Using (1+1)D quantum cellular automata for exploring collective effects in large-scale quantum neural networks.
Central to the field of quantum machine learning is the design of quantum perceptrons and neural network architectures. A key question in this regard is the impact of quantum effects on the way such models process information. Here, we establish a connection between (1+1)D quantum cellular automata, which implement a discrete nonequilibrium quantum many-body dynamics through successive applications of local quantum gates, and quantum neural networks (QNNs), which process information by feeding it through perceptrons interconnecting adjacent layers. Exploiting this link, we construct a class of QNNs that are highly structured-aiding both interpretability and helping to avoid trainability issues in machine learning tasks-yet can be connected rigorously to continuous-time Lindblad dynamics. We further analyze the universal properties of an example case, identifying a change of critical behavior when quantum effects are varied, showing their potential impact on the collective dynamical behavior underlying information processing in large-scale QNNs.


Optimizing Anti-VEGF Treatment Outcomes for Patients with Neovascular Age-Related Macular Degeneration.
The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). Despite this significant progress, gaps and challenges persist in the diagnosis of nAMD, initiation of treatment, and management of frequent intravitreal injections. Thus, nAMD remains a leading cause of blindness in the United States. To present current knowledge, evidence, and expert perspectives on anti-VEGF therapies in nAMD to support managed care professionals and providers in decision making and collaborative strategies to overcome barriers to optimize anti-VEGF treatment outcomes among nAMD patients. Three anti-VEGF therapies currently form the mainstay of treatment for nAMD, including 2 therapies approved by the FDA for treatment of nAMD (aflibercept and ranibizumab) and 1 therapy approved by the FDA for oncology indications and used off-label for treatment of nAMD (bevacizumab). In clinical trials, each of the 3 agents maintained visual acuity (VA) in approximately 90% or more of nAMD patients over 2 years. However, in long-term and real-world settings, significant gaps and challenges in diagnosis, treatment, and management pose barriers to achieving optimal outcomes for patients with nAMD. Many considerations, including individual patient characteristics, on-label versus off-label treatment, repackaging, and financial considerations, add to the complexity of nAMD decision making and management. Many factors may contribute to additional challenges leading to suboptimal long-term outcomes among nAMD patients, such as delays in diagnosis and/or treatment approval and initiation, individual patient response to different anti-VEGF therapies, lapses in physician regimentation of anti-VEGF injection and monitoring, and inadequate patient adherence to treatment and monitoring. These latter factors highlight the considerable logistical, emotional, and financial burdens of long-term, frequent intravitreal injections and the vital importance of personalized approaches to anti-VEGF treatment decision making and management for patients with nAMD. To address these challenges and reduce the number of yearly injections, studies have examined alternative dosing regimens, including extended fixed intervals, as needed, and treat-and-extend strategies in specific nAMD patient populations. New clinical evidence and insights into expert clinical practice discussed in this article can support managed care professionals in the key role they play in addressing challenges in nAMD treatment and management and optimizing patient outcomes through appropriate management of anti-VEGF treatment. PRIME Education is an independent medical education company and has been an accredited provider of continuing education for 23 years. There is no fee for this activity as it is sponsored by PRIME through an educational grant from Regeneron. All authors contributed to the writing and reviewing of the article. Wykoff reports consultancies/research grants from Alcon Laboratories, Genentech/Roche, Clearside, and Iconic Therapeutics; consultancies/honoraria, research grants, and speaker fees from Allergan and Regeneron; research grants from Allegro, Apellis, Aura, NEI, NIH, Novartis, OHR Pharmaceuticals, Ophthotech, pSivida, Roche, Santen, SciFluor, Tyrogenex; and consultancies for Alimera Sciences, Alnylam Pharmaceuticals, Bayer, DORC, ONL Therapeutics, Thrombogenics, and Valeant. Clark reports advisory board work, consultancies, research grants, and speaker fees from Genentech/Roche and Regeneron and consultancy for Bayer. Brill reports consultancies for Aries Pharma, Avella, BaroNova, Braeburn Pharmaceuticals, Cardinal Health, Endogastric Solutions, GeneNews, Halt Medical, Lumendi, Medtronic, Monteris Medical, Natera, Phosphorus, Rebiotix, Seno Medical, UCB, Vermillion, Echosens, and HAP Innovations. Brill is a shareholder in EndoChoice, GeneNews, SonarMD, and SynerZ and reports advisory board work with Nestle Health Sciences, Indivior Pharmaceuticals, Eli Lilly, Blue Earth Diagnostics, Bayer, and AstraZeneca. Nielson reports advisory board work/consultancy and research grants for Genentech/Roche; advisory board work and research grants from Regeneron; and research grants from Alcon and Ophthotech.


Drug resistance in tuberculosis: how to counter the menace?
Tuberculosis is one of the leading global health issues responsible for a significant mortality. The emergence of multidrug resistant (MDR), extensively drug resistant (XDR) and total drug resistant (TDR) strains have further hampered the disease control. Drug resistance has emerged as imperative concern resulting in genetic selection of drug resistance strains making them unresponsive to most of the drugs. In addition iron has been implicated in promoting Mycobacterium tuberculosis (MTB) replication, infection and progression to clinical disease. ideR is an essential gene in Mycobacterium tuberculosis and controls the transcription of mycobacterium by binding to promoters of ideR regulated gene in presence of iron. Iron chelators have the potential to sequester this excess iron hence hampering MTB replication and restoring host defence mechanisms. Iron chelators could be envisaged as promising candidates in iron overload associated prevention and treatment of MTB.


Is transportation a risk factor for African swine fever transmission in Australia: a review.
African swine fever (ASF) is a viral disease of the pigs that was first described in Africa during the early part of the twentieth century. The disease has periodically occurred outside of Africa, including an ongoing epidemic in Europe and Asia that started in 2007; the disease has never occurred in Australia or New Zealand. Once introduced into a country, spread can occur through direct and indirect routes of transmission. Infected feral pig populations have the potential to act as a long-term reservoir for the virus, making eradication difficult. Just before and throughout the period of clinical signs, ASF virus is shed in oronasal fluids, urine, faeces and blood. This results in contamination of the pig's environment, including flooring, equipment and vehicles. Transportation-related risk factors therefore are likely to play an important role in ASF spread, though evidence thus far has been largely anecdotal. In addition to the existing AUSVETPLAN ASF plan, efforts should be made to improve transportation biosecurity, from the time a pig leaves the farm to its destination. Collection of data that could quantify the capabilities and capacity of Australia to clean and disinfect livestock trucks would help to determine if private and/or public sector investment should be made in this area of biosecurity. No peer-reviewed research was identified that described a specific process for cleaning and disinfecting a livestock truck known to be contaminated with ASF virus, though literature suggests that transportation is an important route of transmission for moving the virus between farms and countries.


Co2+ binding to alpha-lactalbumin.
alpha-Lactalbumin possesses multiple Zn2+ binding sites, with the strongest site having an affinity constant of 5 x 10(5) M-1 [Permyakov et al. (1991), J. Protein Chem. 100, 577]. The binding of zinc at secondary sites is accompanied by destabilization of the protein structure and progressive protein aggregation. This pronounced destabilization is reflected in a shift of the thermal denaturation transition temperature by more than 40 degrees. The present work examines Co2+ binding to bovine alpha-lactalbumin, where for this analog of Zn2+, multiple binding sites were also found from spectrofluorimetric titrations. The strong site Co2+ binding constant was 1.3 x 10(6) M-1. However, in contrast to Zn2+ binding, Co2+ does not cause protein aggregation nor any significant thermal destabilization of the protein. Fluorescence energy transfer measurements between Tb3+ in the strong calcium site to Co2+ in the strong Zn2+ site gave a distance in the range of 14-18 A, which was in excellent agreement with recent crystallographic data for human alpha-lactalbumin [Ren et al. (1993), J. Biol. Chem. 268, 19292-19298]. However, the X-ray structure did not identify the additional zinc sites found from earlier solution studies, presumably due to restrictive crystal packing interactions. The results from the current work confirm that the strong cobalt (zinc) site in solution is the same zinc site elucidated by X-ray crystallography.


The latex allergen hev B 5 is an antigen with repetitive murine B-cell epitopes.
Hev b 5 is a potent latex allergen. In this study, we characterize the linear B-cell epitopes for three monoclonal antibodies (mAbs) to Hev b 5. The mAbs included 2 IgG1 (6A10, 3G3) and 1 IgG2b (6F6) isotypes. We used SPOTscan analysis with overlapping octapeptides to identify the binding regions for the antibodies and then methionine substitution analysis to further define the critical amino acids (aa) in each epitope. Site-directed mutagenesis was used to selectively eliminate the IgG binding for each epitope and single and multiple mutations were expressed as recombinant GST fusion proteins. Antibody recognition of the mutant proteins was determined by inhibition ELISA. All three mAbs recognized the same aa sequence by SPOTs analysis with slight variations, and this epitope was repeated 3 times in the Hev b 5 sequence; APETEK (63-68), PAEGEK (120-125), and PAEEEK (126-131). Sequential methionine substitution by SPOTsalogue identified K68, E122, and K131 as critical aa in each epitope to change by site-directed mutagenesis. Inhibition ELISA with the mutant proteins indicated that epitope 126-131 was the dominant epitope, but mutation of epitope 120-125 was also required to eliminate mAb reactivity to Hev b 5. The antibodies did not appear to recognize the epitope 63-68 in the recombinant fusion protein. We identified an immunodominant B-cell epitope in Hev b 5 that is repeated 3 times within the sequence, making Hev b 5 multivalent. Well-characterized monoclonals recognizing repeated epitopes would be a good choice for immunodetection of Hev b 5 in glove extracts where individual epitopes could get altered by the manufacturing process.


Horizontal visual motion modulates focal attention in left unilateral spatial neglect.
Patients with unilateral spatial neglect are impaired in directing focal attention toward the contralesional side of space. Provision of static spatial cues on the neglected side has previously been shown to help overcome this deficit. Common movement of visual stimuli may also guide the allocation of spatial attention, although such effects have not been examined in patients with unilateral spatial neglect. Eleven patients with right hemisphere damage and clinical evidence of left unilateral spatial neglect, and 11 matched, healthy controls were tested on a task of horizontal line bisection. Lines were presented on a computer display, with a neutral, static, or slowly drifting, random dot background. Under conditions of motion, background stimuli drifted either leftward or rightward, across the full width of the display, at speeds that did not elicit optokinetic nystagmus or perceptual aftereffects. Controls were accurate in all conditions, and showed minimal effects of background conditions. By contrast, patients with left unilateral spatial neglect were sensitive to leftward background motion, showing a significant leftward shift in bisection error, relative to neutral, static, and rightward moving backgrounds. There was no significant effect of rightward motion in comparison with the neutral and static conditions. The extent to which patients were susceptible to the effects of background motion was not related to severity of unilateral spatial neglect, as measured by clinical tests. The benefits of leftward motion may reflect activity of preserved motion processing mechanisms, which provide input to an otherwise dysfunctional attentional network. The use of visual motion to assist in contralesionally guiding focal attention may be useful in the rehabilitation of unilateral spatial neglect.


High-Stakes Testing Case Study: A Latent Variable Approach for Assessing Measurement and Prediction Invariance.
The existence of differences in prediction systems involving test scores across demographic groups continues to be a thorny and unresolved scientific, professional, and societal concern. Our case study uses a two-stage least squares (2SLS) estimator to jointly assess measurement invariance and prediction invariance in high-stakes testing. So, we examined differences across groups based on latent as opposed to observed scores with data for 176 colleges and universities from The College Board. Results showed that evidence regarding measurement invariance was rejected for the SAT mathematics (SAT-M) subtest at the 0.01 level for 74.5% and 29.9% of cohorts for Black versus White and Hispanic versus White comparisons, respectively. Also, on average, Black students with the same standing on a common factor had observed SAT-M scores that were nearly a third of a standard deviation lower than for comparable Whites. We also found evidence that group differences in SAT-M measurement intercepts may partly explain the well-known finding of observed differences in prediction intercepts. Additionally, results provided evidence that nearly a quarter of the statistically significant observed intercept differences were not statistically significant at the 0.05 level once predictor measurement error was accounted for using the 2SLS procedure. Our joint measurement and prediction invariance approach based on latent scores opens the door to a new high-stakes testing research agenda whose goal is to not simply assess whether observed group-based differences exist and the size and direction of such differences. Rather, the goal of this research agenda is to assess the causal chain starting with underlying theoretical mechanisms (e.g., contextual factors, differences in latent predictor scores) that affect the size and direction of any observed differences.


Field trial evidence of non-transgenic and transgenic Bt. rice genotypes in north of Iran.
Field-testing genetically modified crops provides scientists with an opportunity to collect information on environmental interactions and agronomic performance, which is critical to a full environmental safety assessment as required by regulatory authorities. As a result, the goal of this research was field trial of transgenic and conventional rice genotypes. The experiment was carried out in a randomized complete blocks design (RCBD) with four replications and seven genotypes in three isolated regions under the biosafety standard protocol in north of Iran in 2016. In this study, four transgenic lines with an active cry1Ab gene in the vegetative stage and three conventional genotypes (control) as treatment were assessed. The findings demonstrated that in all three regions, transgenic lines derived from Khazar cultivar, were similar to their parent(s) in terms of growth phenology, agronomical traits, grain amylose content, gel consistency, and gelatinization temperature. In all the three regions, the highest number of panicle per m2, number of filled spikelet per panicle, and filled spikelet percentage per panicle were obtained for transgenic lines. Khazar cultivar compared to the transgenic lines showed lower paddy yield. In all the three regions, transgenic lines had lower yield loss than their non-transgenic parent. The lowest number of white heads belonged to transgenic Tarom Molaii and transgenic lines. The most positive direct effect on paddy yield was related to the number of filled spikelet per panicle. Thus, this can be a good trait to achieve higher yield derived from reducing the negative indirect effect of dead heart and white heads. It can be concluded that by producing transgenic rice, which is resistant to stem borer with an active promoter in the reproductive stage, farmers can reduce significant part of yield loss resulting from dead heart and white heads directly correlating with the number of filled spikelet per panicle and paddy yield.


Serological evidence of herpesvirus infection in gibbons.
Herpesviruses are not only infectious agents of worldwide distribution in humans, but have also been demonstrated in various non-human primates as well. Seventy-eight gibbons were subjected to serological tests by ELISA for herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). The prevalence of IgG antibodies against HSV-1, HSV-2, EBV and CMV was 28.2%, 28.2%, 14.1% and 17.9%, respectively. Antigenic cross-reactivity is expected to exist between the human herpesviruses and gibbon herpesviruses. Gibbons have antibodies to human herpesviruses that may reflect zoonotic infection with human herpesviruses or infection with indigenous gibbon herpesviruses. Therefore, it is difficult to draw concrete conclusions from serological studies alone. Identification should be based on further isolation and molecular characterization of viruses from seropositive animals.


Non-canonical Hedgehog Signaling Pathway in Cancer: Activation of GLI Transcription Factors Beyond Smoothened.
The Hedgehog-GLI (HH-GLI) pathway is a highly conserved signaling that plays a critical role in controlling cell specification, cell-cell interaction and tissue patterning during embryonic development. Canonical activation of HH-GLI signaling occurs through binding of HH ligands to the twelve-pass transmembrane receptor Patched 1 (PTCH1), which derepresses the seven-pass transmembrane G protein-coupled receptor Smoothened (SMO). Thus, active SMO initiates a complex intracellular cascade that leads to the activation of the three GLI transcription factors, the final effectors of the HH-GLI pathway. Aberrant activation of this signaling has been implicated in a wide variety of tumors, such as those of the brain, skin, breast, gastrointestinal, lung, pancreas, prostate and ovary. In several of these cases, activation of HH-GLI signaling is mediated by overproduction of HH ligands (e.g., prostate cancer), loss-of-function mutations in PTCH1 or gain-of-function mutations in SMO, which occur in the majority of basal cell carcinoma (BCC), SHH-subtype medulloblastoma and rhabdomyosarcoma. Besides the classical canonical ligand-PTCH1-SMO route, mounting evidence points toward additional, non-canonical ways of GLI activation in cancer. By non-canonical we refer to all those mechanisms of activation of the GLI transcription factors occurring independently of SMO. Often, in a given cancer type canonical and non-canonical activation of HH-GLI signaling co-exist, and in some cancer types, more than one mechanism of non-canonical activation may occur. Tumors harboring non-canonical HH-GLI signaling are less sensitive to SMO inhibition, posing a threat for therapeutic efficacy of these antagonists. Here we will review the most recent findings on the involvement of alternative signaling pathways in inducing GLI activity in cancer and stem cells. We will also discuss the rationale of targeting these oncogenic pathways in combination with HH-GLI inhibitors as a promising anti-cancer therapies.


Clinical outcome of peripheral nerve decompression in diabetic and nondiabetic peripheral neuropathy.
Surgical decompression of peripheral nerves in patients with diabetes was reported to restore sensation and improve function. In this study, a retrospective review of 12 diabetic and 20 nondiabetic patients with lower-extremity peripheral neuropathy who underwent surgical decompression was performed. Clinical evaluation by Tinel test, muscle power examination, and 2-point discrimination were performed preoperatively, at 6 months, and between 9 and 15 months postdecompression. Clinical outcomes were classified into excellent, good, or fair based on improvement in symptoms and return of function. Thirty-two patients underwent 36 surgeries, in which 99 lower-extremity nerves were decompressed. There was a statistically significant improvement in muscle function (P < 0.001) and 2-point discrimination for the small toe (P = 0.008) and big toe (P = 0.038). At a mean of 7.7 months, 90% of patients showed significant improvement in pain and function. It is concluded that surgical decompression was associated with significant improvement in clinical outcome in patients with diabetic and idiopathic neuropathy with evidence of superimposed compression.


Vibration-mediated energy transport in bacterial reaction center: Simulation study.
Exciton energy relaxation in a bacterial Reaction Center (bRC) pigment-protein aggregate presumably involves emission of high energy vibrational quanta to cover wide energy gaps between excitons. Here, we assess this hypothesis utilizing vibronic two-particle theory in modeling of the excitation relaxation process in bRC. Specific high frequency molecular vibrational modes are included explicitly one at a time in order to check which high frequency vibrations are involved in the excitation relaxation process. The low frequency bath modes are treated perturbatively within Redfield relaxation theory. The analysis of the population relaxation rate data indicates energy flow pathways in bRC and suggests that specific vibrations may be responsible for the excitation relaxation process.


Effect of a selective endothelin receptor A blocker on cardiovascular remodeling in uninephrectomized spontaneously hypertensive rats of the stroke-prone strain.
The role of endothelin (ET) in cardiovascular remodeling was investigated by treating uninephrectomized spontaneously hypertensive rats of the stroke-prone strain (UNX-SHRsp) on normal- or high (3%)-salt diet with the selective ET(A) receptor blocker LU 135252. SHRsp on normal or high salt were sham-operated (n = 10/11) or UNX; UNX received no treatment (n = 10/15) or 100 mg/kg body weight LU 135252 (n = 10/10). Systolic blood pressure (BP) was measured weekly. After perfusion fixation the heart and the aorta were analyzed using quantitative morphological and stereological techniques. No effect was seen in normal-salt groups. In high-salt animals UNX caused left ventricular (LV) hypertrophy which was prevented by LU 135252 (p < 0.001). LU 135252 only lowered BP during the last 2 weeks of the 12-week experiment. UNX showed hypertrophic remodeling of intramyocardial arterioles. Treatment with LU 135252 caused lower wall:lumen ratio and wall thickness of LV intramyocardial arterioles (p < 0.01). In the descending thoracic aorta UNX caused thickening of the media. The media area and the wall:lumen ratio were lower in UNX + LU 135252 as compared to untreated UNX (p < 0.01 and p < 0.05, respectively). In SHRsp UNX causes hypertrophic cardiovascular remodeling only in the presence of salt loading. These effects are largely BP-independent and prevented by ET(A) receptor blockade.


The timing deficit hypothesis of dyslexia and its implications for Hebrew reading.
Vast amounts of neuropsychological evidence have been collected in recent years in support of the hypothesis that developmental dyslexia is caused not only by phonological deficits, but also by timing deficits that affect all senses (e.g., Tallal, Miller, & Fitch, 1995; Stein & Walsh, 1997). In parallel, recent developments in the study of Hebrew reading place heavy emphasis on root awareness in the mental lexicon and early root extraction in the process of word identification (e.g., Frost, Forster, & Deutch, 1997). The present study creates a link between the timing hypothesis and the special demands of Hebrew reading. The performance of dyslexics and normally reading children is compared on tasks requiring visual extraction of trigrams that approximates extracting roots out of Hebrew words. Partial findings show that dyslexics take longer and make more errors while performing trigram extractions on all levels examined, and that sequentiality in the task affects dyslexics and skilled readers in different ways.


[MINIMALLY INVASIVE PARATHYROIDECTOMY (MIP) UNDER LOCAL ANESTHESIA FOR TREATMENT OF PRIMARY HYPERPARATHYROIDISM (PHPT) CAUSED BY A SINGLE ADENOMA].
Minimally Invasive Parathyroidectomy (MIP) has become the treatment of choice of Primary Hyperparathyroidism (PHPT) caused by an adenoma. In the present investigation we describe our experience with MIP performed under local anesthesia. MIP was performed on 454 of 496 patients (91.5%) with PHPT. In 170 patients (37.4%), MIP was accomplished under local anesthesia. This procedure was elected when the medical condition prohibited general anesthesia, or in accordance with the patient's request. MIP under local anesthesia for PHPT was accomplished in 162 (95.3%) of the patients. In 8 patients the procedure was converted to general anesthesia, while the adenoma was located in 5 of these patients. In 3 patients (1.8%) the adenoma was not located even under general anesthesia and they awaited further investigations. Fifteen patients (8.2%) developed temporary hoarseness, and 20 patients (11.8%) developed temporary hypocalcemia postoperatively. MIP under local anesthesia for PHPT caused by an adenoma is feasible and safe, with a success rate of 95.3% similar to MIP performed under general anesthesia. MIP under local anesthesia has not yet become a prevalent procedure worldwide, as well as in our country. The results of the present study support our conclusions for utilizing this method under local anesthesia.


The challenges and conflictsof facilitating learning in practice: the experiences of two clinical nurse educators.
This is a descriptive paper discussing the experiences of two clinical educators in practice.It highlights some of the practice issues around accountability, advocacy and roleconflicts in clinical teaching roles. The issue of training nurses fit for pr actice giventhe recommendations of Fitness for Practice (UKCC 1999) and Making a Difference (Department of Health 1999) is discussed within the context of the reality of the clinical environment. The number of learners in the clinical area has increased in the last fewyears, and will continue to do so with the increase in nurses promised by t he NHS Planand new initiatives to attract nurses back into the profession. As a result of this the clinical environment, already stretched with service demands, requires additional support to facilitate the development of learners. Recommendations are m ade for the future of generic practice facilitative roles in the light of the current debate to get nurse educators back into practice.


Grain growth associates mechanical properties in nano-hydroxyapatite bone scaffolds.
The sintering behaviors and resulting mechanical properties of nano-hydroxyapatite (HAP) are studied with a self-developed selective laser sintering (SLS) system. All sintered specimens are fabricated in the sintering range of pure nano-HAP (laser energy densities in 1.6-4.0 J/mm2). The grain characteristics and mechanical properties are tested with scanning electron microscopy (SEM) and Vickers hardness tester respectively after the sintered specimens are polished with diamond paste and etched with 0.5% hydrofluoric acid (HF). The studies reveal improvements in the microstructural and mechanical properties of the sintered specimens with increasing laser energy density. However, abnormal grain growth severely decreases the mechanical properties when the laser energy density passes a certain critical point (3.4 J/mm2). The nano-grain ceramic with the Vickers hardness value of 4.54 GPa is obtained at the critical point. It provides guidance to fabricate nano-grain bone scaffold with pure nano-HAP powder by SLS.


Sequence variability of bovine leukemia virus env gene and its relevance to the structure and antigenicity of the glycoproteins.
The nucleotide sequences of the env genes of seven bovine leukemia viruses and the encoded peptide sequence were compared, with the objective of (i) determining the genetic distance separating bovine leukemia virus isolates from different geographical regions, (ii) identifying particular amino acids that contribute to the sequential and conformational epitopes, and (iii) relating such epitopes to their projected position in a three-dimensional model of the structure of the gp51 surface glycoprotein. Two bovine leukemia virus subgroups were clearly identified, a Japanese-American subgroup represented by strains lambda BLV-1, VdM, and FLK-BLV and a European subgroup by strains T15-2, LB285, and LB59. It was possible to identify amino acids that were important in determining three of the epitopes (F, G, and H) recognized by neutralizing monoclonal and polyclonal antibodies. On the model, these epitopes were adjacent and located on the exposed region of the molecule. Amino acid sequences contributing to a fourth cryptic epitope were identified; as predicted by the model, they lay on the opposite side to the neutralizable epitopes in a region involved in glycoprotein subunit association. The fact that this region is not normally exposed on the virion surface provides further evidence for the validity of the model.


The Spanish-Version of the Subjective Vitality Scale: Psychometric Properties and Evidence of Validity.
The Subjective Vitality Scale (SVS) assess the subjective experience of being full of energy and alive, a clinically relevant outcome measure of positive psychological well-being. The purpose of this paper was to translate the 7-item SVS into Spanish and examine its psychometric properties. In Study 1 (n = 790 adolescents) and Study 2 (n = 130 athletes) reliability and exploratory factor analysis (EFA) were carried out. In Study 1 and Study 3 (n = 197 dancers) evidence of validity of inferences based on SVS scores estimating relationships with other variables (life satisfaction, global self-esteem and emotional and physical exhaustion) was obtained. In Study 2 invariance across time was tested. Finally in Study 3, the factorial structure was cross-validated using confirmatory factor analysis (CFA). Results of EFA showed a one-factor solution. CFA also supported a unidimensional factor structure for the Spanish 6-item SVS (RMSEA = .050 (90% CI = .00, .080); NNFI = .993; CFI = .996). Reliability analysis indicated a strong internal consistency in all study samples (α ranged from .82 to .89). Further, results from multi-sample analysis supported the replicability of SVS factor structure across time. Finally, the SVS scores showed the expected correlations patterns (all them significant, p < .01) with the measured outcomes. In conclusion, the Spanish version of the SVS demonstrated adequate psychometric properties, indicating that the scale can be confidently used to measure the experience of possessing energy and aliveness; furthermore, differences across time can be meaningfully carried out.


Differential tissue and flight developmental expression of glycerol-3-phosphate dehydrogenase isozymes in the Chagas disease vector Triatoma infestans.
Glycerol-3-phosphate dehydrogenase (GPDH) isozymes are differentially expressed among tissues and during flight development. GPDH-1 is involved in the flight-muscle metabolism and GPDH-2 provides precursors for lipid biosynthesis in many tissues. We have isolated and characterized from Triatoma infestans, a Chagas disease vector, two cDNAs encoding for GPDH-1 and GPDH-2 isozymes. The inferred amino acid sequences showed high identity with other GPDH sequences from flying insects. A GPDH-2 transcript was found in fifth instar nymphs, thoracic muscles, adult gonads, and fat bodies. Both isozymes are present in 30-day-old adult thoracic muscle transcripts, and the pattern of expression differs between sexes. The expression of GPDH-1 begins earlier in females, and GPDH-2 is expressed more abundantly in female adult thoracic muscles than in those from males. This finding is consistent with those of other investigators who showed a higher flight initiation probability in T. infestans females than in males.


Effect of insulin sensitizer therapy on atherothrombotic and inflammatory profiles associated with insulin resistance.
To determine whether targeted pharmacological improvement of insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory cardiovascular disease (CVD) biomarkers in individuals with insulin resistance. Study 1 was a cross-sectional study of Asian Indians with and without diabetes mellitus and Northern European Americans without diabetes (n=14 each) conducted between December 11, 2003, and July 14, 2006. Study 2 was a secondary analysis of a double-blind randomized controlled study conducted between August 19, 2005, and August 24, 2010, that included 25 individuals with untreated diabetes or impaired fasting glucose who were randomized to receive placebo (n=13) or a combination of metformin, 1000 mg twice daily, and pioglitazone, 45 mg daily (n=12), for 3 months. In both studies, measurements of insulin sensitivity (euglycemic-hyperinsulinemic clamp) and plasma inflammatory and thrombotic factor concentrations were obtained on enrollment (studies 1 and 2) and after intervention (study 2). Study 1 demonstrated significant correlations between insulin sensitivity and plasma adiponectin, high-density lipoprotein cholesterol, plasminogen activator inhibitor 1, interleukin 6, tumor necrosis factor α, and triglycerides. Insulin sensitizer therapy significantly improved insulin sensitivity, inflammatory cytokines except interleukin 6, and thrombotic factors except fibrinogen, without concomitant changes in weight, blood pressure, or body composition. Insulin sensitizer therapy ameliorates inflammatory and thrombotic factors implicated in developing CVD. Interventions to improve insulin sensitivity may thus be considered as therapeutic options to reduce CVD burden in insulin-resistant states, although further research is needed to determine long-term effects on morbidity and mortality.


Lyell's Syndrome and Antimalarials: A Case Report and Clinical Review.
Toxic epidermal necrolysis (TEN) or Lyell's syndrome is a rare, however, life-threatening mucocutaneous disorder with an epidermal detachment of a total body surface area (TBSA) of >30%. It is triggered by an idiosyncratic immune-allergic reaction to a drug, with many possible drugs implicated. Treatment success relies on early diagnosis and withdrawal of suspected/causative drug(s) and supportive care. Clinical evidence for specific therapies is still sparse. It is described a case of Lyell syndrome by sulfonamides for chemoprophylaxis of malaria. The patient presented with an extensive, rapidly evolving skin detachment, which progressed, despite supportive therapy, involving about 80% of TBSA. This led us to initiate a course of immunoglobulin with good clinical response. The aim of this work is to provide a discussion of the case and simultaneously make a practical literature review of TEN.


[Ultrafiltration with different membranes and respiratory function after cardiopulmonary bypass].
To investigate the protective effect of ultrafiltration on pulmonary function after cardiopulmonary bypass (CPB) by comparing two different membranes used in the ultrafiltration. Thirty patients undergoing cardiac surgery with CPB were randomly divided into adsorption group (n=15) and control group (n=15), and in the former group, AN69 membrane was used for ultra-infiltration, with polysulfone (PS) membrane adopted in the control group during CPB. Plateau airway pressure (P(Plateau)), peak airway pressure (P(Peak)), static pulmonary compliance (Cst), dynamic pulmonary compliance (Cdyn) and respiratory index (RI) were measured or calculated before and 5, 60, 120, and 240 min after CPB in each group respectively. During the period of 5 to 240 min after CPB, the increase in P(Plateau), P(Peak), RI and decrease in Cst and Cdyn were much more obvious and lasted for longer time in the adsorption group than in the control group (P<0.05). No operative death or hemoglobinuria occurred in these cases. Ultrafiltration with AN69 membrane more effectively reduces CPB-induced lung injury and improves the postoperative respiratory function than with PS membrane.


Structural basis of the day-night transition in a bacterial circadian clock.
Circadian clocks are ubiquitous timing systems that induce rhythms of biological activities in synchrony with night and day. In cyanobacteria, timing is generated by a posttranslational clock consisting of KaiA, KaiB, and KaiC proteins and a set of output signaling proteins, SasA and CikA, which transduce this rhythm to control gene expression. Here, we describe crystal and nuclear magnetic resonance structures of KaiB-KaiC,KaiA-KaiB-KaiC, and CikA-KaiB complexes. They reveal how the metamorphic properties of KaiB, a protein that adopts two distinct folds, and the post-adenosine triphosphate hydrolysis state of KaiC create a hub around which nighttime signaling events revolve, including inactivation of KaiA and reciprocal regulation of the mutually antagonistic signaling proteins, SasA and CikA.


Health Insurance Coverage among Young Adult Survivors of Pediatric Heart Transplantation.
To describe the change in health insurance after heart transplantation among adolescents, and characterize the implications of this change for long-term transplant outcomes. Patients age 15-18 years receiving first-time heart transplantation between 1999 and 2011 were identified in the United Network for Organ Sharing registry and included in the analysis if they survived at least 5 years. The primary exposure was change or continuity of health insurance coverage between the time of transplant and the 5-year follow-up. Cox proportional hazards models were used to determine the association between insurance status change and long-term (>5 years) patient and graft survival. The analysis included 366 patients (age 16 ± 1 years at transplant), of whom 205 (56%) had continuous private insurance; 96 (26%) had continuous public insurance; and 65 (18%) had a change in insurance status. In stepwise multivariable Cox regression, change in insurance status was associated with greater mortality hazard, compared with continuous private insurance (hazard ratio = 1.9; 95% CI: 1.1, 3.2; P = .016), whereas long-term patient and graft survival did not differ between patients with continuous public and continuous private insurance. Continuity of insurance coverage is associated with improved long-term clinical outcomes among adolescent heart transplant recipients who survive into adulthood.


Transmission-type X-ray linear polarizer with perfect crystals.
Even though conventional X-ray polarizers with multiple-reflection channel-cut structures perform well, they suffer from the disadvantage that the polarized beam is non-stationary as the energy is scanned. In this paper the possibility of using a thin Bragg reflector as a polarizing filter is investigated, so that the transmitted beam (rather than the Bragg-reflected beam) is used. Consequently, the position and direction of the transmitted beam are unchanged as the energy is changed, or even when the polarization direction to be filtered out is changed. Theoretical considerations as well as experimental results on the performance characteristics of the proposed transmission-type X-ray linear polarizer are presented. A polarization ratio, defined as I(H)/I(V), higher than 10(5) was obtained.


Simulated sea surface temperature and heat fluxes in different climates of the Baltic Sea.
The physical state of the Baltic Sea in possible future climates is approached by numerical model experiments with a regional coupled ocean-atmosphere model driven by different global simulations. Scenarios and recent climate simulations are compared to estimate changes. The sea surface is clearly warmer by 2.9 degrees C in the ensemble mean. The horizontal pattern of average annual mean warming can largely be explained in terms of ice-cover reduction. The transfer of heat from the atmosphere to the Baltic Sea shows a changed seasonal cycle: a reduced heat loss in fall, increased heat uptake in spring, and reduced heat uptake in summer. The interannual variability of surface temperature is generally increased. This is associated with a smoothed frequency distribution in northern basins. The overall heat budget shows increased solar radiation to the sea surface, which is balanced by changes of the other heat flux components.


Binding of murine immunoglobulin to human tissues after immunotherapy with anticolorectal carcinoma monoclonal antibody.
An anticolorectal carcinoma antibody, 17-IA, that is of gamma 2a isotype and has been used in previous immunotherapy trials, binds to an antigen on most human colon tumors. This antigen is destroyed by the fixative and embedding procedures employed for routine histologic evaluation of tissues. It can be demonstrated by the avidin/biotin-labelled peroxidase complex (ABC) immunoperoxidase technique on briefly fixed, frozen sections of fresh human tissues. With this assay technique, the antibody is found to bind in vitro to both human colonic carcinoma and normal gastrointestinal epithelia. Tissues removed from patients having received the 17-IA antibody intravenously in an immunotherapy trial show bound antibody 1-2 after administration. This is no longer evident 3 weeks later though the antigen is present on the cell surface and is still capable of binding antibody in vitro.


Management of asthma in the elderly patient.
A significant number of older asthmatics, more often than in previous ages, have poorly controlled asthma, leading to increased morbidity and mortality. On the other hand, current guidelines suggest that most asthmatics can obtain achievement and maintenance of disease control and do not include sections specific to the management of asthma in the elderly so that it is more evident the contrast between poor control of asthma in the elderly and the lack of specific guidance from guidelines on asthma management in older asthmatics. Inhaled corticosteroids are the cornerstone for older asthmatics, eventually with add-on inhaled long-acting beta-agonists; inhaled short acting beta-agonists can be used as rescue medications. Triggers exacerbating asthma are similar for all ages, but inhaled viruses and drug interactions have greater clinical significance in the elderly. Older asthmatics have an increased likelihood of comorbidities and polypharmacy, with possible worsening of asthma control and reduced treatment adherence. Physicians and older asthmatics probably either do not perceive or accept a poor asthma control. We conclude that specific instruments addressed to evaluate asthma control in the elderly with concomitant comorbidities and measurements for improving self-management and adherence could assure better disease control in older asthmatics.


Determining the quality of the medical educational environment at an Irish medical school using the DREEM inventory.
A Cross-Sectional study using the already validated Dundee Ready Educational Environment (DREEM) questionnaire was used to assess the Undergraduate Medical Educational Environment in an Irish Medical School during the first semester 2004/2005. 389 of 476 students (82%) completed the questionnaire. The mean total score was 130 out of a maximum of 200 (65%) indicating relative satisfaction with the environment but with room for improvement. There were no individual areas of excellence identified. The following two areas were identified as being problematic (a) lack of a support system for stressed students (b) over emphasis on memorization of facts. These areas were perceived by clinical students to be greater when compared to pre-clinical students. Female students appeared happier in their environment but male students were more confident about passing exams. Non-Irish students had a lower overall score when compared to Irish students. The DREEM is a useful tool to assess the overall teaching environment and highlight areas of weakness. Use of DREEM as a monitoring tool would be useful to re-evaluate the environment following appropriate intervention.


Cerebral vascular occlusion; angiographic diagnosis.
Cerebral arterial occlusion is a fairly frequent condition. We have diagnosed nine cases by cerebroangiography in the past two years, and there are many patients not given this special examination.Precise diagnosis has become more important as advances in therapy make prognosis more hopeful. The symptoms are various according to the location and degree of occlusion and the amount of collateral circulation.Angiographic diagnosis is not difficult, but repeated demonstration of the block should be insisted on. This is best done with multiple exposures after a single injection of contrast medium. We use 7 cc. of 50 per cent Hypaque(R) and one exposure per second through the arterial, capillary and venous phases. The films should cover the entire head and neck lest an occlusion in the common carotid be overlooked. We have found the Schonander biplane apparatus very satisfactory, using films 14 inches square and exposing them in anteroposterior and lateral projections simultaneously.


The role of sleep in neuromuscular disorders.
Sleep represents a major frontier both in clinical myology and as a new possibility for delivering treatment to neuromuscular patients since various neuromuscular cases present a variable degree of disordered sleep and such conditions should be diagnosed and prevented, i.e., sleep apnea and hypoxemia. These sleep disorders are present in dystrophinopathies and in various types of limb-girdle muscular dystrophies (LGMD). Excessive daytime sleepiness (EDS) is found in patients affected by spastic paraparesis or cerebellar ataxia but is rather common in both myotonic dystrophy type 1 and 2, and the correction of sleep disorders is therefore important to improve their daily quality of life (QoL) and consequent daily functioning. Other types of sleep dysfunction such as insomnia, a reduction in rapid eye movement (REM) sleep, loss of normal REM, or sleep-disordered breathing are found in other disorders including myasthenia, ataxias, spastic paraparesis, Charcot-Marie-Tooth disease, and neurogenic disorders, including polyneuropathies, and need appropriate treatment. Research done on this topic aims to incorporate a variety of nuances in metabolic disorders such as those in late-onset Pompe disease and are such as those in late-onset Pompe disease who are susceptible to enzyme replacement therapy (ERT). The overarching goal is to explore both the diagnosis and methodology of sleep-related problems in both genetic and acquired neuromuscular disorders. We also review the type of available treatment opportunities utilized to improve neuromuscular patients' QoL.


Comparison of technetium-99m methoxyisobutylisonitrile scintimammography and ultrasonography in the diagnosis of breast cancer in patients with mammographically dense breast.
The main purpose of this study was to compare the utility of technetium-99m methoxyisobutylisonitrile (Tc-99m sestamibi) scintimammography with that of ultrasonography for diagnosis of breast cancer in 32 female patients with indeterminate mammographic probability of malignancy because of mammographically dense breast. All breast masses were removed and histopathological diagnosis was obtained in all cases. The results showed 20 of 24 cases of breast carcinoma detected on Tc-99m sestamibi scintimammography. Only one out of eight patients with benign breast lesion had abnormal scintimammographic finding. Ultrasonography diagnosed 22 of the 24 cases of breast carcinoma. However, five out of eight patients with benign breast lesion had positive ultrasonographic findings. In differentiating malignant and benign breast tumors in mammographically dense breast, the diagnostic sensitivities were 83 and 92%, specificities were 88 and 38%, and accuracies were 84 and 78% for Tc-99m sestamibi scintimammography and ultrasonography, respectively. Ultrasonography showed a nonsignificantly higher sensitivity (p < 0.05), but lower specificity, with more false-positive diagnoses made on ultrasonography. Due to its higher sensitivity, ultrasonography is more suitable for screening breast masses. However, Tc-99m sestamibi scintimammography exhibited significantly higher specificity (p < 0.05) and accuracy in detecting malignant breast tumors in the current study. We conclude that Tc-99m sestamibi scintimammography is a safe and useful diagnostic method for detection of breast cancer in patients with nondiagnostic mammogram because of mammographically dense breast.


The exploration of potassium ferrate(VI) as a disinfectant/coagulant in water and wastewater treatment.
This paper aims to explore potassium ferrate(VI) (K2FeO4) as an alternative water treatment chemical for both drinking water and wastewater treatment. The performance of potassium ferrate(VI) was evaluated in comparison with that of sodium hypochlorite (NaOCl) and that of NaOCl plus ferric sulphate (FS) or alum (AS). The dosages of ferrate(VI), NaOCl and FS/AS and sample pH values were varied in order to investigate the effects of these factors on the treatment performance. The study demonstrates that in drinking water treatment, ferrate(VI) can remove 10-20% more UV(254)-abs and DOC than FS for the same dose compared for natural pH range (6 and 8). The THMFP was reduced to less than 100 microg l(-1) by ferrate(VI) at a low dose. In addition to this, ferrate(VI) can achieve the disinfection targets (>6 log10 inactivation of Escherichia coliform (E. coli)) at a very low dose (6 mg l(-1) as Fe) and over wide working pH in comparison with chlorination (10 mg l(-1) as Cl2) plus coagulation (FS, 4 mg l(-1) as Fe). In wastewater treatment, ferrate(VI) can reduce 30% more COD, and kill 3log10 more bacteria compared to AS and FS at a similar or even smaller dose. Also, potassium ferrate(VI) can produce less sludge volume and remove more pollutants, which could make sludge treatment easier.


[Duodenal hematoma in acute alcoholic hepatitis].
Hematoma of the duodenal wall usually occurs after traumata. A case report is given of such a patient who suffered in addition from acute alcoholic hepatitis. The hematoma had led to complete obstruction of the duodenum and compression of the common bile duct. After endoscopy surgery was done and the hematoma removed.


Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation.
Microglia, the resident immune cells in the brain, are the first responders to inflammation or injury in the central nervous system. Recent research has revealed microglia to be dynamic, capable of assuming both pro-inflammatory and anti-inflammatory phenotypes. Both M1 (pro-inflammatory) and M2 (pro-reparative) phenotypes play an important role in neuroinflammatory conditions such as perinatal brain injury, and exhibit differing functions in response to certain environmental stimuli. The modulation of microglial activation has been noted to confer neuroprotection thus suggesting microglia may have therapeutic potential in brain injury. However, more research is required to better understand the role of microglia in disease, and this protocol facilitates that. The protocol described below combines a density gradient centrifugation process to reduce cellular debris, with magnetic separation, producing a highly pure sample of primary microglial cells that can be used for in vitro experimentation, without the need for 2-3 weeks culturing. Additionally, the characterization steps yield robust functional data about microglia, aiding studies to better our understanding of the polarization and priming of these cells, which has strong implications in the field of regenerative medicine.


Energy transfer dynamics and thermalization of two oscillators interacting via chaos.
We consider the classical dynamics of two particles moving in harmonic potential wells and interacting with the same external environment HE, consisting of N noninteracting chaotic systems. The parameters are set so that when either particle is separately placed in contact with the environment, a dissipative behavior is observed. When both particles are simultaneously in contact with HE an indirect coupling between them is observed only if the particles are in near-resonance. We study the equilibrium properties of the system considering ensemble averages for the case N=1 and single trajectory dynamics for N large. In both cases, the particles and the environment reach an equilibrium configuration at long times, but only for large N can a temperature be assigned to the system.


Factors influencing postoperative mortality one year after surgery for hip fracture in Chinese elderly population.
Disability and death following hip fracture is becoming more common as the population ages. Previous reports have focused on the selection of internal fixation methods and the analysis of the perioperative therapeutic results in the Chinese population. Few studies have focused on factors influencing medium and long term survival after surgery for hip fracture. We conducted a retrospective study on the factors influencing survival one year after hip fracture surgery in our elderly Chinese population to provide a reference for improved treatment and to enhance efficacy. Records from patients undergoing treatment for hip fracture at our hospital from October 2009 through June 2011 were retrospectively reviewed. Through telephone follow-up, the health condition of each patient was surveyed, and the 1-year postoperative mortality was analyzed. The patients' age, gender, fracture type, pre-injury health condition, mobility, complications, surgical timing, surgical types, methods of anesthesia, and postoperative complications were analyzed. Univariate and multivariate regression analysis was performed on relevant influencing factors. A total of 184 patients had complete data and were followed-up for 12-23 months (average, 16.5 months). There were 30 deaths (16.3%) at one-year. Univariate analysis revealed that factors such as age, gender, fracture-type, number of co-existing diseases, complications such as chronic obstructive pulmonary disease or sequelae of stroke, American society of Anesthesiology (ASA) scores, anesthesia methods, pre-injury activity, and post-operative complications were significantly different between survival versus mortality groups (P < 0.05). Multivariate regression analysis revealed that age, ASA score, pre-injury mobility and combined chronic obstructive pulmonary disease were independent risk factors for death. Full consideration of medium-/long-term risk factors in the treatment of hip fracture in the elderly, selection of appropriate anesthesia and treatment methods, and improved pre-surgical health conditions would reduce postoperative mortality and enhance surgical efficacy.


Minimum five-year follow-up results of single-radius, high-flex posterior-stabilized TKA.
We studied 75 primary total knee arthroplasties (TKAs) performed using a single-radius, high-flex posterior-stabilized insert design with a minimum 5-year follow-up to document its implant specific complications and clinical results. Nonprogressive osteolysis was observed at zone 4 of the femoral component in 6 knees (8%) and at zone 1 of the tibial component in 6 knees (8%). However, no complications associated with high flexion designs, such as early aseptic loosening, were observed.Preoperatively, mean Knee Society Knee Score and Knee Society Function Score were 55.1 and 45.5, respectively (range, 10-83 and 20-80, respectively). At last follow-up, mean Knee Society Knee Score and Knee Society Function Score improved to 94.9 and 85.9, respectively (range, 70-100 [P<.0001] and 45-100 [P<.0001], respectively). Mean maximal flexion was 122.1 degrees (range, 90 degrees -140 degrees ) and mean range of motion (ROM) was 110.3 degrees (range, 80 degrees -135 degrees ) preoperatively, and these values improved to 128.9 degrees (range, 110 degrees -150 degrees [P<.0001]) and 127.8 degrees (range, 110 degrees -150 degrees [P<.0001]), respectively, at last follow-up. Preoperative ROM was found to be the only factor significantly correlated with postoperative ROM at last follow-up by univariate (P=.0020) and multivariate analysis (P<.0067). Accordingly, clinical results were comparable to previous reports of high-flex implants without implant-specific complications.


Effect of comprehensive nursing on patients with chalazion undergoing intense pulsed light and its influence on postoperative recurrence.
To explore the effect of comprehensive nursing on patients with chalazion undergoing intense pulsed light (IPL) and its influence on postoperative recurrence. In this retrospective study, the medical records of 72 patients who received IPL treatment for chalazion from October 2021 to February 2023 were analyzed. Among them, 33 patients treated with comprehensive nursing were included in the research group (RG) and 39 patients treated with routine nursing were included in the control group (CG). The treatment effect, complications and recurrence were compared between the two groups. The psychological state of patients and their satisfaction about the nursing were recorded and compared between the two groups. After nursing, the severity of unhealthy emotion in the RG was obviously better than that in the CG (P=0.033); The overall response rate in the RG was obviously higher than that in the CG (P=0.035). The nursing satisfaction in RG was significantly higher than that in the CG (P=0.035). The incidence of complications in RG was obviously lower than that in the CG (P=0.045). Comprehensive nursing is effective in improving the therapeutic effect and reducing the postoperative recurrence rate for patients with chalazion.


Telomere length: biological marker of cellular vitality, aging, and health-disease process.
The aging process occurs due to the decline of vital physiological functions and adaptability of the body, being influenced by genetics and lifestyle. With advances in genetics, biological aging can be calculated by telomere length. Telomeres are regions at the ends of chromosomes that play a role in the maintenance and integrity of DNA. With biological aging, telomere shortening occurs, causing cellular senescence. Several studies show that shorter telomeres are associated with acute and chronic diseases, stress, addictions, and intoxications. Even in the current COVID-19 pandemic, telomere shortening is proposed as a marker of severity in individuals infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On the other hand, healthy lifestyle habits increase telomere length and balance of various cellular functions, preventing diseases.


[PROINFLAMMATORY CYTOKINES AND SIGNALING PATHWAYS IN PERIPHERAL BLOOD MONONUCLEAR CELLS IN PATIENTS WITH CORONARY ARTERY DISEASE].
To determine content of mononuclear ells (MNC) in peripheral blood of patients with coronary heart disease (CHD) and factors responsible for their functional state and cytokine production. Concentration of proteinkinases JNK1/2, ERK1/2, MAPK38, AKT1, JAK2, FAK, AMPK, p70S6K, STAT3, STAT5B and STAT6 was determined in MNC lysate by immune-enzyme assay. Interleukin 1β, 2, 4 and y-interferon levels were measured in blood sera. In patients with angina of effort and unstable angina, the JNK level was 59,8% and 53,1% higher than the normal one respectively (р=0,013) and (р=0,012). The level of the nuclear transcription factor was 26,9% (р=0,015) and 27,9% (р=0,017), JAK2 31,5% (р=0,022) and 48,6% (р=0,018), STAT3 49,6% (р=0,025) and 55,3% (р=0,02), STAT5B 21,5% (р=0,018) and 30,2% (р=0,011) lower. These changes were associated with a 13,1% (р=0,047) and 51,4% (р=0,019) rise in the STAT6 level, 30,1% (р=0,025) and 79,4% (р=0,003) FAK level, 7,6% (р=0,09) and 15,2% (р=0,039) АКТ1 level, 65,3 (р=0,02) and 76,2% (р=0,017) p70S6K level. Results of the study suggest persistent pro-inflammatory activation of whole blood cells in CHD patients due to enhanced levels of IL-1 and IL-2, components of the MAPK/SAPK signal pathway in MNC and decreased STAT3 level determining cell sensitivity to IL-10. The elevated intracellular level of ERK and JNK us responsible for high responsiveness of MNC to pro-inflammatory cytokines.


The Waikato Medical Care (WaiMedCa) Survey 1991-1992.
Objective. The main objective of this study is to provide a comprehensive description of general practice in the Waikato, an area which represents many aspects of New Zealand. Accurate, detailed and up to date information in this area is needed for future planning of medical education and the provision of health services. Survey method. The survey was conducted over one year, from September 1991 to August 1992. Participating general practitioners and practice nurses recorded details of a sample of patient encounters in the surgery or on home visits. Each participant was assigned four single weeks for data gathering over the course of the year. A one in five sub-sample of patients was also given questionnaires to complete immediately and two weeks after the consultations. This component of the study was reported elsewhere. Participants. A list of all active general practitioners working within the area covered by the Waikato Area Health board was constructed. All were contacted during May and June 1991 and asked to contribute to the study. During this initial, recruiting stage the practitioners and their practice nurses were asked to provide details of their professional background and to outline the structure, functions and size of their practices. Data collection. The variables studied included: provider characteristics (age, gender, qualifications, type of practice and services offered); patient attributes (age, gender, ethnicity, benefit category and occupation); patient reasons for encounter (up to four per encounter); doctor diagnoses (again up to four per encounter); drugs prescribed and or other treatments provided; tests and investigations ordered and referrals made; planned follow up and subjective view on the encounter. Data were centrally coded by trained staff. Patient reasons for encounter were coded according to NAMCS, practitioner diagnoses were classified into OXMIS, and drugs prescribed were allocated into the ATC classification system. Participation rate. 87% of practitioners (182/209), 89% of practices (95/107), and 80% of practice nurses (150/189) completed the initial recruitment survey. The participation rate at the first phase of the encounter survey was 80.5% (169/210), but this had dropped to 65.7% (136/207) by the fourth collection week. An overall response rate of 68.6% was achieved, representing successful collection of encounter data in 562 of 819 potential doctor recording weeks. On average, general practitioners recorded 109 encounters per week, from which they selected on average a sample of 23 patients for the survey. They described 141 problems per 100 encounters, of which 49 were new. On average general practitioners made less than three home visits per 100 encounters.(ABSTRACT TRUNCATED AT 400 WORDS)


MOLECULAR EVIDENCE OF SPIROMETRA ERINACEIEUROPAEI INFECTION IN SNAKES PTYAS KORROS FROM LAO PDR AND THAILAND AND FROGS HOPLOBATRACHUS RUGULOSUS FROM MYANMAR.
Sparganosis is a parasitic disease in humans and animals caused by plerocercoid larvae (spargana) of the genus Spirometra. Spirometra erinaceieuropaei is the major causative agent of the disease in Asian countries. However, molecular evidence of the causative parasite species in animals remains lacking. A total of 19 spargana specimens were obtained from frogs, Hoplobatrachus rugulosus, collected from Myanmar and snakes, Ptyas korros, from Lao PDR and Thailand. A partial sequence of mitochondrial cytochrome c oxidase subunit1 gene (cox1) was amplified, sequenced, and the phylogenetic relationship was constructed using maximum likelihood method. Results revealed that the level of nucleotide variations in the partial cox1 sequence (429 bp) among the spargana ranged 0-3.5%, with 15 variable sites. Phylogenetic analysis indicated that all spargana specimens were S. erinaceieuropaei. This is the first report of S. erinaceieuropaei in P. korros from Lao PDR and Thailand and H. rugulosus from Myanmar. The results emphasize the need for prevention and control of sparganosis in these regions.


Anomalous Diffusion of Dissipative Solitons in the Cubic-Quintic Complex Ginzburg-Landau Equation in Two Spatial Dimensions.
We demonstrate the occurrence of anomalous diffusion of dissipative solitons in a "simple" and deterministic prototype model: the cubic-quintic complex Ginzburg-Landau equation in two spatial dimensions. The main features of their dynamics, induced by symmetric-asymmetric explosions, can be modeled by a subdiffusive continuous-time random walk, while in the case dominated by only asymmetric explosions, it becomes characterized by normal diffusion.


Interventions for paediatric procedure-related pain in primary care.
As a part of routine and specialized health care, children are subjected to a number of invasive medical procedures (eg, immunizations, venipunctures). These events are anxiety provoking and painful, and can have detrimental short-term and long-term effects. The present paper provides an overview of pharmacological and nonpharmacological techniques for the management of procedure-related pain in children, with a focus on clinically relevant information. Sufficient detail is provided to facilitate the translation of reviewed strategies into standard practice.


No evidence for association of MTHFR 677C>T and 1298A>C variants with placental DNA methylation.
5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in one-carbon metabolism that ensures the availability of methyl groups for methylation reactions. Two single-nucleotide polymorphisms (SNPs) in the MTHFR gene, 677C>T and 1298A>C, result in a thermolabile enzyme with reduced function. These variants, in both the maternal and/or fetal genes, have been associated with pregnancy complications including miscarriage, neural tube defects (NTDs), and preeclampsia (PE), perhaps due to altered capacity for DNA methylation (DNAm). In this study, we assessed the association between MTHFR 677TT and 1298CC genotypes and risk of NTDs, PE, or normotensive intrauterine growth restriction (nIUGR). Additionally, we assessed whether these high-risk genotypes are associated with altered DNAm in the placenta. In 303 placentas screened for this study, we observed no significant association between the occurrence of NTDs (N = 55), PE (early-onset: N = 28, late-onset: N = 20), or nIUGR (N = 21) and placental (fetal) MTHFR 677TT or 1298CC genotypes compared to healthy pregnancies (N = 179), though a trend of increased 677TT genotype in PE/IUGR together was observed (OR 2.53, p = 0.048). DNAm was profiled in 10 high-risk 677 (677TT + 1298AA), 10 high-risk 1298 (677CC + 1298CC), and 10 reference (677CC + 1298AA) genotype placentas. Linear modeling identified no significantly differentially methylated sites between high-risk 677 or 1298 and reference placentas at a false discovery rate < 0.05 and Δβ ≥ 0.05 using the Illumina Infinium HumanMethylation450 BeadChip. Using a differentially methylated region analysis or separating cytosine-guanine dinucleotides (CpGs) by CpG density to reduce multiple comparisons also did not identify differential methylation. Additionally, there was no consistent evidence for altered methylation of repetitive DNA between high-risk and reference placentas. We conclude that large-scale, genome-wide disruption in DNAm does not occur in placentas with the high-risk MTHFR 677TT or 1298CC genotypes. Furthermore, there was no evidence for an association of the 1298CC genotype and only a tendency to higher 677TT in pregnancy complications of PE/IUGR. This may be due to small sample sizes or folate repletion in our Canadian population attenuating effects of the high-risk MTHFR variants. However, given our results and the conflicting results in the literature, investigations into alternative mechanisms that may explain the link between MTHFR variants and pregnancy complications, or in populations at risk of folate deficiencies, are warranted.


Simulated Interprofessional Education Discharge Planning Meeting to Improve Skills Necessary for Effective Interprofessional Practice.
The purpose of this study was to evaluate the use of a simulation-enhanced interprofessional education (Sim-IPE) discharge planning learning experience using simulated patients (SPs), to explore the ability for students to communicate with each other and to a patient/caregiver, and to use clinical thinking to make a safe and appropriate interprofessional discharge recommendation. Educational institution; university simulation center. A Sim-IPE was performed with students from physical therapy (N = 46), nursing (N = 25), and social work (N = 11). Students were placed into interprofessional teams. Presimulation, each student was expected to complete a survey and review several items including the patient case, a communication strategy, and community resources. The team then interacted with SPs portraying the patient and the family member. Postsimulation, facilitators led a debriefing session and students completed a post-IPE survey. The Interprofessional Collaborative Competency Attainment Survey (ICCAS) was completed pre- and postexperience. Most students reported that they strongly or somewhat agreed that the experience improved their clinical thinking skills (67%; n = 55), improved awareness of the patient voice in shared decision-making (72.8%; n = 59), improved ability to prioritize patient's list of impairments (75.3%; n = 61), and improved confidence with discharge planning (69.1%; n = 56). Discharge planning is inherently an interprofessional process. Utilizing a simulation as a method to practice discharge planning may have a positive impact on future clinical practice. Completing the ICCAS may not be the appropriate assessment when evaluating change before and after an IPE experience based on the high scores noted preexperience. The use of a simulated discharge planning meeting may improve skills necessary for effective interprofessional practice.


Specific binding of 17 beta-estradiol in the human thymus.
Many observations suggest that estrogenic preparations can depress cell-mediated immune reactions. Since cell-mediated immunity is thymus-dependent, the estrogen-binding properties of human and mouse thymus tissue were studied with the use of an aqueous two-phase separation system. A high-affinity and low-capacity estrogen binding was found in human thymus tissue from six prepubertal children of both sexes and two grown women. A similar specific binding was found in the mouse thymus and in the human uterus. The association constant (Ka) for the binding in the human thymus was 16.01 +/- 8.98 X 10(9)M-1. The human uterus, which is known to possess estrogen receptors, had Ka values in the same range. The binding seems to be located in the reticuloepithelial cells of the thymus. Data suggest that the human thymus is a target organ for estrogens, which may influence lymphocyte function during therapy.


Laboratory findings in patients with psoriasis, with special reference to immunological parameters, associations with arthropathy and sacro-iliitis.
Twenty-five male and 25 female consecutive patients hospitalized because of psoriasis were examined. The clinical and radiographical findings are presented in detail elsewhere. Increased serum IgA, C3, C4, and C3PA concentrations were found in patients both with and without arthropathy and/or sacro-iliitis. Increased IgG concentrations were found in patients without arthropathy, and of C1 inhibitor concentrations in patients with arthropathy and/or sacro-iliitis. IgG and IgA concentrations were lower in patients with arthropathy than in those without, the difference being most significant in patients with arthropathy of large joints. An association was found between increased C4 concentration and sacro-iliitis, increased CRP concentration and sacro-iliitis and increased C3 concentration and phalangeal joint arthropathy. C4 and CRP concentrations were not associated. A close association between CRP and SAA was observed. Our results indicate that psoriatic arthropathy is not a single uniform joint disease, but represents different forms of arthropathy.


Total laparoscopic excision of retroperitoneal cystic lymphangioma.
Retroperitoneal cystic lymphangioma is a rare benign tumor of the retroperitoneal lymphatics that usually manifests in infancy. If surgical excision is used in treatment, it needs to be as complete as possible to reduce the risk of recurrence. Two pediatric patients, an 18-month-old girl and a 4-yearold boy, underwent laparoscopic excision of symptomatic retroperitoneal cystic lymphangiomas. Macroscopically, the resection was complete in both cases. The postoperative course in both cases was uneventful. Both children remained asymptomatic and no recurrence was observed at 18-month follow-up. Complete laparoscopic excision should be considered as a therapeutic option to treat retroperitoneal cystic lymphangioma.


The Protein Data Bank. A computer-based archival file for macromolecular structures.
The Protein Data Bank is a computer-based archival file for macromolecular structures. The Bank stores in a uniform format atomic co-ordinates and partial bond connectivities, as derived from crystallographic studies. Text included in each data entry gives pertinent information for the structure at hand (e.g. species from which the molecule has been obtained, resolution of diffraction data, literature citations and specifications of secondary structure). In addition to atomic co-ordinates and connectivities, the Protein Data Bank stores structure factors and phases, although these latter data are not placed in any uniform format. Input of data to the Bank and general maintenance functions are carried out at Brookhaven National Laboratory. All data stored in the Bank are available on magnetic tape for public distribution, from Brookhaven (to laboratories in the Americas), Tokyo (Japan), and Cambridge (Europe and worldwide). A master file is maintained at Brookhaven and duplicate copies are stored in Cambridge and Tokyo. In the future, it is hoped to expand the scope of the Protein Data Bank to make available co-ordinates for standard structural types (e.g. alpha-helix, RNA double-stranded helix) and representative computer programs of utility in the study and interpretation of macromolecular structures.


Disaster Preparedness Among Michigan's Licensed Child Care Programs.
This study aimed to assess if Michigan child care directors have created disaster management plans, and if local resources were used to develop and implement plans. From December 2013 to March 2014, the Early Childhood Investment Corporation conducted a survey of licensed child care programs in Michigan. An online survey regarding disaster preparedness and training resources was distributed to the directors of a convenience sample of registered child care centers among the Early Childhood Investment Corporation's statewide network of 11 resource centers. A total of 210 child care programs responded. Most (91%) of respondents had a disaster plan, but 40% did not include accommodations for special needs children, 51% did not have a family/child identification or reunification plan, and 67% did not have car safety devices and a predetermined route for evacuation. Fewer than 9% made disaster plans available online. Few collaborated with local fire (22%), police (27%), or pediatric or emergency medicine organizations (11%). Online modules were the most desirable training format. In a state without mandated child care guidelines for disaster preparedness, a substantial proportion of child care programs were missing critical components of disaster planning. Future interventions must focus on increasing partnerships with local organizations and developing guidelines and training to include plans for special needs children, family/child identification and reunification, and evacuation/relocation.


Alcohol induced burr cell (echinocytic) haemolytic anaemia and haemochromatosis.
A 51-year-old man with chronic alcoholic liver disease developed a severe haemolytic anaemia characterized by the presence of circulating burr-shaped cells (echinocytes). Several transfusions of packed red cells were ineffective in raising the haemoglobin concentration, showing that the abnormality was acquired by the transfused cells. Liver biopsies revealed haemochromatosis. Haematological parameters normalized four months after the patient stopped drinking alcohol, but burr cells were still present and erythrocyte life-span was still markedly shortened at one year follow-up. Since serum cholesterol, HDL-cholesterol, and Apo-AI and Apo-B lipoproteins were considerably decreased, the lipid composition of the red cell membrane was studied. Findings showed that echinocytosis occurred with no change in membrane cholesterol content, nor in cholesterol:phospholipid ratio, but with an alteration in the phosphatidylserine and phosphatidylinositol concentrations. While haemochromatosis was most likely the cause of the erythrocyte anomaly, alcohol intake was probably responsible for the acute onset of haemolytic anaemia with effects directly on the erythrocyte membrane as well as mediated by the progressive hepatic injury, with alterations in the plasma and successively in the intramembrane lipid composition.


Elucidation of antifungal toxicity of Callistemon lanceolatus essential oil encapsulated in chitosan nanogel against Aspergillus flavus using biochemical and in-silico approaches.
The antifungal and aflatoxin B1 (AFB1) inhibitory effect of chemically characterised Callistemon lanceolatus essential oil (CLEO), chitosan nanoparticles, and CLEO loaded chitosan nanoparticles (CLEO-ChNPs) were investigated. Scanning electron microscope observation exhibited the spherical shape of prepared CLEO-ChNPs with an average range of 20-70 nm. An in-vitro release study revealed the controlled volatilisation of CLEO from CLEO-ChNPs. The CLEO-ChNPs caused complete inhibition of growth (4.5 µl/ml) and AFB1 (4.0 µl/ml) production by A. flavus at a low dose compared to free CLEO (5.0 µl/ml). The antifungal and AFB1 inhibitory toxicity of CLEO-ChNPs were elucidated using biochemical (effect on ergosterol biosynthesis, membrane cations, mitochondrial membrane potential, C-sources utilisation and cellular methylglyoxal level) and in-silico (interaction with the gene product Erg 28, Cytochrome c oxidase subunit Va, Omt-A, Ver-1, and Nor-1) approaches.


Effective internalization of U251-MG-secreted exosomes into cancer cells and characterization of their lipid components.
Exosomes, the natural vehicles of various biological molecules, have been examined in several research fields including drug delivery. Although understanding of the biological functions of exosomes has increased, how exosomes are transported between cells remains unclear. We hypothesized that cell tropism is important for effective exosomal intercellular communication and that parental cells regulate exosome movement by modulating constituent exosomal molecules. Herein, we demonstrated the strong translocation of glioblastoma-derived exosomes (U251exo) into their parental (U251) cells, breast cancer (MDA-MB-231) cells, and fibrosarcoma (HT-1080). Furthermore, disruption of proteins of U251exo by enzymatic treatment did not affect their uptake. Therefore, we focused on lipid molecules of U251exo with the expectation that they are crucial for effective incorporation of U251exo by cancer cells. Phosphatidylethanolamine was identified as a unique lipid component of U251-MG cell-derived extracellular vesicles. From these results, valuable insight is provided into the targeting of U251exo to cancer cells, which will help to develop a cancer-targeted drug delivery system.


Molecular signatures in the transport properties of molecular wire junctions: what makes a junction "molecular"?
The simplest component of molecular electronics consists of a single-molecule transport junction: a molecule sandwiched between source and drain electrodes, with or without a third gate electrode. In this Concept article, we focus on how molecules control transport in metal-electrode molecular junctions, and where the molecular signatures are to be found. In the situation where the molecule is relatively short and the gap between injection energy and molecular eigenstates is large, transport occurs largely by elastic tunneling, stochastic switching is common, and the vibronic signature can be found using inelastic electron tunneling spectroscopy (IETS). As the energy gaps for injection become smaller, one begins to see stronger molecular signatures - these include Franck-Condon-like structures in the current/voltage characteristic and strong vibronic interactions, which can lead to hopping behavior at the polaron limit. Conformational changes induced by the strong electric field lead to another strong manifestation of the molecular nature of the junction. We overview some of this mechanistic landscape, focusing on significant effects of switching (both stochastic and controlled by the electric field) and of molecular vibronic coupling.


Oxidative stress is enhanced by hypothermia imposed on cerulein-induced pancreatitis in rats.
Hypothermia is a frequent event in severe acute pancreatitis (AP) and its real effects on the normal pancreas have not been well demonstrated. Moreover, neither have its effects on the outcome of acute pancreatitis been fully investigated. One hypothesis is that oxidative stress may be implicated in lesions caused or treated by hypothermia. To investigate the effect of hypothermia in cerulein-induced acute pancreatitis (CIAP) in rats and the role played by oxidative stress in this process. Male Wistar rats were divided into hypothermic and normothermic groups. Hypothermia was induced with a cold mattress and rectal temperature was kept at 30 masculineC for one hour. Acute pancreatitis was induced with 2 doses of cerulein (20 ìg/kg) administered at a one-hour interval. Serum amylase, pancreas vascular permeability by Evan's blue method, pancreas wet-to-dry weight ratio and histopathology were analyzed in each group. When compared with normothermic rats, hypothermic animals, with cerulein-induced acute pancreatitis, showed higher levels of pancreatic vascular permeability (p < 0.05), pancreas wet-to-dry weight ratio (p = 0.03), and histologically verified edema (p < 0.05), but similar serum amylase levels. The hypothermic group showed a higher oxidized-reduced glutathione ratio than the normothermic group. Moderate hypothermia produced a greater inflammatory response in established acute pancreatitis induced by cerulein in rats. Moreover, this study suggests that oxidative stress may be one of the mechanisms responsible for the worse outcome in hypothermic rats with cerulein-induced acute pancreatitis.


Basepairing of oligonucleotides to the 3' end of 16S ribosomal RNA is not stabilized by ribosomal proteins.
We have studied the binding of the octanucleotide (5'-3')d(AAGGAGGT) which is fully complementary to the 3' end of 16S ribosomal RNA, to ribosomes and to the isolated target sequence (5'-3') (ACCUCCUUA). The binding constant for 30S or 70S ribosomes is (5 +/- 2) X 10(7) mol-1, whereas the duplex containing the octa- and the nonanucleotide has an association constant of (6 +/- 3) X 10(7) mol-1. The two values are the same within the experimental error. This result suggests that basepairing at the 3' end of 16S rRNA is not stabilized by ribosomal proteins.


The Construction and Identification of Induced Pluripotent Stem Cells Derived from Acute Myelogenous Leukemia Cells.
The present study aimed to establish an induced pluripotent stem cell (iPSC) line from acute myelogenous leukemia (AML) cells in vitro and identify their biological characteristics. Cells from the AML-infiltrated skin from an M6 patient were infected with a lentivirus carrying OCT4, SOX2, KLF4 and C-MYC to induce iPSCs. The characteristics of the iPSCs were confirmed by alkaline phosphatase (ALP) staining. The proliferation ability of iPSCs was detected with a CCK-8 assay. The expression of pluripotency markers was measured by immunostaining, and the expression of stem cell-related genes was detected by qRT-PCR; distortion during the induction process was detected by karyotype analysis; the differentiation potential of iPSCs was determined by embryoid body-formation and teratoma-formation assays. ALP staining confirmed that these cells exhibited positive staining and had the characteristics of iPSCs. The CCK-8 assay showed that the iPSCs had the ability to proliferate. Immunostaining demonstrated that iPSC clones showed positive expression of NANOG, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. qRT-PCR results revealed that the mRNA expression of Nanog, Lin28, Cripto, FOX3, DNMT3b, DPPA2, and DPPA4 significantly increased in iPSCs. Karyotype analysis found no chromosome aberration in the iPSCs. The results of the embryoid body-formation and teratoma-formation assays indicated that the iPSCs had the potential to differentiate into all three germ layers. Our study provided evidence that an iPSC line derived from AML cells was successfully established.


Rates of Comorbidities in Very Low Birth Weight Infants Fed an Exclusive Human Milk Diet Versus a Bovine Supplemented Diet.
Background: Our level III neonatal intensive care unit (NICU) implemented the use of an exclusive human milk diet (EHD) and sought to determine its effect on the severe co-morbidities of preterm infants as well as the potential cost-savings due to the anticipated reduction in these co-morbidities. Methods: A retrospective cohort study was completed to determine if an EHD statistically decreased the rate of co-morbidities including length of stay (LOS), days on total parental nutrition (TPN), rates of late onset sepsis, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), and severe retinopathy of prematurity (ROP). Results: An EHD significantly decreased the odds of severe ROP (adjusted odds-ratio (aOR)=0.349; 95%CI [0.156, 0.739]; p=0.008) and late onset sepsis (aOR=0.323; 95%CI [0.123, 0.768]; p=0.014). Analysis of cost-effectiveness of an EHD relative to a BSD based on the incremental costs of these co-morbidities determined the net loss in direct hospital costs per patient were estimated to be $420 in 2016 US dollars; however, given the long-term health-care costs and non-pecuniary damages from the co-morbidities of severe ROP and sepsis this net loss appears negligible. Conclusion: This study found that an EHD significantly decreased the odds of severe ROP and late onset sepsis; though not significant, there was a positive trend in decreasing cases of medical NEC; our surgical NEC rates dropped to 0. The benefits of human milk are vital, and the costs are nominal.


[The course of illness and rehabilitation of schizophrenic patients in ambulatory vocational therapy. A prospective study over 3 years].
Within the framework of a study on vocational rehabilitation of the mentally ill, we examined 83 schizophrenic outpatients enrolled in a work therapy program. The course of illness and rehabilitation was documented over a 3-year period by means of annual follow-up examinations. The sample comprised 44 men and 39 women with an average age of 35 years (SD +/- 8.5). The majority were chronically ill patients with a history of frequent and long psychiatric hospitalization. After 3 years, 22% of the patients were integrated into the general labor market, 26% had sheltered employment, 23% were still in work therapy, and 29% were unemployed. Besides the patients' subjective expectations, early introduction of rehabilitative measures and a favourable course of illness were found to be predictors of a successful rehabilitation leading to vocational integration. Outpatient work therapy is a contemporary, effective organizational form of sociotherapy. It may contribute to improved vocational competence and integration, reduced psychiatric hospitalization and stabilized psychopathology.


Efficient one-pot synthesis of arylated pyrazole-fused pyran analogs: as leads to treating diabetes and Alzheimer's disease.
Background: To discover novel lead molecules against diabetes, Alzheimer's disease and oxidative stress, a library of arylated pyrazole-fused pyran derivatives, 1-20, were synthesized in a one-pot reaction. Materials & methods:1H-NMR spectroscopic and electron ionization mass spectrometry techniques were used to characterize the synthetic hybrid molecules 1-20. Analogs were screened against four indispensable therapeutic targets, including α-amylase, α-glucosidase, acetylcholinesterase and butyrylcholinesterase enzymes. Results: Except for derivatives 17 and 18, all other compounds exhibited varying degrees of inhibitory activities against target enzymes. The kinetic studies revealed that the synthetic molecules followed a competitive-type mode of inhibition for α-amylase and acetylcholinesterase enzymes, as well as a non-competitive mode of inhibition for α-glucosidase and butyrylcholinesterase enzymes. In addition, molecular docking studies identified crucial binding interactions of ligands with the enzyme's active site. Conclusion: These molecules may serve as a potential drug candidate to cure diabetes, Alzheimer's disease and oxidative stress in the future.


Cardiac progenitor reprogramming for heart regeneration.
Myocardial infarction leads to the loss of a huge number of cardiomyocytes and the reparatory response to this phenomenon is scar tissue formation, which impairs heart function. Direct reprogramming technology offers an alternative strategy for the generation of functional cardiomyocytes not only in vitro, but also in vivo in the site of injury. Results have demonstrated cardiac tissue regeneration and improvement in heart function after myocardial infarction following local injection of vectors encoding reprogramming transcription factors or miRNAs. This shows the great potential of cardiac reprogramming technology for heart regeneration. However, in addition to cardiomyocytes, other cell types, including endothelial cells and smooth muscle cells are also required to be generated in the damaged area in order to achieve complete cardiac tissue regeneration. To this aim induced proliferative/expandable cardiovascular progenitor cells (iCPCs) appear to be an appropriate cell source, which is capable of differentiation into three cardiovascular lineages both in vitro and in vivo. In this regard, this study goes over in vitro and in vivo cardiac reprogramming technology and specifically deals with cardiac progenitor reprogramming and its potential for heart regeneration.


Management of common ailments requiring referral in the pharmacy: a mystery shopping intervention study.
Background Pharmacists can play a key role in managing ailments through their primary roles of supplying over-the-counter (non-prescription) medicines and advice-giving. It must be ensured that pharmacy staff practise in an evidence-based, guideline-compliant manner. To achieve this, mystery shopping can be used as an intervention to assess and train pharmacy staff. Objective To determine if repeated student pharmacist mystery shopping with immediate feedback affected the outcome of scenarios requiring referral to a medical practitioner. To determine what, if any, factors may influence whether referral occurred. Setting Thirteen community pharmacies across metropolitan Sydney, Australia. Methods Sixty-one student pharmacist mystery shoppers visited 13 community pharmacies across metropolitan Sydney once weekly over nine weeks between March-October 2015 to conduct audio-recorded mystery shopping visits with assigned scenarios (asthma, dyspepsia, diarrhoea). Students returned to the pharmacy immediately to provide staff members with feedback. Pharmacy staff were scored by mystery shoppers according to a standardised scoresheet. Score data and other characteristics, such as the assigned scenario, were analysed via correlation and logistic regression modelling. Main outcome measure Whether a student mystery shopper was appropriately referred to a medical practitioner based on the presenting symptoms. Results 158 visits were eligible for analysis. Referral to a medical practitioner was appropriately made in 66% of visits. The regression model provided an R2 value of 0.73; the questioning score of the interaction and if a pharmacist was involved in the interaction were significant predictor of appropriate outcome (p < 0.001 and p < 0.01 respectively). Statistically significant differences were found between median questioning and total scores of interactions involving a pharmacist compared to those that did not (p < 0.001). No statistically significant correlation was found between the number of visits and appropriate outcome (p > 0.05). Conclusions Mystery shopping with feedback did not improve pharmacy staff performance over time. Increased questioning and involvement of a pharmacist in the interaction were significant predictors of referral to a medical practitioner occurring.


Generative models for protein sequence modeling: recent advances and future directions.
The widespread adoption of high-throughput omics technologies has exponentially increased the amount of protein sequence data involved in many salient disease pathways and their respective therapeutics and diagnostics. Despite the availability of large-scale sequence data, the lack of experimental fitness annotations underpins the need for self-supervised and unsupervised machine learning (ML) methods. These techniques leverage the meaningful features encoded in abundant unlabeled sequences to accomplish complex protein engineering tasks. Proficiency in the rapidly evolving fields of protein engineering and generative AI is required to realize the full potential of ML models as a tool for protein fitness landscape navigation. Here, we support this work by (i) providing an overview of the architecture and mathematical details of the most successful ML models applicable to sequence data (e.g. variational autoencoders, autoregressive models, generative adversarial neural networks, and diffusion models), (ii) guiding how to effectively implement these models on protein sequence data to predict fitness or generate high-fitness sequences and (iii) highlighting several successful studies that implement these techniques in protein engineering (from paratope regions and subcellular localization prediction to high-fitness sequences and protein design rules generation). By providing a comprehensive survey of model details, novel architecture developments, comparisons of model applications, and current challenges, this study intends to provide structured guidance and robust framework for delivering a prospective outlook in the ML-driven protein engineering field.


An IrVO4+ Cluster Catalytically Oxidizes Four CO Molecules: Importance of Ir-V Multiple Bonding.
The generation and characterization of multiple metal-metal (M-M) bonds between early and late transition metals is vital to correlate the nature of multiple M-M bonds with the related reactivity in catalysis, while the examples with multiple M-M bonds have been rarely reported. Herein, we identified that the quadruple bonding interactions were formed in a gas-phase ion IrV+ with a dramatically short Ir-V bond. Oxidation of four CO molecules by IrVO4+ is a highly exothermic process driven by the generation of stable products IrV+ and CO2, and then IrV+ can be oxidized by N2O to regenerate IrVO4+. This finding overturns the general impression that vanadium oxide clusters are unwilling to oxidize multiple CO molecules because of the strong V-O bond and that at most two oxygen atoms can be supplied from a single V-containing cluster in CO oxidation. This study emphasizes the potential importance of heterobimetallic multiple M-M bonds in related heterogeneous catalysis.


Prenatal oral (gavage) developmental toxicity study of decabromodiphenyl oxide in rats.
Decabromodiphenyl oxide (DBDPO) is a highly effective flame retardant that is primarily used in electrical and electronic equipment with a secondary, but important, application in upholstery textiles. DBDPO, the second largest volume brominated flame retardant in use today, has undergone a wide range of toxicology tests in mammalian species with the results indicating a no-adverse-effect level of approximately 1000 mg/kg/day in oral repeated-dose studies. An oral prenatal developmental toxicity study of the commercial DBDPO product (97% purity) was performed under current EPA OPPTS and OECD guidelines. Female Sprague-Dawley rats (25 mated females/group) received 0,100, 300 or 1000 mg DBPDO/kg/ day via gavage in corn oil during gestation days 0 through 19. All females survived until scheduled sacrifice. No clinical signs of toxicity were observed. Pregnancy rates in the control and treated groups ranged from 96% to 100% and provided 23 or more litters in each group for evaluation on gestation day 20. No effect of treatment was seen in maternal gestational parameters (body weight, body weight gain, and food consumption), uterine implantation data, liver weight, or necropsy findings. Likewise, no effect of treatment was seen in fetal body weights, fetal sex distribution, or during the fetal external, visceral, or skeletal examinations. The NOEL (no-observable-effect level) for maternal and developmental toxicity was 1000 mg DBPDO/kg/day, the highest dose level administered on gestation days 0 to 19.