ability to carry out atomistic simulations. This is offering new insights into the very concept of strain. In crystalline materials, the presence of well-defined, stable atomic planes allows defining strain as the relative change in the interplanar spacing. However, the presence of disorder, e.g. locally around defects such as dislocation cores, and particularly the pervasive atomic disorder in amorphous materials challenge existing paradigms: disorder prevents a reference configuration being defined, and allows strain to be accommodated in a different manner to crystalline materials. As an illustration, using experimental pair distribution function analysis in combination with Molecular Dynamic (MD) simulations, we highlight the importance of bond angle change vs bond stretching for strain accommodation in amorphous systems.


Antibodies against alpha-fodrin are associated with sicca syndrome in the general population.
The significance of antibodies against alpha-fodrin compared to antibodies against Ro (SSA) as markers of Sjögren's syndrome has been controversially discussed. We therefore compared the association of alpha-fodrin and Ro antibodies with dry eyes and dry mouth in the general population. In 168 "normal" participants, the prevalence of IgA antibodies against alpha-fodrin was 5% and of IgG antibodies against alpha-fodrin was 3%. IgA antibodies against alpha-fodrin were present in 3 of 4 and IgG antibodies against alpha-fodrin in 2 of 4 participants with the combination of dry eyes and dry mouth (P = 0.0002 and 0.005). Only one participant had antibodies against Ro and had dry eyes but normal saliva production. Antibodies against alpha-fodrin are associated with sicca syndrome and may be valuable diagnostic markers in patients with Sjögren's syndrome lacking Ro antibodies.


Male-specific volume expansion of the human hippocampus during adolescence.
To clarify the developmental brain changes during adolescence, brain morphology was compared between healthy younger adolescent and elder adolescent subjects using both voxel-based morphometry (VBM) and volumetric region-of-interest (ROI) analysis of magnetic resonance imaging (MRI). High-resolution three-dimensional MRI scans were acquired in 23 (10 males and 13 females) younger adolescent subjects (13-14 years) and 30 (15 males and 15 females) elder adolescent subjects (19-21 years). Whole-brain analysis by VBM revealed that the elder adolescent subjects had significantly more gray matter in the left medial temporal regions than the younger adolescent subjects and significantly less gray matter in the left medial frontal region (Brodmann area 6). In the volumetric analysis, significantly less cerebral gray matter volume and significantly greater cerebral white matter volume were found in elder adolescents compared with younger adolescents. The volume of the hippocampus was significantly larger in male elder adolescents than in male younger adolescents. The volume of the parahippocampal gyrus did not differ between younger and elder adolescent subjects. These results suggest a robust maturational process ongoing in the human hippocampus during adolescence, especially in males. The possible relevance of these findings to progress in myelination and implications in psychiatric disorders were discussed.


Antisocial behaviour and psychopathy: Uncovering the externalizing link in the P3 modulation.
In 2009, Gao and Raine's meta-analysis analysed P3 modulation over the antisocial spectrum. However, some questions remained open regarding the P3 modulation patterns across impulsive and violent manifestations of antisocial behaviour, phenotypic components of psychopathy, and P3 components. A systematic review of 36 studies was conducted (N=3514) to extend previous results and to address these unresolved questions. A clear link between decreased P3 amplitude and antisocial behaviour was found. In psychopathy, dimensional approaches become more informative than taxonomic models. Distinct etiological pathways of psychopathy were evidenced in cognitive tasks: impulsive-antisocial psychopathic traits mainly predicted blunted P3 amplitude, while interpersonal-affective psychopathic traits explained enhanced P3 amplitude. Supporting the low fear hypothesis, the interpersonal-affective traits were associated with reduced P3 amplitude in emotional-affective learning tasks. From the accumulated knowledge we propose a framework of P3 amplitude modulation that uncovers the externalizing link between psychopathy and antisocial behaviour. However, the main hypotheses are exploratory and call for more data before stablishing robust conclusions.


Magnesium and the anaesthetist.
Magnesium plays an important role as a cofactor in many of the body's critical functions and reactions. A deficiency or excess of extracellular magnesium can produce significant signs and symptoms. Hypomagnesaemia is a common finding in hospitalised patients, especially those in critical care areas. Anaesthetising hypomagnesaemic patients may exacerbate pre-existing cardiovascular disease and increase the risk of perioperative dysrhythmias. A low serum magnesium level usually suggests a total body deficiency of magnesium. Treatment of magnesium deficiency is by parenteral magnesium and should be instituted prior to surgery. Hypermagnesaemia is often iatrogenic and is more likely in patients with renal dysfunction who are receiving oral or parenteral magnesium. The specific antidote is intravenous calcium. Anaesthetised patients with high serum magnesium levels are at risk from hypotension, potentiation of non-depolarising neuromuscular blockers, postoperative respiratory failure and cardiac arrest.


A fast photoswitch for minimally perturbed peptides: investigation of the trans-->cis photoisomerization of N-methylthioacetamide.
Thio amino acids can be integrated into the backbone of peptides without significantly perturbing their structure. In this contribution we use ultrafast infrared and visible spectroscopy as well as state-of-the-art ab initio computations to investigate the photoisomerization of the trans form of N-methylthioacetamide (NMTAA) as a model conformational photoswitch. Following the S2 excitation of trans-NMTAA in water, the return of the molecule into the trans ground state and the formation of the cis isomer is observed on a dual time scale, with a fast component of 8-9 ps and a slow time constant of approximately 250 ps. On both time scales the probability of isomerization to the cis form is found to be 30-40%, independently of excitation wavelength. Ab initio CASPT2//CASSCF photochemical reaction path calculations indicate that, in vacuo, the trans-->cis isomerization event takes place on the S1 and/or T1 triplet potential energy surfaces and is controlled by very small energy barriers, in agreement with the experimentally observed picosecond time scale. Furthermore, the calculations identify one S2/S1 and four nearly isoenergetic S1/S0 conical intersection decay channels. In line with the observed isomerization probability, only one of the S1/S0 conical intersections yields the cis conformation upon S1-->S0 decay. A substantially equivalent excited-state relaxation results from four T1/S0 intersystem crossing points.


Towards direct enzyme wiring: a theoretical investigation of charge carrier transfer mechanisms between glucose oxidase and organic semiconductors.
In this work, a general theoretical and numerical approach based on semiconductor theory, which could be applied to a study of direct enzyme wiring, has been discussed. Marcus-Hush theory was applied to evaluate the potential transfer of charge carriers (holes and electrons) between glucose oxidase (GOx) and organic semiconductors. Two mechanisms of multistep hopping of charge to/from the oxidised/reduced flavin-based moiety through residues of aromatic amino acids located in GOx and long range charge direct tunnelling from the cofactor to the organic semiconductor surface have been proposed and evaluated. It was determined that the hole-hopping mechanism is possible and proceeds at a low ionization potential of the organic semiconductor. The calculations reveal that hopping of electrons is blocked, but direct electron tunnelling between the cofactor and the organic semiconductor is still probable. The most optimal conditions and tunable characteristics of GOx-based biosensors such as the ionization potential, electron affinity of organic semiconductors and distance between the enzyme and surface were estimated for the first time.


Loss of Mitochondrial Protease CLPP Activates Type I IFN Responses through the Mitochondrial DNA-cGAS-STING Signaling Axis.
Caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP) is a serine protease that degrades damaged or misfolded mitochondrial proteins. CLPP-null mice exhibit growth retardation, deafness, and sterility, resembling human Perrault syndrome, but also display immune system alterations. However, the molecular mechanisms and signaling pathways underlying immunological changes in CLPP-null mice remain unclear. In this study, we report the steady-state activation of type I IFN signaling and antiviral gene expression in CLPP-deficient cells and tissues, resulting in marked resistance to RNA and DNA virus infection. Depletion of the cyclic GMP-AMP (cGAS)-stimulator of IFN genes (STING) DNA sensing pathway reduces steady-state IFN-I signaling and abrogates the broad antiviral phenotype of CLPP-null cells. Moreover, we report that CLPP deficiency leads to mitochondrial DNA (mtDNA) instability and packaging alterations. Pharmacological and genetic approaches to deplete mtDNA or inhibit cytosolic release markedly reduce antiviral gene expression, implicating mtDNA stress as the driver of IFN-I signaling in CLPP-null mice. Our work places the cGAS-STING-IFN-I innate immune pathway downstream of CLPP and may have implications for understanding Perrault syndrome and other human diseases involving CLPP dysregulation.


Schizophrenia from a neuropsychiatric perspective.
Our understanding of schizophrenia has increased substantially in recent years. This is due to technological advances that have improved our ability to assess neuropsychiatric function and the genetic underpinnings of the disease. While diagnostic classification still relies on the presentation of the more overt symptoms of the disease, the neuropsychiatric perspective provides a more accurate and comprehensive understanding of the illness. This perspective provides insight into the etiology and treatment of schizophrenia. This article provides an overview of schizophrenia from the broad viewpoint of neuropsychiatry.


The application of GnRH analogues in the treatment of uterine myomas in perimenopausal women.
Our objective was to determine whether long GnRH agonists induce effective and persistent shrinkage of uterine myomas in perimenopausal women, as well as to determine the usefulness of Doppler sonography study in evaluating the therapy benefit. The study covers 30 patients with symptomatic myomas in perimenopausal period. We used long GnRH agonist-Decapeptyl (Ferring) at 28 days intervals in the course of 4 months. After discontinuing the application of Decapeptyl, medroxyprogesterone acetate was introduced for 6 months. The GnRH/gestagens therapy is useful and effective in treatment of symptomatic myomas in perimenopausal patients, and may be a valid alternative to hysterectomy. Doppler sonography is reliable in monitoring of uterine circulation in patients under GnRH therapy.


GAL4 transactivation-based assay for the detection of selective intercellular protein movement.
Several plant proteins function as intercellular messenger to specify cell fate and coordinate plant development. Such intercellular communication can be achieved by direct, selective, or nonselective (diffusion-based) trafficking through plasmodesmata (PD), the symplasmic membrane-lined nanochannels adjoining two cells. A trichome rescue trafficking assay was reported to allow the detection of protein movement in Arabidopsis leaf tissue using transgenic gene expression. Here, we provide a protocol to dissect the mode of intercellular protein movement in Arabidopsis root. This assay system involves a root ground tissue-specific GAL4/UAS transactivation expression system in combination with fluorescent reporter proteins. In this system, mCherry, a red fluorescent protein, can move cell to cell via diffusion, while mCherry-H2B is tightly cell autonomous. Thus, a protein fused to mCherry-H2B that can move out from the site of synthesis likely contains a selective trafficking signal to impart a cell-to-cell gain-of-trafficking function to the cell-autonomous mCherry-H2B. This approach can be adapted to investigate the cell-to-cell trafficking properties of any protein of interest.


Reporting peak expiratory flow in older persons.
Peak expiratory flow ("peak flow") predicts important outcomes in older persons. Nevertheless, its clinical application is uncertain because prior strategies for reporting peak flow may not be valid. We thus determined the frequency distribution of peak flow by the conventional strategy of percent predicted (%predicted) and by an alternative method termed standardized residual (SR) percentile, and evaluated how these two metrics relate to health status in older persons. Participants included 754 community-dwelling persons aged >/= 70 years. Data included chronic conditions, frailty indicators, and peak flow. Mean age was 78.4 years, with 63.7% reporting a smoking history, 17.4% chronic lung disease, and 77.1% having one or more frailty indicators. Peak flow >/= 80 %predicted was recorded in 67.5% of participants, whereas peak flow >/= 80th SR percentile was only noted in 15.9%. A graded relationship was observed between peak flow and health status, but %predicted yielded health risk at peak flows currently considered normal (80-100 %predicted), whereas SR percentile conferred health risk only at severely reduced peak flows (< 50th SR percentile). Peak flow expressed as SR percentile attains a frequency distribution more consistent with the characteristics of our elderly cohort, and establishes health risk at more appropriate levels of reduced peak flow. These findings establish the need for longitudinal studies based on SR percentile to further evaluate the use of peak flow as a risk assessment tool in older persons and to determine if pulmonary function, in general, is better reported in older persons as SR percentile, rather than as %predicted.


Surface functionalization-specific binding of coagulation factors by zinc oxide nanoparticles delays coagulation time and reduces thrombin generation potential in vitro.
Zinc oxide nanoparticles (ZnO NPs) have many biomedical applications such as chemotherapy agents, vaccine adjuvants, and biosensors but its hemocompatibility is still poorly understood, especially in the event of direct contact of NPs with blood components. Here, we investigated the impact of size and surface functional groups on the platelet homeostasis. ZnO NPs were synthesized in two different sizes (20 and 100 nm) and with three different functional surface groups (pristine, citrate, and L-serine). ZnO NPs were incubated with plasma collected from healthy rats to evaluate the coagulation time, kinetics of thrombin generation, and profile of levels of coagulation factors in the supernatant and coronated onto the ZnO NPs. Measurements of plasma coagulation time showed that all types of ZnO NPs prolonged both active partial thromboplastin time and prothrombin time in a dose-dependent manner but there was no size- or surface functionalization-specific pattern. The kinetics data of thrombin generation showed that ZnO NPs reduced the thrombin generation potential with functionalization-specificity in the order of pristine > citrate > L-serine but there was no size-specificity. The profile of levels of coagulation factors in the supernatant and coronated onto the ZnO NPs after incubation of platelet-poor plasma with ZnO NPs showed that ZnO NPs reduced the levels of coagulation factors in the supernatant with functionalization-specificity. Interestingly, the pattern of coagulation factors in the supernatant was consistent with the levels of coagulation factors adsorbed onto the NPs, which might imply that ZnO NPs simply adsorb coagulation factors rather than stimulating these factors. The reduced levels of coagulation factors in the supernatant were consistent with the delayed coagulation time and reduced potential for thrombin generation, which imply that the adsorbed coagulation factors are not functional.


[Incidence of benign and malignant lesions of eyelid and conjunctival tumors].
To examine the incidence of benign and malignant eyelid lesions and conjunctival tumors. One-hundred-and twenty-eight cases (131 eyes) which were treated during the period from January 1990 to February 2004 were histopathologically diagnosed for eyelid or conjunctival tumors (87 cases of eyelid tumors and 41 cases of conjunctival tumors) in retrospective evaluations. The incidence of benign or malignant lesions, the pathological classification, age, sex, and clinical diagnostic accuracy were all investigated. Sixty-four (73%) of the tumors were found to be benign eyelid tumors. The common benign eyelid tumors were 14 nevocellular nevi, 9 seborrheic keratosis, 7 epidermoid cysts, and 6 papillomas. Twenty-four (27%) eyelid tumors were malignant. These included 9 basal cell carcinomas, 9 sebaceous gland carcinomas, 4 malignant lymphomas, and 2 metastatic tumors. Thirty-four (79%) conjunctival tumors were benign, and the common benign conjunctival tumors were 9 nevocellular nevi and 7 papillomas. Nine (21%) conjunctival tumors were malignant, comprising 7 malignant lymphomas and 2 squamous cell carcinomas. The mean ages of malignant eyelid and conjunctival tumor patients were significantly older than those of benign tumor patients. Clinical accuracy in predicting basal cell carcinoma and sebaceous gland carcinoma was 11.1% and 44.4%, respectively. Approximately 70 approximately 80% of all eyelid and conjunctival tumors are benign. Clinicians should suspect that the lesions are malignant when seeing elderly patients with eyelid or conjunctival tumors. Excised eyelid lesions should be submitted for histopathologic confirmation because there are some cases where clinical diagnosis does not match pathological diagnosis.


Acute small subcortical infarctions on diffusion weighted MRI: clinical presentation and aetiology.
To determine the clinical presentation and aetiology of small subcortical infarctions as found on diffusion weighted magnetic resonance imaging (DWI). DWI is both sensitive and specific in the early detection of acute ischaemic brain lesions irrespective of pre-existing vascular damage. Ninety three patients were identified showing subcortical or brainstem DWI lesions <1.5 cm in diameter within a maximum of 7 days from the onset of stroke symptoms. The patients' clinical status on admission was reviewed according to the Oxfordshire Community Stroke Project (OCSP). The results of procedures searching for cerebrovascular risk factors, large artery disease, and potential sources of cardiac embolism were included to determine stroke aetiology. Magnetic resonance imaging scans were also reviewed for concomitant changes that could support the aetiologic classification. Only 41 (44.1%) patients presented clinically with a lacunar syndrome according to OCSP criteria. The nine (9.7%) patients who showed two or more DWI lesions in different vascular territories were also significantly more likely to have potential sources of cardiac embolism (5/9, 55.6% v 20/84, 23.8%). Hypertension was significantly more prevalent in the group of patients who showed a microangiopathy related imaging pattern, but this pattern did not exclude the presence of large artery disease or a possible cardioembolic source of stroke. Identification of small subcortical infarctions as the cause of stroke appears quite uncertain based on clinical characteristics only. DWI adds significant aetiologic information but does not obviate the search for other potentially causative mechanisms.


[Abviser Kit intra-abdominal pressure monitoring].
The authors explain what an Abviser Kit consists of as an appropriate technique to measure intra-abdominal pressure, especially for patients in critical condition who have a depressed immune system since this deals with a closed system which prevents the movements a bladder catheter causes. This method minimizes the risk of infection, shortening hospital stays.


Comprehensive study of the exposome and omic data using rexposome Bioconductor Packages.
Genomics has dramatically improved our understanding of the molecular origins of certain human diseases. Nonetheless, our health is also influenced by the cumulative impact of exposures experienced across the life course (termed 'exposome'). The study of the high-dimensional exposome offers a new paradigm for investigating environmental contributions to disease etiology. However, there is a lack of bioinformatics tools for managing, visualizing and analyzing the exposome. The analysis data should include both association with health outcomes and integration with omic layers. We provide a generic framework called rexposome project, developed in the R/Bioconductor architecture that includes object-oriented classes and methods to leverage high-dimensional exposome data in disease association studies including its integration with a variety of high-throughput data types. The usefulness of the package is illustrated by analyzing a real dataset including exposome data, three health outcomes related to respiratory diseases and its integration with the transcriptome and methylome. rexposome project is available at https://isglobal-brge.github.io/rexposome/. Supplementary data are available at Bioinformatics online.


Clubfoot treatment in China before and after the advent of the Ponseti technique: a historical narrative review.
Congenital clubfoot (CF) was first described by Hippocrates in approximately 400 B.C. In ancient China, manipulations were widely used to correct CF, but the outcomes were frequently unsatisfactory with residual deformity even if corrective devices were used. The advent of aseptic surgery and anesthesia has favored the development of different surgical procedures to manage children with CF. Surgical treatment became extremely popular in China during the years 1960-1990 due to the good clinical foot appearance post-surgery. However, the poor mid- to long-term results of surgical treatment facilitated the return of conservative treatment, i.e., the Ponseti technique. Over the past decade, the Ponseti technique has become very popular in China. The Ponseti technique is essentially conservative and it is based on a good understanding of CF pathophysiology. Casts are changed once a week and Achilles tenotomy is performed if equinus persists at the end of treatment. Although highly successful on the short to mid-term, the Ponseti technique is not able to completely eradicate surgery, and recurrence is still possible. As the etiology of CF is still unclear, the first mission for doctors and researchers all over the world is to truly understand the pathogenesis of the deformity. Even though genetics seems to play an important role, successful gene therapy is still a distant goal. This narrative review aims to investigate the history of CF treatment in China, to describe its tortuous process and to potentially inspire new ideas to create new effective methods of treatment.


Mesoporous anion-cation-codoped Co9S8 nanorings for enhanced electrocatalytic oxygen evolution reactions.
Recently, the design and synthesis of Co9S8 micro/nanostructures have attracted attention as electrochemical energy storage and conversion devices due to their low cost and environmental friendliness. Herein, Co9S8 nanorings were synthesized via a one-step solvothermal method with the incorporation of Fe ions, subsequently, properly selenized to boost their electrocatalytic performance. The morphology and structure of the series of cation and anion regulated Co9S8 nanorings were characterized, the electrochemical oxygen evolution reaction (OER) properties were assessed. It is worth noting that the as-prepared catalysts, especially the innovative Fe and Se ions double doped Co9S8 nanorings, denoted as Se/Fe-Co9S8-0.14, exhibited good electrocatalytic OER performance with low overpotential (298 mV) and high durability under alkaline conditions. This work provides a new perspective to develop non-noble metal Co9S8-based OER electrocatalysts with a superior electrocatalytic performance.


Pre-clinical studies of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 (TG-C).
The aim was to evaluate cartilage regeneration in animal models involving induced knee joint damage. Through cell-mediated gene therapy methods, a cell mixture comprising a 3:1 ratio of genetically unmodified human chondrocytes and transforming growth factor beta-1 (TGF-beta1)-secreting human chondrocytes (TG-C), generated via retroviral transduction, resulted in successful cartilage proliferation in damaged regions. Non-clinical toxicology assessments for efficacy, biodistribution and local/systemic toxicity of single intra-articular administration of the cell mixture in mice, rabbits and goats was conducted. Administration of the mixture was tolerated well in all of the species. There was evidence of cartilage proliferation in rabbits and goats. As an additional precautionary step, the efficacy of TGF-beta1 secretion in irradiated human chondrocytes was also demonstrated. Four studies in rabbits and goats demonstrated the safety and efficacy of TG-C following direct intra-articular administration in animal models involving induced knee joint damage. Based on these pre-clinical studies authorization has been received from the USA Food and Drug Administration (FDA) to proceed with an initial phase I clinical study of TG-C for degenerative arthritis.


Clonal evolution in relapsed and refractory diffuse large B-cell lymphoma is characterized by high dynamics of subclones.
Little information is available about the role of certain mutations for clonal evolution and the clinical outcome during relapse in diffuse large B-cell lymphoma (DLBCL). Therefore, we analyzed formalin-fixed-paraffin-embedded tumor samples from first diagnosis, relapsed or refractory disease from 28 patients using next-generation sequencing of the exons of 104 coding genes. Non-synonymous mutations were present in 74 of the 104 genes tested. Primary tumor samples showed a median of 8 non-synonymous mutations (range: 0-24) with the used gene set. Lower numbers of non-synonymous mutations in the primary tumor were associated with a better median OS compared with higher numbers (28 versus 15 months, p=0.031). We observed three patterns of clonal evolution during relapse of disease: large global change, subclonal selection and no or minimal change possibly suggesting preprogrammed resistance. We conclude that targeted re-sequencing is a feasible and informative approach to characterize the molecular pattern of relapse and it creates novel insights into the role of dynamics of individual genes.