Transcutaneous electrical nerve stimulation (TENS) for the treatment of rheumatoid arthritis in the hand.
Rheumatoid arthritis (RA) is a chronic, inflammatory, system disease. It commonly affects the small peripheral joints (such as fingers and wrist). The main goals of intervention for RA are preventing joint deformity, preserving joint function, and reducing inflammation and pain. Transelectrical nerve stimulation (TENS) is a form of electrotherapy and is thought to produce analgesia according to the gate control theory. To determine the efficacy and safety of TENS in the treatment of RA of the hand. The primary outcomes of interest were relief of grip pain and resting pain intensity, relief of joint tenderness, number of tender joints and patient assessment of disease. The secondary objective was to determine the most effective mode of TENS application in pain control. We searched for relevant studies, in English, in the Cochrane field of physical and related therapies, the Cochrane Controlled Trials Register, MEDLINE, EMBASE, HEALTHSTAR, Sports Discus, CINAHL, Current Contents, and the PEDro database, up to October 2002. Two independent reviewers selected the trials that met predetermined inclusion criteria. Study results were extracted by two independent reviewers. Continuous outcomes were analyzed by weighted mean difference (WMD) using a fixed effects model. Three RCTs, involving 78 people, were included in this review. AL-TENS and C-TENS were compared to placebo and to each other. Administration of 15 minutes of AL-TENS a week, for 3 weeks, resulted in a significant decrease in rest pain (67% relative benefit, 45 points absolute benefit on 100 mm VAS scale) but not in grip pain compared to placebo. AL-TENS did result in a clinical beneficial improvement in muscle power scores with a relative difference of 55%, and an absolute benefit of 0.98, compared to placebo. No significant difference was found between one 20-minute treatment duration of C-TENS versus AL-TENS, or C-TENS versus placebo on decrease in mean scores for rest pain or grip pain, or on the number of tender joints. Results showed a statistically significant reduction in joint tenderness, but no clinical benefit from C-TENS over placebo in relief of joint tenderness. No statistically significant difference was shown between 15 days of treatment with C-TENS or AL-TENS in relief of joint pain, although there was a clinically important benefit of C-TENS over AL-TENS on patient assessment of change in disease (risk difference 21%, NNT 5). There are conflicting effects of TENS on pain outcomes in patients with RA. AL-TENS is beneficial for reducing pain intensity and improving muscle power scores over placebo while, conversely, C-TENS resulted in no clinical benefit on pain intensity compared with placebo. However C-TENS resulted in a clinical benefit on patient assessment of change in disease over AL-TENS. More well designed studies with a standardized protocol and adequate number of subjects are needed to fully conclude the effect of C-TENS and AL-TENS in the treatment of RA of the hand.


Vitamin D and skin physiology: a D-lightful story.
Throughout evolution, exposure to sunlight and the photosynthesis of vitamin D(3) in the skin has been critically important for the evolution of land vertebrates. During exposure to sunlight, the solar UVB photons with energies 290-315 nm are absorbed by 7-dehydrocholesterol in the skin and converted to previtamin D(3). Previtamin D(3) undergoes a rapid transformation within the plasma membrane to vitamin D(3). Excessive exposure to sunlight will not result in vitamin D intoxication because both previtamin D(3) and vitamin D(3) are photolyzed to several noncalcemic photoproducts. During the winter at latitudes above approximately 35 degrees , there is minimal, if any, previtamin D(3) production in the skin. Altitude also has a significant effect on vitamin D(3) production. At 27 degrees N in November, very little ( approximately 0.5%) previtamin D(3) synthesis was detected in Agra (169 m) and Katmandu (1400 m). There was an approximately 2- and 4-fold increase in previtamin D(3) production at approximately 3400 m and at Everest base camp (5300 m), respectively. Increased skin pigmentation, application of a sunscreen, aging, and clothing have a dramatic effect on previtamin D(3) production in the skin. It is estimated that exposure in a bathing suit to 1 minimal erythemal dose (MED) is equivalent to ingesting between 10,000 and 25,000 IU of vitamin D(2). The importance of sunlight for providing most humans with their vitamin D requirement is well documented by the seasonal variation in circulating levels of 25-hydroxyvitamin D [25(OH)D]. Vitamin D deficiency [i.e., 25(OH)D < 20 ng/ml] is common in both children and adults worldwide. Exposure to lamps that produce UVB radiation is an excellent source for producing vitamin D(3) in the skin and is especially efficacious in patients with fat malabsorption syndromes. The major cause of vitamin D deficiency globally is an underappreciation of sunlight's role in providing humans with their vitamin D(3) requirement. Very few foods naturally contain vitamin D, and those that do have a very variable vitamin D content. Recently it was observed that wild caught salmon had between 75% and 90% more vitamin D(3) compared with farmed salmon. The associations regarding increased risk of common deadly cancers, autoimmune diseases, infectious diseases, and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being.


Resolution of conformational activation in the kinetic mechanism of plasminogen activation by streptokinase.
Streptokinase (SK) activates plasminogen (Pg) by specific binding and nonproteolytic expression of the Pg catalytic site, initiating Pg proteolysis to form the fibrinolytic proteinase, plasmin (Pm). The SK-induced conformational activation mechanism was investigated in quantitative kinetic and equilibrium binding studies. Progress curves of Pg activation by SK monitored by chromogenic substrate hydrolysis were parabolic, with initial rates (v(1)) that indicated no transient species and subsequent rate increases (v(2)). The v(1) dependence on SK concentration for [Glu]Pg and [Lys]Pg was hyperbolic with dissociation constants corresponding to those determined in fluorescence-based binding studies for the native Pg species, identifying v(1) as rapid SK binding and conformational activation. Comparison of [Glu]Pg and [Lys]Pg activation showed an approximately 12-fold higher affinity of SK for [Lys]Pg that was lysine-binding site dependent and no such dependence for [Glu]Pg. Stopped-flow kinetics of SK binding to fluorescently labeled Pg demonstrated at least two fast steps in the conformational activation pathway. Characterization of the specificity of the conformationally activated SK.[Lys]Pg* complex for tripeptide-p-nitroanilide substrates demonstrated 5-18- and 10-130-fold reduced specificity (k(cat)/K(m)) compared with SK.Pm and Pm, respectively, with differences in K(m) and k(cat) dependent on the P1 residue. The results support a kinetic mechanism in which SK binding and reversible conformational activation occur in a rapid equilibrium, multistep process.


Nutrition and metabolic support recommendations for the bariatric patient.
Managing the metabolic needs of the patient with obesity is a challenge unto itself without the added demands of accounting for an altered gastrointestinal tract. Nevertheless, with about 200,000 bariatric procedures being performed annually in the United States, clinicians must be prepared to manage the critically ill bariatric surgery patient. This article reviews the recent literature relating to nutrient needs and metabolic support for the bariatric patient. Bariatric patients are at risk for several micronutrient deficiencies, including vitamins D and B₁₂, calcium, and iron; some bariatric procedures affect macronutrient needs as well. Literature on nutrition support guidelines for the bariatric population is limited. However, with an understanding of the anatomical and physiological effects of bariatric surgery, recent guidelines for critically ill patients with obesity can be applied to the bariatric surgery population. The unique needs of the bariatric population, such as susceptibility to micronutrient deficiencies and specialized access routes, must be considered to provide safe and efficacious nutrition support. Further research is necessary to develop specific nutrition support recommendations for the bariatric population.


Multiscale simulations of critical interfacial failure in carbon nanotube-polymer composites.
Computational investigation of interfacial failure in composite materials is challenging because it is inherently multi-scale: the bond-breaking processes that occur at the covalently bonded interface and initiate failure involve quantum mechanical phenomena, yet the mechanisms by which external stresses are transferred through the matrix occur on length and time scales far in excess of anything that can be simulated quantum mechanically. In this work, we demonstrate and validate an adaptive quantum mechanics (QM)/molecular mechanics simulation method that can be used to address these issues and apply it to study critical failure at a covalently bonded carbon nanotube (CNT)-polymer interface. In this hybrid approach, the majority of the system is simulated with a classical forcefield, while areas of particular interest are identified on-the-fly and atomic forces in those regions are updated based on QM calculations. We demonstrate that the hybrid method results are in excellent agreement with fully QM benchmark simulations and offers qualitative insights missing from classical simulations. We use the hybrid approach to show how the chemical structure at the CNT-polymer interface determines its strength, and we propose candidate chemistries to guide further experimental work in this area.


Validity of the adductor pollicis muscle as a component of nutritional screening in the hospital setting: A systematic review.
The thickness of the adductor pollicis muscle (TAPM) is the only muscle that can be directly measured with a caliper. Recent studies demonstrate that the TAPM could be used as part of nutritional screening, but this has not been systematically reviewed. We aimed to review the validity and reliability of TAPM in identifying malnutrition risk. PubMed, CINAHL and Scopus were systematically searched. Eligible studies were cross-sectional, case-control or cohort studies which recruited adult patients in the hospital, measured the TAPM along with a valid nutritional assessment tool and evaluated the validity of TAPM with univariate, multivariate, discriminative and/or agreement statistics. The Quality Assessment of Diagnostic Accuracy Studies-II was used to evaluate the risk-of-bias. Nine out of 39 studies identified were eligible, and all had some risk-of-bias. Subjective Global Assessment (SGA) was used as the criterion standard in all nine studies. The TAPM amongst malnourished patients were significantly different from their counterparts but this may be over-estimated since all measurements of the SGA and TAPM were non-blinded. Concordance between the TAPM and SGA ranged from poor to good (kappa ranged from 0.04 to 0.25; specificity ranged from 97.8% to 100%), and this may be due to the varied cut-off values used amongst the studies. There were also disparities in the measurement instruments and methods. Reliability was not reported. More studies are needed to establish the reliability of TAPM measurement and cut-off values before the TAPM can be used as a component of nutritional screening.


Molecular structure influences the stability of membrane penetrating biointerfaces.
Nanoscale patterning of hydrophobic bands on otherwise hydrophilic surfaces allows integration of inorganic structures through biological membranes, reminiscent of transmembrane proteins. Here we show that a set of innate molecular properties of the self-assembling hydrophobic band determine the resulting interface stability. Surprisingly, hydrophobicity is found to be a secondary factor with monolayer crystallinity the major determinate of interface strength. These results begin to establish guidelines for seamless bioinorganic integration of nanoscale probes with lipid membranes.


Mutation-dependent alteration in cellular distribution of peripheral myelin protein 22 in nerve biopsies from Charcot-Marie-Tooth type 1A.
The hereditary demyelinating neuropathy Charcot-Marie-Tooth type 1A is caused by duplication or by point mutations of the PMP22 gene. Histopathological differences in these genotypes suggest distinct disease mechanisms. In the present investigation we demonstrate a pathologically altered cellular distribution of PMP22 in sural nerve biopsies of patients with PMP22 point mutations. In these patients, in contrast to findings in patients with PMP22 duplication, PMP22 partially accumulates in the Schwann cells instead of being inserted in the myelin sheath. These findings may explain the different histopathology and may suggest different mechanisms of pathogenesis in these genotypes.


Connectivity and dynamics of neural information processing.
In this article, we systematically review the current literature on neural connectivity and dynamics, or equivalently, structure and function. In particular, we discuss how changes in the connectivity of a neural network affect the spatiotemporal network dynamics qualitatively. The three major criteria of comparison are, first, the local dynamics at the network nodes which includes fixed point dynamics, oscillatory and chaotic dynamics; second, the presence of time delays via propagation along connecting pathways; and third, the properties of the connectivity matrix such as its statistics, symmetry, and translational invariance. Since the connection topology changes when anatomical scales are traversed, so will the corresponding network dynamics change. As a consequence different types of networks are encountered on different levels of neural organization.


A sock for foot-drop: a preliminary study on two chronic stroke patients.
Foot-drop is a common motor impairment of chronic stroke patients, which may be addressed with an ankle foot orthosis. Although there is reasonable evidence of effectiveness for ankle foot orthoses, user compliance is sometimes poor. This study investigated a new alternative to the ankle foot orthosis, the dorsiflex sock. The dorsiflex sock was evaluated using an A-B single case experimental design. Two community-dwelling, chronic stroke patients with foot-drop participated in this study. Measures were selected to span the International Classification of Function, Disability and Health domains and user views on the dorsiflex sock were also collected. The dorsiflex sock was not effective in improving participants' walking symmetry, speed or energy expenditure. Participant 1 showed improvement in the distance he could walk in 6 min when using the dorsiflex sock, but this was in keeping with a general improvement trend over the course of this study. However, both participants viewed the dorsiflex sock positively and reported a positive effect on their walking. Despite positive user perceptions, the study found no clear evidence that dorsiflex sock is effective in improving foot-drop. Although the dorsiflex sock offers an attractive alternative to an ankle foot orthosis, the case studies found no clear evidence of its efficacy. Clinicians should view this device with caution until further research becomes available.


Recombination at ColE1 cer requires the Escherichia coli xerC gene product, a member of the lambda integrase family of site-specific recombinases.
Site-specific recombination at the plasmid ColE1 cer site requires the Escherichia coli chromosomal gene xerC. The xerC gene has been localized to the 85-min region of the E. coli chromosome, between cya and uvrD. The nucleotide sequences of the xerC gene and flanking regions have been determined. The xerC gene encodes a protein with a calculated molecular mass of 33.8 kDa. This protein has substantial sequence similarity to the lambda integrase family of site-specific recombinases and is probably the cer recombinase. The xerC gene is expressed as part of a multicistronic unit that includes the dapF gene and two other open reading frames.


Impact of viral hepatitis aetiology on survival outcomes in hepatocellular carcinoma: A large multicentre cohort study.
While HBV and HCV are risk factors for HCC, uncertainty exists as to whether these viral infections have prognostic significance in HCC. Thus, we compared the overall survival of patients with HBV, HCV and nonviral HCC, and evaluated whether the presence of HBV and HCV predicts patient outcomes. We conducted a multicentre study of HCC cases diagnosed at six Melbourne tertiary hospitals between Jan 2000-Dec 2014. Patient demographics, liver disease and tumour characteristics and patient outcomes were obtained from hospital databases, computer records and the Victorian Death Registry. Survival outcomes were compared between HBV, HCV and nonviral hepatitis cases and predictors of survival determined using Cox proportional hazards regression. There were 1436 new HCC cases identified including 776 due to viral hepatitis (HBV 235, HCV 511, HBV-HCV 30) and 660 from nonviral causes. The median survival of HBV, HCV and nonviral HCC patients was 59.1, 28.4 and 20.9 months, respectively (P<.0001). On multivariate analysis, independent risk factors for survival included HCC aetiology, gender, BCLC stage, serum AFP, total number and size of lesions, and serum creatinine and albumin. After adjusting for these and method of detection, HBV remained an independent predictor of improved overall survival when compared to both nonviral (HR 0.60%, 95% CI 0.35-0.98; P=.03) and HCV-related HCC (HR 0.51%, 95% CI 0.30-0.85; P=.01). In this large multicentre study, HBV is independently associated with improved overall survival compared with HCV and nonviral-related HCC. Further studies are needed to determine the underlying factor(s) responsible.


Retinol palmitate in management of chronic Steven-Johnson Syndrome with ocular surface keratinization.
To study the outcomes of topical Retinol Palmitate ophthalmic solution in chronic Stevens-Johnson Syndrome with ocular surface keratinisation. It was a comparative interventional study conducted at Rajendra Prasad Centre for Ophthalmic Sciences, Delhi, India from 2020 to 2022 evaluating outcomes of addition of topical Retinol Palmitate to conventional treatment objectively as well as subjectively from baseline up to 12 weeks. A statistically significant improvement was seen in patients who received topical Retinol palmitate at 12 weeks in terms of Schirmer-1 test(p=<0.01), tear prism height on ASOCT(p = 0.02), Rose Bengal staining score of cornea(p = 0.01) and conjunctiva (p < 0.01), reduction of ocular surface keratinisation on impression cytology(p = 0.01) and subjective evaluation using OSDI questionnaire(p = 0.04).Impression cytology revealed goblet cells in Retinol palmitate group at 1 week after initiation of therapy, which increased further at 1 month follow up but reduced at 3 months. No goblet cells were seen in control group at any follow-up. No significant difference was noted between the two groups in terms of visual acuity, tear film breakup time, inflammatory cells on impression cytology and inflammatory markers in tears. Topical Retinol palmitate is a safe and effective drug in cases of chronic SJS with ocular surface keratinisation. It has the potential to reverse keratinisation of the ocular surface and promote development of goblet cells. However, the survival of goblet cells is not long lasting.


Relationship between the rate of gastric emptying and glucose and insulin responses to starchy foods in young healthy adults.
Twelve young healthy adults (five men, seven women) ingested four test meals on four occasions so we could examine the relationship between the rate of gastric emptying (GE) and the glucose response to different starchy foods. Each meal consisted of one food product containing 50 g starch: spaghetti, rice, French bread, or mashed potato. Basal and postprandial glucose and insulin responses were measured for 3 h. The foods were labeled with 3.7 MBq Tc99m-albumin and GE was studied by scintigraphy for 3 h. The rate of GE (expressed by the GE half-time) was fastest for mashed potatoes, then bread, rice, and slowest for spaghetti. Blood glucose and serum insulin responses were similar. A significant negative correlation was found between the GE half-time and the maximum variation in blood glucose level (r = -0.6, p less than 0.0001). The glucose response to all four foods is strongly related to the GE rate.


Response of combination platinum and gemcitabine chemotherapy for recurrent epithelial ovarian carcinoma.
It has been postulated that gemcitabine inhibits DNA repair, and platinum resistance is due to increased DNA repair activity. The addition of gemcitabine to platinum-based agents may have synergistic tumoricidal activity. Retrospective chart review of all patients with recurrent, persistent, or progressive fallopian tube or ovarian carcinoma treated with a platinum-based compound and gemcitabine from 2001 to present was performed. Twenty-nine patients on second to eight line chemotherapy met inclusion criteria. The median age was 53 years. Twenty-two patients received cisplatin and gemcitabine, and 7 patients received carboplatin and gemcitabine based on results of chemoresistance assays or prior chemorelated toxicities. The intent to treat was with six cycles of gemcitabine (1000 mg/m(2)) and either cisplatin (75 mg/m(2)) or carboplatin (AUC 5) day 1 and gemcitabine only on day 8 of a 21-day cycle. The median number of cycles administered was six. There were 20 grade 3 and 4 toxicities and 63% of patients by cycle 6 needed erythropoietin marrow support and 19% needed GCSF support by cycle 4. Twenty-one patients required discontinuation of day 8 that most commonly occurred at cycle 4. Eleven (38%) had CR, 5 (17%) had PR, 6 (21%) had SD, and 7 (24%) had PD, which is a 55% overall response. Nineteen of 29 patients (66%) showed platinum resistance to initial therapy. Of those, four (21%) had CR, four (21%) had PR, six (32%) had SD, and five (26%) with PD, which demonstrates a 42% overall response rate for this particular subset of patients. Adjuvant combination platinum-based agent with gemcitabine is a very effective and well-tolerated treatment for recurrent fallopian tube or ovarian carcinoma; even in those who exhibit initial platinum resistance.


Beyond Technologies of Electroencephalography-Based Brain-Computer Interfaces: A Systematic Review From Commercial and Ethical Aspects.
The deployment of electroencephalographic techniques for commercial applications has undergone a rapid growth in recent decades. As they continue to expand in the consumer markets as suitable techniques for monitoring the brain activity, their transformative potential necessitates equally significant ethical inquiries. One of the main questions, which arises then when evaluating these kinds of applications, is whether they should be aligned or not with the main ethical concerns reported by scholars and experts. Thus, the present work attempts to unify these disciplines of knowledge by performing a comprehensive scan of the major electroencephalographic market applications as well as their most relevant ethical concerns arising from the existing literature. In this literature review, different databases were consulted, which presented conceptual and empirical discussions and findings about commercial and ethical aspects of electroencephalography. Subsequently, the content was extracted from the articles and the main conclusions were presented. Finally, an external assessment of the outcomes was conducted in consultation with an expert panel in some of the topic areas such as biomedical engineering, biomechatronics, and neuroscience. The ultimate purpose of this review is to provide a genuine insight into the cutting-edge practical attempts at electroencephalography. By the same token, it seeks to highlight the overlap between the market needs and the ethical standards that should govern the deployment of electroencephalographic consumer-grade solutions, providing a practical approach that overcomes the engineering myopia of certain ethical discussions.


Analysis of the liver lipidome reveals insights into the protective effect of exercise on high-fat diet-induced hepatosteatosis in mice.
The accumulation of lipid at ectopic sites, including the skeletal muscle and liver, is a common consequence of obesity and is associated with tissue-specific and whole body insulin resistance. Exercise is well known to improve insulin resistance by mechanisms not completely understood. We performed lipidomic profiling via mass spectrometry in liver and skeletal muscle samples from exercise-trained mice to decipher the lipid changes associated with exercise-induced improvements in whole body glucose metabolism. Obesity and insulin resistance were induced in C57BL/6J mice by high-fat feeding for 4 wk. Mice then underwent an exercise training program (treadmill running) 5 days/wk (Ex) for 4 wk or remained sedentary (Sed). Compared with Sed, Ex displayed improved (P < 0.01) whole body metabolism as measured via an oral glucose tolerance test. Deleterious lipid species such as diacylglycerol (P < 0.05) and cholesterol esters (P < 0.01) that accumulate with high-fat feeding were decreased in the liver of trained mice. Furthermore, the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) (the PC/PE ratio), which is associated with membrane integrity and linked to hepatic disease progression, was increased by training (P < 0.05). These findings occurred without corresponding changes in the skeletal muscle lipidome. A concomitant decrease (P < 0.05) was observed for the fatty acid transporters CD36 and FATP4 in the liver, suggesting that exercise stimulates a coordinated reduction in fatty acid entry into hepatocytes. Given the important role of the liver in the regulation of whole body glucose homeostasis, hepatic lipid regression may be a key component by which exercise can improve metabolism.


Depressive symptoms and deliberate self-harm in a community sample of adolescents: a prospective study.
The associations between depressive symptoms and deliberate self-harm were studied by means of a 2-wave longitudinal design in a community sample of 1052 young adolescents, with longitudinal data for 83.6% of the sample. Evidence was found for a bidirectional relationship in girls, with depressive symptoms being a risk factor for increased self-harm one year later and self-harm a risk factor for increased depressive symptoms. Cluster analysis of profiles of depressive symptoms led to the identification of two clusters with clear depressive profiles (one severe, the other mild/moderate) which were both characterized by an overrepresentation of girls and elevated levels of self-harm. Clusters with more circumscribed problems were also identified; of these, significantly increased levels of self-harm were found in a cluster characterized by negative self-image and in a cluster characterized by dysphoric relations to parents. It is suggested that self-harm serves more to regulate negative self-related feelings than sadness.


Retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGA1.
Cyclic nucleotide-gated (CNG) channels are important mediators in the transduction pathways of rod and cone photoreceptors. Native CNG channels are heterotetramers composed of homologous A and B subunits. Biallelic mutations in CNGA1 or CNGB1 genes result in autosomal recessive retinitis pigmentosa (RP). To investigate the pathogenic mechanism of CNG channel-associated retinal degeneration, we developed a mouse model of CNGA1 knock-out using CRISPR/Cas9 technology. We observed progressive retinal thinning and a concomitant functional deficit in vivo as typical phenotypes for RP. Immunofluorescence and TUNEL staining showed progressive degeneration in rods and cones. Moreover, microglial activation and oxidative stress damage occurred in parallel. RNA-sequencing analysis of the retinae suggested down-regulated synaptic transmission and phototransduction as early as 9 days postnatal, possibly inducing later photoreceptor degeneration. In addition, the down-regulated PI3K-AKT-mTOR pathway indicated upregulation of autophagic process, and chaperone-mediated autophagy was further shown to coincide with the time course of photoreceptor death. Taken together, our studies add to a growing body of research exploring the mechanisms of photoreceptor death during RP progression and provide a novel CNGA1 knockout mouse model for potential development of therapies.


Molecular Engineering Powered Dual-Readout Point-of-Care Testing for Sensitive Detection of Escherichia coli O157:H7.
Escherichia coli O157:H7 (E. coli O157:H7) has become one of the major threats to public health and food safety. However, the culture method as a gold standard for the detection of E. coli O157:H7 requires laborious operations and a long processing time. Herein, we developed a dual-readout aggregation-induced emission nanoparticle-based lateral flow immunoassay (LFIA) for sensitive detection of E. coli O157:H7 to achieve a qualitative and quantitative assay for satisfying the applications under varying scenarios. 2,3-Bis(4-(bis(4-(tert-butyl)phenyl)amino)phenyl)fumaronitrile (BAPF), an aggregation-induced emission luminogen, was designed to achieve a strong molar extinction coefficient (3.0 × 104 M-1 cm-1) and high quantum yield (33.28%), which was further verified by a large rotation angle and low energy gap. Subsequently, BAPFs were integrated into a nanostructured system to form excellent water-soluble nanoparticles (BAPFNPs) for the detection of E. coli O157:H7 with colorimetric and fluorescent readout. The designed BAPFNPs-based LFIA (BAPFNPs-LFIA) exhibited nearly qualitative ability with gold nanoparticles-LFIA (AuNPs-LFIA) and a 9 times enhancement compared with quantum beads-LFIA (QBs-LFIA) in quantitative aspect. Especially, FL-BAPFNPs-LFIA could detect E. coli O157:H7 earlier than QBs-LFIA and AuNPs-LFIA when samples with low E. coli O157:H7 concentrations were cultured. Overall, the proposed strategy revealed that versatile BAPFNPs have great potential as reporters for dual-readout ability and enhancing detection sensitivity for rapid and accurate pathogenic bacteria assay.


Physical activity and acculturation among adult Hispanics in the United States.
Understanding the prevalence and demographic correlates of physical activity is important for public health and epidemiological research. This analysis examines the association between acculturation and physical activity in a large (approximately 5,000) sample of Hispanic adults from the 2000 National Health Interview Survey. Scores for eight questions concerning language use were summed to produce an acculturation index. Factor analysis indicated that these questions assessed a single underlying construct. Self-reported adherence to recommendations concerning leisure time physical activity increased from 22. 6% in the least acculturated tertile to 47% in the most acculturated tertile. In contrast, prevalence of walking or bicycling for errands decreased from 25.2 to 18.2%, and prevalence of standing or walking during most of the day decreased from 82.8 to 65.6% as acculturation increased. Thus, patterns of physical activity associated with leisure versus nonleisure time differed among Hispanics with varying acculturation levels. Alternatively, cultural factors may have differential effects on responses to questions concerning leisure and nonleisure time physical activity. In either case, assessing both types of activity is important for monitoring and understanding Hispanic health behaviors and interpreting epidemiological studies that involve physical activity in Hispanics.


Conversations About Financial Issues in Routine Oncology Practices: A Multicenter Study.
To describe the frequency, content, dynamics, and patterns of cost conversations in academic medical oncology across tumor types. We reviewed 529 audio recordings between May 3, 2012, to September 23, 2014, from a prospective three-site communication study in which patients at any stage of management for any solid tumor malignancy were seen in routine oncology appointments. Recordings were deidentified, transcribed, and flagged for any mention of cost. We coded encounters and used qualitative thematic analysis. Financial issues were discussed in 151 (28%) of 529 recordings. Conversations lasted shorter than 2 minutes on average. Patients/caregivers raised a majority of discussions (106 of 151), and 40% of cost concerns raised by patients/caregivers were not verbally acknowledged by clinicians. Social service referrals were made only six times. Themes from content analysis were related to insurance eligibility/process, work insecurity, cost of drugs, cost used as tool to influence medical decision making, health care-specific costs, and basic needs. Financial concerns influenced oncology work processes via test or medication coverage denials, creating paperwork for clinicians, potentially influencing patient involvement in trials, and leading to medication self-rationing or similar behaviors. Typically, financial concerns were associated with negative emotions. Financial issues were raised in approximately one in four academic oncology visits. These brief conversations were usually initiated by patients/caregivers, went frequently unaddressed by clinicians, and seemed to influence medical decision making and work processes and contribute to distress. Themes identified shed light on the kinds of gaps that must be addressed to help patients with cancer cope with the rising cost of care.


The gender paradox in suicidal behavior and its impact on the suicidal process.
An important gender difference has been reported regarding suicidal behavior with an overrepresentation of females in nonfatal suicidal behavior and a preponderance of males in completed suicide, also known as the 'gender paradox of suicidal behavior'. The concept of a 'suicidal process' classifies suicidal behavior chronologically; this process starts with suicidal ideation and then implies a progression of suicidality ranging from suicidal ideation over plans to suicide attempts and finally fatal suicide. The current paper aims to deepen the knowledge on the gender paradox by collecting and discussing the recent literature on this topic: the most relevant, impacting gender-related factors will be discussed within the suicidal process concept. Several factors had a gender-dependent impact on suicidal behavior: psychosocial life stressors such as stressful life events but also sociodemographical or socio-economical factors, and sexual abuse. The gender differences in psychiatric (co)morbidity and in response to or attitude towards antidepressant treatment also appear to have an impact. Furthermore, not only suicide methods but also the gender-dependent variation in reporting suicide has an influence. Finally, the gender differences in help seeking behavior as well as region-dependent cultural beliefs and societal attitudes are discussed. Especially life-events seem to exert an important influence at the beginning of a suicidal process, whereas the other factors occur at a further stage in the process, however without a fixed chronology. Also, the duration of the suicidal process is much shorter in male than in females. Finally, some implications with regard to clinical practice and suicide prevention are suggested.


Identification of a monoclonal antibody-defined breast carcinoma antigen in body fluids.
The monoclonal antibody NCRC-11 defines antigens associated with secretory glandular epithelia as well as most epithelial malignancies. These components have been identified in, and isolated from, normal body fluids including urine and skim milk. The immunoadsorbent purified antigens from urine and milk were very similar to those purified from breast and ovarian carcinomas; by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) and immunoblotting, NCRC-11 antibody-binding antigens from all sources were of high apparent molecular weight (greater than 400 kD) with the major component(s) present as a single band or a doublet. Also, by analysing epitope profiles, all purified antigen preparations were shown to react in a characteristic manner with a panel of monoclonal antibodies which were originally produced against human milk products or materials from tumours. Since it was shown that NCRC-11 antigens were released from tissues in a soluble form, the possibility that these antigens might represent a diagnostic marker for breast cancer was evaluated. The findings obtained indicated that NCRC-11 antigens were elevated in the serum of advanced breast cancer patients in comparison to healthy control females, so that access to the circulation was available to these products released from the tumour but not to those released from normal epithelia.


Distributive health literacy and medication management: A longitudinal qualitative study with Bhutanese former refugees in Tasmania.
Tasmania, Australia is home to a population of Bhutanese former refugees who have resettled since 2007. Their refugee journey and disrupted education opportunities have resulted in gaps in literacy in their primary language (Nepali), and many suffer one or more chronic conditions (ongoing communicable or noncommunicable diseases (NCDs)). This research explored how this community perceives chronic conditions and managed their medication using the concept of distributed health literacy. A longitudinal qualitative method was used whereby 15 former refugees and their carers were interviewed 3-4 times over 9 months. Data were thematically analysed using a hybrid approach of inductive and deductive coding and theme development. Four themes related to distributed health literacy were identified. These were "barriers to medication literacy and adherence," "support people as health literacy mediators," "understandings of chronic disease" and "strengthening distributed health literacy." Participants described managing relatively low levels of knowledge about their chronic conditions and medications by appointing support people who acted as health literacy mediators. This resulted in interactions with health professionals, information gathering and medication use being enacted collectively between family members. Carers felt responsible for supporting others who were new to the Australian health system to learn new skills in addition to assisting with tasks such as informal interpreting. SO WHAT?: Interventions to improve the health literacy of former refugees should focus on collective critical health literacy action rather than just the functional health literacy of individuals. Health literacy mediators are a vital form of support for former refugees managing chronic conditions, so must be included in education and support programs.


In Vivo Applicability of Neosartorya fischeri Antifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis.
As a consequence of emerging numbers of vulvovaginitis cases caused by azole-resistant and biofilm-forming Candida species, fast and efficient treatment of this infection has become challenging. The problem is further exacerbated by the severe side effects of azoles as long-term-use medications in the recurrent form. There is therefore an increasing demand for novel and safely applicable effective antifungal therapeutic strategies. The small, cysteine-rich, and cationic antifungal proteins from filamentous ascomycetes are potential candidates, as they inhibit the growth of several Candida spp. in vitro; however, no information is available about their in vivo antifungal potency against yeasts. In the present study, we investigated the possible therapeutic application of one of their representatives in the treatment of vulvovaginal candidiasis, Neosartorya fischeri antifungal protein 2 (NFAP2). NFAP2 inhibited the growth of a fluconazole (FLC)-resistant Candida albicans strain isolated from a vulvovaginal infection, and it was effective against both planktonic cells and biofilm in vitro We observed that the fungal cell-killing activity of NFAP2 is connected to its pore-forming ability in the cell membrane. NFAP2 did not exert cytotoxic effects on primary human keratinocytes and dermal fibroblasts at the MIC in vitro. In vivo murine vulvovaginitis model experiments showed that NFAP2 significantly decreases the number of FLC-resistant C. albicans cells, and combined application with FLC enhances the efficacy. These results suggest that NFAP2 provides a feasible base for the development of a fundamental new, safely applicable mono- or polytherapeutic topical agent for the treatment of superficial candidiasis.


Adjuvant effect of inhaled particulate matter containing free radicals following house-dust mite induction of asthma in mice.
Exposures to particulate matter (PM) from combustion sources can exacerbate preexisting asthma. However, the cellular and molecular mechanisms by which PM promotes the exacerbation of asthma remain elusive. We used a house dust mite (HDM)-induced mouse model of asthma to test the hypothesis that inhaled DCB230, which are PM containing environmentally persistent free radicals (EPFRs), will aggravate asthmatic responses. Groups of 8-10-week-old C57BL/6 male mice were exposed to either air or DCB230 aerosols at a concentration of 1.5 mg/m3 4 h/day for 10 days with or without prior HDM-induction of asthma. Aerosolized DCB230 particles formed small aggregates (30-150 nm). Mice exposed to DCB230 alone showed significantly reduced lung tidal volume, overexpression of the Muc5ac gene, and dysregulation of 4 inflammation related genes, Ccl11, Ccl24, Il-10, and Tpsb2. This suggests DCB230 particles interacted with the lung epithelium inducing mucous hypersecretion and restricting lung volume. In addition to reduced lung tidal volume, compared to respective controls, the HDM + DCB230-exposed group exhibited significantly increased lung tissue damping and up-regulated expression of Muc5ac, indicating that in this model, mucous hypersecretion may be central to pulmonary dysfunction. This group also showed augmented lung eosinophilic inflammation accompanied by an up-regulation of 36 asthma related genes. Twelve of these genes are part of IL-17 signaling, suggesting that this pathway is critical for DCB230 induced toxicity and adjuvant effects in lungs previously exposed to HDM. Our data indicate that inhaled DCB230 can act as an adjuvant, exacerbating asthma through IL-17-mediated responses in a HDM mouse model.


Towards sustainable production and utilization of plant-biomass-based nanomaterials: a review and analysis of recent developments.
Plant-biomass-based nanomaterials have attracted great interest recently for their potential to replace petroleum-sourced polymeric materials for sustained economic development. However, challenges associated with sustainable production of lignocellulosic nanoscale polymeric materials (NPMs) need to be addressed. Producing materials from lignocellulosic biomass is a value-added proposition compared with fuel-centric approach. This report focuses on recent progress made in understanding NPMs-specifically lignin nanoparticles (LNPs) and cellulosic nanomaterials (CNMs)-and their sustainable production. Special attention is focused on understanding key issues in nano-level deconstruction of cell walls and utilization of key properties of the resultant NPMs to allow flexibility in production to promote sustainability. Specifically, suitable processes for producing LNPs and their potential for scaled-up production, along with the resultant LNP properties and prospective applications, are discussed. In the case of CNMs, terminologies such as cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs) used in the literature are examined. The term cellulose nano-whiskers (CNWs) is used here to describe a class of CNMs that has a morphology similar to CNCs but without specifying its crystallinity, because most applications of CNCs do not need its crystalline characteristic. Additionally, progress in enzymatic processing and drying of NPMs is also summarized. Finally, the report provides some perspective of future research that is likely to result in commercialization of plant-based NPMs.


Dairy foods and health in Asians: Taiwanese considerations.
The health relevance of dairy products has mostly been judged by their abundant nutrients (protein, calcium and riboflavin) and recommendations for these derived in lactase-persistent Caucasian populations. Extrapolation to Asians who are generally lactase non-persisters may not be biologically, culturally or environmentally sound. A number of studies, especially among north-east Asians as in Taiwan, provide guidance for their optimal dairy intakes. In Taiwan, the NAHSIT (Nutrition and Health Surveys in Taiwan) linked to the National Health Insurance and Death Registry data bases provide most of the evidence. Cultural and socio-economic barriers create population resistance to increase dairy consumption beyond one serving per day as reflected in food balance sheet and repeat survey trend analyses. For the morbidity and mortality patterns principally seen in Asia, some, but not too much, dairy is to be preferred. This applies to all-cause and cardiovascular, especially stroke, mortality, to the risk of overfatness (by BMI and abdominal circumference) and diabetes and very likely to fracture and its sequelae. In Taiwan, there is no apparent association with total cancer mortality, but among Europeans, there may be protection. Historically, while fermented mammalian milks have been consumed in south Asia and various Asian subgroups and regions, most of the uptake of dairy in Asia after World War 2 has been from imported powdered milk or fresh liquid milk, encouraged further by the use of yogurts and popularization of milk teas and coffee. Asian dietary guidelines and clinical nutrition protocols need to encourage a modest, asymptomatic dairy intake.


Predictable Fluctuations in Excitatory Synaptic Strength Due to Natural Variation in Presynaptic Firing Rate.
Many controlled in vitro studies have demonstrated how postsynaptic responses to presynaptic spikes are not constant but depend on short-term synaptic plasticity (STP) and the detailed timing of presynaptic spikes. However, the effects of short-term plasticity (depression and facilitation) are not limited to short, subsecond timescales. The effects of STP appear on long timescales as changes in presynaptic firing rates lead to changes in steady-state synaptic transmission. Here, we examine the relationship between natural variations in the presynaptic firing rates and spike transmission in vivo Using large-scale spike recordings in awake male and female mice from the Allen Institute Neuropixels dataset, we first detect putative excitatory synaptic connections based on cross-correlations between the spike trains of millions of pairs of neurons. For the subset of pairs where a transient, excitatory effect was detected, we use a model-based approach to track fluctuations in synaptic efficacy and find that efficacy varies substantially on slow (∼1 min) timescales over the course of these recordings. For many connections, the efficacy fluctuations are correlated with fluctuations in the presynaptic firing rate. To understand the potential mechanisms underlying this relationship, we then model the detailed probability of postsynaptic spiking on a millisecond timescale, including both slow changes in postsynaptic excitability and monosynaptic inputs with short-term plasticity. The detailed model reproduces the slow efficacy fluctuations observed with many putative excitatory connections, suggesting that these fluctuations can be both directly predicted based on the time-varying presynaptic firing rate and, at least partly, explained by the cumulative effects of STP.SIGNIFICANCE STATEMENT The firing rates of individual neurons naturally vary because of stimuli, movement, and brain state. Models of synaptic transmission predict that these variations in firing rates should be accompanied by slow fluctuations in synaptic strength because of short-term depression and facilitation. Here, we characterize the magnitude and predictability of fluctuations in synaptic strength in vivo using large-scale spike recordings. For putative excitatory connections from a wide range of brain areas, we find that typical synaptic efficacy varies as much as ∼70%, and in many cases the fluctuations are well described by models of short-term synaptic plasticity. These results highlight the dynamic nature of in vivo synaptic transmission and the interplay between synaptic strength and firing rates in awake animals.


SERS on periodic arrays of coupled quadrate-holes and squares.
We have set up a novel quasi-3D structure, periodic arrays of two-layer coupled quadrate-holes and squares. SERS measurements show that for 514 nm excitation the average enhancement factor of periodic arrays of the coupled structure over the normal Ag film can reach 4 x 10(2), much higher than the known experimental result for periodic arrays of nanoholes. The simulation shows that the SERS enhancement caused by the coupled two-layer structure is about 2.4 orders of magnitude higher than that of a simple one-layer structure, which verifies the advantages of the structure with two-layer coupled pairs of quadrate-holes and squares over the structure with one-layer nanoholes for SERS measurement.


Cardiovascular complications of anorexia nervosa: A systematic review.
Anorexia nervosa portends the highest mortality among psychiatric diseases, despite primarily being a disease of adolescents and younger adults. Although some of this mortality risk is attributable to suicide, many deaths are likely cardiovascular in etiology. Recent studies suggest that adverse myocardial structural changes occur in this condition, which could underlie the increased mortality. Given limited prevalence of severe anorexia there is a paucity of clinical and autopsy data to discern an exact cause of death. Given this background we conducted a systematic review of the medical literature to provide a contemporary summary of the pathobiologic sequelae of severe anorexia nervosa on the cardiovascular system. We sought to elucidate the impact of anorexia nervosa in four cardiovascular domains: structural, repolarization/conduction, hemodynamic, and peripheral vascular. A number of cardiac abnormalities associated with anorexia nervosa have been described in the literature, including pericardial and valvular pathology, changes in left ventricular mass and function, conduction abnormalities, bradycardia, hypotension, and dysregulation in peripheral vascular contractility. Despite the prevalent theory that malignant arrhythmias are implicated as a cause of sudden death in this disorder, data to support this causal relationship are lacking. It is reasonable to obtain routine electrocardiography and measurements of orthostatic vital signs in patients presenting with anorexia nervosa. Echocardiography is generally not indicated unless prompted by clinical signs of disease. Admission to an inpatient unit with telemetry monitoring is recommended for patients with severe sinus bradycardia or junction rhythm, marked prolongation of the corrected QT interval, or syncope.


Potential toxicity of pesticides measured in midwestern streams to aquatic organisms.
Society is becoming increasingly aware of the value of healthy aquatic ecosystems as well as the effects that man's activities have on those ecosystems. In recent years, many urban and industrial sources of contamination have been reduced or eliminated. The agricultural community also has worked towards reducing off-site movement of agricultural chemicals, but their use in farming is still growing. A small fraction, estimated at <1 to 2% of the pesticides applied to crops are lost from fields and enter nearby streams during rainfall events. In many cases aquatic organisms are exposed to mixtures of chemicals, which may lead to greater non-target risk than that predicted based on traditional risk assessments for single chemicals. We evaluated the potential toxicity of environmental mixtures of 5 classes of pesticides using concentrations from water samples collected from approximately 50 sites on midwestern streams during late spring or early summer runoff events in 1989 and 1998. Toxicity index values are calculated as the concentration of the compound in the sample divided by the EC50 or LC50 of an aquatic organism. These index values are summed within a pesticide class and for all classes to determine additive pesticide class and total pesticide toxicity indices. Toxicity index values greater than 1.0 indicate probable toxicity of a class of pesticides measured in a water sample to aquatic organisms. Results indicate that some samples had probable toxicity to duckweed and green algae, but few are suspected of having significant toxicity to bluegill sunfish or chorus frogs.


Reprogramming non-mammary and cancer cells in the developing mouse mammary gland.
The capacity of any portion of the murine mammary gland to produce a complete functional mammary outgrowth upon transplantation to an epithelium-divested fat pad is unaffected by the age or reproductive history of the donor. Likewise, through serial transplantations, no loss of potency is detected when compared to similar transplantations of the youngest mammary tissue tested. This demonstrates that stem cell activity is maintained intact throughout the lifetime of the animal despite aging and the repeated expansion and depletion of the mammary epithelium through multiple rounds of pregnancy, lactation and involution. These facts support the contention that mammary stem cells reside in protected tissue locales (niches), where their reproductive potency remains essentially unchanged through life. Disruption of the tissue, to produce dispersed cells results in the desecration of the protection afforded by the "niche" and leads to a reduced capacity of dispersed epithelial cells (in terms of the number transplanted) to recapitulate complete functional mammary structures. Our studies demonstrate that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary cells, including mouse and human cancer cells, may be sequestered and reprogrammed to perform mammary epithelial cell functions including those ascribed to mammary stem/progenitor cells.


Drinking behaviour in the cat induced by renin, angiotensin I, II and isoprenaline.
1. Angiotensin I, II and hog renin, infused into the lateral cerebral ventricles (I.C.V.) of water replete cats, each induced water drinking behaviour. 2. Intravenous infusion of high doses of angiotensin I or II also elicited a drinking response. The dipsogenic effect of I.V. renin was not marked. 3. Drinking in response to I.C.V. angiotensin II was abolished after autonomic ganglion blockade with I.V. hexamethonium or pempidine and was significantly reduced after I.V. atropine methonitrate. 4. The dipsogenic response to I.C.V. angiotensin II was unaffected by either peripheral adrenergic neurone blockade with I.V. bethanidine, alpha-adrenoceptor blockade with phentolamine or beta-adrenoceptor blockade with sotalol. 5. Atropine, atropine methonitrate, hexamethonium and pempidine given I.C.V did not inhibit the diposgenic response to I.C.V. angiotensin II. 6. Bethanidine I.C.V. produced a dose related reduction in the dipsogenic response to I.C.V. angiotensin II. 7. The alpha-adrenoceptor blocking agents tolazoline and phenoxybenzamine given I.C.V did not affect angiotensin induced drinking but the response was regularly inhibited by phentolamine I.C.V. 8. The beta-adrenoceptor blocking agents propranolol and practolol given I.C.V. each inhibited angiotensin induced drinking. The L-isomer of propranolol was a more effective blocker than the D-isomer. 9. Isoprenaline given I.C.V induced drinking in ten of sixteen cats. Subcutaneous administration of isoprenaline also elicited drinking but the onset of the response was delayed and the amount consumed slightly less than after I.C.V infusion.


Parents' attributions of their child's jigsaw-puzzle performance: comparing two genetic syndromes.
Parents' attributions of the jigsaw-puzzle performance of their child with Prader-Willi syndrome (n = 20) or Williams syndrome (n = 21) were examined. Parents in both groups placed more importance on internal versus external attributions. Parents of children with Prader-Willi syndrome exhibited a hedonic bias by attributing their child's success to internal factors (particularly when the child was good at puzzles), downplayed the role of chance when their child had higher puzzle skills and higher cognitive functioning, and differentiated between internal and external attributions. In contrast, parents of children with Williams syndrome showed an inconsistent attributional pattern. These findings help identify how parents understand the intellectual performance of their child with disabilities and how interventions might be beneficial.


Controlling periodic Fano resonances of quantum acoustic waves with a giant atom coupled to a microwave waveguide.
Nanoscale Fano resonances, with applications from telecommunications to ultra-sensitive biosensing, have prompted extensive research. We demonstrate that a superconducting qubit, jointly coupled to microwave waveguides and an inter-digital transducer composite device, can exhibit acoustic Fano resonances. Our analytical framework, leveraging the Taylor series approximation, elucidates the origins of these quantum acoustic resonances with periodic Fano-like interference. By analyzing the analytical Fano parameter, we demonstrate that the Fano resonances and their corresponding Fano widths near the resonance frequency of a giant atom can be precisely controlled and manipulated by adjusting the time delay. Moreover, not just the near-resonant Fano profiles, but the entire periodic Fano resonance features can be precisely modulated from Lorentz, Fano to quasi-Lorentz shapes by tuning the coupling strength of the microwave waveguide. Our analytical framework offers insights into the control and manipulation of periodic Fano resonances in quantum acoustic waves, thereby presenting significant potential for applications such as quantum information processing, sensing, and communication.


[Immunohistochemical expression of P53 and Ki-67 in diethylnitrosamine-induced carcinomas esophageal: experimental model].
To evaluate the expression of P53 and Ki-67 during esophageal diethylnitrosamine (DEN)-induced carcinogenesis in 100 mice by immunohistochemistry. The animals were assigned to 4 groups, receiving water and food ad libitum. Control groups I and II received weekly esophageal gavage with cold (room temperature) or hot (60-70 degrees C) water, respectively. Experimental groups III and IV were treated with DEN for 3 consecutive days during the week, and one weekly gavage as above. The mice were sacrificed in different periods from day 30 to day 150 after the beginning of the experiment, for collection of esophageal samples which were then submitted to microscopic and immunohistochemical analyses. The temperature of the water administered by gavage was not related to the frequency of esophageal tumors. The expression of Ki-67 was significantly higher in high-grade intraepithelial lesion (I.L.), and the expression of P53 was also higher in low-grade I.L. The results emphasize the direct relationship of the carcinogenic process with early cell alterations detected by immunohistochemistry.


Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment.
The relationships between lymphomas and their microenvironment appear to follow 3 major patterns: (1) an independent pattern; (2) a dependent pattern on deregulated interactions; and (3) a dependent pattern on regulated coexistence. Typical examples of the third pattern are hepatitis C virus (HCV)-associated marginal zone lymphomas (MZLs) and mucosa-associated lymphoid tissue lymphomas. In these lymphomas, a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs. At least initially, however, tumor development and cell growth largely depend on external signals from the microenvironment, such as viral antigens, cytokines, and cell-cell interactions. The association between HCV infection and B-cell lymphomas is not completely defined, although this association has been demonstrated by epidemiological studies. MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection. Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis; antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas. Recently, antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas. Importantly, clinically responses were linked to the eradication of the HCV-RNA, providing a strong argument in favor of a causative link between HCV and lymphoproliferation.


Confirmation of the role of diabetes in the local recurrence of surgically resected non-small cell lung cancer.
We recently demonstrated that diabetes mellitus was an independent risk factor for local recurrence (LR) for patients undergoing resection of non-small cell lung cancer (NSCLC). This investigation was performed to confirm or refute this finding in a different patient cohort. Patients were eligible if they did not have a second primary cancer within 5 years of the original diagnosis, had at least 3-month follow-up, and did not receive radiotherapy. There were 373 and 168 patients in the original (P1) and confirmatory (P2) cohorts, respectively, with 66 and 30 patients with diabetes. The median follow-up was 33 months (range, 3-98 months). Diabetes was an independent risk factor for LR in a Cox model in both the P2 (p=0.05, hazard ratio [HR] 2.15) and P1 (p=0.008, HR 1.90) cohorts, separately from BMI, glucose control, and the presence of the metabolic syndrome. The rates of LR in the patients with diabetes after combining the cohorts at 2, 3, and 5 years were 23%, 33%, and 56%, respectively; these rates were 15%, 19%, and 26% in non-diabetics. In multivariate Cox regression and competing risk analysis of the combined cohorts, the HRs for LR in patients with diabetes exceeded those of more established risk factors for LR including a 1-cm increase in tumor size and lymphovascular invasion. Diabetes was confirmed to be an independent predictor of the risk of LR following resection of NSCLC.


The consensus statement on the locoregional treatment of abdominal sarcomatosis.
Abdominal sarcomatosis (AS) is a rare condition characterized by soft tissue sarcoma spreading throughout the abdomen, in the absence of extra-abdominal dissemination. Retroperitoneal sarcomas, pelvic sarcomas, particularly uterine leiomyosarcoma, and gastrointestinal stromal tumors (GISTs) most frequently give rise to AS. Systemic chemotherapy is the standard of care for AS from non-GIST sarcomas, but with an essentially palliative aim and major limitations. Innovative targeted therapies has deeply affected the natural history of GIST, at least in prolonging significantly survival in responsive patients. In this context, the notion that abdominal spread in the lack of extra-peritoneal lesions may typically occur in a number of patients, along with the dismal prognosis generally carried by AS, has prompted a few centers to perform cytoreductive surgery and perioperative intraperitoneal chemotherapy. To date, the rarity of these presentations makes it difficult to evaluate the clinical results and the role of combined local-regional treatment is still a matter of debate. This article presents the results of a group of experts from around the World trying to achieve a consensus statement in AS comprehensive management. A questionnaire was placed on the website of the 5th International Workshop on Peritoneal Surface Malignancy and the experts voted via internet.


In vivo monitoring of adult neurogenesis in health and disease.
Adult neurogenesis, i.e., the generation of new neurons in the adult brain, presents an enormous potential for regenerative therapies of the central nervous system. While 5-bromo-2'-deoxyuridine labeling and subsequent histology or immunohistochemistry for cell-type-specific markers is still the gold standard in studies of neurogenesis, novel techniques, and tools for in vivo imaging of neurogenesis have been recently developed and successfully applied. Here, we review the latest progress on these developments, in particular in the area of magnetic resonance imaging (MRI) and optical imaging. In vivo in situ labeling of neural progenitor cells (NPCs) with micron-sized iron oxide particles enables longitudinal visualization of endogenous progenitor cell migration by MRI. The possibility of genetic labeling for cellular MRI was demonstrated by using the iron storage protein ferritin as the MR reporter-gene. However, reliable and consistent results using ferritin imaging for monitoring endogenous progenitor cell migration have not yet been reported. In contrast, genetic labeling of NPCs with a fluorescent or bioluminescent reporter has led to the development of some powerful tools for in vivo imaging of neurogenesis. Here, two strategies, i.e., viral labeling of stem/progenitor cells and transgenic approaches, have been used. In addition, the use of specific promoters for neuronal progenitor cells such as doublecortin increases the neurogenesis-specificity of the labeling. Naturally, the ultimate challenge will be to develop neurogenesis imaging methods applicable in humans. Therefore, we certainly need to consider other modalities such as positron emission tomography and proton magnetic resonance spectroscopy ((1)H-MRS), which have already been implemented for both animals and humans. Further improvements of sensitivity and neurogenesis-specificity are nevertheless required for all imaging techniques currently available.


Predicting visceral pleural invasion in lung adenocarcinoma presenting as part-solid density utilizing a nomogram model combined with radiomics and clinical features.
To develop and validate a preoperative nomogram model combining the radiomics signature and clinical features for preoperative prediction of visceral pleural invasion (VPI) in lung nodules presenting as part-solid density. We retrospectively reviewed 156 patients with pathologically confirmed invasive lung adenocarcinomas after surgery from January 2016 to August 2019. The patients were split into training and validation sets by a ratio of 7:3. The radiomic features were extracted with the aid of FeAture Explorer Pro (FAE). A CT-based radiomics model was constructed to predict the presence of VPI and internally validated. Multivariable regression analysis was conducted to construct a nomogram model, and the performance of the models were evaluated with the area under the receiver operating characteristic curve (AUC) and compared with each other. The enrolled patients were split into training (n = 109) and validation sets (n = 47). A total of 806 features were extracted and the selected 10 optimal features were used in the construction of the radiomics model among the 707 stable features. The AUC of the nomogram model was 0.888 (95% CI: 0.762-0.961), which was superior to the clinical model (0.787, 95% CI: 0.643-0.893; p = 0.049) and comparable to the radiomics model (0.879, 95% CI: 0.751-0.965; p > 0.05). The nomogram model achieved a sensitivity of 90.5% and a specificity of 76.9% in the validation dataset. The nomogram model could be considered as a noninvasive method to predict VPI with either highly sensitive or highly specific diagnoses depending on clinical needs.


Predictors of difficult carotid stenting as determined by aortic arch angiography.
Although different aortic arch classifications exist to help determine carotid artery stenting (CAS) difficulty, they are not validated. We compared quantitative angiographic characteristics of aortic arch between easy and difficult CAS. We defined difficult procedures as requiring the longest fluoroscopy time (FT) (90th percentile) and easy procedures as the shortest FT (10th percentile) from our CAS database. We excluded patients undergoing additional procedures, intraprocedural complications or those with difficult vascular access. We analyzed 24 patients with difficult CAS (median fluoroscopy time of 58 minutes) and 24 with easy CAS (median fluoroscopy time of 19 minutes). The two groups were similar with respect to demographics, comorbidities and clinical presentation at the time of CAS. Patients with difficult procedures had a longer distance from the origin of treated artery to the beginning of the descending aorta (D1; 50 +/- 17 mm vs. 40 +/- 16 mm; p = 0.04), severe tortuosity (T) of the common carotid and internal carotid vessels (T; 50.0% vs. 16.7%; p = 0.03) and a trend in the presence of a Type 3 arch (33.3% vs. 25.0%; p = 0.18) and angulated takeoff (20.8% vs. 4.3%; p = 0.19). There was no difference in the severity of stenosis or index lesion calcification, ulceration and eccentricity between the two groups. On multivariate analysis, independent predictors of procedural difficulty were D1 (odds ratio 1.04 per mm; 95% CI, 1.01-1.09; p = 0.04), and T (odds ratio 4.77; 95% CI 1.3-42.9; p = 0.03). Distance from the origin of the treated artery to the beginning of the D1 and target vessel T determine prolonged fluoroscopy time during CAS.


A New Glycosyltransferase Enzyme from Family 91, UGT91P3, Is Responsible for the Final Glucosylation Step of Crocins in Saffron (Crocus sativus L.).
Crocetin is an apocarotenoid formed from the oxidative cleavage of zeaxanthin, by the carotenoid cleavage enzymes CCD2 (in Crocus species) and specific CCD4 enzymes in Buddleja davidii and Gardenia jasminoides. Crocetin accumulates in the stigma of saffron in the form of glucosides and crocins, which contain one to five glucose molecules. Crocetin glycosylation was hypothesized to involve at least two enzymes from superfamily 1 UDP-sugar dependent glycosyltransferases. One of them, UGT74AD1, produces crocins with one and two glucose molecules, which are substrates for a second UGT, which could belong to the UGT79, 91, or 94 families. An in silico search of Crocus transcriptomes revealed six candidate UGT genes from family 91. The transcript profiles of one of them, UGT91P3, matched the metabolite profile of crocin accumulation, and were co-expressed with UGT74AD1. In addition, both UGTs interact in a two-hybrid assay. Recombinant UGT91P3 produced mostly crocins with four and five glucose molecules in vitro, and in a combined transient expression assay with CCD2 and UGT74AD1 enzymes in Nicotiana benthamiana. These results suggest a role of UGT91P3 in the biosynthesis of highly glucosylated crocins in saffron, and that it represents the last missing gene in crocins biosynthesis.


Current Status of Point-of-Care Testing for Human Immunodeficiency Virus Drug Resistance.
Healthcare delivery has advanced due to the implementation of point-of-care testing, which is often performed within minutes to hours in minimally equipped laboratories or at home. Technologic advances are leading to point-of-care kits that incorporate nucleic acid-based assays, including polymerase chain reaction, isothermal amplification, ligation, and hybridization reactions. As a limited number of single-nucleotide polymorphisms are associated with clinically significant human immunodeficiency virus (HIV) drug resistance, assays to detect these mutations have been developed. Early versions of these assays have been used in research. This review summarizes the principles underlying each assay and discusses strategic needs for their incorporation into the management of HIV infection.


Parsimonious module inference in large networks.
We investigate the detectability of modules in large networks when the number of modules is not known in advance. We employ the minimum description length principle which seeks to minimize the total amount of information required to describe the network, and avoid overfitting. According to this criterion, we obtain general bounds on the detectability of any prescribed block structure, given the number of nodes and edges in the sampled network. We also obtain that the maximum number of detectable blocks scales as sqrt[N], where N is the number of nodes in the network, for a fixed average degree ⟨k⟩. We also show that the simplicity of the minimum description length approach yields an efficient multilevel Monte Carlo inference algorithm with a complexity of O(τNlogN), if the number of blocks is unknown, and O(τN) if it is known, where τ is the mixing time of the Markov chain. We illustrate the application of the method on a large network of actors and films with over 10(6) edges, and a dissortative, bipartite block structure.


FRET imaging.
Förster (or Fluorescence) Resonance Energy Transfer (FRET) is unique in generating fluorescence signals sensitive to molecular conformation, association, and separation in the 1-10 nm range. We introduce a revised photophysical framework for the phenomenon and provide a systematic catalog of FRET techniques adapted to imaging systems, including new approaches proposed as suitable prospects for implementation. Applications extending from a single molecule to live cells will benefit from multidimensional microscopy techniques, particularly those adapted for optical sectioning and incorporating new algorithms for resolving the component contributions to images of complex molecular systems.


Oligomer Electrolytes for Light-Emitting Electrochemical Cells: Influence of the End Groups on Ion Coordination, Ion Binding, and Turn-on Kinetics.
The electrolyte is an essential constituent of the light-emitting electrochemical cell (LEC), since its operating mechanism is dependent on the redistribution of mobile ions in the active layer. Recent developments of new ion transporters have yielded high-performance devices, but knowledge about the interactions between the ionic species and the ion transporters and the influence of these interactions on the LEC performance is lacking. We therefore present a combined computational and experimental effort that demonstrates that the selection of the end group in a star-branched oligomeric ion transporter based on trimethylolpropane ethoxylate has a paramount influence on the ionic interactions in the electrolyte and thereby also on the performance of the corresponding LECs. With hydroxyl end groups, the cation from the salt is strongly coordinated to the ion transporter, which leads to suppression of ion pairing, but the penalty is a hindered ion release and a slow turn-on for the LEC devices. With methoxy end groups, an intermediate coordination strength is seen together with the formation of contact ion pairs, but the LEC performance is very good with fast turn-on. Using a series of ion transporters with alkyl carbonate end groups, the ion transporter:cation coordination strength is lowered further, but the turn-on kinetics are slower than what is seen for devices comprising the methoxy end-capped ion transporter.


1,25(OH)2D3 dependent overt hyperactivity phenotype in klotho-hypomorphic mice.
Klotho, a protein mainly expressed in kidney and cerebral choroid plexus, is a powerful regulator of 1,25(OH)2D3 formation. Klotho-deficient mice (kl/kl) suffer from excessive plasma 1,25(OH)2D3-, Ca(2+)- and phosphate-concentrations, leading to severe soft tissue calcification and accelerated aging. NH4Cl treatment prevents tissue calcification and premature ageing without affecting 1,25(OH)2D3-formation. The present study explored the impact of excessive 1,25(OH)2D3 formation in NH4Cl-treated kl/kl-mice on behavior. To this end kl/kl-mice and wild-type mice were treated with NH4Cl and either control diet or vitamin D deficient diet (LVD). As a result, plasma 1,25(OH)2D3-, Ca(2+)- and phosphate-concentrations were significantly higher in untreated and in NH4Cl-treated kl/kl-mice than in wild-type mice, a difference abrogated by LVD. In each, open field, dark-light box, and O-maze NH4Cl-treated kl/kl-mice showed significantly higher exploratory behavior than untreated wild-type mice, a difference abrogated by LVD. The time of floating in the forced swimming test was significantly shorter in NH4Cl treated kl/kl-mice compared to untreated wild-type mice and to kl/kl-mice on LVD. In wild-type animals, NH4Cl treatment did not significantly alter 1,25(OH)2D3, calcium and phosphate concentrations or exploratory behavior. In conclusion, the excessive 1,25(OH)2D3 formation in klotho-hypomorphic mice has a profound effect on murine behavior.


Stigma in the HIV/AIDS epidemic: a review of the literature and recommendations for the way forward.
Although stigma is considered a major barrier to effective responses to the HIV/AIDS epidemic, stigma reduction efforts are relegated to the bottom of AIDS programme priorities. The complexity of HIV/AIDS-related stigma is often cited as a primary reason for the limited response to this pervasive phenomenon. In this paper, we systematically review the scientific literature on HIV/AIDS-related stigma to document the current state of research, identify gaps in the available evidence and highlight promising strategies to address stigma. We focus on the following key challenges: defining, measuring and reducing HIV/AIDS-related stigma as well as assessing the impact of stigma on the effectiveness of HIV prevention and treatment programmes. Based on the literature, we conclude by offering a set of recommendations that may represent important next steps in a multifaceted response to stigma in the HIV/AIDS epidemic.


Muscle fatigue in old animals. Unique aspects of fatigue in elderly humans.
Muscle atrophy, weakness, injury, and fatigue are inevitable and immutable concomitants of old age. Atrophy results from a gradual process of fiber denervation with loss of some fibers and atrophy of others. Fast fibers show more denervation and atrophy than slow fibers. Some fast fibers are reinnervated by axonal sprouting from slow fibers resulting in remodeling of motor units. With aging, the decreases in strength and power are greater than expected from the loss in muscle mass. Contraction-induced injury is proposed as a mechanism of the fast fiber denervation. With atrophy and weakness, human beings show a dramatic decrease in endurance and increase in fatigability with aging, but strength and endurance training slows the process.


[Effects of stress at different times after irradiation on capacity of humoral immune response in mice].
It was shown, that sensitivity of immune response to stress in postirradiated period essentially depends from the dose of irradiation (1, 2 Gy) and the period after irradiation. The sensitivity was not distinguished from intact mice in early period further the sensitivity of immune response can be increased (1 Gy) or can be decreased (2 Gy), stress can be stimulated of the antibody-formation to sheep red blood cells in late period after irradiation.


The structure of personality pathology: Both general ('g') and specific ('s') factors?
Recent editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013) conceptualize personality disorders (PDs) as categorical constructs, but high PD co-occurrence suggests underlying latent dimensions. Moreover, several borderline PD criteria resemble Criterion A of the new DSM-5 Section III general criteria for personality pathology (i.e., self and interpersonal dysfunction). We evaluated a bifactor model of PD pathology in which a general factor and several specific factors of personality pathology (PD 'g' and 's' factors, respectively) account for the covariance among PD criteria. In particular, we examined the extent to which the borderline PD criteria would load exclusively onto the g-factor versus on both the g- and one or more s-factors. A large (N = 966) sample of inpatients were interviewed for six DSM-IV (American Psychiatric Association, 1994) PDs using the (Structured Clinical Interview for Personality Disorders (SCID-II; First, Spitzer, Gibbon, Williams, & Benjamin, 1994) with no skip-outs. We ran a series of confirmatory, exploratory, and bifactor exploratory factor analyses on the rated PD criteria. The confirmatory analysis largely replicated the DSM PDs, but with high factor correlations. The "standard" exploratory analysis replicated four of the DSM PDs fairly well, but nearly half the criteria cross-loaded. In the bifactor analysis, borderline PD criteria loaded only on the general factor; the remaining PDs loaded either on both the general and a specific factor or largely only on a specific factor. Results are interpreted in the context of several possibilities to define the nature of the general factor.


Drug-metabolism research challenges in the new millennium: individual variability in drug therapy and drug safety.
One of the most challenging research areas in pharmacology in the new millennium is to understand why individuals respond differently to drug therapy and to what extent that individual variability in disposition is responsible for the observed differences in therapeutic efficacy and adverse reactions. To answer these complex questions, drug-metabolism research will rely on multidisciplinary approaches more than ever to investigate the many components involved in drug metabolism and disposition. Major research challenges include the following: (1) the genetic variation of drug targets (receptors, enzymes, etc.), drug transporters (multispecific organic anion transporter, P-glycoprotein, alpha-1-acid glycoprotein, etc.), and drug-metabolizing enzymes (cytochrome P450s and other enzymes); (2) the structure and function of all genetic variants of drug receptors, transporters, and metabolizing enzymes; (3) the induction, repression, and inhibition of all components involved in drug disposition; (4) the development of noninvasive in vivo methods to determine the physiological significance of various components in the handling of specific therapeutic agents in humans; (5) the mechanism of idiosyncratic adverse drug reactions; and (6) the pharmacokinetic and pharmacodynamic relationships to explain the individual differences in therapeutic efficacy and drug safety. Thus successful drug-metabolism research in the new millennium must integrate receptor biology, enzymology, recombinant DNA technology, biochemical toxicology, and drug disposition into study design and conduct balanced in vitro and in vivo experiments to allow a full understanding of the mechanisms of individual variability in drug therapy and drug safety.


Digital economy drives regional industrial structure upgrading: Empirical evidence from China's comprehensive big data pilot zone policy.
With the development of the digital economy, industrial structure upgrading plays an important role in realizing high-quality development. Exploiting the quasi-natural experimental setting provided by the Big Data Comprehensive Pilot Zone (BDCPZ) policy in China in 2016, this study evaluates the impacts of the BDCPZ policies on regional industrial structure upgrading using a combination of propensity score matching and difference-in-differences (PSM-DID) with panel data of 30 regions for the period 2008-2021. The results are as follows: (1) BDCPZ policies significantly promote regional industrial structure upgrading. This finding holds after conducting the placebo test and replacing explained variables. (2) BDCPZ policies enhance upgrading through technological innovation and financial deepening. (3) Heterogeneity analysis shows that the promotional effect of BDCPZ policies on industrial structure upgrading is more obvious in economically developed regions, megacities, and east-central regions; overall, regions with high industrialization benefit more. These findings have important implications: First, they provide new empirical evidence from the perspective of policy evaluation on how the digital economy affects industrial structure upgrading. Second, this study sheds light on the mechanism underlying this relationship, helping us understand how the digital economy can further affect the development of the industrial structure. Third, the policy effect is heterogenous, providing a scientific basis for the government to formulate differentiated implementation policies for different regions. This can help local industrial transformation and upgrading, and economic development in these regions through the implementation of big data and digital technologies.


Differentiation of branchial cleft cysts and malignant cystic adenopathy of pharyngeal origin.
There is an increasing incidence of head and neck cancers that present as neck masses in a nonsmoking nondrinking population. These masses can be confused with benign cystic neck masses. The purpose of this study was to determine imaging criteria to differentiate benign lateral neck cysts from malignant cystic adenopathy. A retrospective analysis of patients who underwent contrast-enhanced neck CT between July 2003 and July 2011 was performed. Patients were diagnosed with either a branchial cleft cyst or pharyngeal squamous cell cancer. Each examination was reviewed by a neuroradiologist, and, for each cyst or cystic lymph node, the anatomic level in the neck, dimensions, wall thickness, septations, homogeneity, extracapsular spread, calcifications, and fat stranding were recorded. Data analysis was performed using Student t tests and chi-square tests. Twenty-one patients with branchial cleft cysts and 29 patients with squamous cell carcinoma met the inclusion criteria. Significant differences between the groups were found with regard to size, homogeneity, and extracapsular spread. Branchial cleft cysts were found to be larger on the long axis (p < 0.001), short axis (p < 0.001), and height (p < 0.001). They were less likely to have extracapsular spread (p = 0.044) or septations (p = 0.059) and more likely to be homogeneous (p < 0.001). Misdiagnosis of malignant cysts in the neck may lead to delay in diagnosis, a violated neck, tumor spillage, and spread. Differences in radiographic criteria can guide clinical decision making in the patient with a neck mass. However, fine-needle aspiration may be necessary to confirm the diagnosis.


A randomized, double-blind, placebo-controlled study of aripiprazole for the treatment of psychosis in nursing home patients with Alzheimer disease.
To evaluate the efficacy and safety of aripiprazole treatment for psychotic symptoms associated with Alzheimer disease (AD). In this parallel group, randomized, double-blind, placebo-controlled, flexible-dose trial, institutionalized subjects with AD and psychotic symptoms were randomized to aripiprazole (n = 131) or placebo (n = 125) for 10 weeks. The aripiprazole starting dose was 2 mg/day, and could be titrated to higher doses (5, 10, and 15 mg/day) based on efficacy and tolerability. No significant differences in mean change [2 x SD] from baseline between aripiprazole (mean dose approximately 9 mg/day at endpoint; range = 0.7-15.0 mg) and placebo were detected in the coprimary efficacy endpoints of Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) Psychosis score (aripiprazole, -4.53 [9.23]; placebo, -4.62 [9.56]; F = 0.02, df = 1, 222, p = 0.883 [ANCOVA]) and Clinical Global Impression (CGI)-Severity score (aripiprazole, -0.57 [1.63]; placebo, -0.43 [1.65]; F = 1.67, df = 1, 220, p = 0.198 [ANCOVA]) at endpoint. However, improvements in several secondary efficacy measures (NPI-NH Total, Brief Psychiatric Rating Scale Total, CGI - improvement, Cohen-Mansfield Agitation Inventory and Cornell Depression Scale scores) indicated that aripiprazole may confer clinical benefits beyond the primary outcome measures. Treatment-emergent adverse events (AEs) were similar in both groups, except for somnolence (aripiprazole, 14%; placebo, 4%). Somnolence with aripiprazole was of mild or moderate intensity, and not associated with accidental injury. Incidence of AEs related to extrapyramidal symptoms was low with aripiprazole (5%) and placebo (4%). In nursing home residents with AD and psychosis, aripiprazole did not confer specific benefits for the treatment of psychotic symptoms; but psychological and behavioral symptoms, including agitation, anxiety, and depression, were improved with aripiprazole, with a low risk of AEs.


Vocal tract and register changes analysed by real-time MRI in male professional singers-a pilot study.
Changes of vocal tract shape accompanying changes of vocal register and pitch in singing have remained an unclear field. Dynamic real-time magnetic resonance imaging (MRI) was applied to two professional classical singers (a tenor and a baritone) in this pilot study. The singers sang ascending scales from B3 to G#4 on the vowel /a/, keeping the modal register throughout or shifting to falsetto register for the highest pitches. The results show that these singers made few and minor modifications of vocal tract shape when they changed from modal to falsetto and some clear modifications when they kept the register. In this case the baritone increased his tongue dorsum height, widened his jaw opening, and decreased his jaw protrusion, while the tenor merely lifted his uvula. The method used seems promising and should be applied to a greater number of singer subjects in the future.


Synergistic effects of anti-PDL-1 with ablative radiation comparing to other regimens with same biological effect dose based on different immunogenic response.
Irradiation can induce multiple inhibitory and stimulatory effects on the immune system. In recent studies, it has been noted that administration of radiation with various doses and fractionation plans may influence on immune responses in microenvironment of tumor. But in radiobiology, the Biologically Effective Dose (BED) formula has been designed for calculating isoeffect doses in different regimens of daily clinical practice. In other words, BED has also been used to predict the effects of fractionation schedules on tumor cells. In our study, three different regimens with BEDs of 40 gray (Gy) were analyzed in BALB/c mice. These included conventional fractionated radiotherapy (RT) (3Gyx10), high-dose hypofractionated RT (10Gyx2), and single ablative high-dose RT (15Gyx1). As BED predicts, all three similarly decreased tumor volumes and increased survival times relative to controls, but after high dose exposure in ablative group, the expression of IFNγ was increased following high infiltration of CD8 cells into the tumor microenvironment. When anti-PDL-1 was combined with RT, single ablative high-dose radiation enhanced antitumor activity by increasing IFNγ in tumors and CD8+ tumor-infiltrating lymphocytes; as a result, this combining therapy had enhanced antitumor activity and lead to control tumor volume effectively and improve significantly survival rate and finally the recurrence of tumor was not observed. Results show distinct radiation doses and fractionation schemes with same BED have different immunogenic response and these findings can provide data helping to design regimens of radiation combined with immune checkpoint blockers (ICBs).


Predicting First Grade Reading Performance from Kindergarten Response to Tier 1 Instruction.
Many schools are beginning to implement multi-tier response to intervention (RTI) models for the prevention of reading difficulties and to assist in the identification of students with learning disabilities (LD). The present study was part of our larger ongoing longitudinal RTI investigation within the Florida Learning Disabilities Center grant. This study used a longitudinal correlational design, conducted in 7 ethnically and socio-economically diverse schools. We observed reading instruction in 20 classrooms, examined response rates to kindergarten Tier 1 instruction, and predicted students' first grade reading performance based upon kindergarten growth and end of year reading performance (n = 203). Teachers followed an explicit core reading program and overall, classroom instruction was rated as effective. Results indicate that controlling for students' end of kindergarten reading, their growth across kindergarten on a variety of language and literacy measures suppressed predictions of first grade performance. Specifically, the steeper the students' trajectory to a satisfactory outcome, the less likely they were to demonstrate good performance in first grade. Implications for future research and RTI implementation are discussed.


A tail withdrawal procedure for assessing analgesic activity in rhesus monkeys.
Rhesus monkeys were restrained in chairs from which their tails hung free so that their tails could be immersed into a thermos of water. Monkeys consistently kept their tails in 38-40 degrees C water for at least 20 sec, but withdrew them from 55 degrees C water in 1-4 sec. Tail withdrawal latencies from 55 degrees C water remained consistent over a period of 3 hr. Morphine produced dose-dependent increases in tail withdrawal latencies from 55 degrees C water, whereas pentobarbital, haloperidol, and phencyclidine did not increase tail withdrawal latencies except at doses that produced marked sedation.


[Epidemiology of dementia].
Because of the increasing life expectancy during the next decades the number of demented will steeply rise. The estimated number of people suffering from dementia in Austria will increase from 90,500 persons in the year 2000 to 233,800 persons in the year 2050. During the same period the estimated number of those developing a dementia within one year will rise from 23,600 to 59,500. In contrast, in the next five decades, the population being in an employable age will decrease to 77%. Thus, the proportion of demented in relation to employable people will considerably increase. While in year 2000 there were 56 employable persons per one demented person, in the year 2050 there will be only 17 employable persons per one demented person. Dementing disorders are a main reason for being admitted to nursing homes. In Austrian nursing homes 63.5% of those newly admitted suffer from dementia. Despite of the fact that a large proportion of dementia sufferers are being cared in nursing homes, the majority lives in their private households supported by their family members. Relatives of demented persons experience a large amount of burden, and need more professional help than is available today. The costs of dementing disorders are high and a large proportion is paid by the patients family. In the future, in Austria more specialized day care facilities for the demented and more nursing homes are necessary.


Associations Between Polygenic Risk Score Loading, Psychosis Liability, and Clozapine Use Among Individuals With Schizophrenia.
Predictors consistently associated with psychosis liability and course of illness in schizophrenia (SCZ) spectrum disorders (SSD), including the need for clozapine treatment, are lacking. Longitudinally ascertained medication use may empower studies examining associations between polygenic risk scores (PRSs) and pharmacotherapy choices. To examine associations between PRS-SCZ loading and groups with different liabilities to SSD (individuals with SSD taking clozapine, individuals with SSD taking other antipsychotics, their parents and siblings, and unrelated healthy controls) and between PRS-SCZ and the likelihood of receiving a prescription of clozapine relative to other antipsychotics. This genetic association study was a multicenter, observational cohort study with 6 years of follow-up. Included were individuals diagnosed with SSD who were taking clozapine or other antipsychotics, their parents and siblings, and unrelated healthy controls. Data were collected from 2004 until 2021 and analyzed between October 2021 and September 2022. Polygenic risk scores for SCZ. Multinomial logistic regression was used to examine possible differences between groups by computing risk ratios (RRs), ie, ratios of the probability of pertaining to a particular group divided by the probability of healthy control status. We also computed PRS-informed odd ratios (ORs) for clozapine use relative to other antipsychotics. Polygenic risk scores for SCZ were generated for 2344 participants (mean [SD] age, 36.95 years [14.38]; 994 female individuals [42.4%]) who remained after quality control screening (557 individuals with SSD taking clozapine, 350 individuals with SSD taking other antipsychotics during the 6-year follow-up, 542 parents and 574 siblings of individuals with SSD, and 321 unrelated healthy controls). All RRs were significantly different from 1; RRs were highest for individuals with SSD taking clozapine (RR, 3.24; 95% CI, 2.76-3.81; P = 2.47 × 10-46), followed by individuals with SSD taking other antipsychotics (RR, 2.30; 95% CI, 1.95-2.72; P = 3.77 × 10-22), parents (RR, 1.44; 95% CI, 1.25-1.68; P = 1.76 × 10-6), and siblings (RR, 1.40; 95% CI, 1.21-1.63; P = 8.22 × 10-6). Polygenic risk scores for SCZ were positively associated with clozapine vs other antipsychotic use (OR, 1.41; 95% CI, 1.22-1.63; P = 2.98 × 10-6), suggesting a higher likelihood of clozapine prescriptions among individuals with higher PRS-SCZ. In this study, PRS-SCZ loading differed between groups of individuals with SSD, their relatives, and unrelated healthy controls, with patients taking clozapine at the far end of PRS-SCZ loading. Additionally, PRS-SCZ was associated with a higher likelihood of clozapine prescribing. Our findings may inform early intervention and prognostic studies of the value of using PRS-SCZ to personalize antipsychotic treatment.