Validation of the Spanish version of the SCOFF questionnaire for the screening of eating disorders in primary care.
To assess the performance of the Spanish version of a new screening tool (the SCOFF) for the detection of eating disorders (EDs) in primary care. validation study. The psychiatric interview Schedules for Clinical Assessment in Neuropsychiatry (SCAN) was used as the "gold standard." Blinding was applied to administration of the SCOFF and the clinical interview. six primary health care centers in Zaragoza and Huesca, Spain. 203 female patients, between the ages of 15 and 53 years, with a probable diagnosis of ED. validity as assessed by sensitivity, specificity, positive predictive value and negative predictive value. In addition, test-retest reliability and the receiver operating characteristics (ROC) curve were calculated. The best threshold point in the Spanish version was 2+ positive answers, the same as that recommended in the original British study. This cutoff point provided 97.7% sensitivity and 94.4% specificity for the detection of EDs in primary care. For each specific ED, sensitivity and specificity with this threshold point were, respectively, the following: bulimia, 97.8% and 94.4%; anorexia, 93.1% and 94.4%; and ED not otherwise specified (EDNOS), 100% and 94.4%. The Spanish version of the SCOFF questionnaire shows excellent psychometric properties for the early detection of EDs in primary settings.


Influence of abutment macro- and micro-geometry on morphologic and morphometric features of peri-implant connective tissue.
The aim of the present human observational study is to provide morphologic and morphometric analysis of peri-implant connective tissue next to abutments with divergent or convergent macro-geometry and different surface micro-characteristics. Thirty patients were rehabilitated with single implants in the posterior area and one out of three different healing abutments with a one-stage technique: machined divergent abutment (DIV-MAC), machined convergent abutment (CONV-MAC) or convergent abutment with ultrathin threaded surface (CONV-UTM). At 3 months postimplant insertion, peri-implant soft tissue was harvested; the following outcomes were investigated: histomorphometry (vertical width of connective and epithelial components) as detected by histology and polarized light; and connective tissue vertical width and 3D organization as detected by synchrotron-based high-resolution phase-contrast-based tomography (PhC-μCT). Significant differences in connective tissue vertical dimension (aJE-AM) were found between DIV-MAC and both CONV-MAC and CONV-UTM, both by histology and PhC-μCT, with significantly higher values for the last two groups. Moreover, 2D histological analysis did not find significant differences in the junctional epithelium vertical dimension (PM-aJE). Importantly, PhC-μCT analysis revealed, at 3D level, significant greater amount and density of collagen bundles for CONV-UTM compared with the other two groups. Convergent abutment profiles, regardless of their surface micro-geometry, seem to favor axial development of peri-implant connective tissue. Moreover, ultrathin threaded surfaces seem associated with denser and greater connective tissue organization, which might improve peri-implant soft tissue seal.


The accuracy of navigated versus freehand curettage in bone tumors: a cadaveric model study.
Navigation has been suggested to guide complex benign bone tumor curettage procedures, but the contribution of navigation to the accuracy of curettage has never been quantified. We explored the accuracy of navigated curettage in a cadaveric observational pilot study, comparing navigated to freehand curettage, performed independently by an expert and a novice user. The expert performed curettage on 20 cadaveric bones prepared with a paraffin wax mixture tumor, 10 freehand and 10 navigated. We re-used 12 bones for the novice experiments, 6 freehand and 6 navigated. Tumor and curettage cavity volumes were segmented on pre- and post-cone-beam CT scans. Accuracy was quantified using the Dice Similarity Coefficient (DSC), and with remaining tumor volume, bone curettage volume, maximal remaining width and procedure times compared between navigation and freehand groups for both users. There were little differences in curettage accuracy between a navigated (DSC 0.59[0.17]) and freehand (DSC 0.64[0.10]) approach for an expert user, but there were for a novice user with DSC 0.67(0.14) and 0.83(0.06), respectively. All navigated and freehand procedures had some amount of remaining tumor, generally located in a few isolated spots with means of 2.2(2.6) cm3 (mean 20% of the tumor volume) and 1.5(1.4) cm3 (18%), respectively, for the expert and more diffusely spaced with means of 5.1(2.8) cm3 (33%) and 3.0(2.2) cm3 (17%), respectively, for the novice. In an explorative study on 20 cadaveric bone tumor models, navigated curettage in its current setup was not more accurate than freehand curettage. The amount of remaining tumor, however, confirms that curettage could be further improved. The novice user was less accurate using navigation than freehand, which could be explained by the learning curve. Furthermore, the expert used a different surgical approach than the novice, focusing more on removing the entire tumor than sparing surrounding bone.


Foliole movement and canopy architecture of Larrea tridentata (DC.) Cov. in Mexican deserts.
The creosote bush (Larrea tridentata) is a common desert perennial with bifoliate, amphistomatic, divaricate leaves. The leaves can vertically close their folioles and vary their profile with respect to direct solar radiation. Field data from different Mexican deserts showed a significant correlation between foliole aperture and mean foliole inclination: in plants in which folioles were more open, the foliole surfaces were less vertical. In a series of field experiments in the Chihuahuan Desert, foliole aperture varied significantly with the water-status of the plant and the hour of the day. In moist plants, folioles opened in the early morning and closed in the afternoon. Water-stressed plants showed significantly lower foliole apertures. A simulation of the light interception patterns of the plants showed that foliole closure in water-stressed individuals reduces direct radiation interception by around 24%. Most (64%) of the reduction in interception was due to the vertical inclination of the photosynthetic surfaces induced by foliole closure in the water-stressed plants. The rest (36%) of the reduction in interception was due to differential self-shading between foliole pairs, which was higher in the closed folioles of the water-stressed plants, but operated more towards the early hours of the day.


Promoting good nutrition in patients with dementia.
This article aims to raise awareness of good nutrition, the specific nutritional needs of individuals with dementia and the importance and implementation of protected mealtimes to prevent malnutrition in the hospital setting.


Low-grade myofibroblastic sarcoma of the parapharyngeal space.
Low-grade myofibroblastic sarcoma was recently described as representing malignant mesenchymal tumours that show myofibroblastic differentiation; few cases have been reported. Here, a low-grade myofibroblastic sarcoma of the parapharyngeal space is described. A 42-year-old man presented with swelling on the right side of the temporal bone. Based on histological and immunohistochemical features, the diagnosis of low-grade myofibroblastic sarcoma was established. The tumour had invaded the orbit and the brain, and therefore surgical excision was not possible. There are thought to have been no cases affecting this region reported previously in the English-language literature.


The baseline levels and risk factors for high-sensitive C-reactive protein in Chinese healthy population.
Recent studies show that C-reactive protein (CRP) is not only a biomarker but also a pathogenic mediator contributing to the development of inflammation and ageing-related diseases. However, serum levels of CRP in the healthy ageing population remained unclear, which was investigated in the present study. Serum levels of high sensitive C-reactive protein (hs-CRP), glucose (Glu), triglyceride (TG), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), superoxide dismutase (SOD), serum creatinine (SCr), serum uric acid (SUA) were measured in 6060healthy subjects (3672 male and 2388 female, mean age:45.9 years) who received routine physical examination at Sun Yat-sen Memorial Hospital, Guangzhou, China. In total of 6060 healthy people, serum levels of hs-CRP were significantly increased with ageing (P < 0.05), particularly in those with age over 45-year-old (1.31[0.69-2.75] vs 1.05[0.53-2.16]mg/L, P < 0.001). Interestingly, levels of serum hs-CRP were significantly higher in male than female population (1.24[0.65-2.57] vs 1.07[0.53-2.29]mg/L, P < 0.001). Correlation analysis also revealed that serum levels of hs-CRP positively correlated with age and SUA, but inversely correlated with serum levels of HDL-c and SOD (all P < 0.05). Baseline levels of serum hs-CRP are increased with ageing and are significantly higher in male than female healthy population. In addition, elevated serum levels of hs-CRP are also associated with increased SUA but decreased HDL-c and SOD. Thus, serum levels of hs-CRP may be an indicator associated with ageing in healthy Chinese population.


T-cell dynamics after high-dose chemotherapy in adults: elucidation of the elusive CD8+ subset reveals multiple homeostatic T-cell compartments with distinct implications for immune competence.
Recovery of total T cell numbers after in vivo T-cell depletion in humans is accompanied by complex perturbation within the CD8+ subset. We aimed to elucidate the reconstitution of CD8+ T cells by separate analysis of putative naïve CD95- CD28+, memory CD95+ CD28+ and CD28- T cell compartments after acute maximal depletion by high-dose chemotherapy (HD-ChT) in women with high-risk breast cancer. We found that recovery of putative naïve CD8+ CD95- CD28+ and CD4+ CD95- CD28+ T cells, was compatible with a thymus-dependent regenerative pathway since their recovery was slow and time-dependent, their values were tightly related to each other, and their reconstitution patterns were inversely related to age. By analysing non-naïve T cells, a striking diversion between putative memory T cells and CD28- T cells was found. These latter increased early well beyond normal values, thus playing a pivotal role in total T-cell homeostasis, and contributed to reduce the CD4 : CD8 ratio. In contrast, putative memory T cells returned to values not significantly different from those seen in patients at diagnosis, indicating that this compartment may recover after HD-ChT. At 3-5 years after treatment, naïve T cells persisted at low levels, with expansion of CD28- T cells, suggesting that such alterations may extend further. These findings indicate that CD28- T cells were responsible for 'blind' T-cell homeostasis, but support the notion that memory and naïve T cells are regulated separately. Given their distinct dynamics, quantitative evaluation of T-cell pools in patients undergoing chemotherapy should take into account separate analysis of naïve, memory and CD28- T cells.


Striped catfish (Pangasianodon hypophthalmus) exploit food sources across anaerobic decomposition- and primary photosynthetic production-based food chains.
Dietary information from aquatic organisms is instrumental in predicting biological interactions and understanding ecosystem functionality. In freshwater habitats, generalist fish species can access a diverse array of food sources from multiple food chains. These may include primary photosynthetic production and detritus derived from both oxic and anoxic decomposition. However, the exploitation of anoxic decomposition products by fish remains insufficiently explored. This study examines feeding habits of striped catfish (Pangasianodon hypophthalmus) at both adult and juvenile stages within a tropical reservoir, using stable carbon, nitrogen, and sulfur isotope ratios (δ13C, δ15N, and δ34S, respectively) and fatty acid (FA) analyses. The adult catfish exhibited higher δ15N values compared to primary consumers that feed on primary photosynthetic producers, which suggests ingestion of food sources originating from primary photosynthetic production-based food chains. On the other hand, juvenile catfish demonstrated lower δ15N values than primary consumers, correlating with low δ34S value and large proportions of bacterial FA but contained small proportions of polyunsaturated FA. This implies that juveniles utilize food sources from both anoxic decomposition and primary photosynthetic production-based food chains. Our results indicate that food chains based on anoxic decomposition can indeed contribute to the dietary sources of tropical fish species.


Association between Modic changes, disc degeneration, and neck pain in the cervical spine: a systematic review of literature.
The contribution of Modic changes (MCs) in relation to spinal pain and degenerative changes has been evaluated frequently. However, most studies focus on lumbar spine. The association between MCs, neck pain, and cervical disc degeneration is not clear. The objective of this study was to review current literature on the association between MCs, cervical disc degeneration, and neck pain. A systematic review METHODS: A literature search was performed in PubMed, Embase, and Web of Science using a sensitive search string combination. Studies were selected by predefined selection criteria and risk of bias was assessed using a validated Cochrane Checklist adjusted for this purpose. Fourteen articles that associated MCs with neck pain and/or cervical disc degeneration were included in the present study. Ten articles showed low risk of bias and four showed intermediate risk of bias. The prevalence of MCs in cervical spine varied from 5% to 40% and type II was predominant. Patients with MCs were reported to experience more neck pain and disability. Cervical disc degeneration was detected more frequently in patients with MCs. Modic changes were found to be associated with neck pain and with disc degeneration. Therefore, the large variation in prevalence that is reported is highly dependent on the nature of the studied population.


DJ-1 inhibits glutathione degradation by downregulating CHAC1 expression in astrocytes.
The PARK7 gene, which encodes DJ-1 protein, is the causative gene of autosomal recessive early-onset Parkinson's disease. DJ-1 has many biological functions, including regulating glutathione (GSH) levels. However, the molecular mechanism by which DJ-1 regulates GSH levels in astrocytes remains unclear. With high throughput sequencing, we discovered that DJ-1 knockout could significantly upregulate the expression of ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1). We demonstrate that DJ-1 can bind with the basic leucine zipper domain of activating transcription factor 3 (ATF3) through bimolecular fluorescence complementation. Besides, DJ-1 inhibits ATF3 binding to the CHAC1 promoter and downregulates the expression of CHAC1 to reduce GSH degradation. Our research suggests that the loss of DJ-1 in astrocytes promotes the degradation of GSH, leading neurons more vulnerable to oxidative damage. It provides a theoretical basis for developing drugs targeting DJ-1 and GSH in the brain.


Oligosaccharyltransferase-subunit mutations in nonsyndromic mental retardation.
Mental retardation (MR) is the most frequent handicap among children and young adults. Although a large proportion of X-linked MR genes have been identified, only four genes responsible for autosomal-recessive nonsyndromic MR (AR-NSMR) have been described so far. Here, we report on two genes involved in autosomal-recessive and X-linked NSMR. First, autozygosity mapping in two sibs born to first-cousin French parents led to the identification of a region on 8p22-p23.1. This interval encompasses the gene N33/TUSC3 encoding one subunit of the oligosaccharyltransferase (OTase) complex, which catalyzes the transfer of an oligosaccharide chain on nascent proteins, the key step of N-glycosylation. Sequencing N33/TUSC3 identified a 1 bp insertion, c.787_788insC, resulting in a premature stop codon, p.N263fsX300, and leading to mRNA decay. Surprisingly, glycosylation analyses of patient fibroblasts showed normal N-glycan synthesis and transfer, suggesting that normal N-glycosylation observed in patient fibroblasts may be due to functional compensation. Subsequently, screening of the X-linked N33/TUSC3 paralog, the IAP gene, identified a missense mutation (c.932T-->G, p.V311G) in a family with X-linked NSMR. Recent studies of fucosylation and polysialic-acid modification of neuronal cell-adhesion glycoproteins have shown the critical role of glycosylation in synaptic plasticity. However, our data provide the first demonstration that a defect in N-glycosylation can result in NSMR. Together, our results demonstrate that fine regulation of OTase activity is essential for normal cognitive-function development, providing therefore further insights to understand the pathophysiological bases of MR.


Concomitant Drug-Coated Balloon Angioplasty With Bail-Out Use of Eluvia Drug-Eluting Stent: Is There Any Downside to a Double Dose of Paclitaxel?
The application of 2 distinct and simultaneously applied drug-delivery platforms for the treatment of peripheral artery disease (PAD) has not been studied. This study investigated the outcomes of femoropopliteal disease treated with drug-coated balloon (DCB) followed by placement of drug-eluting stent (DES) when a bail-out procedure is required. This was a single-center, retrospective study enrolling 22 consecutive patients (23 limbs) treated with DCB + DES. Bail-out stenting was performed for flow-limiting postangioplasty dissections and/or suboptimal angiographic result, such as residual stenosis. Procedural success (<30% residual stenosis) and the incidence of major adverse limb event (MALE) during an average follow-up of 15.2 months were estimated. Among the 22 patients (23 limbs), 14 presented with claudication and 8 with critical limb ischemia. The majority of the lesions were Trans-Atlantic Inter-Society Consensus class C/D, with a mean lesion length of 321 ± 130 mm. DCB angioplasty was performed with Stellarex (Philips) in 6 cases and In.Pact DCB (Medtronic) in 16 cases. Eluvia DES (Boston Scientific) was used for bail-out stenting in all cases (in 10 limbs for flow-limiting dissection and in 13 limbs for suboptimal angiographic result due to significant residual stenosis and/or recoil). A single Eluvia DES was used in 15 cases, while multiple Eluvia DESs were used in 8 cases. Procedural success was achieved in all but 1 case where persistent recoil occurred in a heavily calcified lesion. During an average follow-up of 15 months, restenosis or reocclusion of the target vessel was observed in 6 cases (26.1%), although only 3 patients required repeat revascularization (13.0%). During follow-up, 1 death and 1 major amputation occurred, both in patients who had originally presented with critical limb ischemia. Additionally, on routine duplex ultrasound, there were no cases of aneurysm formation at the sites of Eluvia stent placement. DCB with provisional DES implantation could be a viable treatment option for cases of suboptimal DCB results, without apparent additional cardiovascular or limb-related risks. Additional studies are needed to determine the risks and benefits of double-dose paclitaxel approach, especially for those patients with significant residual stenosis after DCB.


Use of terlipressin in critically ill children with liver disease.
Terlipressin, a long-acting synthetic analogue of vasopressin has been used in the adult population for various indications including hepatorenal syndrome (HRS-AKI), esophageal variceal hemorrhage (EVH) and shock, but its use in pediatrics is still limited to individualized cases and data on safety and efficacy is scant. We reviewed the patient records of children with liver disease and Acute Kidney Injury requiring terlipressin admitted to the Paediatric Intensive Care Unit (PICU) of King's College Hospital, London from January 2010-December 2017, with special emphasis on its effect on renal parameters and adverse event profile. Twenty-one terlipressin administration records in a total of 16 patients (median) (IQR) 10 years (6.1-14.4) were included. The drug was initially given as a bolus dose in all cases, followed by either bolus or infusion with median dosage being 5.2 (3.8-6.7) mcg/kg/hour. After administration, a sustained increase of mean arterial pressure was observed. There was an improvement in serum creatinine (Cr) (at 24 h; p = 0.386) and increase in urine output (UO), especially in the hepatorenal syndrome subgroup (HRS-AKI). We found minimal evidence of gastrointestinal side effects including feeding intolerance and vasoconstrictive side effects including cyanosis / ischaemia of extremities. Terlipressin was found to be safe in critically sick children with liver disease with positive impact on renal parameters which might be taken as a surrogate marker of HRS reversal, though effects on outcomes are difficult to ascertain. It is important to be aware of all its side-effects and actively watch for them. Future prospective studies are warranted to validate these findings.


Effects of Secondhand Smoke Exposure on Hearing and Auditory Evoked Potentials, ABR and AMLR in Young Adults.
Population health is impacted by environmental secondhand smoke (SHS) exposure. Although the negative health effects of SHS exposure include respiratory problems in children (nonsmokers) as seen in cigarette smokers, other health impacts such as sensory function are not assumed to be the same for both passive nonsmokers and smokers. However, hearing loss was recently reported in adolescents and aging adults with SHS exposure, suggesting that SHS might impact auditory function similarly to cigarette smoking. Specific effects of SHS exposure on the central auditory system have not been fully described. To measure auditory function via pure-tone audiometry and evoked potentials in young nonsmoking adults aged 18-23 yr who reported exposure to environmental SHS. Participants were selected for the SHS-exposed (SHS-E) group first, followed by age and gender matched individuals for the SHS-unexposed (SHS-U) group. Self-reported nonsmoker status was confirmed by biochemical analysis of urine for cotinine level. Potential participants (N = 208) completed a questionnaire about health, smoking history, SHS exposure, and hearing ability. Individuals with any neurological conditions, alcohol/drug dependencies, excessive noise exposure, using certain medications, or current smokers were excluded. Twenty-two nonsmokers in excellent health consented to participate. Participants in the SHS-E group reported SHS exposure in home, work, or social settings for an extensive time period. Participants in the SHS-U group did not live with smokers and reported no SHS exposure, medication use, tinnitus, or any chemical exposures. Statistical analysis was conducted on data from 20 participants, 10 per group with a mean age of 20 yr. Participants underwent auditory procedures in one session in an IAC sound-treated room, including otoscopy, tympanometry, pure-tone threshold evaluation, auditory brainstem response per ear, and a three-channel auditory middle latency response in the right ear. The primary study outcomes were hearing thresholds measured (dB HL) at five frequencies, and evoked potential wave latencies (I, III, V, Na, Pa, Nb, Pb) and amplitudes (V-I, Na-Pa, Pa-Nb, Nb-Pb). It was hypothesized that SHS-exposed individuals would have poorer hearing sensitivity (threshold >25 dB HL) and abnormal central auditory function (longer latencies; smaller amplitudes) based on evoked potentials. Statistical analyses focused on identification of group differences in hearing and central auditory function. All participants had normal hearing sensitivity (thresholds ≤25 dB HL) with no significant group differences. The V/I amplitude ratio in the right ear was significantly decreased in SHS-exposed individuals (p < 0.05). Auditory brainstem response latencies were not significantly different between participant groups or ears. Wave Pb latency was significantly increased in SHS-exposed individuals (p < 0.01). Auditory middle latency response relative amplitudes were significantly different from each other at every electrode site (Cz, Fz, C4) but not between groups. Overall, the Na-Pa complex was highest in amplitude at all three electrode sites. This preliminary study indicated toxic effects of SHS exposure by evoked potentials with decreased V/I amplitude ratio and longer (delayed) Pb latency in young adults. Further studies should corroborate these findings to facilitate clinical recommendations.


The passive transfer of severe allergic neuritis in Lewis rats with lymphoid cells preincubated with P2 protein.
The passive transfer of both clinical signs and histologic lesions characteristic of allergic neuritis was successfully performed in Lewis rats using pooled spleen and lymph node cells, or T lymphocytes therefrom, if first preincubated in petri dishes with P2 protein for 72 hr. For passive transfer, cells were taken from donors 8-16 days after sensitization with P2 protein or myelin in Freund's complete adjuvant, and administered via the tail vein; clinical signs appeared 12-13 days later. This study supports the importance of cell-mediated immunity in EAN and the antigenic role of the P2 protein.


Child socioemotional behavior and adult temperament as predictors of physical activity and sedentary behavior in late adulthood.
Most studies investigating the association of temperament with physical activity and sedentary behavior have examined children or adolescents, employed cross-sectional or longitudinal designs that do not extend from childhood into adulthood, and utilized self- or parent-reported data on physical activity and sedentary behavior. This longitudinal study investigated whether socioemotional behavior in childhood and temperament in middle adulthood predict accelerometer-measured physical activity and sedentary behavior in late adulthood. This study was based on the Jyväskylä Longitudinal Study of Personality and Social Development (JYLS). Socioemotional behavior (behavioral activity, well-controlled behavior, negative emotionality) was assessed at age 8 based on teacher ratings, whereas temperament (surgency, effortful control, negative affectivity, orienting sensitivity) was assessed at age 42 based on self-rating. Moderate-to-vigorous physical activity and sedentary behavior were assessed at age 61 using an accelerometer. Data (N = 142) were analyzed using linear regression analysis. In women, behavioral activity at age 8 predicted higher levels of daily sedentary behavior at age 61. The association did not remain statistically significant after controlling for participant's occupational status. In addition, women's negative affectivity at age 42 predicted lower daily moderate-to-vigorous physical activity at age 61, particularly during leisure time. No statistically significant results were observed in men. Although few weak associations of socioemotional behavior and temperament with physical activity and sedentary behavior were detected in women, they were observed over several decades, and thus, deserve attention in future studies. In addition to other factors contributing to physical activity and sedentary behavior, health professionals may be sensitive to individual characteristics, such as a tendency to experience more negative emotions, when doing health counseling or planning for health-promoting interventions targeting physical activity and sedentary behavior.


[Methodological fundamentals for the development of the guideline].
The guideline was developed by 10 scientific societies and 2 patient self-help organizations and coordinated by the German Association of Pain Therapy (DIVS). The guideline was approved by the Association of the Scientific Medical Societies in Germany AWMF (AWMF number 041/004), april 17, 2008. No direct or indirect financial support by pharmaceutical companies was involved and there were no potential conflicts of interest for any of the 58 participants of the guideline group. The results of a systematic search of the literature (Cochrane Library [1993-12/2006], Medline [1980-12/2006], PsychInfo [1966-12/2006] and Scopus [1980-12/2006]) were analyzed by 8 working groups. A balanced composition of the working groups as to sex, level of medical care and position in medical or scientific hierarchy of their members was realized. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. Grading of the strengths of recommendations was done according to the German program for disease management guidelines. Standardized, formal procedures to reach a consensus on recommendations were used. The guideline was reviewed by the board of directors of the societies engaged in the development of the guideline. The guideline will be published in complete and short scientific versions, clinical practice and patient versions.


Bilaterian-like promoters in the highly compact Amphimedon queenslandica genome.
The regulatory systems underlying animal development must have evolved prior to the emergence of eumetazoans (cnidarians and bilaterians). Although representatives of earlier-branching animals - sponges ctenophores and placozoans - possess most of the developmental transcription factor families present in eumetazoans, the DNA regulatory elements that these transcription factors target remain uncharted. Here we characterise the core promoter sequences, U1 snRNP-binding sites (5' splice sites; 5'SSs) and polyadenylation sites (PASs) in the sponge Amphimedon queenslandica. Similar to unicellular opisthokonts, Amphimedon's genes are tightly packed in the genome and have small introns. In contrast, its genes possess metazoan-like core promoters populated with binding motifs previously deemed to be specific to vertebrates, including Nrf-1 and Krüppel-like elements. Also as in vertebrates, Amphimedon's PASs and 5'SSs are depleted downstream and upstream of transcription start sites, respectively, consistent with non-elongating transcripts being short-lived; PASs and 5'SSs are more evenly distributed in bidirectional promoters in Amphimedon. The presence of bilaterian-like regulatory DNAs in sponges is consistent with these being early and essential innovations of the metazoan gene regulatory repertoire.


Day-to-day individual alpha frequency variability measured by a mobile EEG device relates to anxiety.
The individual alpha frequency (IAF) has previously been identified as a unique neural signature within the 8-12 Hz alpha frequency band. However, the day-to-day variability of this feature is unknown. To investigate this, healthy participants recorded their own brain activity daily at home using the Muse 2 headband, a low-cost consumer-grade mobile electroencephalography (EEG) device. Resting-state recordings of all participants using a high-density (HD) EEG were also collected in lab before and after the at-home data collection period. We found that the IAF extracted from the Muse 2 was comparable to that of location-matched HD-EEG electrodes. No significant difference was found between these IAF values before and after the at-home recording period for the HD-EEG device. Similarly, there was also no statistically significant difference between the beginning and end of the at-home recording period for the Muse 2 headband over 1 month. Despite the group-level stability of IAF, the individual-level day-to-day IAF variability carried mental health-relevant information: Exploratory analyses revealed a relationship between IAF day-to-day variability and trait anxiety. We also noted that the IAF systematically varied across the scalp and although the Muse 2 electrodes do not cover the occipital lobe where alpha oscillations were the strongest, IAFs measured in the temporal lobe and occipital lobe were strongly correlated. Altogether, these results show that mobile EEG devices are useful for studying IAF variability. The relationship between day-to-day variability of region-specific IAF and the dynamics of psychiatric symptoms, particularly anxiety, should be further investigated.


Logic as a tool for clinical training in social work.
The paper is an attempt to illustrate the usefulness of logic as a technique in the clinical training of mental health professionals. The specific concepts that are examined include the nature of deductive and inductive reasoning, hypothesis testing, necessary and sufficient conditions, "if-then" propositions, and the nature of clinical evidence. Knowledge and use of these concepts was tested in a tutorial program directed toward students who were beginning graduate studies in the field of social work. Some of the difficulties encountered by these students, especially in the clinical aspects of their training, were directly related to an inadequate understanding of these logical forms of reasoning. It is suggested that a portion of the clinical training in mental health fields be directed towards a deeper understanding and utilization of these basic concepts.


Metabolism of 5'-ether prodrugs of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil in rats.
1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) is a selective antiherpesviral agent that has been shown to be metabolically stable in mice. However, E-5-(2-bromovinyl)uracil (BVU) is the major metabolite found after oral dosing in animals other than mice. When BV-araU was given orally to germ-free rats, only small amounts of BVU were found in the plasma, suggesting an important role of enterobacteria in the formation of BVU. Then, the metabolism of BV-araU prodrugs was studied in specific-pathogen free rats to select oral prodrugs of BV-araU with enhanced metabolic stability. 5'-O-Ethyl BV-araU (Et-BV-araU) gave about a 2-fold higher BV-araU blood concentration 3 and 6 hr after administration than after oral dosing of BV-araU, while the level of BVU was lower. Other aliphatic alkyl prodrugs also gave a lower level of BVU, but did not give the same elevation in blood concentration of BV-araU as did Et-BV-araU. Dosing of 5'-O-acetyl BV-araU resulted in blood concentrations of BV-araU and BVU similar to those after oral administration of BV-araU. 5'-O-Aromatic alkyl prodrugs showed poor bioavailability. A nearly 2-fold higher urinary recovery rate was seen for Et-BV-araU than for BV-araU or 5'-O-acetyl BV-araU. The conversion of Et-BV-araU to BV-araU was demonstrated in vitro using rat liver extract in the presence of co-factors, although the reaction was slow. The 5'-O-aliphatic alkyl prodrugs were completely resistant to degradation by enterobacteria, whereas the esters were partially degraded to BVU. Et-BV-araU may be a useful oral prodrug of BV-araU due to its increased metabolic stability and bioavailability.


Worry-specific versus self-tailored internet-based treatments for generalized anxiety disorder, with scheduled support or support on demand: A pilot factorial design trial.
Studies suggest that internet-delivered cognitive behaviour therapy (ICBT) can be effective when treating generalized anxiety disorder (GAD). This pilot factorial design study examined the effects of two types of ICBT (worry-specific and self-tailored treatment), and two support types (scheduled weekly support and support on demand), on measures of worry, anxiety, and depressive symptoms. Participants (N = 85) were randomized into four treatment groups. Post-treatment measures were completed by 76.5% after eight weeks (n = 65). Intention to treat analysis showed significant improvements, with moderate to large within-group effects on the primary outcome measure, Penn State Worry Questionnaire (Cohen's d = 0.77-1.43). Minor to large effects on the secondary measures were found in all groups (Cohen's d = 0.13-1.66). No significant differences in outcome measures were found between the groups. Receiving scheduled support and self-tailored treatment was rated as more positive than receiving support on demand and the worry-specific program. A limitation is the low number of participants. The pilot results suggest that GAD can be treated with both worry-specific and self-tailored treatments, and that ICBT can be supported both with scheduled and support on demand.


Development of tyrosine hydroxylase-immunoreactive systems in the brain of the larval lamprey Lampetra fluviatilis.
The development of the catecholaminergic system of the brain of the lamprey (Lampetra fluviatilis) was studied with immunocytochemistry in a series of larvae of different sizes by using two different antibodies directed against tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. In group 1 larvae (length: 29-54 mm, ages: 8 months to 1.5 years), the only TH-immunoreactive somata observed were located in the caudal wall of the recessus praeopticus (RP) and in the nucleus tuberculi posterioris (NTP). In group 2 larvae (length: 55-80 mm, ages: 1.5-2.5 years), the somata of immunolabeled cells of the NTP give rise to fibers, most of which are ascending and terminate in the corpus striatum. Additional immunoreactive cells are observed in the nucleus praeopticus (NP), which has differentiated, and in the spinal cord. In group 3 larvae (length: 81-110 mm, ages: 2.5-4 years), the spatial distribution of TH-immunoreactive elements (somata, fibers, and terminals) bears many resemblances to that seen in the adult. Immunolabeled cells may be observed in the olfactory bulb, in the nucleus commissurae postopticae (NCP), and in the nucleus dorsalis hypothalami (NDH). Nevertheless, some groups of TH-immunoreactive cells found in the adult are not observed in group 3 larvae; these may appear during the metamorphic phase. By comparative analysis, we show that, in spite of several differences, the spatiotemporal sequence of appearance of TH-immunoreactive cell bodies and fibers in the lamprey presents many similarities to that described in gnathostomes.


[Lethal effects of various antimicrobial agents and clinically usable alternatives in rabbits and rodents].
The lethal effects of antibiotics which may be observed in rabbits and some rodent species are reviewed. A selection of antibiotics and chemotherapeutic agents and their respective dosages are referred to, which may be used therapeutically in these animals. Suggestions are made for the treatment of enterocolitis induced by antibiotics in rabbits.


Pars Plana Vitrectomy for Idiopathic Epiretinal Membrane: OCT Biomarkers of Visual Outcomes in 322 Eyes.
To investigate OCT-based biomarkers of visual acuity (VA) in eyes with idiopathic epiretinal membranes (ERMs) undergoing surgical intervention. To assess the surgical outcomes of pars plana vitrectomy (PPV) and membrane peel (MP) surgery in eyes with idiopathic ERM and to identify potential imaging-based biomarkers of vision outcomes. Retrospective, consecutive case series of eyes with idiopathic ERM that underwent PPV and MP surgery between January 1, 2017, and January 1, 2019. A previously described ERM grading scale was utilized for OCT analysis. The primary outcome was VA at postoperative month 6 and at final follow-up. The secondary outcome was the association of OCT structural features, including ectopic inner foveal layers (EIFLs), inner microcystoid changes, and ellipsoid zone (EZ) disruption, with VA outcomes. A total of 322 eyes with idiopathic ERM were included. The mean (± standard deviation) follow-up was 506.6 ± 324.6 days after MP surgery. VA improved from logarithm of the minimal angle of resolution value of 0.49 ± 0.27 (Snellen 20/61) before MP surgery to 0.41 ± 0.30 (Snellen 20/51, P < 0.001) at 6 months after MP surgery and to 0.31 ± 0.29 (Snellen 20/41, P < 0.001) at the final follow-up. A total of 21 (6.5%) eyes were graded as stage 1, 38 (11.8%) as stage 2, 188 (58.4%) as stage 3, and 75 (23.3%) as stage 4, with higher ERM stages associated with worse pre-MP VA (P < 0.001). The presence of inner microcystoid changes was associated with worse pre-MP VA (P = 0.04). Stage 4 ERM characteristics (P = 0.03), the presence of EZ disruption (P = 0.01) at month 3, and the presence of inner microcystoid changes at month 3 (P = 0.02) were associated with worse VA at 6 months. The presence of EIFL was not associated with the 6-month or final VA on multivariate analysis. When analyzed within defined age groups, patients older than 80 years had worse final VA (P = 0.02) and were more likely to have inner microcystoid changes on OCT (P = 0.01). VA improvement was noted after surgery in eyes with idiopathic ERM across all stages. Preoperative stage 4 characteristics were associated with worse VA at 6 months. Postoperative inner microcystoid changes and EZ disruption at month 3 were additional OCT biomarkers associated with worse 6-month and final VA outcomes.


An evaluation system for financial compensation in traditional Chinese medicine services.
To describe the major factors influencing financial compensation in traditional Chinese medicine (TCM) and prioritize what TCM services should be compensated for. Two structured questionnaires-a TCM service baseline questionnaire and a service cost questionnaire-were used to collect information from TCM public hospitals on TCM services provided in certain situations and service cost accounting. The cross-sectional study examined 110 TCM services provided in four county TCM public hospitals in Shandong province. From the questionnaire data, a screening index system was established via expert consultation and brainstorming. Comprehensive evaluation of TCM services was performed using the analytic hierarchy process method. Weighted coefficients were used to measure the importance of each criterion, after which comprehensive evaluation scores for each service were ranked to indicate what services should receive priority for financial compensation. Economy value, social value, and efficacy value were the three main criteria for screening for what TCM services should be compensated for. The economy value local weight had the highest value (0.588), of which the profit sub-criterion (0.278) was the most important for TCM financial compensation. Moxibustion was tied for the highest comprehensive evaluation scores, at 0.65 while Acupuncture and Massage Therapy were tied for the second and third highest, with 0.63 and 0.58, respectively. Government and policymakers should consider offer financial compensation to Moxibustion, Acupuncture, Massage Therapy, and TCM Orthopedics as priority services. In the meanwhile, it is essential to correct the unreasonable pricing, explore compensation methods, objects and payment, and revise and improve the accounting system for the costs of TCM services.


Novel GRP78 molecular chaperone expression down-regulators JBIR-04 and -05 isolated from Streptomyces violaceoniger.
In the course of our screening program for regulators of the expression of GRP78 molecular chaperone, JBIR-04 (1) and -05 (2) were isolated from Streptomyces violaceoniger 4541-SVS3 as congeners of prunustatin A (3). The structures of 1 and 2 were determined by the analyses of the spectroscopic data. These compounds mainly consist of an amino acid and amino acid derived alpha-hydroxy acid residues. 1 and 2 inhibited the expression of GRP78 induced by 2-deoxyglucose in human fibrosarcoma HT1080 cells, but their activities were highly reduced compared with those of 3 and SW-163A.


Microarray profiling of circular RNAs and the potential regulatory role of hsa_circ_0071410 in the activated human hepatic stellate cell induced by irradiation.
Radiation-induced liver fibrosis (RILF) is considered as a major complication of radiation therapy for liver cancer. Circular RNA (circRNA) has been recently identified as a functional noncoding RNA involving in various biological processes. However, the expression pattern and regulatory capacity of circRNA in the irradiated hepatic stellate cell (HSC), the main fibrogenic cell type, still remain unclear. A circRNA microarray was used to identify circRNA expression profiles in irradiated and normal HSC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm the dysregulated circRNAs. Bioinformatic analyses including gene ontology (GO), KEGG pathway and circRNA/microRNA interaction network analysis were applied to predict the potential functions of circRNAs. Compared with the normal HSC, 179 circRNAs were found to be up-regulated and 630 circRNAs were down-regulated in irradiated HSC (fold change ≥2.0 and P<0.05). Six dysregulated circRNAs selected randomly were successfully verified by qRT-PCR. Bioinformatic analyses indicated that dysregulated circRNA might be involved in the cell response to irradiation and biological processes of hepatic fibrosis. Furthermore, inhibition of hsa_circ_0071410 increased the expression of miR-9-5p, resulting in the attenuation of irradiation induced HSC activation. In summary, this study revealed the expression profile and potential function of differentially expressed circRNAs in irradiated HSC, which provides novel clues for RILF study.


[Distribution of calcitonin gene-related peptide-like immunoreactive fibres in the temporomandibular joint of rat].
To observe the distribution of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerve fibres in rat's temporomandibular joint (TMJ). The avidin-biotin-peroxidase complex method and image analysis were employed to detect CGRP-LI nerve fibres in frozen sections of TMJs in eight rats. CGRP-LI nerve fibres were plentifully distributed in TMJs except the central disc band and bone, mainly in the periphery of blood vessels, especially arteries. Density: anterior disc attachment and capsule, (454.6 +/- 72.8) mm(2); posterior portion, (302.7 +/- 43.4) mm(2); lateral portion, (240.2 +/- 23.6) mm(2); medial portion, (229.6 +/- 25.0)mm(2); and peripheral portion of disc, (202.4 +/- 35.2) mm(2). CGRP-LI nerve fibres were widely distributed in rat TMJ and were a part of trigeminal sensory nerve. Density was highest in anterior disc attachment and capsule.


Surgical margins and the risk of local-regional recurrence after mastectomy without radiation therapy.
Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR. The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR. The median follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close (≤2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR. Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable features is likely to be small.


Pseudomonas aeruginosa meningitis treated with ceftazidime.
A case of pseudomonas aeruginosa meningitis secondary to chronic otitis media was successfully treated with ceftazidime and gentamicin intravenously. No intrathecal antibiotics were necessary. Treatment of pseudomonas meningitis has been simplified with the advent of third generation cephalosporins.


The use of bispectral index to monitor barbiturate coma in severely brain-injured patients with refractory intracranial hypertension.
Barbiturate therapy in severely traumatic brain-injured (TBI) patients is usually monitored by an electroencephalogram (EEG) with burst-suppression pattern as a target. The Bispectral Index (BIS) is derived from EEG and considers cortical silence. We sought to determine whether a BIS range could predict a specific burst-suppression pattern. Eleven TBI patients treated with barbiturate were included prospectively. EEG was recorded daily for 1 h. Every 5 min, the number of bursts and the suppression ratio (suppression ratio from EEG [SR(EEG)]: percentage of last 60 s in cortical silence) was calculated for 1 min on the raw EEG and compared to concomitant data from the BIS-XP (BIS and suppression ratio [SR(BIS)]). The optimal level of barbiturate coma was defined as 2-5 bursts/min in the EEG. A BIS range predictive of optimal level was determined from all data and its accuracy was studied for each examination. Agreement between SR(EEG) and SR(BIS) was high (interclass correlation coefficient 0.94 [95% confidence interval: 0.90-0.96]). There was a significant association between SR(EEG) and BIS. Significant disagreements were observed in some examinations. The best accuracy to predict optimal pattern was obtained with a BIS range from 6 to 15. The relationship between BIS and SR(EEG) was high in TBI patients treated with barbiturates. The rate of barbiturate infusion might be decreased if BIS is <6 or increased if BIS is >15. Correspondence between BIS and suppression pattern should periodically be checked by observation of the EEG analogical signal (as displayed by BIS-XP).


Identification of TH1 as an interaction partner of A-Raf kinase.
A-Raf is an important intermediate of the growth factor Ras-MAP kinase pathway. In a two-hybrid screen of human fetal liver cDNA library, TH1 was detected as a new interaction partner of A-Raf. TH1 is a highly conserved and widely expressed protein, which was recently cloned by Bonthron DT group. The binding between A-Raf and TH1 was specific, as no binding between TH1 and B-Raf or c-Raf was observed, and the amino-terminal 162 amino acids in the A-Raf regulatory domain were found to be sufficient for this interaction. This specific interaction may have played a critical role in the activation of A-Raf.


Cardiac electrophysiologic effects of etafenone hydrochloride (Dialicor), a new antiarrhythmic agent.
The electrophysiologic effects of etafenone hydrochloride (Dialicor) were studied in isolated rabbit hearts and canine or rabbit cardiac tissues with intracellular microelectrode techniques. The concentration range used was 0.25-10 mg/L, except in experiments with direct addition of etafenone into the tissue bath. Etafenone depressed automaticity in the sinus node, atrioventricular junction and Purkinje fibers at concentrations not affecting the action potential contour. In both atrial and ventricular fibers, etafenone prolonged the action potential duration and total refractory period. The action potential upstroke was slowed and conduction time increased. Higher concentrations reduced the resting potential, causing incomplete depolarization. Atrial action potentials were affected at lower concentrations than ventricular and Purkinje action potentials. Occasi-nally, etafenone produced localized conduction block within the atria, usually sparing internodal conduction. In electrically driven hearts, direct recording of His bundle potential as well as surface electrograms revealed marked prolongation of intraatrial and intranodal conduction times, with some increase in His-Purkinje and ventricular conduction times. Depression of atrioventricular conduction was insignificant under sinus rhythm. Possible therapeutic implications of these electrophysiologic effects are discussed.


Bifidobacteria and the infant gut: an example of co-evolution and natural selection.
Throughout the human life, the gut microbiota interacts with us in a number of different ways, thereby influencing our health status. The acquisition of such an interactive gut microbiota commences at birth. Medical and environmental factors including diet, antibiotic exposure and mode of delivery are major factors that shape the composition of the microbial communities in the infant gut. Among the most abundant members of the infant microbiota are species belonging to the Bifidobacterium genus, which are believed to confer beneficial effects upon their host. Bifidobacteria may be acquired directly from the mother by vertical transmission and their persistence in the infant gut is associated with their saccharolytic activity toward glycans that are abundant in the infant gut. Here, we discuss the establishment of the infant gut microbiota and the contribution of bifidobacteria to this early life microbial consortium.


Rapid detection and differentiation of Newcastle disease virus by real-time PCR with melting-curve analysis.
In order to rapidly detect and differentiate Newcastle disease virus (NDV) isolates, a method based on real-time PCR SYBR Green I melting-curve analysis of the fusion (F) protein gene was developed. The detection limit of real-time PCR was 9 x 10(2) plasmid copies and was 100 times more sensitive than conventional PCR. Thirty eight reference NDV strains were rapidly identified by their distinctive melting temperatures (T(m)s): 89.23 +/- 0.27 degrees C for velogenic strains, 90.17 +/- 0.35 degrees C for pigeon mesogenic strains, 91.25 +/- 0.14 degrees C for two lentogenic strains (B1 and Ishii). No amplification was detected from unrelated RNA samples by this method. This real-time PCR directly detected NDV from infected tissues and eliminated the gel electrophoretic step for analyzing PCR product using ethidium bromide. The total time for a PCR run was less than 1 hour. The results obtained in this study showed that the real-time PCR presented here is a good screening test for the identification of NDV.


Educational paper: the podocytopathies.
In the recent past, hereditary podocytopathies have increasingly been recognized to be involved in the development of steroid-resistant nephrotic syndrome (SRNS). Mutations in podocyte genes substantially alter the development and structural architecture of the podocyte including its interdigitating foot processes. These constitute the basis of the slit diaphragm which is an essential part of the glomerular filtration barrier. Depending on the affected protein, the clinical course is variable with respect to onset and severity of the disease as well as treatment options. In general, hereditary podocytopathies are associated with a poorer renal outcome than the non-genetic variants. In addition, they require a different approach with respect to the applied therapeutic strategies as most patients do not respond to immunosuppressive agents. Therefore, genetic testing of podocyte genes should be considered as a routine diagnostic tool for patients with SRNS because the identification of a genetic origin has a direct implication on clinical course, renal outcome, and genetic counseling. In this educational paper, we will give an overview over the podocyte genes identified so far to be involved into the pathophysiology of hereditary podocytopathies.


Early Growth Trajectory of Infants With Simple Congenital Heart Disease and Complex Congenital Heart Disease Undergoing Cardiac Repair: A Prospective Cohort Study in China.
We aimed to evaluate the growth trajectory of infants with congenital heart disease (CHD) and to analyze the effects of disease classification on their growth trajectory. A prospective cohort of infants with CHD was enrolled and divided into 2 groups: simple CHD (SC) and complex CHD (CC) groups. All patients were followed up for 6 months after CHD surgery. Weight for age (WAZ), length for age (LAZ), weight for length (WLZ), and head circumference for age were compared between the 2 groups using mixed-effects linear regression. Between September 2018 and November 2019, 801 patients had data collected. The z-score trend decreased (e.g., ΔWAZ: 1.29±1.44) and then increased (e.g., ΔWAZ: 1.06±1.13), and all z-scores were below 0 from birth to 6 months postoperatively. Mixed-effects linear regression models indicated that the postoperative WAZ and WLZ scores of the CC group were lower than those of the SC group after adjustment (WAZ: β = -0.72; 95% confidence interval [CI], -1.37 to -0.07; P = .03) (WLZ: β = -0.93, 95% CI, -1.67 to -0.19; P = .01). The models also showed an interaction effect between disease classification and preoperative growth status on infant growth outcome (WAZ: interaction β = -0.48; 95% CI, -0.88 to -0.07; P = .02) (WLZ: interaction β = -0.36; 95% CI, -0.60 to -0.12; P = .004) (LAZ: interaction β = -0.29; 95% CI, -0.56 to -0.02; P = .04). Compared with SC children, CC children have deficits in their early growth trajectories. The type of disease and preoperative growth status synergistically affect the early postoperative growth trajectory.


Metoclopramide and homicidal ideation: a case report and literature review.
Metoclopramide is an anti-emetic and gastrointestinal pro-motility agent associated with well-known neuropsychiatric adverse effects, such as dyskinesia, akathisia, and depression. It has never been reported to be associated with homicidal ideation. The authors review the literature on metoclopramide-induced adverse neuropsychiatric reactions and the mechanisms by which these may occur. The authors present a case report of a patient who developed anxiety, agitation, suicidal and homicidal ideation following brief exposure to metoclopramide. The adverse effects of agitation and homicidal ideation were temporally related to the starting and stopping of metoclopramide. The patient subsequently developed agitation without homicidal ideation when given a serotonergic antidepressant a week later, suggesting that serotonin handling may have played a significant role in causing the patient's symptoms. Although metoclopramide is well-known for its side effects related to dopamine blockade, its action at 5-HT₃ and 5-HT₄ receptors may also be clinically significant in the genesis of neuropsychiatric side effects, especially related to mood and behavior.


Clinic, neuropathology and molecular genetics of frontotemporal dementia: a mini-review.
Frontotemporal lobar degeneration (FTLD) represents a group of clinically, neuropathologically and genetically heterogeneous disorders with plenty of overlaps between the neurodegenerative mechanism and the clinical phenotype. FTLD is pathologically characterized by the frontal and temporal lobar atrophy. Frontotemporal dementia (FTD) clinically presents with abnormalities of behavior and personality and language impairments variants. The clinical spectrum of FTD encompasses distinct canonical syndromes: behavioural variant of FTD (bvFTD) and primary progressive aphasia. The later includes nonfluent/agrammatic variant PPA (nfvPPA or PNFA), semantic variant PPA (svPPA or SD) and logopenic variant PPA (lvPPA). In addition, there is also overlap of FTD with motor neuron disease (FTD-MND or FTD-ALS), as well as the parkinsonian syndromes, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The FTLD spectrum disorders are based upon the predominant neuropathological proteins (containing inclusions of hyperphosphorylated tau or ubiquitin protein, e.g transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) and fusedin-sarcoma protein in neurons and glial cells) into three main categories: (1) microtubule-associated protein tau (FTLD-Tau); (2) TAR DNA-binding protein-43 (FTLD-TDP); and (3) fused in sarcoma protein (FTLD-FUS). There are five main genes mutations leading clinical and pathological variants in FTLD that identified by molecular genetic studies, which are chromosome 9 open reading frame 72 (C9ORF72) gene, granulin (GRN) gene, microtubule associated protein tau gene (MAPT), the gene encoding valosin-containing protein (VCP) and the charged multivesicular body protein 2B (CHMP2B). In this review, recent advances on the different clinic variants, neuroimaging, genetics, pathological subtypes and clinicopathological associations of FTD will be discussed.


Early mortality and neurologic outcomes following mitral valve surgery in the very elderly.
Valve repair is the gold standard for treatment of degenerative mitral valve disease. As the population ages, patients undergoing valve degeneration and therefore considered for mitral valve surgery will naturally be getting older. We sought to evaluate whether mitral repair retained a survival advantage over replacement in patients ≥80 years old. A retrospective cohort study was performed using data acquired from the United Kingdom National Adult Cardiac Surgery Audit for the outcomes of in-hospital mortality and postoperative cerebrovascular event (CVA). Individual multivariable logistic regression models were created to investigate adjusted associations between these outcomes and type of mitral valve operation, repair or replacement. Additionally, associations between the individual model parameters and in-hospital mortality and CVA were investigated. A total of 1140 patients underwent mitral repair (66.4%, median age 82.3), and 577 patients underwent mitral replacement (33.6%, median age 82.1). The overall age range was 80-92. The incidence of in-hospital mortality favored the repair group (4.4% vs. 8.3%, p = .001). Multivariable logistic regression modeling demonstrated an increased adjusted odds of in-hospital mortality for mitral valve replacement (MVR) (odd ratio [OR]: 2.01, 1.15-3.50, p = .01). The only other parameter associated with an increased adjusted odds of in-hospital mortality was postoperative dialysis (OR: 14.2, 7.67-26.5, p < .001). There was not a demonstrated association between MVR and perioperative CVA (OR: 1.11, 0.49-2.4, p = .8). In patients ≥80 years old, mitral valve repair (MVr) was shown to be associated with a decreased adjusted odds of mortality, with a null association with CVA. These results suggest that, if feasible, MVr should remain the preferred management strategy, even in the very elderly.


Molecular and Cellular In Utero Therapy.
Significant advances in maternal-fetal medicine and gene sequencing technology have fostered a new frontier of in utero molecular and cellular therapeutics, including gene editing, enzyme replacement therapy, and stem cell transplantation to treat single-gene disorders with limited postnatal treatment strategies. In utero therapies take advantage of unique developmental properties of the fetus to allow for the correction of monogenic disorders before irreversible disease pathology develops. While early preclinical studies in animal models are encouraging, more studies are needed to further evaluate their safety and efficacy prior to widespread clinical use.


Methane potential of fruit and vegetable waste: an evaluation of the semi-continuous anaerobic mono-digestion.
The anaerobic digestion (AD) of a high diversity blend of fruit and vegetable waste (FVW) generated in tropical conditions as a single substrate was performed. A continuously stirred tank reactor (CSTR) operated in semi-continuous regime was used for AD. The reactor performance was monitored with gradually increasing organic loading rates (OLRs) from 0.5 up to 5.0 gVS L-1 d-1. The biochemical methane potential (BMP) of FVW determined by batch bottles was 360 LN CH4 kgVS-1, with a biodegradability of 79%. A stable pH with an adequate level of buffering capacity was observed during the entire experiment. Methane yield indicated the best performance at an OLR of 3.0 gVS L-1 d-1, with 285 LN CH4 kgVS-1 added, reaching 79% of BMP. At an OLR over 3.0 gVS L-1 d-1 accumulation of volatile fatty acids (VFA) was detected; in particular, propionic acid was monitored, and a decreased methane yield was detected. Biogas production rate was 1.55 LN L-1 d-1 and showed linear increase according to increases in the OLR.


Funnel tracking control for nonlinear servo drive systems with unknown disturbances.
In this paper, a novel robust tracking control strategy based on funnel control is proposed for servo drive systems with unknown disturbances. A modified funnel variable is defined and incorporated into the control design to guarantee the tracking error within a prescribed boundary. To reject the bounded disturbances, a robust integral of the sign of the error (RISE) controller based on the funnel variable is proposed for servo drive systems. Moreover, the desired compensation technique is incorporated into the developed controller to reduce the sensor noise. The proposed robust controller theoretically guarantees asymptotic tracking control performance with external disturbances. The closed-loop system convergence is analyzed via the Lyapunov stability theory. Comparative numerical and experimental results of the servo drive system are provided.


Effects of a detailed sexual behavior interview on perceived risk of HIV infection: preliminary experimental analysis in a high risk sample.
Effects of the HIV-Risk Timeline Followback Interview (TLFB), which uses detailed memory cues to assess retrospectively sexual behavior and substance use on a day-by-day basis, on HIV risk-reduction motivation were tested. Thirty-four adults (76% male, 100% African American) were randomly assigned to three interview conditions: (a) HIV-Risk TLFB Interview, (b) 27 sexual behavior frequency questions, and (c) diet and nutrition using the TLFB format. Participants completed measures of HIV risk-reduction motivation immediately before and after the experimental assessment component. The a priori hypotheses that the HIV-Risk TLFB group would exhibit greater increases on indices of HIV risk reduction motivation than participants in either of the other two groups and that participants in the nutrition interview condition would exhibit greater increases in motivation for dietary improvement were supported, indicating that participating in detailed health behavior interviews, but not cursory assessments, may lead to increased motivation for behavior change.


Sleep time and quality associated with depression and social anxiety among children and adolescents aged 6-18 years, stratified by body composition.
Sleep has been suggested as risk factors for depression and social anxiety in children and adolescents, but little is known about the role of individual body composition on these association. We conducted a cross-sectional survey of children and adolescents aged 6-18 years in Beijing, China, in 2020, and assessed body composition by using iDXA dual-energy X-ray bone densitometer. Generalized liner model (GLM) and restricted cubic spline (RCS) were employed to analyze the associations between sleep and depression and social anxiety with different body composition. The attributable fraction (AFs) to assess the benefits of improvements of sleep in reducing depression and social anxiety odds. Depression and social anxiety accounted for 13.1 % and 30.3 % of the study population. Sleep time was significantly associated with depression (HR = 2.35[1.58, 3.50]), and social anxiety (HR = 1.65[1.24, 2.20]); and sleep quality was significantly associated with depression (HR = 7.27[4.87, 10.84]), and social anxiety (HR = 2.54 [1.99, 3.25]) among children and adolescents. The exposure to both insufficient sleep time and poor sleep quality were associated with a higher odd of depression and social anxiety, but lower BF%, higher muscle rate and FFM/FM alleviated the adverse effects of sleep quality on depression and social anxiety. Conclusions about causality remain speculative because of the cross-sectional design. Insufficient sleep time, poor sleep quality, high BF%, low muscle rate and FFM/FM can jointly associate with anxiety and depression. This study provides new evidence support for accurate prevention and control of mental diseases in children and adolescents with different body types.


Determining the potential use of biosurfactants in preventing endodontic infections.
Microbial biofilms play a dominant role in the failure of endodontic therapies. Bacterial adhesion is the first step in the establishment of biofilms, activating the host immune response leading to tissue damage. Biosurfactants are microbe-derived tensioactive molecules with latent anti-adhesive and anti-microbial activity. This study reports the extraction and characterization of a biosurfactant from Lactobacillus (L.) plantarum (Lp-BS) and investigates its anti-microbial and anti-adhesive properties compared to rhamnolipid, a commercially available biosurfactant. Lp-BS, extracted from L. plantarum during the growth phase, was characterized as a glycoprotein, able to reduce surface tension and emulsify non-polar liquids. Proteomic analysis of Lp-BS identified three bacterial adhesin-like proteins, suggesting roles in hindering bacterial adhesion. Lp-BS did not show significant anti-microbial activity against endodontic pathogens from the Streptococcus (Strep.) anginosus group or Enterococcus (Ent.) faecalis at 50 mg/ml. However, anti-adhesive activity on abiotic surfaces was observed against both Strep. anginosus and Strep. intermedius. Rhamnolipid exhibited strong anti-microbial activity, with minimum inhibitory concentrations of 0.097 mg/ml against Strep. anginosus, and 0.048 mg/ml against Strep. constellatus and Strep. intermedius, in addition to a marked anti-adhesive activity. These findings offer preliminary evidence for the potential application of biosurfactants as an anti-microbial and/or anti-adhesive pharmacotherapy in endodontics.


Hormone therapy in hypospadias surgery: a systematic review.
Surgical correction of hypospadias is proposed to improve the aesthetic and functional quality of the penis. Hormone therapy preceding surgical correction is indicated to obtain better surgical conditions. However, there is divergence in the literature regarding the hormone therapy of choice, time of its use before surgery, appropriate dose, and route of application. To try to elucidate this matter, an electronic survey of the databases PubMed and Cochrane Central Library was conducted, limited to articles in English published since 1980. Search strategy identified 14 clinical trials that matched the inclusion criteria. Analysis was made in terms of study design, classification of hypospadias, association with chordee and cryptorchidism, type of hormone, route of application, dose and duration of treatment, penile length before and after hormone therapy, glans circumference before and after hormone therapy, adverse effects, and surgical complications. From the trials evaluated it was not possible to determine the ideal neoadjuvant treatment. A preference for use of testosterone was observed. Intramuscular administration seems to have fewer adverse effects than topical treatment. Side effects were seldom described, and treated patients were not followed on a long-term basis. The scarcity of randomized and controlled clinical trials regarding the topic impairs the establishment of a protocol. In conclusion, although preoperative hormone therapy is currently used before hypospadias surgery, its real benefit in terms of improvement of the penis and surgical results has not been defined.


The respiration-impairing effect of rubroskyrin, a toxic metabolite.
The toxic effect of rubroskyrin, a modified bis-anthraquinone pigment fromPenicillium islandicum Sopp, on mitochondrial respiration has been studied by using isolated rat liver mitochondria, comparing with those of luteoskyrin and rugulosin which are well knownislandicum toxins. It was found that rubroskyrin exerted an uncoupling effect on mitochondrial respiration, abating the respiratory control ratio (RCR) by a dose dependent manner (UD50: 10 μM) and markedly depressed state 3 respiration at high concentrations, whereas such respiration-impairing effects of luteoskyrin and rugulosin were not detected at the concentrations tested (max. 35 μM). The involvement of redox-reaction was not detected in the uncoupling effect of the quinone pigment, rubroskyrin.Spectroscopic study at various pHs revealed that rubroskyrin possessed a pK value within the range of physiological pH, suggesting that rubroskyrin is a weak acid-type uncoupler capable of conducting protons across mitochondrial inner membrane.


Dietary keto-acid feed-back on pituitary activity in gilthead sea bream: effects of oral doses of AKG. A proteomic approach.
The influence of a daily oral dose of alpha-ketoglutarate (AKG, 0.1 g/kg body weight), an intermediate metabolite in the Krebs cycle and a dietary additive, on the pituitary proteome of gilthead sea bream was determined by two-dimensional electrophoresis (2-DE). A high-resolution map of the sea bream pituitary proteome was generated. Proteins with a modified expression between Controls and AKG treated fish were further analysed by MALDI-TOF/TOF-MS and liquid chromatography combined with a nanoelectrospray (LC-MS/MS). The main changes in the proteome induced by AKG treatment were grouped. Metabolic proteins up-regulated with AKG supplementation included fructose-bis-phosphate aldolase, glyceraldehyde-phosphate dehydrogenase and malate dehydrogenase, all related to glucose metabolism (p<0.000). Protein folding related up-regulation with AKG supplementation included two isoforms of heat shock proteins as well as cyclophylin and chaperonin (p<0.000). An unexpected form of apolipoprotein-A-1 with lower molecular weight (15-16 kDa) was evidenced as being highly abundant in the pituitary proteome of Controls, yet it was down-regulated by AKG treatment. Finally, proteins found to be associated with regeneration of neural function namely cofilin and Vat-protein were up-regulated after AKG supplementation. The only hormone to be modified by AKG treatment was somatolactin, which was significantly down-regulated cf. Controls. In summary, these results provide evidence of a potential endocrine/metabolic regulatory loop activated by AKG supplementation.


Quantification of ischemic damage in the rat retina: a comparative study using evoked potentials, electroretinography, and histology.
To identify objective criteria to quantify visual function in the rat for developing therapeutic strategies to protect neuronal cells after ischemia. The impact of ocular ischemia on luminance and frequency-modulated contrast vision was compared with the function of outer retinal cells and the number of intact retinal ganglion cells (RGCs). Ischemia was induced in Brown-Norway rats by elevating the intraocular pressure to 120 mm Hg for 30, 45, 60, and 90 minutes. Visual function was evaluated by visual evoked potentials (VEPs) in awake, freely moving rats. Retinal function was analyzed with scotopic and photopic electroretinography (ERG). RGCs were quantified in retinal flatmounts after postischemic injection of tracer into the superior colliculus. The response to flicker stimulation in VEP recordings decreased as the ischemic episodes increased. The susceptibility to ischemic damage was more pronounced when potentials were evoked with stimuli at higher frequencies. In ERG recordings, ischemia reduced oscillatory potentials and photopic flicker responses more intensely than scotopic a- and b-waves. In counting the RGCs, the reduced cell density correlated significantly with all electrophysiological parameters. The duration of ischemia with half-maximal inhibitory effect was between 36 and 58 minutes for VEPs and between 36 and 41 minutes for ERG, and it was 51 minutes for RGCs. The amounts of reduction in VEPs, ERG, and RGCs differed as the duration of ischemia increased. The electrophysiological parameters presented in this study may serve as a useful addition to morphologic evaluations in future neuroprotection studies in vivo.


IFN-γ-Stimulated Apoptotic Keratinocytes Promote Sclerodermatous Changes in Chronic Graft-Versus-Host Disease.
Patients with graft-versus-host disease (GVHD) develop characteristic mucocutaneous phenomena consisting of erosive erythema with histopathological findings including interface dermatitis and keratinocyte (KC) death, resulting in widespread sclerodermatous changes. We found that KCs exhibit marked production of TGFβ1 in skin lesions of chronic GVHD but not in those of acute GVHD. To further investigate the roles of KCs, the main targets of donor T cells, in sclerodermatous changes followed by interface dermatitis, we established a murine model of chronic GVHD-like sclerodermatous changes followed by acute GVHD-like mucocutaneous injury in genetically modified mice transferred with KC-specific CD8 T cells. Although transfer of granzyme B-deficient CD8 T cells did not result in either mucocutaneous injury or sclerodermatous changes in recipients, IFN-γ-deficient CD8 T-cell recipients developed severe acute mucocutaneous injury but milder sclerodermatous changes than wild-type CD8 T-cell recipients. Moreover, IFN-γ-deficient CD8 T-cell recipients had a lower expression of TGFβ1 in the epidermis than the control. Murine primary KCs undergoing FasL-induced apoptosis and incubated with IFN-γ produced TGFβ1, the production of which was inhibited by a pan-caspase inhibitor. Our results indicate that IFN-γ promotes TGFβ1 production by apoptotic KCs, which mediates the development of widespread sclerodermatous changes in KC-targeting GVHD.


Randomized comparison of sirolimus-eluting stent versus standard stent for percutaneous coronary revascularization in diabetic patients: the diabetes and sirolimus-eluting stent (DIABETES) trial.
Outcomes after percutaneous coronary interventions in diabetic patients are shadowed by the increased rate of recurrence compared with nondiabetic patients. We conducted a multicenter, randomized trial to demonstrate the efficacy of sirolimus-eluting stents compared with standard stents to prevent restenosis in diabetic patients with de novo lesions in native coronary arteries. The primary end point of the trial was in-segment late lumen loss as assessed by quantitative coronary angiography at 9-month follow-up. The trial was stratified by diabetes treatment status. One hundred sixty patients were randomized to sirolimus-eluting stents (80 patients; 111 lesions) or standard stent implantation (80 patients; 110 lesions). On average, reference diameter was 2.34+/-0.6 mm, lesion length was 15.0+/-8 mm, and 13.1% of lesions were chronic total occlusions. In-segment late lumen loss was reduced from 0.47+/-0.5 mm for standard stents to 0.06+/-0.4 mm for sirolimus stents (P<0.001). Target-lesion revascularization and major adverse cardiac event rates were significantly lower in the sirolimus group (31.3% versus 7.3% and 36.3% versus 11.3%, respectively; both P<0.001). Non-insulin- and insulin-requiring patients demonstrated similar reductions in angiographic and clinical parameters of restenosis after sirolimus-eluting stent implantation. During the 9-month follow-up, stent thrombosis occurred in 2 patients after standard stent implantation. Conversely, this phenomenon was not seen in the sirolimus stent group. This randomized trial demonstrated that sirolimus stent implantation is safe and efficacious in reducing both angiographic and clinical parameters of restenosis compared with standard stents in diabetic patients with de novo coronary stenoses.


Validating Kohler's Taxonomy of Transition Programming for adolescents with intellectual disability in the Chinese context.
School-to-work transition programmes play a crucial role in the achievement of post-secondary outcomes for young adults with intellectual disability (ID). Although special education in China has progressed in the last two decades, systematically planned transition education and services are not usually available for Chinese school leavers. The present study aimed to validate Kohler's Taxonomy of Transition Programming (KTTP) in the Chinese context for adolescents with ID. Five Chinese transition experts reviewed KTTP items, 14 Chinese transition teachers and 14 parents of adolescents with ID who would transition from school in the next 12 months were interviewed, and 329 transition teachers were surveyed. Most items in KTTP were found to be important and relevant to the Chinese context. Based on KTTP, a modified transition framework appropriate to the Chinese context was generated. The Chinese transition framework may assist parents and professionals to better support adolescents with ID in China. Future validation checks of the framework will add confidence that the framework captures the essential components of effective transition practices appropriate in the Chinese context.


Multiple response measures during classical conditioning.
Animal research assessing multiple responses during Pavlovian conditioning has revealed a dichotomy between the central nervous system (CNS) substrates for somatomotor and visceral CRs. These findings have implications for the study of clinical/applied problems in human subjects, since differences in the acquisition functions for these response systems may suggest which CNS structures are involved in various neuropsychiatric disorders. The present paper describes methods and procedures utilized to assess the somatomotor conditioned eyeblink (EB) response and accompanying visceral changes in human subjects. Methods are described for assessing concomitant EB conditioned and unconditioned responses and the accompanying heart rate, skin conductance, and respiratory changes during Pavlovian conditioning in human subjects. It is stressed that utilization of concomitant conditioning of these different response systems may lead to inferences regarding the central nervous system structures involved in a variety of different kinds of clinical problems.


Induction of cell-cycle regulators in simian immunodeficiency virus encephalitis.
Neuronal degeneration associated with human immunodeficiency virus encephalitis has been attributed to neurotoxicity of signaling molecules secreted by activated, infected macrophages. We hypothesized that the barrage of signals present in the extracellular milieu of human immunodeficiency virus-infiltrated brain causes inappropriate activation of neuronal cell-cycle machinery. We examined the presence of three members of the cell-cycle control machinery: pRb, E2F1, and p53 in the simian immunodeficiency virus encephalitis (SIVE) model. Compared to noninfected and simian immunodeficiency virus-infected, nonencephalitic controls, we observed increased protein expression of E2F1 and p53 and aberrant cellular localization of E2F1 and pRb. In SIVE, E2F1 was abundant in the cytoplasm of neurons in both neurons and astrocytes proximal to SIVE pathology in the basal ganglia. pRb staining was nuclear and cytoplasmic in cortical neurons of SIVE cases. Antibodies to phosphorylated pRb also labeled the cytoplasm of cortical neurons. These data suggest that in SIVE, cell signaling results in phosphorylation of pRb which may result in subsequent alteration in E2F1 activity. As increased E2F1 and p53 activities have been linked to cell death, these data suggest that the neurodegeneration in SIVE could in part be because of changes in expression and activity of cell-cycle machinery.


Molecular genotyping of HIV-1 in 61 patients with AIDS from Lomé, Togo.
To study the distribution of HIV types and genotypes, in Lomé, Togo, a random population of patients who met the clinical criteria of the Bangui definition of AIDS and were positive with two independent screening assays for antibodies to HIV-1 group M, HIV-2, and HIV-1 group O was selected. HIV RNA from serum samples was reverse-transcribed and amplified with degenerate primers annealing to conserved regions of the HIV-1, HIV-2, and HIV-O gag gene. Amplicons were directly sequenced using an automated sequencer. A 262-271-bp (strain-dependent) fragment of the gag gene from each patient was phylogenetically analyzed and compared to the corresponding gag sequences of published HIV-1 sequences of known African genotypes. Genotype A was found in 48 of 60 patient amplicons (80%), subdivided into two clusters. Ten patients (16.7%) were HIV-1 genotype G; one was genotype D and one genotype H. HIV-1 genotype B was not found. Amplicons from two patients contained sequence ambiguities, requiring cloning and sequencing of the gag insert. One patient (T52) was apparently infected with HIV-1 genotypes A and G; whereas HIV-1 from patient T139 was of genotype A, with 2/10 clones having a three-codon insertion at nucleotide position 1142 of the gag gene. HIV-1 genotype A is dominant in Togo; genotype G is frequent and genotype B has not been found.


Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD).
Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes phosphatidylcholine synthesis. PEMT knockout mice have fatty livers, and it is possible that, in humans, nonalcoholic fatty liver disease (NAFLD) might be associated with PEMT gene polymorphisms. DNA samples from 59 humans without fatty liver and from 28 humans with NAFLD were genotyped for a single nucleotide polymorphism in exon 8 of PEMT, which leads to a V175M substitution. V175M is a loss of function mutation, as determined by transiently transfecting McArdle-RH7777 cells with constructs of wild-type PEMT open reading frame or the V175M mutant. Met/Met at residue 175 (loss of function SNP) occurred in 67.9% of the NAFLD subjects and in only 40.7% of control subjects (P<0.03). For the first time we report that a polymorphism of the human PEMT gene (V175M) is associated with diminished activity and may confer susceptibility to NAFLD.


Comparison of 2-phenylspiroindenes and 2-phenylspiroindenediones as estrogen receptor ligands--modeling and binding data don't agree!
A series of 2-phenylspiroindenediones was prepared. The spiroindenediones were found to be less active than the corresponding spiroindenes as estrogen receptor ligands and failed to demonstrate the receptor subtype selectivity that had been anticipated from molecular modeling.


Targeted PET/CT imaging of vulnerable atherosclerotic plaques: microcalcification with sodium fluoride and inflammation with fluorodeoxyglucose.
A significant majority of atherosclerotic plaque ruptures occur in coronary arteries exhibiting none or only modest luminal narrowing on coronary angiography. Emerging data suggest the biological composition of an atherosclerotic plaque (vulnerability to rupture) rather than its degree of stenosis or size is the major determinants for acute clinical events. Thus, the pursuit for noninvasive molecular imaging probes that target plaque composition, such as inflammation and/or microcalcification is a creditable goal. 18 F-fluorodioxyglucose (18 F-FDG) is a metabolic probe that can be imaged using positron emission tomography (PET)/computer tomography (CT) technology to target plaque macrophage glucose utilization and inflammation. Vascular plaque 18 F-FDG uptake has been linked to cardiovascular events such as myocardial infarction and stroke. More recently, another molecular probe 18 F-sodium fluoride (18 F-NaF) was introduced for PET imaging, which targets active microcalcifications in atherosclerotic plaques. Little is known regarding the role of early microcalcification in the initiation and progression of plaque, partly because of lack of a noninvasive imaging modality targeting molecular calcification. 18 F-NaF PET/CT imaging could provide new insights into the complex interaction of plaque, and facilitate understanding the mechanism of plaque calcification. Moreover, when these 2 molecular probes, 18 F-FDG and 18 F-NaF, that target distinct biological processes in an atherosclerotic plaque are used in combination, they may further elucidate the link between local inflammation, microcalcification, progression to plaque rupture, and cardiovascular event.


A Simple Approach to Characterize Gas-Aqueous Liquid Two-phase Flow Configuration Based on Discrete Solid-Liquid Contact Electrification.
In this study, we first suggest a simple approach to characterize configuration of gas-aqueous liquid two-phase flow based on discrete solid-liquid contact electrification, which is a newly defined concept as a sequential process of solid-liquid contact and successive detachment of the contact liquid from the solid surface. This approach exhibits several advantages such as simple operation, precise measurement, and cost-effectiveness. By using electric potential that is spontaneously generated by discrete solid-liquid contact electrification, the configurations of the gas-aqueous liquid two-phase flow such as size of a gas slug and flow rate are precisely characterized. According to the experimental and numerical analyses on parameters that affect electric potential, gas slugs have been verified to behave similarly to point electric charges when the measuring point of the electric potential is far enough from the gas slug. In addition, the configuration of the gas-aqueous liquid two-phase microfluidic system with multiple gas slugs is also characterized by using the presented approach. For a proof-of-concept demonstration of using the proposed approach in a self-triggered sensor, a gas slug detector with a counter system is developed to show its practicality and applicability.


Functional and Clinical Characteristics for Predicting Sarcopenia in Institutionalised Older Adults: Identifying Tools for Clinical Screening.
Recently, the European Working Group on Sarcopenia in Older People (EWGSOP2) has updated the sarcopenia definition based on objective evaluation of muscle strength, mass and physical performance. The aim of this study was to analyse the relationship between sarcopenia and clinical aspects such as functionality, comorbidity, polypharmacy, hospitalisations and falls in order to support sarcopenia screening in institutionalised older adults, as well as to estimate the prevalence of sarcopenia in this population using the EWGSOP2 new algorithm. A multicentre cross-sectional study was conducted on institutionalised older adults (n = 132, 77.7% female, mean age 82 years). Application of the EWGSOP2 algorithm consisted of the SARC-F questionnaire, handgrip strength (HG), appendicular skeletal muscle mass index (ASMI) and Short Physical Performance Battery (SPPB). Clinical study variables were: Barthel Index (BI), Abbreviated Charlson's Comorbidity Index (ACCI), number of medications, hospital stays and falls. Age, BI and ACCI were shown to be predictors of the EWGSOP2 sarcopenia definition (Nagelkerke's R-square = 0.34), highlighting the ACCI. Sarcopenia was more prevalent in older adults aged over 85 (p = 0.005), but no differences were found according to gender (p = 0.512). BI and the ACCI can be considered predictors that guide healthcare professionals in early sarcopenia identification and therapeutic approach.


Limits to the accuracy of vessel diameter measurement in MR angiography.
This work addresses the fundamental limits imposed by the MRI process on the accuracy with which vessel diameters and cross-sectional areas can be derived from time-of-flight (TOF) and phase-contrast (PC) MR source images. By means of simulations and in vitro experiments, it is demonstrated that, even in the absence of flow-related artifacts, severe inaccuracies in the determination of diameters or cross-sectional areas may occur solely because of the physical process of the MR image acquisition. Resolution and intraluminal saturation have strong effects on the vessel appearance and thus on the diameter estimation error. It is shown that low resolution leads to diameter overestimation or even underestimation and that intraluminal saturation causes severe underestimation, even for relatively low flip angles. Velocity and velocity encoding do not have a major influence on lumen appearance in PC images. Accurate diameter estimations can be attained only if lumen diameters constitute at least three pixels for both TOF and PC acquisitions, provided that intraluminal saturation is suppressed or avoided. Additionally, since the constitution of TOF and PC images is dissimilar, lumina should be analyzed differently to obtain accurate diameters and cross-sectional areas.


Analysis of amino acids in individual wheat embryonic protoplast.
Amino acids analysis in single wheat embryonic protoplast was performed using capillary electrophoresis equipped with laser-induced fluorescence (CE-LIF), combination with tissue culture technique. Reagent fluorescein isothiocyanate (FITC) was introduced into living protoplasts by electroporation for intracellular derivatization. A special osmotic buffer (0.6 mol/L mannitol, 5 mmol/L CaCl2) was used to keep the osmotic balance of embryonic protoplasts during the protoplasts derivatization. After completion of the derivatization reaction in the protoplasts, a single protoplast was drawn into the capillary tip by electroosmotic flow. Then a 0.1 M NaOH lysing solution was injected by diffusion. The derivatized amino acids were separated by capillary electrophoresis and detected by laser-induced fluorescence detection after the protoplast was lysed Nine amino acids were quantitatively and qualitatively determined and compared in lysate and single protoplast of wheat embryonic cells respectively, with mean concentrations of amino acids ranging from 2.68 x 10(-5) mol/L to 18.18 x 10(-5) mol/L in single protoplast.


The hidden imbalance in neighbourhood nutrition environment: a perspective from lower-middle-income country setting.
Neighbourhood environment plays a pivotal role in determining the individual's nutrition through availability and accessibility of healthy food options. This community-based cross-sectional descriptive study examined neighbourhood spatial attributes using Geographical Information System (GIS) and describe perceived nutrition environment among adult residents in urban Puducherry, India. The density of grocery shops, fruits and vegetable shops, food outlets and restaurants were 64.4, 74.8 and 88.7 per km2, respectively. Out of 200 participants, 191 (95.5%) and 190 (95%) reported easy accessibility to fruits and vegetables shops and restaurants, respectively, while 192 (96%) agreed on availability of unhealthy food options in shops. Current study provides framework for assessment of objective and perceived neighbourhood nutrition environment in lower-middle-income countries with a user-friendly and easily administrable tool.


Emergency department revisits.
We reviewed the charts of patients returning within 72 hours to our emergency department to determine whether monitoring revisits is a useful quality assurance indicator. Patient visits for June and December 1987 were selected to eliminate a potential seasonal difference. Of the 13,261 visits during these two months, 455 (3.4%) were revisits within 72 hours. Charts were available on 444 patients, of whom 407 (91.7%) represented cases in which the return and the initial visits were clearly related. Charts were reviewed for deficiencies in medical management, appropriate prescribed follow-up, patient education, and patient compliance. Suspected medical management problems were discussed by the three senior authors, and a consensus decision was made. Return visits were considered avoidable if a deficiency was noted in at least one of the areas listed above. There were 297 unscheduled related return visits, 96 (32.3%) of which were avoidable. Of these avoidable visits, 38 (39.6%) had medical management deficiencies, 14 (14.6%) had inappropriate prescribed follow-up, 20 (20.8%) had not been given proper education, and 35 (36.5%) were due to patient noncompliance. Of the 110 scheduled return visits, there was one (0.9%) deficiency in medical management and none in the other categories. Of the unscheduled return visits, 146 (49.2%) returned within 24 hours; 89 (30.0%) between 24 and 48 hours; and 62 (20.8%) between 48 and 72 hours. Of the avoidable visits, 85% returned within 48 hours, as did 92% of those with medical management deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)


Significance of native PLGA nanoparticles in the treatment of Alzheimer's disease pathology.
Alzheimer's disease (AD) is believed to be triggered by increased levels/aggregation of β-amyloid (Aβ) peptides. At present, there is no effective disease-modifying treatment for AD. Here, we evaluated the therapeutic potential of FDA-approved native poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles on Aβ aggregation and in cellular/animal models of AD. Our results showed that native PLGA can not only suppress the spontaneous aggregation but can also trigger disassembly of preformed Aβ aggregates. Spectroscopic studies, molecular dynamics simulations and biochemical analyses revealed that PLGA, by interacting with the hydrophobic domain of Aβ1-42, prevents a conformational shift towards the β-sheet structure, thus precluding the formation and/or triggering disassembly of Aβ aggregates. PLGA-treated Aβ samples can enhance neuronal viability by reducing phosphorylation of tau protein and its associated signaling mechanisms. Administration of PLGA can interact with Aβ aggregates and attenuate memory deficits as well as Aβ levels/deposits in the 5xFAD mouse model of AD. PLGA can also protect iPSC-derived neurons from AD patients against Aβ toxicity by decreasing tau phosphorylation. These findings provide unambiguous evidence that native PLGA, by targeting different facets of the Aβ axis, can have beneficial effects in mouse neurons/animal models as well as on iPSC-derived AD neurons - thus signifying its unique therapeutic potential in the treatment of AD pathology.