Biochemical profile and in vitro biological activities of extracts from seven folk medicinal plants growing wild in southern Tunisia.
Recently, much attention has been paid to the extracts obtained from plant species in order to analyse their biological activities. Due to the climate diversity in Tunisia, the traditional pharmacopoeia consists of a wide arsenal of medicinal plant species since long used in folk medicine, in foods as spices, and in aromatherapy. Although many of these species are nearly facing extinction, only a small proportion of them have been scientifically studied. Therefore, this study explores the biochemical properties of seven spontaneous plants, which were harvested in the arid Tunisian desert: Marrubium vulgare (L.), Rhus tripartita (Ucria) D.C., Thymelaea hirsute (L.) Endl., Plantago ovata (Forsk.), Herniaria fontanesii (J. Gay.), Ziziphus lotus (L.) and Hyoscyamus albus (L.). Extracts from these plants were found to contain different types of secondary metabolites (polyphenols, flavonoids, condensed tannins, crude saponins, carotenoids and alkaloids) that are involved in important biological activities. The biological activity of the extracts obtained from each Tunisian plant was assessed: first of all, leukaemia and colon cancer cell lines (K-562 and CaCo-2 respectively) were treated with different concentrations of extracts, and then the anti-proliferative activity was observed. The results showed, in particular, how the plant extract from Rhus tripartita significantly inhibits cell proliferation, especially on the K-562 tumour cell line. Subsequently, the anti-inflammatory activity was also assessed, and the results showed that Herniaria fontanesii and Marrubium vulgare possess the highest activity in the group of analysed plants. Finally, the greatest acetylcholinesterase inhibitory effect was exhibited by the extract obtained from Rhus tripartita. In conclusion, all the Tunisian plants we analysed were shown to contain a remarkable amount of different bio-active compounds, thus confirming their involvement in several biological activities. Rhus tripartita and Ziziphus lotus were shown to be particularly effective in anti-proliferative activity, while Herniaria fontanesii were shown to have the best anti-inflammatory activity.


Validation of an instrument to measure the impact of coronary disease on patient's daily life.
To evaluate the psychometric Instrument to Measure the Impact of Coronary Disease on Patient's Everyday Life (IDCV) when applied on patients with coronary disease being followed at an outpatient clinic. One hundred and fifty-three patients with coronary disease were registered. Patients were analysed in terms of acceptability, ceiling and floor effect, reliability (using Cronbach's alpha coefficient) and convergent construct validity (by means of Spearman correlation) between the domains of IDCV and of 'Medical Outcomes Trust Short-form Health Survey (SF-36)' and 'MacNew Heart Disease Health-related Quality of Life Questionnaire'. Evidence was found for high acceptability of IDCV. No evidence was found for ceiling and floor effects regarding the total score of IDCV; however, ceiling and floor effects were found from the adjustment to the disease domain. Evidence was found for reliability of the instrument as a whole and for its domains (Cronbach's α ranged between 0·70-0·85). Similar domains on the IDCV, MacNew and SF-36 were correlated: Physical impact - symptoms on the IDCV with the physical function domain on MacNew (r = -0·64) and with most domains on the SF-36 related to the physical dimension; Social impact and emotional impact on the IDCV with emotional function (r = -0·53) and social function (r = -0·55) on the MacNew and mental health on SF-36 (r = -0·55). However, smaller correlations of moderate/high magnitude were found between different constructs entre: Social and emotional impact on the IDCV with physical function on the MacNew (r = -0·56) and with the following domains: Functional capacity (r = -0·50), general health (r = -0·52) and vitality (r = -0·50) on SF-36. The IDCV is an instrument with evidence regarding reliability and convergent validity also for the population of patients with coronary disease. Further studies to validate its factor structure could offer contributions for understanding the psychometric performance of the IDCV among patients with coronary disease.


Biochemical and immunocytological characterizations of Arabidopsis pollen tube cell wall.
During plant sexual reproduction, pollen germination and tube growth require development under tight spatial and temporal control for the proper delivery of the sperm cells to the ovules. Pollen tubes are fast growing tip-polarized cells able to perceive multiple guiding signals emitted by the female organ. Adhesion of pollen tubes via cell wall molecules may be part of the battery of signals. In order to study these processes, we investigated the cell wall characteristics of in vitro-grown Arabidopsis (Arabidopsis thaliana) pollen tubes using a combination of immunocytochemical and biochemical techniques. Results showed a well-defined localization of cell wall epitopes. Low esterified homogalacturonan epitopes were found mostly in the pollen tube wall back from the tip. Xyloglucan and arabinan from rhamnogalacturonan I epitopes were detected along the entire tube within the two wall layers and the outer wall layer, respectively. In contrast, highly esterified homogalacturonan and arabinogalactan protein epitopes were found associated predominantly with the tip region. Chemical analysis of the pollen tube cell wall revealed an important content of arabinosyl residues (43%) originating mostly from (1-->5)-alpha-L-arabinan, the side chains of rhamnogalacturonan I. Finally, matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of endo-glucanase-sensitive xyloglucan showed mass spectra with two dominant oligosaccharides (XLXG/XXLG and XXFG), both being mono O-acetylated, and accounting for over 68% of the total ion signals. These findings demonstrate that the Arabidopsis pollen tube wall has its own characteristics compared with other cell types in the Arabidopsis sporophyte. These structural features are discussed in terms of pollen tube cell wall biosynthesis and growth dynamics.


Characterization of Pax3 and Sox10 transgenic Xenopus laevis embryos as tools to study neural crest development.
The neural crest is a multipotent population of cells that originates a variety of cell types. Many animal models are used to study neural crest induction, migration and differentiation, with amphibians and birds being the most widely used systems. A major technological advance to study neural crest development in mouse, chick and zebrafish has been the generation of transgenic animals in which neural crest specific enhancers/promoters drive the expression of either fluorescent proteins for use as lineage tracers, or modified genes for use in functional studies. Unfortunately, no such transgenic animals currently exist for the amphibians Xenopus laevis and tropicalis, key model systems for studying neural crest development. Here we describe the generation and characterization of two transgenic Xenopus laevis lines, Pax3-GFP and Sox10-GFP, in which GFP is expressed in the pre-migratory and migratory neural crest, respectively. We show that Pax3-GFP could be a powerful tool to study neural crest induction, whereas Sox10-GFP could be used in the study of neural crest migration in living embryos.


In vitro activity of commercial probiotic Lactobacillus strains against uropathogenic Escherichia coli.
Urinary tract infection (UTI) is one of the most prevalent infections in humans. In ≥80% of cases, the etiologic agents are strains of uropathogenic Escherichia coli (UPEC), which commonly reside in the gastrointestinal tract. Lactobacilli have been shown to prevent UTI reoccurrence by restoring the urogenital microbiota when administered vaginally or orally. The goal of this study was to determine if commercial probiotic Lactobacillus spp. reduce or clear UPEC in vitro. Results show that it is likely that lactobacilli may, in addition to restoring a healthy urogenital microbiota through acidification of their environment, also displace adhering UPEC and cause a reduction of infection.


Solubility-limited extrinsic n-type doping of a high electron mobility polymer for thermoelectric applications.
The thermoelectric properties of a highperformance electron-conducting polymer, (P(NDIOD-T2), extrinsically doped with dihydro-1H-benzoimidazol-2-yl (NDBI) derivatives, are reported. The highest thermoelectric power factor that has been reported for a solution-processed n-type polymer is achieved; and it is concluded that engineering polymerdopant miscibility is essential for the development of organic thermoelectrics.


The assessment of neurotoxicity using the cockroach nerve cord.
The acute central nervous system toxicity of chemicals may be detected and analysed with relative ease in the isolated abdominal ventral nerve cord of the American cockroach. Stable electrophysiological measurements of axonal and both inhibitory and excitatory synaptic transmission can be made for several hours with extracellular electrodes using a mannitol-gap technique. Dose-response curves can be obtained for the effects of the chemicals. These can be analysed in terms of site of action, be it on the axons, the presynaptic nerve terminal, the postsynaptic receptors or the termination of neurotransmitter action. Possible non-specific sites are also considered.


[Information model of systemic organization of human mental functions: new approach to the problem of artificial intelligence].
The information model of systemic functions of the human brain reproduces important features of human intelligence: goal planning, prediction of needed results, behavior correction by feedback from the parameters of the results obtained and their comparison with the acceptor of action results. Human behavior imitation in the model is statistically proved by testing the model on a computer. An Adaptron apparatus based on the model quantitatively estimates the parameters of an important mechanism of the brain, namely human intuitive learning. With the Adaptron, the ade-dependent properties and some human intellectual dysfunctions are estimated, which reflect the mechanisms of prediction of future results, the building of memory traces in intuitive learning when the findings coincide with the planned results and the restructure of memory and respective behavior changes when the findings do not coincide with the planned ones.


Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal Squamous Metaplasia.
Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients. RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors. We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin (IVL), small proline rich protein 1B (SPRR1B), and keratin 16 (KRT16). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by SPRR1B, hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal cells in iSGS. Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.


BRCA1 susceptibility markers and postmenopausal breast cancer: the Iowa Women's Health Study.
Much research on early-onset breast cancer families has been performed and has shown that breast cancer in many of these families is linked to either BRCA1 or BRCA2. Fewer studies have examined the role of genetic predisposition in postmenopausal breast cancer. A nested case-control family study of breast cancer was conducted within the Iowa Women's Health Study, a population-based prospective study of 41,836 postmenopausal women. Probands were 251 incident cases diagnosed between 1988 and 1989. Three-generation pedigrees were developed through mailed questionnaires. From this collection of pedigrees, thirteen were identified for more detailed genetic analysis. Sibling-pair linkage analyses were performed using polymorphic markers in candidate regions in these 13 families with multiple cases of breast and other cancers. Four of the DNA markers are located on chromosome 17, and two of these (D17S579 and THRA1) flank the BRCA1 locus. Significant evidence for linkage to D17S579 was obtained in the total sample, in a model without inclusion of covariates or age at onset (P = 0.005), and in a model adjusted for five measured covariates and for variable age at onset (P = 0.008). Complete sequencing of the BRCA1 gene in these families, including all intron/exon boundaries, failed to reveal any mutations in 24 women with breast cancer from the 13 families. These data suggest that in some families identified by postmenopausal breast cancer cases, breast cancer risk may be mediated by a gene (or genes) in the BRCA1 region, but not BRCA1 itself.


[Contents analysis of zinc, manganese, copper and iron in 7 kinds of treatment gastritis Chinese traditional medicines].
The contents of Zn, Mn, Cu and Fe in 7 kinds of treatment gastritis Chinese traditional medicines are determined by FAAS. The results show that element Fe in medicines is very rich, but element Cu is lower. The relationship between trace elements and the factor that causes gastritis is discussed. It provides useful reference data for discussing the relations of trace elements and treatment of gastroenteritis.


Amyloid-β and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus.
Amyloid-β (Aβ1 - 42), total tau (T-tau), and phosphorylated tau (P-tau181) in the cerebrospinal fluid (CSF) are the most promising biomarkers of Alzheimer's disease (AD). Still, little is known about the dynamics of these molecules in the living brain. In a transgenic mouse brain, soluble Aβ decreases with increasing age and advanced Aβ pathology as seen similarly in CSF. To assess the relationship between AD-related pathological changes in human brain tissue, ventricular and lumbar CSF, and brain interstitial fluid (ISF). Altogether 11 patients with suspected idiopathic normal pressure hydrocephalus underwent frontal cortical brain biopsy, 24-h intraventricular pressure monitoring, and a microdialysis procedure. AD-related biomarkers were analyzed from brain tissue, CSF, and ISF. ISF T-tau levels decreased strongly within the first 12 h, then plateauing until the end of the experiment. Aβ1 - 42 and P-tau181 remained stable during the experiment (n = 3). T-tau and P-tau were higher in the ISF than in ventricular or lumbar CSF, while Aβ1 - 42 levels were within similar range in both CSF and ISF samples. ISF P-tau correlated with the ventricular CSF T-tau (r = 0.70, p = 0.017) and P-tau181 (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF Aβ1 - 42 levels than those six without amyloid pathology. This is the first study to report ISF Aβ and tau levels in the human brain without significant brain injury. The set-up used enables sampling from the brain ISF for at least 24 h without causing adverse effects due to the microdialysis procedure to follow the dynamics of the key molecules in AD pathogenesis in the living brain at various stages of the disease.


Prediction of a novel robust superconducting state in TaS2 under high pressure.
In this work, we performed first-principles structure-searching calculations to investigate the behaviors of tantalum disulfide (TaS2) under compression. Beside the well-known 1T and 2H phases at ambient pressure, our results reveal two new phases with the space group of C2/m (in the pressure range of 27-59 GPa) and I4/mmm (stable above 59 GPa). The C2/m and I4/mmm phases adopt three-dimensional covalent framework structures possessing highly eight-fold and ten-fold coordinated Ta, respectively. Strikingly, we observed an unusual superconductor-metal-superconductor transition in TaS2 with the increase of pressure. The predicted C2/m structure exhibits metallic character, while all the other low-pressure (1T and 2H) and high pressure (I4/mmm) phases of TaS2 show superconductivity under pressure. A robust superconductivity of I4/mmm-TaS2 is predicted up to a maximum transition temperature of 7.62 K at 60 GPa and can be stable up to 200 GPa. Our findings, therefore, provide important information to further understand the intrinsic physics of pressure-driven behaviors in transition metal dichalcogenides and related materials.


The role of dietary fiber in gastrointestinal disease.
The most consistent benefit of consumption of adequate dietary fiber is regular laxation; this effect alone justifies inclusion of fiber in the diet, in view of the enormous expenditure on drugs for digestive diseases. Dietary fiber has proved effective in decreasing symptoms of diverticular disease, Crohn's disease, and hemorrhoids in a limited number of small clinical studies. Fiber may also reduce the incidence of gallstone formation. Fiber is currently being touted as protection against colon cancer. However, the epidemiological and experimental data do not provide convincing evidence that fiber alone is a major determinant of risk for colon cancer. Furthermore, the data from international comparisons indicating that fiber is protective against colon cancer can be used in a similar simplistic manner to suggest that fiber may be a risk factor for stomach cancer. This should not dissuade individuals from obtaining adequate fiber from a wide variety of foods but should caution them against consumption of excessive amounts of fiber from a single source or from dietary supplements.


Psychological State Among the General Chinese Population Before and During the COVID-19 Epidemic: A Network Analysis.
Background: The infectious disease Coronavirus Disease 2019 (COVID-19) outbroke in 2019 spread to multiple countries. The quick spread of the virus and isolation strategies may trigger psychological problems. Our aim was to explore the dynamic network structure of the psychological state before and during the epidemic. Methods: A web-based survey was conducted in two stages: the T1 stage (1 January 2019 to 31 December 2019) and the T2 stage (1 February 2020 to 8 March 2020). In both stages, the Patient Health Questionnaire-9, General Anxiety Disorder-7, and Pittsburgh Sleep Quality Index were used to assess depression, anxiety, and sleep, respectively. Results: We matched the data based on IP addresses. We included 1,978, 1,547, and 2,061 individuals who completed the depression, anxiety, and sleep assessments, respectively, at both stages. During epidemics, psychomotor agitation/retardation, inability to relax, restless behavior, and the frequency of using medicine had high centrality. Meanwhile, the network structure of psychological symptoms becomes stronger than before the epidemic. Conclusion: Symptoms of psychomotor agitation/retardation, inability to relax, and restless behavior should be treated preferentially. It is necessary to provide mental health services, including timely and effective early psychological intervention. In addition, we should also pay attention to the way patients use medicines to promote sleep quality.


An analysis of IL-36 signature genes and individuals with IL1RL2 knockout mutations validates IL-36 as a psoriasis therapeutic target.
Interleukin (IL)-36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (TH17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. This enabled us to demonstrate a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associated with the disease in genome-wide studies. Next, we investigated the impact of in vivo and ex vivo IL-36 receptor blockade using a neutralizing antibody or a recombinant antagonist. Both inhibitors had marked anti-inflammatory effects on psoriatic skin, demonstrated by statistically significant reductions in IL-17 expression, keratinocyte activation, and leukocyte infiltration. Finally, we explored the potential safety profile associated with IL-36 blockade by phenotyping 12 individuals carrying knockout mutations of the IL-36 receptor gene. We found that normal immune function was broadly preserved in these individuals, suggesting that IL-36 signaling inhibition would not substantially compromise host defenses. These observations, which integrate the results of transcriptomics and model system analysis, pave the way for early-stage clinical trials of IL-36 antagonists.


Phase plane modeling of leg motion.
Phase plane analysis of dynamical systems, in which variables are plotted against their time derivatives, has been recently emphasized as a general method for reconstructing system dynamics from data. The purpose of this experiment was to develop a model of leg movement in a stepping task using the phase plane approach. In this model, the leg is represented as a three-body linkage and the motion of the leg is assumed to be planar with four degrees of freedom. Experimental data was collected on one subject stepping six times, using a two dimensional videomotion analysis system with reflective markers placed on the lower limb joints. A computer program able to solve the equations of motion and compute the state of the system for a given task was implemented. This computer program was written to generate the motion of the leg for a given task using inverse kinematics and a preplanned foot path. Foot trajectories with cycloidal, constant acceleration/deceleration and sinusoidal velocity profiles were studied. From the results, an attempt was made to identify the variables which are measured and to determine the motion characteristics during stepping. The preliminary results support the concept of a hierarchical control structure with open-loop control during normal operation. During routine activity there is no direct intervention of the Central Nervous System (CNS). The results support the existence of preprogramming and provide a starting point for the study of the development of control in multiarticulate movements.


Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor.
Several G-protein coupled receptors, such as the beta1-adrenergic receptor (beta1-AR), contain polyproline motifs within their intracellular domains. Such motifs in other proteins are known to mediate protein-protein interactions such as with Src homology (SH)3 domains. Accordingly, we used the proline-rich third intracellular loop of the beta1-AR either as a glutathione S-transferase fusion protein in biochemical "pull-down" assays or as bait in the yeast two-hybrid system to search for interacting proteins. Both approaches identified SH3p4/p8/p13 (also referred to as endophilin 1/2/3), a SH3 domain-containing protein family, as binding partners for the beta1-AR. In vitro and in human embryonic kidney (HEK) 293 cells, SH3p4 specifically binds to the third intracellular loop of the beta1-AR but not to that of the beta2-AR. Moreover, this interaction is mediated by the C-terminal SH3 domain of SH3p4. Functionally, overexpression of SH3p4 promotes agonist-induced internalization and modestly decreases the Gs coupling efficacy of beta1-ARs in HEK293 cells while having no effect on beta2-ARs. Thus, our studies demonstrate a role of the SH3p4/p8/p13 protein family in beta1-AR signaling and suggest that interaction between proline-rich motifs and SH3-containing proteins may represent a previously underappreciated aspect of G-protein coupled receptor signaling.


Glucose control in acutely ill patients: a survey of Israeli internal medicine departments.
Tight glucose control has been shown to improve the outcome of patients with severe acute illnesses who are hospitalized in intensive care units and on intravenous insulin-based regimens. To clarify the attitudes of internists towards tight control of glucose levels in acutely ill patients hospitalized in general medical wards. A questionnaire on intensive glucose control in acutely ill patients hospitalized in medical wards was mailed to each of the 100 heads of internal medicine departments in Israel. Fifty physicians responded. Of these, 80% considered tight glucose control to be a major treatment target, but only two-thirds had defined it as a goal in their ward. Furthermore, only about half had a defined protocol for such an intervention. Most physicians considered patients with acute coronary syndrome, stroke and infectious diseases as candidates for a tight glucose control protocol. The most frequently used modalities were multiple blood glucose measurements and repeated injections of short-acting subcutaneous insulin. The main reasons given for not having a defined protocol were lack of guidelines, no evidence of a clear benefit during hospitalization on a medical ward, and a shortage of adequately trained staff. Inconsistencies in physicians' attitudes and in treatment protocols regarding tight control of glucose levels in acutely ill patients hospitalized on a medical ward need to be addressed. Evaluation of the feasibility, effectiveness and side effects of a defined protocol is needed before any regimen can be approved by the heads of the internal medicine departments.


Impact of a new distal attachment on colonoscopy performance in an academic screening center.
Distal attachments placed on the colonoscope tip may positively affect performance by assisting insertion and polyp detection. The original Endocuff (ARC Medical Design, Leeds, United Kingdom) appears to improve adenoma detection rate (ADR), but no data assess the performance of the second-generation Endocuff Vision. A pilot service evaluation study (April 2013 to September 2014) was conducted on patients with positive fecal occult blood tests within the National Bowel Cancer Programme during 3 consecutive periods: precuff/no device used, during-cuff/device used, and postcuff/no device used. During the middle period the use of the Endocuff Vision by the 4 screening-accredited colonoscopists was discretional (nonrandomized design). Data were analyzed using pairwise comparisons during the 3 designated periods to examine key performance indicators: adenoma detection, procedural time, sedation requirements, and patient comfort. Four hundred ten complete colonoscopies were performed (137 precuff, 136 cuff, and 137 postcuff period). Overall, there was a notable increase in the mean ADR of 16% (P < .03) and in the mean number adenoma per procedure (MAP) of 83% (P = .007) from precuff to cuff period. The mean cecal intubation time was statistically lower during the cuff period (7 minutes) in relation to the precuff period (8 minutes; reduction of 12.5%, P = .002) and the postcuff period (9 minutes; increase of 28.6%, P = .002). The mean negative colonoscopy withdrawal time was also significantly lower during the cuff period (8 minutes, 30 seconds) when compared with the precuff (12 minutes) or postcuff period (9 minutes, 45 seconds; P ≤ .001). Multivariate regression analysis showed that the use of the Endocuff Vision was not associated with sedation requirements or patient discomfort scores. No adverse events were reported from the use of the Endocuff Vision, although it was electively removed in 6 patients where severe sigmoid colon diverticulosis was encountered and 2 patients because of discomfort during anal insertion. In this pilot service evaluation study, the use of the Endocuff Vision appears to be associated with an improvement in overall colonoscopy operator performance. We found increased ADR and MAP as well as decreased time for colonoscope insertion and withdrawal time with no increase in sedation requirements or patient discomfort.


Nurse therapists in behavioural psychotherapy.
Five registered mental nurses (R.M.N.s) were trained over two years to become behavioural psychotherapists for adult neurotic disorders. They achieved results comparable to those obtained with similar patients and methods by psychologists and psychiatrists. Similar results were maintained when over a third year the therapists were seconded to work in four hospitals and a general practice. Patients were satisfied at being treated by nurses. After initial teething difficulties nurse therapists became valuable members of treatment teams during both training and secondment, becoming accepted by most nurses, psychologists, and psychiatrists with whom they came into contact. The training of further nurse therapists would facilitate treatment of many disabled neurotics who would otherwise go without effective treatment. Training nurse therapists takes less time and money than training psychologists and psychiatrists because less of their education is redundant to the skills involved. The pool of R.M.N.s suitable for training is much larger than that of psychiatrists and psychologists. The nurse therapists can be integrated relatively easily into treatment teams. The present nursing structure imposes restrictions on the advancement of clinical nurse specialists and a clinical tree is badly needed parallel with present administrative and teaching hierarchies. An 18-month course in adult behavioural psychotherapy has been recognized by the Joint Board of Clinical Nursing Studies for England and Wales so that nurse therapists seem destined to be a lasting feature of future treatment teams.


Diazoxide accelerates wound healing by improving EPC function.
Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing. Diazoxide treatment (30 mg/kg/d, intragastrically) for 28 days accelerated wound closure and stimulated angiogenesis in the diabetic mice. Circulating endothelial progenitor cells (EPCs) increased significantly in the diazoxide-treated diabetic mice. The adhesion, migration, and tube formation abilities of bone marrow (BM)-EPCs were impaired by diabetes, and these impairments were improved by diazoxide treatment. The expression of both p53 and TSP-1 increased in diabetic mice compared to that in the controls, and these increases were inhibited significantly by diazoxide treatment. In vitro, diazoxide treatment improved the impaired BM-EPC function and diminished the increased expression of p53 and TSP-1 in cultured BM-EPCs caused by high glucose levels. We conclude that diazoxide improved BM-EPC function in mice with STZ-induced diabetes, possibly via a p53- and TSP-1-dependent pathway.


Cord Compression Caused by a Tangled and Warped Lumbar Catheter After Lumboperitoneal Shunt Placement.
The present study reports the case of an 81-year-old woman who underwent lumboperitoneal shunt (LPS) placement for idiopathic normal-pressure hydrocephalus. After LPS placement, the patient presented with radicular pain. A computed tomography scan revealed that the intradural lumbar catheter was tangled at the T11 vertebra; therefore, we decided to remove the catheter under local anesthesia. When 1 cm of the lumbar catheter was withdrawn, the patient suddenly complained of complete loss of bilateral leg sensation and muscle strength. Emergency magnetic resonance imaging revealed that the lumbar catheter was tangled and wedged into the ventral spinal cord at T11, causing severe spinal cord compression. In the operating room under general anesthesia, the lumbar catheter was removed through a right T12 hemilaminectomy. Postoperatively, her neurological function was fully restored. Although LPS placement is frequently indicated for idiopathic normal-pressure hydrocephalus, recognition of this rare complication is important for proper LPS management.


The cell division protein ZapE is targeted by the antibiotic aztreonam to induce cell filamentation in Escherichia coli.
Bacterial division is mediated by a protein complex called the Z-ring, and Z-ring associated protein E (ZapE) is a Z-ring-associated protein that acts as its negative regulator. In the present study, we show that treatment of Escherichia coli with the antibiotic aztreonam stabilized the Z-ring, induced filamentation, and reduced viability, with similar phenotypes being observed in ZapE deletion strains. Aztreonam treatment decreased ZapE expression, and the overexpression of ZapE rescued filamentous morphology significantly and viability partially. However, overexpression of filamentous temperature sensitive I (FtsI), a known target of aztreonam, could not rescue the filamentation. Interestingly, overexpression of ZapE and FtsI together was able to rescue both filamentous morphology and cell viability. Using in silico and biochemical analyses, we show that aztreonam directly interacts with ZapE. Our study suggests that the inhibitory effects of aztreonam in E. coli could be mediated by targeting ZapE.


Human-animal relationships and interactions during the Covid-19 lockdown phase in the UK: Investigating links with mental health and loneliness.
The Covid-19 pandemic raises questions about the role that relationships and interactions between humans and animals play in the context of widespread social distancing and isolation measures. We aimed to investigate links between mental health and loneliness, companion animal ownership, the human-animal bond, and human-animal interactions; and to explore animal owners' perceptions related to the role of their animals during lockdown. A cross-sectional online survey of UK residents over 18 years of age was conducted between April and June 2020. The questionnaire included validated and bespoke items measuring demographics; exposures and outcomes related to mental health, wellbeing and loneliness; the human-animal bond and human-animal interactions. Of 5,926 participants, 5,323 (89.8%) had at least one companion animal. Most perceived their animals to be a source of considerable support, but concerns were reported related to various practical aspects of providing care during lockdown. Strength of the human-animal bond did not differ significantly between species. Poorer mental health pre-lockdown was associated with a stronger reported human-animal bond (b = -.014, 95% CI [-.023 - -.005], p = .002). Animal ownership compared with non-ownership was associated with smaller decreases in mental health (b = .267, 95% CI [.079 - .455], p = .005) and smaller increases in loneliness (b = -.302, 95% CI [-.461 - -.144], p = .001) since lockdown. The human-animal bond is a construct that may be linked to mental health vulnerability in animal owners. Strength of the human-animal bond in terms of emotional closeness or intimacy dimensions appears to be independent of animal species. Animal ownership seemed to mitigate some of the detrimental psychological effects of Covid-19 lockdown. Further targeted investigation of the role of human-animal relationships and interactions for human health, including testing of the social buffering hypothesis and the development of instruments suited for use across animal species, is required.


Effect of salting procedures on quality of hake (Merluccius hubbsi) fillets.
The influence of salting procedures on the proximate analysis, mechanical parameters, and color of hake (Merluccius hubbsi) was investigated. Three procedures were comparatively evaluated: dry salting (DS), mixed salting (MS) and brining (BS). MS samples had the highest fat content, a considerable protein content and an equilibrium salt content similar to BS. MS samples had a great water loss, as DS method, but hardness and other mechanical parameters were similar to that obtained with BS, i.e. significantly lower than DS. All samples showed color parameters significantly different as compared to fresh hake, turning more red-orange as the salting time increased. Lightness diminished, a∗ values increased and b∗ values did not show a clear trend throughout the salting time. Principal component analysis (PCA) described the relationship between some variables (zNaCl, color, and mechanical parameters) with salting time. High Pearson's correlation coefficients were found between zNaCl and hardness, springiness, cohesiveness and a∗ parameter (r = 0.76, p < 0.001; r = 0.93, p < 0.0001; r = 0.95, p < 0.001 and r = 0.93, p < 0.0001, respectively). Luminosity was negatively correlated with zNaCl (r = -0.87, p = 0.0001). The correlation curves showed nonlinear relationships (R2 adj between 83.7 % and 97.4 %), which could be used to predict quality attributes of hake fillets as a function of salting time. This work contributed to know the effect of different salting procedures on the quality attributes of a species widely available in the Southwest Atlantic Ocean.


Comparison of pain levels in patients treated with 3 different orthodontic appliances - a randomized trial.
To compare pain levels experienced during initial alignment with three different orthodontic appliance types and to correlate pain with male and female differences, if any. A prospective, randomized 3-arm parallel trial allocated 36 adult orthodontic patients into three appliance groups: MBT 0.022" slot (Mini Twin, Ormco, Glendora, USA), self ligating 0.022" slot Damon 3MX (Ormco, Glendora, USA) and clear aligners (Smile align, Mumbai, India). The level of discomfort was assessed through a questionnaire based on the visual analogue scale at four hours, twenty four hours, third and seventh day after appliance placement. Patients treated with clear aligners reported less pain than patients treated with conventional and self ligating fixed appliances. Patients treated with MBT conventional appliances showed greater pain levels than Damon appliances. A significantly higher visual analogue scale score was observed at 24 hours and the least visual analogue scale scores on the seventh day post appliance placement. During the first week of orthodontic treatment, patients treated with clear aligners reported lower pain than those treated with conventional and self-ligating appliances.


The evolution of medical students' preparedness for clinical practice during the transition of graduation: a longitudinal study from the undergraduate to postgraduate periods.
Graduating from medical school and beginning independent practice appears to be a major transition for medical students across the world. It is often reported that medical graduates are underprepared for independent practice. Most previous studies on undergraduates' preparedness are cross-sectional. This study aimed to characterize the development and trend of medical students' preparedness and its association with other objective and subjective indicators from the undergraduate to postgraduate periods. This was a prospective cohort study. The participants were recruited and followed from two years before graduation to the postgraduate period. The preparedness for independent practice, professional identity, and teamwork experience were biannually measured using previously validated questionnaires. The participants' basic demographic information, clinical learning marks from the last two years, and national board exam scores were also collected. A total of 85 participants completed 403 measurements in the 5 sequential surveys. The mean age at recruitment was 23.6, and 58 % of participants were male. The overall total preparedness score gradually increased from 157.3 (SD=21.2) at the first measurement to 175.5 (SD=25.6) at the fifth measurement. The serial individual preparedness scores revealed both temporal differences within the same learner and individual differences across learners. Despite the variations, a clear, steady increase in the overall average score was observed. Participants were least prepared in the domain of patient management at first, but the score increased in the subsequent measurements. The participants with better final preparedness had better professional identity (p<0.01), better teamwork experience (p < 0.01), and higher average clinical rotation marks (p<0.05). The preparedness for practice of medical students from the undergraduate to postgraduate periods is associated with their professional identity, teamwork experience, and objective clinical rotation endpoint. Although preparedness generally increases over time, educators must understand that there are temporal fluctuations and individual differences in learners' preparedness.


Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle.
Smooth muscle myosin regulatory light chain (RLC) is phosphorylated by Ca2+ /calmodulin-dependent myosin light chain kinase and dephosphorylated by myosin light chain phosphatase (MLCP). Tracheal smooth muscle contains significant amounts of myosin binding subunit 85 (MBS85), another myosin phosphatase targeting subunit (MYPT) family member, in addition to MLCP regulatory subunit MYPT1. Concentration/temporal responses to carbachol demonstrated similar sensitivities for bovine tracheal force development and phosphorylation of RLC, MYPT1, MBS85 and paxillin. Electrical field stimulation releases ACh from nerves to increase RLC phosphorylation but not MYPT1 or MBS85 phosphorylation. Thus, nerve-mediated muscarinic responses in signalling modules acting on RLC phosphorylation are different from pharmacological responses with bath added agonist. The conditional knockout of MYPT1 or the knock-in mutation T853A in mice had no effect on muscarinic force responses in isolated tracheal tissues. MLCP activity may arise from functionally shared roles between MYPT1 and MBS85, resulting in minimal effects of MYPT1 knockout on contraction. Ca2+ /calmodulin activation of myosin light chain kinase (MLCK) initiates myosin regulatory light chain (RLC) phosphorylation for smooth muscle contraction with subsequent dephosphorylation for relaxation by myosin light chain phosphatase (MLCP) containing regulatory (MYPT1) and catalytic (PP1cδ) subunits. RLC phosphorylation-dependent force development is regulated by distinct signalling modules involving protein phosphorylations. We investigated responses to cholinergic agonist treatment vs. neurostimulation by electric field stimulation (EFS) in bovine tracheal smooth muscle. Concentration/temporal responses to carbachol demonstrated tight coupling between force development and RLC phosphorylation but sensitivity differences in MLCK, MYPT1 T853, MYPT1 T696, myosin binding subunit 85 (MBS85), paxillin and CPI-17 (PKC-potentiated protein phosphatase 1 inhibitor protein of 17 kDa) phosphorylations. EFS increased force and phosphorylation of RLC, CPI-17 and MLCK. In the presence of the cholinesterase inhibitor neostigmine, EFS led to an additional increase in phosphorylation of MYPT1 T853, MYPT1 T696, MBS85 and paxillin. Thus, there were distinct pharmacological vs. physiological responses in signalling modules acting on RLC phosphorylation and force responses, probably related to degenerate G protein signalling networks. Studies with genetically modified mice were performed. Expression of another MYPT1 family member, MBS85, was enriched in mouse, as well as bovine tracheal smooth muscle. Carbachol concentration/temporal-force responses were similar in trachea from MYPT1SM+/+ , MYPT1SM-/- and the knock-in mutant mice containing nonphosphorylatable MYPT1 T853A with no differences in RLC phosphorylation. Thus, MYPT1 T853 phosphorylation was not necessary for regulation of RLC phosphorylation in tonic airway smooth muscle. Furthermore, MLCP activity may arise from functionally shared roles between MYPT1 and MBS85, resulting in minimal effects of MYPT1 knockout on contraction.


Implementation of Health Links coordinated care plans for adults with intellectual and developmental disabilities: Cross-sectoral pilot program.
Adults with intellectual and developmental disabilities (IDD) are a complex population that could benefit from improved care coordination across health and social sectors, as they experience poorer health and have higher rates of emergency department use and hospitalization due to ambulatory care-sensitive conditions. To pilot a novel, enhanced model of care coordination for complex patients with IDD. Health Links is a provincial care-coordination program for patients with complex health care needs. This pilot program adapted Health Links to include a guide and training specific to adults with IDD to ensure that these patients' needs were met and high-quality, efficient care was provided. A tailored care-coordination approach for adults with IDD was able to identify complex patients in need and successfully bridge cross-sectoral care.


Designing the quality factor of infiltrated photonic wire slot microcavities.
One-dimensional photonic wire (nanobeam) microcavities are becoming preferred tools for the investigation of enhanced light-matter interaction. Here, the Q-factor of a locally infiltrated slot microcavity in a nanobeam is theoretically investigated. The electric field of the cavity mode is concentrated in the slot region leading to a large overlap with the infiltrated material. Tapering the spacing and diameter of the pores of the adjacent Bragg mirrors a maximum Q-factor of 35,000 is predicted. General design rules for the minimization of scattering losses and the enhancement of quality factors are reviewed and discussed.


Psychological interventions for loneliness and social isolation among older adults during medical pandemics: a systematic review and meta-analysis.
There is little research conducted to systematically synthesize the evidence on psychological interventions for social isolation and loneliness among older adults during medical pandemics. This systematic review aims to address this information gap and provides guidance for planning and implementing interventions to prevent and reduce loneliness and social isolation for older adults, especially during medical pandemics. Four electronic databases (EMBASE, PsychoInfo, Medline and Web of Science) and grey literature from 1 January 2000 to 13 September 2022 were searched for eligible studies on loneliness and social isolation. Data extraction and methodological quality assessment on key study characteristics were conducted independently by two researchers. Both qualitative synthesis and meta-analysis were used. The initial search yielded 3,116 titles. Of the 215 full texts reviewed, 12 intervention articles targeting loneliness during the COVID-19 pandemic met the inclusion criteria. No studies were found concerning intervention with respect to social isolation. Overall, interventions targeting social skills and the elimination of negativities effectively alleviated the feelings of loneliness in the older population. However, they had only short-term effects. This review systematically summarised the key characteristics and the effectiveness of existing interventions addressing loneliness in older adults during the COVID-19 pandemic. Future interventions should focus on social skills and eliminating negativities and be tailored to the needs and characteristics of older people. Repeated larger-scale randomized controlled trials and long-term effectiveness evaluations on this topic are warranted.


Unit-based care teams and the frequency and quality of physician-nurse communications.
To determine whether reorganizing physicians into unit-based teams in general pediatric wards is associated with greater ability to identify other care team members, increased face-to-face communication between physicians and nurses, greater perception that their patient care concerns were met, and decreased number of pages to residents. Prospective intervention study with data collected before and at 2 time points after implementation of unit-based teams. General pediatric wards at an urban, tertiary care, freestanding children's hospital from April 1, 2008, through June 30, 2009. Pediatric residents rotating in the medical wards (n = 60) and ward-based pediatric nurses (n = 154). We reorganized resident-physician care teams to be based on specific inpatient units, with residents admitting and caring only for patients on their assigned unit. Anonymous physician and nurse self-reports of communication practices and number of pages residents received. In the unit-based team system, physicians were more likely to be able to identify the nurse for their patients with the most complex conditions (62.3% vs 82.8% vs 82.5%, P = .05), to report contacting (27.3% vs 64.9% vs 56.9%, P = .01) and being contacted by (7.7% vs 48.2% vs 55.2%, P = .002) that nurse in person, and to believe their patient care concerns were met (44.2% vs 82.1% vs 81.8%, P = .009). Nurses reported parallel improvements in communication patterns. The mean number of pages per day to residents decreased by 42.1% (19 vs 10 vs 11, P < .001). Unit-based teams improve the frequency and quality of multidisciplinary communication, which may create an improved climate for patient safety.


Effects of secukinumab on metabolic and liver parameters in plaque psoriasis patients.
Psoriasis is associated with metabolic, liver and cardiovascular comorbidity. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, has shown significant and sustained efficacy in the treatment of moderate to severe psoriasis. This was an exploratory post hoc analysis of pooled data from three phase 3 studies in plaque psoriasis patient populations. The objective was to show the course of metabolic and liver parameters under secukinumab, etanercept or placebo treatment over time. A further objective was to assess the impact of selected comorbidities and metabolic characteristics on high-sensitivity C-reactive protein (hs-CRP), as a surrogate marker of systemic inflammation. Data from the phase 3 randomized controlled trials [FIXTURE (NCT01358578), ERASURE (NCT01365455) and SCULPTURE (NCT01406938); n = 3010] were included in this analysis. Patients were treated with secukinumab 150 mg or 300 mg, placebo or etanercept 50 mg (FIXTURE only) as active comparator. A set of metabolic and liver parameters was longitudinally assessed over 52 weeks. Multivariate regression analyses assessed the impact of selected comorbidities and metabolic characteristics on hs-CRP levels at baseline and under treatment. Secukinumab treatment reduced hs-CRP levels. Body weight and uric acid levels tended to decrease over 52 weeks with secukinumab. Secukinumab showed a neutral effect on fasting plasma glucose, lipid parameters and liver enzymes. Psoriatic arthritis, metabolic syndrome, obesity, impaired glucose metabolism, and hyperuricemia were each associated with increased hs-CRP levels at baseline. Concomitant obesity attenuated the decline in hs-CRP under treatment. These analyses suggest neutral to favourable long-term trends in metabolic and liver parameters under secukinumab treatment. Metabolic comorbidities were associated with increased hs-CRP levels, reflecting the role of systemic inflammatory processes in their pathophysiology.


Salivary contribution to exhaled nitric oxide.
Dietary and metabolic nitrate is distributed from the blood to the saliva by active uptake in the salivary glands, and is reduced to nitrite in the oral cavity by the action of certain bacteria. Since it has been reported that nitric oxide may be formed nonenzymatically from nitrite this study aimed to determine whether salivary nitrite could influence measurements of exhaled NO. Ten healthy subjects fasted overnight and ingested 400 mg potassium nitrate, equivalent to approximately 200 g spinach. Exhaled NO and nasal NO were regularly measured with a chemiluminescence technique up to 3 h after the ingestion. Measurements of exhaled NO were performed with a single-breath procedure, standardized to a 20-s exhalation, at a flow of 0.15 L x s(-1), and oral pressure of 8-10 cmH2O. Values of NO were registered as NO release rate (pmol x s(-1)) during the plateau of exhalation. Exhaled NO increased steadily over time after nitrate load and a maximum was seen at 120 min (77.0+/-15.2 versus 31.2+/-3.0 pmol x s(-1), p<0.01), whereas no increase was detected in nasal NO levels. Salivary nitrite concentrations increased in parallel; at 120 min there was a four-fold increase compared with baseline (1.56+/-0.44 versus 0.37+/-0.09 mM, p<0.05). The nitrite-reducing conditions in the oral cavity were also manipulated by the use of different mouthwash procedures. The antibacterial agent chlorhexidine acetate (0.2%) decreased NO release by almost 50% (p<0.01) 90 min after nitrate loading and reduced the preload control levels by close to 30% (p<0.05). Sodium bicarbonate (10%) also reduced exhaled NO levels, but to a somewhat lesser extent than chlorhexidine acetate. In conclusion, salivary nitric oxide formation contributes to nitric oxide in exhaled air and a large intake of nitrate-rich foods before the investigation might be misinterpreted as an elevated inflammatory activity in the airways. This potential source of error and the means for avoiding it should be considered in the development of a future standardized method for measurements of exhaled nitric oxide.


A rare cause of seizure masquerading as neoplasm.
The authors report the case of a young man with no significant medical history who presented with new-onset seizure and mass-like lesions isolated to the left cerebral hemisphere relating to malignancy. Biopsy revealed findings consistent with angiitis and investigations for secondary causes of angiitis was negative. The diagnosis of primary angiitis of the central nervous system was made and the patient has responded well to treatment.


Fractal structures in nonlinear plasma physics.
Fractal structures appear in many situations related to the dynamics of conservative as well as dissipative dynamical systems, being a manifestation of chaotic behaviour. In open area-preserving discrete dynamical systems we can find fractal structures in the form of fractal boundaries, associated to escape basins, and even possessing the more general property of Wada. Such systems appear in certain applications in plasma physics, like the magnetic field line behaviour in tokamaks with ergodic limiters. The main purpose of this paper is to show how such fractal structures have observable consequences in terms of the transport properties in the plasma edge of tokamaks, some of which have been experimentally verified. We emphasize the role of the fractal structures in the understanding of mesoscale phenomena in plasmas, such as electromagnetic turbulence.


On a triple infection of strigeid metacercariae in an Indian fresh-water fish, Xenentodon cancilla.
Three new species of strigeid metacercariae viz., Neascus hoffmani n. sp., Neascus nanaksagarensis n. sp. and Tetracotyle aglandulata n. sp. are described here from a fresh-water fish, Xenentodon cancilla (Ham.); of these, the former two resemble N. xenentodoni PANDEY, 1970 as well as N. hepatica CHAKRABARTI, 1970 while the latter one T. xenentodoni CHAKRABARTI, 1969. - N. hoffmani and N. nanaksagarensis are pharyngeate forms and each has its own pattern of reserve excretory system. N. hoffmani has a spinose body, while N. nanaksagarensis has an aspinose body. - Tetracotyle aglandulata has a lobed hold-fast organ, but lacks a hold-fast gland. Further, in this form fore-body and hind-body is not marked and it has its own characteristic reserve excretory system.


Effect of the inositol polyphosphate InsP(6) on DNA-PK-dependent phosphorylation.
Inositol hexakisphosphate (InsP(6)) is a member of the inositol polyphosphate group that participates in numerous intracellular signaling pathways. Cheung and colleagues previously reported that InsP(6) stimulated double-strand break repair by nonhomologous end joining (NHEJ) in cell-free extracts and that InsP(6) binding by the Ku70/80 subunit of the DNA-dependent protein kinase (DNA-PK) was required for stimulation of NHEJ in vitro. This report describes InsP(6)-dependent phosphorylation of two NHEJ factors, XRCC4 and XLF, in partially purified human cell extracts. XRCC4 and XLF are known substrates for DNA-PK, which does not require InsP(6) for protein kinase activity. Consistent with a role for DNA-PK in these reactions, InsP(6)-dependent phosphorylation of XRCC4 and XLF was DNA dependent and not observed in the presence of DNA-PK inhibitors. Depletion of the Ku70/80 DNA-, InsP(6)-binding subunit of DNA-PK resulted in loss of InsP(6)-dependent phosphorylation and showed a requirement for Ku70/80 in these reactions. Complementation of Ku70/80-depleted reactions with recombinant wild-type Ku70/80 restored InsP(6)-dependent phosphorylation of XRCC4 and XLF. In contrast, addition of a Ku70/80 mutant with reduced InsP(6) binding failed to restore InsP(6)-dependent phosphorylation. While additional protein kinases may participate in InsP(6)-dependent phosphorylation of XRCC4 and XLF, data presented here describe a clear requirement for DNA-PK in these phosphorylation events. Furthermore, these data suggest that binding of the inositol polyphosphate InsP(6) by Ku70/80 may modulate the substrate specificity of the phosphoinositide-3-kinase-related protein kinase DNA-PK.


Biodegradable shape memory polymers functionalized with anti-biofouling interpenetrating polymer networks.
A novel type of shape memory polyurethane (SMPU) with high mechanical properties and biodegradability was constructed using a lactone copolymer (poly(ε-caprolactone-co-γ-butyrolactone), PCLBL), a diol- or triol-based chain extender (1,5-pentanediol, glycerol and 2-amino-2-hydroxymethyl-1,3-propanediol) and a diisocyanate cross-linker (1,6-hexamethylene diisocyanate). All types of SMPUs possessed high mechanical properties, and the shape recovery test indicated that the SMPU sheets prepared using a triol-chain extender with an amine group recovered completely the original shape at 80 °C. Moreover, the degradation products of the SMPUs were innoxious, which is an important property for use in the biomedical field. Furthermore, the SMPU sheets were interpenetrated with a zwitterionic polymer, poly(carboxymethyl betaine) (PCMB), using the interpenetrating polymer network (IPN) method to additionally introduce an anti-biofouling property. Water contact angle measurements of the surface of PCMB-introduced SMPU sheets showed a drastic reduction from 87° to approximately 30° due to the exposure of the PCMB chains from the SMPU sheets. These SMPU-IPN sheets suppressed significantly both protein adsorption and cell adhesion. Consequently, the PCLBL-PU-based SMPUs interpenetrated with PCMB are promising materials for biomedical devices because of their high mechanical, shape memory, biodegradable, and anti-biofouling properties. These materials are expected to be applied to biomaterials such as embolization materials for aneurysms and a novel type of membrane for postoperative adhesion prevention.


How to identify indolent thyroid tumors unlikely to recur and cause cancer death immediately after surgery-Risk stratification of papillary thyroid carcinoma in young patients.
Current histopathological diagnosis methods cannot distinguish the two types of thyroid carcinoma: clinically significant carcinomas with a potential risk of recurrence, metastasis, and cancer death, and clinically insignificant carcinomas with a slow growth rate. Both thyroid tumors are diagnosed as "carcinoma" in current pathology practice. The clinician usually recommends surgery to the patient and the patient often accepts it because of cancer terminology. The treatment for these clinically insignificant carcinomas does not benefit the patient and negatively impacts society. The author proposed risk stratification of thyroid tumors using the growth rate (Ki-67 labeling index), which accurately differentiates four prognostically relevant risk groups based on the Ki-67 labeling index, ≥30%, ≥10 and <30%, >5 and <10%, and ≤5%. Indolent thyroid tumors with an excellent prognosis have the following four features: young age, early-stage (T1-2 M0), curatively treated, and low proliferation index (Ki-67 labeling index of ≤5%), and are unlikely to recur, metastasize, or cause cancer death. Accurate identification of these indolent tumors helps clinicians select more conservative treatments to avoid unnecessary aggressive (total thyroidectomy followed by radio-active iodine) treatments. Clinicians can alleviate the fears of patients by confirming these four features, including the low proliferation rate, in a pathology report immediately after surgery when patients are most concerned.


Keys to managing systemic lupus erythematosus.
The keys to coping with the variability seen in SLE are accurate differentiation of active disease from past damage and consistent monitoring for new disease manifestations and medication side effects. Common clinical problems are reviewed.


Brief report: validity of Finnish registry-based diagnoses of autism with the ADI-R.
The aim of the study was to explore the validity of registry-based diagnoses of autism in Finland using the Autism Diagnostic Interview - Revised (ADI-R). This study was designed for the Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A), an ongoing research project where registry-based diagnoses will be used for epidemiological studies. In this small pilot study, a clinical sample of 95 subjects diagnosed with childhood autism or pervasive developmental disorder/pervasive developmental disorder - not otherwise specified (PDD/PDD-NOS) or Asperger's syndrome according to the Finnish Hospital Discharge Register (FHDR) was gathered nationwide. A small control group consisting of siblings without any registered diagnoses of those being examined was also included in the study. Diagnoses were further re-evaluated by interviewing parents with the ADI-R. The mean scores of autistic subjects clearly exceeded cut-off limits for autism on all three ADI-R domains and 96% of the subjects with registered diagnosis of childhood autism fulfilled the criteria based on the instrument as well. These results suggest that the validity of Finnish registry-based diagnoses of childhood autism can be considered good. Our findings lay important groundwork for further population- based studies of the aetiology of autism.


Is routine ureteral stenting really necessary after retrograde intrarenal surgery?
To investigate the situations in which ureteral double-J stent should be used after retrograde intrarenal surgery (RIRS). Patients with no ureteral double-J stent after RIRS constituted Group 1, and those with double- J stent after RIRS constituted Group 2. Patients' age and gender, renal stone characteristics (location and dimension), stone-free status, VAS score 8 hours after surgery, post-procedural renal colic attacks, length of hospitalization, requirement for re-hospitalization, time to rehospitalization and secondary procedure requirements were analyzed. RIRS was performed on 162 renal units. Double-J stent was used in 121 (74.6%) of these after RIRS, but not in the other 41 (25.4%). At radiological monitoring at the first month postoperatively after RIRS, complete stone-free status was determined in 122 (75.3%) renal units, while residual stone was present in 40 (24.6%). No significant differences were observed between the groups in terms of duration of fluoroscopy (p = 0.142), operation (p = 0.108) or hospitalization times (p = 0.798). VAS values determined routinely on the evening of surgery were significantly higher in Group 1 than in Group 2 (p = 0.025). Twenty-eight (17.2%) presentations were made to the emergency clinic due to renal colic within 1 month after surgery. Double-J catheter was present in 24 (85.7%) of these patients. Routine double-J stent insertion after RIRS is not essential since it increases costs, morbidity and operation time.


[New viewpoints on old cases: pneumonia. 1841].
In this third presentation of reviewed old case histories a lecture by the famous clinician Schoenlein held in 1841 at the Charité on a patient with pneumonia is commented on. This case is in many ways instructive and interesting. The lecture at first reveals the numerous diagnostic difficulties in medicine 150 years ago and then demonstrates the great innovation brought to physical examination by ausculatation introduced to the clinic by Schoenlein against great opposition. For the first time the clinical diagnosis of pulmonary lesions had become possible whereby the diagnostic criteria for pneumonia obtained by auscultation and percussion were already precisely established. Furthermore the utilized therapeutic measures are in part still applicable. This impressive didactic demonstration reveals why Schoenlein was regarded as the most important clinical teacher of his time introducing modern scientific medicine.


Quantitative Assessment of Learning and Retention in Virtual Vocal Function Exercises.
Purpose Successful voice therapy requires the patient to learn new vocal behaviors, but little is currently known regarding how vocal motor skills are improved and retained. To quantitatively characterize the motor learning process in a clinically meaningful context, a virtual task was developed based on the Vocal Function Exercises. In the virtual task, subjects control a computational model of a ball floating on a column of airflow via modifications to mean airflow (L/s) and intensity (dB-C) to keep the ball within a target range representing a normative ratio (dB × s/L). Method One vocally healthy female and one female with nonphonotraumatic vocal hyperfunction practiced the task for 11 days and completed retention testing 1 and 6 months later. The mapping between the two execution variables (airflow and intensity) and one error measure (proximity to the normative ratio) was evaluated by quantifying distributional variability (tolerance cost and noise cost) and temporal variability (scaling index of detrended fluctuation analysis). Results Both subjects reduced their error over practice and retained their performance 6 months later. Tolerance cost and noise cost were positively correlated with decreases in error during early practice and late practice, respectively. After extended practice, temporal variability was modulated to align with the task's solution manifold. Conclusions These case studies illustrated, in a healthy control and a patient with nonphonotraumatic vocal hyperfunction, that the virtual floating ball task produces quantitative measures characterizing the learning process. Future work will further investigate the task's potential to enhance clinical assessment and treatments involving voice control. Supplemental Material https://doi.org/10.23641/asha.13322891.


Quality of Life of People with Severe Mental Health Problems: Testing an Interactive Model.
Improvement of subjective quality of life (QoL) is seen as an important treatment outcome in clinical practice. The aim of this study is to test the theoretical model of Cummins, which includes a homeostatic management system. According to this model, objective variables are almost irrelevant to general well-being, while the feeling of having an influence on one's circumstances (perceived deficit) is related to subjective QoL. The variables of the Cummins model were operationalised based on the Lancashire Quality of Life Profile, a structured interview to assess the subjective QoL of people with severe mental health problems. The Cummins model was tested using structural equation modelling and a mediator model between Objective QoL, Subjective QoL and Perceived Deficit. Subjective QoL and General Well-Being were significantly related and having a meaningful perspective in life was related to General Well-Being. Contrary to the Cummins model, both Objective QoL and Perceived Deficit had a significant relation to Subjective QoL and Perceived Deficit was a partial mediator between Objective QoL and Subjective QoL. Cummins' theoretical model was partially confirmed. The current study suggests that meaningful (treatment) evaluation of subjective QoL can only be performed if objective QoL, General Well-Being and subjective evaluation (Perceived Deficit and Framework) are taken into account.


New medication treatment options for bipolar disorders.
To assess new treatment options for bipolar disorders. Controlled studies of new treatments for bipolar disorders were identified by computerized searches and reviews of scientific meeting proceedings, and were compiled by drug category. Two main categories of medications, newer anticonvulsants and newer antipsychotics, are yielding emerging new treatment options for bipolar disorders. Newer anticonvulsants have diverse psychotropic profiles, and although not generally effective for acute mania, may have utility for other aspects of bipolar disorders (e.g. lamotrigine for maintenance or acute bipolar depression), or for comorbid conditions (e.g. gabapentin for anxiety or pain, topiramate for obesity, bulimia, alcohol dependence, or migraine, and zonisamide for obesity). In contrast, newer antipsychotics generally appear effective for acute mania, and some may ultimately prove effective in acute depression (e.g. olanzapine combined with fluoxetine, quetiapine) and maintenance (e.g. olanzapine). Emerging research is yielding new treatment options for bipolar disorders and comorbid conditions.


The transmembrane tyrosine of micro-heavy chain is required for BCR destabilization and entry of antigen into clathrin-coated vesicles.
The B cell antigen receptor (BCR) delivers antigen to the endocytic compartment and transduces signals that regulate the stability of the receptor complex. Previous studies showed that BCR-mediated signal transduction dissociates micro-heavy chain (microm) from Ig-alpha/Ig-beta, facilitating the delivery of antigen to clathrin-coated vesicles (CCVs). Herein, we demonstrate that the dissociation of Ig-alpha/Ig-beta from microm requires tyrosine-587 of the microm transmembrane domain. Receptors expressing a mutation at tyrosine-587 (Y587F) transduced signals that were comparable to wild type, yet they failed to dissociate microm from Ig-alpha/Ig-beta. Further, receptors harboring the Y587F mutation failed to associate with CCVs, resulting in diminished antigen in the lysosome-associated membrane protein-1 (LAMP-1(+)) compartment and severely impaired antigen presentation, indicating that endocytosis through CCVs is required for antigen presentation. Thus, the transmembrane tyrosine of mum mediates destabilization of the BCR complex, facilitating antigen processing by promoting the association of antigen with CCVs.


The binding protein BiP attenuates stress-induced cell death in soybean via modulation of the N-rich protein-mediated signaling pathway.
The molecular chaperone binding protein (BiP) participates in the constitutive function of the endoplasmic reticulum (ER) and protects the cell against stresses. In this study, we investigated the underlying mechanism by which BiP protects plant cells from stress-induced cell death. We found that enhanced expression of BiP in soybean (Glycine max) attenuated ER stress- and osmotic stress-mediated cell death. Ectopic expression of BiP in transgenic lines attenuated the leaf necrotic lesions that are caused by the ER stress inducer tunicamycin and also maintained shoot turgidity upon polyethylene glycol-induced dehydration. BiP-mediated attenuation of stress-induced cell death was confirmed by the decreased percentage of dead cell, the reduced induction of the senescence-associated marker gene GmCystP, and reduced DNA fragmentation in BiP-overexpressing lines. These phenotypes were accompanied by a delay in the induction of the cell death marker genes N-RICH PROTEIN-A (NRP-A), NRP-B, and GmNAC6, which are involved in transducing a cell death signal generated by ER stress and osmotic stress through the NRP-mediated signaling pathway. The prosurvival effect of BiP was associated with modulation of the ER stress- and osmotic stress-induced NRP-mediated cell death signaling, as determined in transgenic tobacco (Nicotiana tabacum) lines with enhanced (sense) and suppressed (antisense) BiP levels. Enhanced expression of BiP prevented NRP- and NAC6-mediated chlorosis and the appearance of senescence-associated markers, whereas silencing of endogenous BiP accelerated the onset of leaf senescence mediated by NRPs and GmNAC6. Collectively, these results implicate BiP as a negative regulator of the stress-induced NRP-mediated cell death response.


A comparison of modified versions of the Static-99 and the Sex Offender Risk Appraisal Guide.
The predictive validity of 2 risk assessment instruments for sex offenders, modified versions of the Static-99 and the Sex Offender Risk Appraisal Guide, was examined and compared in a sample of 258 adult male sex offenders. In addition, the independent contributions to the prediction of recidivism made by each instrument and by various phallometric indices were explored. Both instruments demonstrated moderate levels of predictive accuracy for sexual and violent (including sexual) recidivism. They were not significantly different in terms of their predictive accuracy for sexual or violent recidivism, nor did they contribute independently to the prediction of sexual or violent recidivism. Of the phallometric indices examined, only the pedophile index added significantly to the prediction of sexual recidivism, but not violent recidivism, above the Static-99 alone.


Variation in metabolic rate between populations of a geographically widespread lizard.
In geographically widespread ectotherms, variation in life history phenotypes may be caused by differences in maintenance metabolism of individuals. I estimated daily and annual maintenance metabolism of eastern fence lizards, Sceloporus undulatus, from two populations with markedly different life histories; lizards in South Carolina grow faster, mature earlier, and have greater annual reproductive output than lizards in New Jersey. I measured diel cycles of resting metabolic rate (RMR) at four temperatures (20 degrees, 30 degrees, 33 degrees, and 36 degrees C) during spring, summer, and fall. In all seasons, RMR increased significantly from 20 degrees to 33 degrees C but did not differ significantly between 33 degrees and 36 degrees C. Adults from New Jersey had a higher RMR than adults from South Carolina in summer and fall but not in spring. Juveniles from South Carolina had a higher RMR than juveniles from New Jersey in summer but not in spring or fall. Annual maintenance metabolism of New Jersey lizards (53.7 kJ) was greater than that of South Carolina lizards (45.8 kJ), despite the shorter duration of activity in New Jersey. I conclude that the difference in maintenance metabolism between populations contributes to the greater production by S. undulatus in South Carolina.


Interplays between copper and Mycobacterium tuberculosis GroEL1.
The recalcitrance of pathogenic Mycobacterium tuberculosis, the agent of tuberculosis, to eradication is due to various factors allowing bacteria to escape from stress situations. The mycobacterial chaperone GroEL1, overproduced after macrophage entry and under oxidative stress, could be one of these key players. We previously reported that GroEL1 is necessary for the biosynthesis of phthiocerol dimycocerosate, a virulence-associated lipid and for reducing antibiotic susceptibility. In the present study, we showed that GroEL1, bearing a unique C-terminal histidine-rich region, is required for copper tolerance during Mycobacterium bovis BCG biofilm growth. Mass spectrometry analysis demonstrated that GroEL1 displays high affinity for copper ions, especially at its C-terminal histidine-rich region. Furthermore, the binding of copper protects GroEL1 from destabilization and increases GroEL1 ATPase activity. Altogether, these findings suggest that GroEL1 could counteract copper toxicity, notably in the macrophage phagosome, and further emphasizes that M. tuberculosis GroEL1 could be an interesting antitubercular target.


Random walks and search in time-varying networks.
The random walk process underlies the description of a large number of real-world phenomena. Here we provide the study of random walk processes in time-varying networks in the regime of time-scale mixing, i.e., when the network connectivity pattern and the random walk process dynamics are unfolding on the same time scale. We consider a model for time-varying networks created from the activity potential of the nodes and derive solutions of the asymptotic behavior of random walks and the mean first passage time in undirected and directed networks. Our findings show striking differences with respect to the well-known results obtained in quenched and annealed networks, emphasizing the effects of dynamical connectivity patterns in the definition of proper strategies for search, retrieval, and diffusion processes in time-varying networks.


Characterization and Identification of Drought-Responsive ABA-Aldehyde Oxidase (AAO) Genes in Potato (Solanum tuberosum L.).
Abscisic acid (ABA) is an important stress hormone that affects plants' tolerance to stress. Changes in the content of abscisic can have an impact on plant responses to abiotic stress. The abscisic acid aldehyde oxidase (AAO) plays a crucial role in the final step in the synthesis of abscisic acid; therefore, understanding the function of the AAO gene family is of great significance for insight into plants' response to abiotic stresses. In this study, Solanum tuberosum AAO (StAAO) members were exhaustively explored using genome databases, and nine StAAOs were identified. Chromosomal location analysis indicated that StAAO genes mapped to 4 of the 14 potato chromosomes. Further analyses of gene structure and motif composition showed that members of the specific StAAO subfamily showed relatively conserved characteristics. Phylogenetic relationship analysis indicated that StAAOs proteins were divided into three major clades. Promoter analysis showed that most StAAO promoters contained cis-elements related to abiotic stress response and plant hormones. The results of tissue-specific expression analysis indicated that StAAO4 was predominantly expressed in the roots. Analysis of transcriptome data revealed that StAAO2/4/6 genes responded significantly to drought treatments. Moreover, further qRT-PCR analysis results indicated that StAAO2/4/6 not only significantly responded to drought stress but also to various phytohormone (ABA, SA, and MeJA) and abiotic stresses (salt and low temperature), albeit with different expression patterns. In summary, our study provides comprehensive insights into the sequence characteristics, structural properties, evolutionary relationships, and expression patterns of the StAAO gene family. These findings lay the foundation for a deeper understanding of the StAAO gene family and offer a potential genetic resource for breeding drought-resistant potato varieties.


The relation of ST segment deviations in 12-lead conventional Electrocardiogram, right and posterior leads with the site of occlusion in acute inferior myocardial infarction.
In addition to diagnosing the acute myocardial infarction (MI), stratifying high-risk patients and proper treatment strategies are important issues in managing patients complaining of chest pain and suspecting MI. Many studies have been conducted to predict the occlusion site by interpreting the ST segment deviations in Electrocardiogram (ECG).Additional posterior and right precordial leads are suggested in literature to increase the sensitivity of prediction. The goal of this study was to determine the relation of ST segment changes in ECG (conventional 12 leads ECG besides right and posterior leads) with the site of occlusion within the vessel. Retrospectively, from total 138 patients, 76 of them were analyzed as single vessel acute Inferior ST elevation Myocardial infarction (I-STEMI)-ST which 56 (74%) had Right Coronary Artery (RCA) occlusion [22(29.3%) proximal RCA, 24(32%) middle RCA and 10(13.3%) distal occlusion of RCA], 19(25%) had Left Circumflex artery (LCx) lesion and one had middle Left Anterior Descending (LAD) artery occlusion. On admission ECGs and coronary artery intervention films, were reported within maximum time of 6 days in hospital stay, and re-evaluated by two cardiologists. Fiol's algorithm was 93% sensitive and 50% specific for predicting RCA occlusion. The ST elevation in lead III was associated with RCA stenosis (Odds Ratio (OR): 12, Confidence Interval (CI): 2.2-68.9), the association between ST elevation in lead II with LCx involvement was not significant. The V4R was a good marker for RV involvement on-admission, (OR=8, CI: 1.6-37.5). Sum of ST deviation in posterior leads (V7 to V9) ≥ 2mm had positive and significant relation to LCx stenosis (OR=4, CI: 1.3-14). Benefit of adding posterior and right leads to 12-lead ECG is shown to be noteworthy in present and prior studies, in identifying LCx stenosis and poor prognosis involvement.


Porous-membrane-protected polyaniline-coated SBA-15 nanocomposite micro-solid-phase extraction followed by high-performance liquid chromatography for the determination of parabens in cosmetic products and wastewater.
A SBA-15/polyaniline para-toluenesulfonic acid nanocomposite supported micro-solid-phase extraction procedure has been developed for the extraction of parabens (methylparaben, ethylparaben, and propylparaben) from wastewater and cosmetic products. The variables of interest in the extraction process were pH of sample, sample and eluent volumes, sorbent amount, salting-out effect, extraction and desorption time, and stirring rate. A Plackett-Burman design was performed for the screening of variables in order to determine the significant variables affecting the extraction efficiency. Then, the significant factors were optimized by using a central composite design. The optimum experimental conditions found at 50 mL sample solution, extraction and desorption times of 40 and 20 min, respectively, 500 μL of 3% v/v acetic acid in methanol as eluent, 0.01 M salt addition, and 10 mg of the sorbent. Under the optimum conditions, the developed method provided detection limits in the range of 0.08-0.4 ng/mL with good repeatability (RSD% < 7) and linearity (r(2) = 0.997-0.999) for the three parabens. Finally, this fast and efficient method was employed for the determination of target analytes in cosmetic products and wastewater, and satisfactory results were obtained.


Synthesis of strontium chondroitin sulfate and the evaluation of its capability to attenuate osteoarthritis.
Osteoarthritis (OA) is the most prevalent musculoskeletal disorder and the leading cause of joint disability in elderly patients. In this study, we fabricated strontium chondroitin sulfate (SrCS), a new polysaccharide-metal ion complex that is the combination of chondroitin sulfate and strontium, which are two widely adopted chemicals in OA clinical management. The structural, chemical compositions and morphology of as-fabricated SrCS were systematically investigated. Cell proliferation test, RT-PCR and preliminary animal studies were conducted to evaluate the clinical potential of SrCS on OA treatment. The materials characterization results verified that the Sr was successfully integrated into CS by replacing sodium in the original structure and formed a new polysaccharide-metal ion complex. The cell proliferation results indicated that the SrCS has excellent biocompatibility for both chondrocyte and osteoblast. The RT-PCR results showed that the SrCS can significantly increase the expression of COLII and ACAN, decrease MMP1 and MMP13 in chondrocyte and decrease the IL-6 and IL-1β in both chondrocyte and osteoblast. Preliminary animal studies demonstrated that SrCS can effectively simulate the articular cartilage formation in SD-rats after modified Hulth's OA modeling surgery. We therefore believed that the SrCS should be a rather effective chemical for OA clinical management as well as a beneficial component for various biomaterials in cartilage tissue engineering.


COLOCdb: a comprehensive resource for multi-model colocalization of complex traits.
Large-scale genome-wide association studies (GWAS) have provided profound insights into complex traits and diseases. Yet, deciphering the fine-scale molecular mechanisms of how genetic variants manifest to cause the phenotypes remains a daunting task. Here, we present COLOCdb (https://ngdc.cncb.ac.cn/colocdb), a comprehensive genetic colocalization database by integrating more than 3000 GWAS summary statistics and 13 types of xQTL to date. By employing two representative approaches for the colocalization analysis, COLOCdb deposits results from three key components: (i) GWAS-xQTL, pair-wise colocalization between GWAS loci and different types of xQTL, (ii) GWAS-GWAS, pair-wise colocalization between the trait-associated genetic loci from GWASs and (iii) xQTL-xQTL, pair-wise colocalization between the genetic loci associated with molecular phenotypes in xQTLs. These results together represent the most comprehensive colocalization analysis, which also greatly expands the list of shared variants with genetic pleiotropy. We expect that COLOCdb can serve as a unique and useful resource in advancing the discovery of new biological mechanisms and benefit future functional studies.


Efficient semiparametric estimation of short-term and long-term hazard ratios with right-censored data.
The proportional hazards assumption in the commonly used Cox model for censored failure time data is often violated in scientific studies. Yang and Prentice (2005) proposed a novel semiparametric two-sample model that includes the proportional hazards model and the proportional odds model as sub-models, and accommodates crossing survival curves. The model leaves the baseline hazard unspecified and the two model parameters can be interpreted as the short-term and long-term hazard ratios. Inference procedures were developed based on a pseudo score approach. Although extension to accommodate covariates was mentioned, no formal procedures have been provided or proved. Furthermore, the pseudo score approach may not be asymptotically efficient. We study the extension of the short-term and long-term hazard ratio model of Yang and Prentice (2005) to accommodate potentially time-dependent covariates. We develop efficient likelihood-based estimation and inference procedures. The nonparametric maximum likelihood estimators are shown to be consistent, asymptotically normal, and asymptotically efficient. Extensive simulation studies demonstrate that the proposed methods perform well in practical settings. The proposed method successfully captured the phenomenon of crossing hazards in a cancer clinical trial and identified a genetic marker with significant long-term effect missed by using the proportional hazards model on age-at-onset of alcoholism in a genetic study.


Fucoxanthin, a Functional Food Ingredient: Challenges in Bioavailability.
Fucoxanthin is an orange-red xanthophyll carotenoid found in brown seaweeds and known for its many bioactive properties. In recent years, the bioactive properties of fucoxanthin have been widely explored, making it a compound of immense interest for various health applications like anti-cancer, anti-tumour, anti-diabetic and anti-obesity properties. However, the poor bioavailability and instability of fucoxanthin in the gastrointestinal tract have major limitations. Encapsulation is a promising approach to overcome these challenges by enclosing fucoxanthin in a protective layer, such as liposomes or nano-particles. Encapsulation can improve the stability of fucoxanthin by protecting it from exposure to heat, pH, illumination, gastric acids and enzymes that can accelerate its degradation. Studies have shown that lipid-based encapsulation systems such as liposomes or nano-structured lipid carriers may solubilise fucoxanthin and enhance its bioavailability (from 25 to 61.2%). In addition, encapsulation can also improve the solubility of hydrophobic fucoxanthin, which is important for its absorption and bioavailability. This review highlights the challenges involved in the absorption of fucoxanthin in the living system, role of micro- and nano-encapsulation of fucoxanthin and their potential to enhance intestinal absorption.


Internal heavy atom effects in phenothiazinium dyes: enhancement of intersystem crossing via vibronic spin-orbit coupling.
The effect of substituting the intra-cyclic sulphur of thionine by oxygen (oxonine) and selenium (selenine) on the intersystem crossing (ISC) efficiency has been studied using high level quantum mechanical methods. The ISC rate constants are considerably increased when going from O towards Se while the fluorescence rate constants remain unchanged. For the three dyes, all accessible ISC channels are driven by vibronic spin-orbit coupling (SOC) between ππ* states. The interplay between the ground and low-lying excited states has been investigated in order to determine the dominant relaxation pathways. In oxonine the relaxation to the ground state after photoexcitation in water proceeds essentially via fluorescence from the S1(πHπL*) bright state (kF = 2.10 × 10(8) s(-1)), in agreement with the high experimental fluorescence quantum yield. In aqueous solution of thionine, the ISC rate constant (kISC ∼ 1 × 10(9) s(-1)) is one order of magnitude higher than fluorescence (kF = 1.66 × 10(8) s(-1)) which is consistent with its high triplet quantum yield observed in water (ϕT = 0.53). Due to a stronger vibronic SOC in selenine, the ISC rate is very high (kISC ∼ 10(10) s(-1)) and much faster than fluorescence (kF = 1.59 × 10(8) s(-1)). This suggests selenine-based dyes as very efficient triplet photosensitizers.


Uptake, Translocation, and Subcellular Distribution of Strobilurin Fungicides in Cucumber (Cucumis sativa L.).
The absorption, transport, and subcellular distribution of strobilurin fungicides (azoxystrobin, pyraclostrobin, and trifloxystrobin) have been studied in cucumbers. Under hydroponic laboratory conditions, pyraclostrobin and trifloxystrobin mainly accumulated in cucumber roots whereas azoxystrobin accumulated in cucumber leaves. In the subcellular distribution experiment, azoxystrobin mainly accumulated as a soluble component. Pyraclostrobin and trifloxystrobin accumulated more in the organelles and cell walls. Azoxystrobin and pyraclostrobin enter the root primarily through the apoplast pathway, whereas trifloxystrobin enters the root through the symplastic pathway. Azoxystrobin can be transported in cucumber through anion and cation channels, whereas pyraclostrobin and trifloxystrobin can be transported only through anion channels. This study has great significance in evaluating environmental risks and food safety.


Cross talk between Id1 and its interactive protein Dril1 mediate fibroblast responses to transforming growth factor-beta in pulmonary fibrosis.
The presence of activated fibroblasts or myofibroblasts represents a hallmark of progressive lung fibrosis. Because the transcriptional response of fibroblasts to transforming growth factor-beta(1) (TGF-beta(1)) is a determinant of disease progression, we investigated the role of the transcriptional regulator inhibitor of differentiation-1 (Id1) in the setting of lung fibrosis. Mice lacking the gene for Id1 had increased susceptibility to bleomycin-induced lung fibrosis, and fibroblasts lacking Id1 exhibited enhanced responses to TGF-beta(1). Because the effect of Id1 on fibrosis could not be explained by known mechanisms, we performed protein interaction screening and identified a novel binding partner for Id1, known as dead ringer-like-1 (Dril1). Dril1 shares structural similarities with Id1 and was recently implicated in TGF-beta(1) signaling during embryogenesis. To date, little is known about the function of Dril1 in humans. Although it has not been previously implicated in fibrotic disease, we found that Dril1 was highly expressed in lungs from patients with idiopathic pulmonary fibrosis and was regulated by TGF-beta(1) in human fibroblasts. Dril1 enhanced activation of TGF-beta(1) target genes, whereas Id1 decreased expression of these same molecules. Id1 inhibited DNA binding by Dril1, and the two proteins co-localized in vitro and in vivo, providing a potential mechanism for suppression of fibrosis by Id1 through inhibition of the profibrotic function of Dril1.


A Fast and Efficient Method for Training Categorical Radial Basis Function Networks.
This brief presents a novel learning scheme for categorical data based on radial basis function (RBF) networks. The proposed approach replaces the numerical vectors known as RBF centers with categorical tuple centers, and employs specially designed measures for calculating the distance between the center and the input tuples. Furthermore, a fast noniterative categorical clustering algorithm is proposed to accomplish the first stage of RBF training involving categorical center selection, whereas the weights are calculated through linear regression. The method is applied on 22 categorical data sets and compared with several different learning schemes, including neural networks, support vector machines, naïve Bayes classifier, and decision trees. Results show that the proposed method is very competitive, outperforming its rivals in terms of predictive capabilities in the majority of the tested cases.


Dynamic state of collagen: pathways of collagen degradation in vivo and their possible role in regulation of collagen mass.
There is now evidence that collagen turnover in normal tissues can occur at rapid rates. In skin of adult rats, the mean rate lies between 3 and 5%/day, but rates of greater than 10%/day have been reported in some tissues, such as lung and periodontal ligament. The major sites of this degradation are still uncertain. Intracellular degradation, which occurs within minutes of synthesis, may be extensive, but its magnitude varies between tissues. This process may have evolved to allow the adaptive advantages of rapid turnover without compromising the supportive role of fibrillar collagen. There is now abundant evidence that changes in collagen degradation play an important role in the regulation of collagen mass. Increased breakdown of extracellular collagens may be required whether the mass is increased or decreased. However, preliminary evidence suggests that the degradation of newly synthesized collagen may be up- or down-regulated, depending on the direction of the change in content.


Sexual and Gender Minority Youth Alcohol Use: Within-Group Differences in Associations with Internalized Stigma and Victimization.
Sexual and gender minority (SGM) youth are more likely to use alcohol than their heterosexual cisgender peers. At the same time, SGM youth experience sexuality- and gender identity-specific stressors known to exacerbate negative health outcomes. Though scholars have established a link between minority stressors (e.g., internalized stigma and victimization) and increased alcohol use for SGM youth as a whole, there is little indication of whether internalized stigma and victimization are more strongly associated with alcohol use for specific groups of SGM youth. A United States sample of 11,811 racially and geographically diverse 13-17 year old SGM youth was used to employ a series of gender-stratified multivariable regression models to examine the association among internalized stigma, victimization, and alcohol-related behaviors, and whether they differed for specific groups of sexual minority youth. Sexual orientation moderated several associations between sexual minority stressors (i.e., victimization and stigma) and youth's alcohol use (i.e., recent use and heavy episodic drinking) across models stratified by gender (i.e., male, female, and non-binary). For example, bisexual boys had stronger associations between SGM-specific victimization and alcohol use frequency and heavy episodic drinking relative to gay boys; conversely, victimization and alcohol use frequency were more weakly associated among bisexual girls relative to lesbian/gay girls. Pansexual girls showed weaker associations between internalized stigma and alcohol use frequency compared to lesbian/gay girls. This paper demonstrates who among SGM youth are more likely to engage in alcohol-related behaviors as a function of differential forms of SGM-related victimization and stigma. These findings can inform substance use interventions that are tailored to youth of diverse sexual orientations and gender identities.