Target discovery of bioactive natural products with native-compound-coupled CNBr-activated Sepharose 4B beads (NCCB): Applications, mechanisms and outlooks.
Natural products (NPs) represent a treasure trove for drug discovery and development due to their chemical structural diversity and a broad spectrum of biological activities. Uncovering the biological targets and understanding their molecular mechanism of actions are crucial steps in the development of clinical therapeutics. However, the structural complexity of NPs and intricate nature of biological system present formidable challenges in target identification of NPs. Although significant advances have been made in the development of new chemical tools, these methods often require high levels of synthetic skills for preparing chemical probes. This can be costly and time-consuming relaying on operationally complicated procedures and instruments. In recent efforts, we and others have successfully developed an operationally simple and practical chemical tool known as native-compound-coupled CNBr-activated Sepharose 4B beads (NCCB) for NP target identification. In this approach, a native compound readily reacts with commercial CNBr-activated Sepharose 4B beads with a process that is easily performed in any biology laboratory. Based on NCCB, our group has identified the direct targets of more than 60 NPs. In this review, we will elucidate the application scopes, including flavonoids, quinones, terpenoids and others, characteristics, chemical mechanisms, procedures, advantages, disadvantages, and future directions of NCCB in specific target discovery.


A possible link between genetic hemochromatosis and autoimmune thyroiditis.
The systemic involvement that often characterizes genetic hemochromatosis is well known. Although evidence of iron storage in endocrine glands has been reported, the possible functional changes due to altered thyroid in course of hemochromatosis have been not clearly defined so far. Thyroid may be directly affected by iron storage in the gland as well as functionally altered due to iron accumulation occurring in the pituitary. The prevalence and the pathogenetic mechanisms of primary thyroid illness in patients with genetic hemochromatosis are still largely unknown. Hereby, we describe two patients affected by genetic hemochromatosis who developed Hashimoto's thyroiditis. Taking into consideration the possible links occurring among iron overload, thyroid gland damage and thyroid dysfunction, we hypothesize that hemochromatosis could have been an enhancing factor for the development of primary thyroid disease in these patients. Potentially, this process might also determine new onset anti-thyroid autoimmunity or overlap it. We conclude that systematic studies in large and heterogeneous populations will be necessary in order to assess the risk of development of primary thyroid disorders in course of genetic hemochromatosis and, more generally, chronic iron overload conditions. In our mind, thyroid function should be periodically checked in all patients with chronic iron overload conditions.


Cholesterol removal from human plasma with biologically modified cryogels.
In this study, low molecular weight heparin immobilized P(HEMA) cryogels were fabricated for the removal of LDL-C in hypercholesterolemic human plasma. After characterization studies for P(HEMA) cryogels, effects of the parameters including medium pH, CNBr concentration, heparin concentration and contact time on heparin immobilization were investigated. Blood compatibility and cell adhesion tests were also performed, and platelet and leucocyte loss for P(HEMA)-Hp cryogels were found to be 2.95% and 4.91%, respectively. Maximum adsorption capacity for LDL-C from hypercholesterolemic human plasma was found to be 26.7 mg/g for P(HEMA)-Hp cryogel while it was only 1.67 mg/g for bare P(HEMA) cryogel. The P(HEMA)-Hp cryogels exhibit high desorption ratios up to 96% after 10 adsorption-desorption cycles with no significant decrease in the adsorption capacity. The findings indicated that these reusable P(HEMA)-based cryogels proposed good alternative adsorbents for removal of LDL-C.


Impact of a Pharmacy Management Course for Pharmacists Working Within Brazil's Public Health System.
Objective. To assess the impact of a continuing education course that focused on the development of management competencies on pharmacists working in Brazil's public health system.Methods. A specialization blended in-service course (360 hours) entitled Pharmaceutical Service and Access to Medicine Management was offered to pharmacists working within the Brazilian public health system. Data on course outcomes were collected through individual interviews with pharmacists who worked in the Brazilian public health system, as well as from focus groups and records of researchers' observations. The analysis was based on models of learning and training evaluation theory.Results. The findings showed proximal outcomes on students' knowledge, skills, and attitudes; behavioral changes; and programmatic outcomes in the organization and management of health services, promoting the recognition and integration of the "pharmaceutical services division" - a dedicated sector within the health departments in municipalities and states. The inputs (course content, structure, and in-service hands-on activities) were directly linked to the outcomes reported by participants and helped them to overcome some of the barriers to using knowledge and skills in the workplace.Conclusion. A well-structured course including leaning activities to intervene in the workplace had a positive impact on pharmacists' behavior and contributed to the capacity building of the organizations in which they operate.


Pathology assessment of pancreatic cancer following neoadjuvant treatment: Time to move on.
Neoadjuvant treatment has increasingly become an integral part of the multimodal management of patients with pancreatic cancer. In patients who are able to undergo surgery following preoperative therapy, tumour regression grading remains the diagnostic gold standard for the histomorphological assessment of the effect of neoadjuvant treatment. In recent years, however, there has been growing concern about inherent flaws of tumour regression grading systems as well as their imprecise and impractical criteria that result in divergence of practice and lack of interobserver agreement. Furthermore, existing tumour regression systems differ in their defining criteria and thresholds, leading to incomparability of data. In this review, the principles and limitations of the main existing tumour regression systems are discussed, and potential alternative assessment approaches and novel markers are presented.


Mate sampling and choosiness in the sand goby.
To date, mate choice studies have mostly focused on establishing which mates are chosen or how the choices are performed. Here, we combined these two approaches by empirically testing how latency to mate is affected by various search costs, variation in mate quality and female quality in the sand goby (Pomatoschistus minutus). Our results show that females adjust their mating behaviour according to the costs and benefits of the choice situation. Specifically, they mated sooner when access to males was delayed and when the presence of other females presented a mate sampling cost. We also found a positive link between size variation among potential mating partners and spawning delay in some (but not all) experimental conditions. By contrast, we did not find the number of available males or the females' own body size ('quality') to affect mating latency. Finally, female mating behaviour varied significantly between years. These findings are notable for demonstrating that (i) mate sampling time is particularly sensitive to costs and, to a lesser degree, to variation among mate candidates, (ii) females' mating behaviour is sensitive to qualitative rather than to quantitative variation in their environment, and (iii) a snapshot view may describe mate sampling behaviour unreliably.


Clinical and molecular-genetic markers of ADHD in children.
The objective was to make a contribution to deepening the knowledge of the etiopathogenesis of ADHD. In an association study design, an analysis of polymorphisms of selected genes was conducted in 119 hyperkinetic boys and a control group of boys, aged 7-13. Furthermore several psychologically determined subgroups were identified. A connection between psychological functions (endophenotypes) and genes were looked for. There was a statistically significant difference found in allelic and genotype frequencies of the TaqI A polymorphism of the DRD2 gene. The frequency of the allele A1 in hyperkinetic boys and the control subjects was 0.26 and 0.15, respectively (p<0.003). A statistically significant occurrence of atypical genotypes (8/10, 7/10 and 10/11) of the DAT1 gene was also found in hyperkinetic boys and a connection between the M235 polymorphism of the angiotensinogene gene and the positive family history of psychiatric illness was found in probands (p=0.031). Significant correlations between the results of some neuropsychological tests and genes for neuro-/immunomodulators (IL-6, TNF-alpha) and the gene for the brain-derived neurotrophic factor (BDNF) were found. The study showed a statistically significant prevalence of A1 allele of the DRD gene in the hyperkinetic group. We also found a significantly higher incidence of atypical DAT genotypes in the hyperkinetic group. Furthermore we found significant connections with particular gene polymorphisms which may hypothetically represent a neurodevelopmental risk factor in the etiopathogenesis of the disorder (IL-2, IL-6, TNF-alpha, BDNF). We further found a connection of the M235 polymorphism of the AGT (angiotensinogene) gene to positive family history of psychiatric illness (p=0.031). As for cognitive characteristics, we identified three subtypes with different cognitive performance profiles. This finding shows interindividual variability of cognitive style in the group of hyperkinetic boys.


Phase-driven magneto-electrical characteristics of single-layer MoS2.
Magnetism of the MoS2 semiconducting atomic layer was highlighted for its great potential in the applications of spintronics and valleytronics. In this study, we demonstrate an evolution of magneto-electrical properties of single layer MoS2 with the modulation of defect configurations and formation of a partial 1T phase. With Ar treatment, sulfur was depleted within the MoS2 flake leading to a 2H (low-spin) → partial 1T (high-spin) phase transition. The phase transition was accompanied by the development of a ferromagnetic phase. Alternatively, the phase transition could be driven by the desorption of S atoms at the edge of MoS2via O2 treatment while with a different ordering magnitude in magnetism. The edge-sensitive magnetism of the single-layer MoS2 was monitored by magnetic force microscopy and validated by a first-principle calculation with graded-Vs (sulfur vacancy) terminals set at the edge, where band-splitting appeared more prominent with increasing Vs. Treatment with Ar and O2 enabled a dual electrical characteristic of the field effect transistor (FET) that featured linear and saturated responses of different magnitudes in the Ids-Vds curves, whereas the pristine MoS2 FET displayed only a linear electrical dependency. The correlation and tuning of the Vs-1T phase transition would provide a playground for tailoring the phase-driven properties of MoS2 semiconducting atomic layers in spintronic applications.


Mechanisms of action for α1-adrenoceptor blockers in storage symptoms with new insights into the micturition reflex.
Elderly patients suffering from lower urinary tract symptoms with benign prostatic hyperplasia (BPH) are widely prescribed α1-adrenoceptor blockers (α1-blockers) to improve voiding and storage symptoms. The mechanism of action for improvements in voiding symptoms is well understood; tonus of the urethra and prostate are decreased and urinary flow rate is increased by α1-blockers. However, the mechanisms underlying storage symptoms have remained unclear, although detrusor hyperactivity has been identified as a significant factor. Previous investigations have yielded informative results, such as amelioration of reduced blood flow and afferent C-fiber activation, and the importance of the urothelium. Recently, the fascinating role of α1A- and α1D-adrenoceptor subtypes have been investigated for bladder function. Furthermore, the scope of this pathology covers both the bladder and that part of the central nervous system related to the micturition reflex. This review describes the beneficial effects of α1-blockers on storage symptoms and the pathogenesis of storage symptoms related to BPH, discusses the mechanisms of action for α1-blockers with reference to results from cystometry to suggest improvements in management that suppress detrusor hyperactivity, and examines the potential influence of α1A- and α1D-adrenoceptor subtypes on bladder activity.


NATO survey of mental health training in army recruits.
To-date, there has been no international review of mental health resilience training during Basic Training nor an assessment of what service members perceive as useful from their perspective. In response to this knowledge gap, the North Atlantic Treaty Organization (NATO) Human Factors & Medicine Research & Technology Task Group "Mental Health Training" initiated a survey and interview with seven to twenty recruits from nine nations to inform the development of such training (N = 121). All nations provided data from soldiers joining the military as volunteers, whereas two nations also provided data from conscripts. Results from the volunteer data showed relatively consistent ranking in terms of perceived demands, coping strategies, and preferences for resilience skill training across the nations. Analysis of data from conscripts identified a select number of differences compared to volunteers. Subjects also provided examples of coping with stress during Basic Training that can be used in future training; themes are presented here. Results are designed to show the kinds of demands facing new recruits and coping methods used to overcome these demands to develop relevant resilience training for NATO nations.


Nonself RNA rewires IFN-β signaling: A mathematical model of the innate immune response.
Type I interferons (IFNs) are key coordinators of the innate immune response to viral infection, which, through activation of the transcriptional regulators STAT1 and STAT2 (STAT1/2) in bystander cells, induce the expression of IFN-stimulated genes (ISGs). Here, we showed that in cells transfected with poly(I:C), an analog of viral RNA, the transcriptional activity of STAT1/2 was terminated because of depletion of the interferon-β (IFN-β) receptor, IFNAR. Activation of RNase L and PKR, products of two ISGs, not only hindered the replenishment of IFNAR but also suppressed negative regulators of IRF3 and NF-κB, consequently promoting IFNB transcription. We incorporated these findings into a mathematical model of innate immunity. By coupling signaling through the IRF3-NF-κB and STAT1/2 pathways with the activities of RNase L and PKR, the model explains how poly(I:C) switches the transcriptional program from being STAT1/2 induced to being IRF3 and NF-κB induced, which converts IFN-β-responding cells to IFN-β-secreting cells.


Skeletal site-related variation in human trabecular bone transcriptome and signaling.
The skeletal site-specific influence of multiple genes on bone morphology is recognised, but the question as to how these influences may be exerted at the molecular and cellular level has not been explored. To address this question, we have compared global gene expression profiles of human trabecular bone from two different skeletal sites that experience vastly different degrees of mechanical loading, namely biopsies from iliac crest and lumbar spinal lamina. In the lumbar spine, compared to the iliac crest, the majority of the differentially expressed genes showed significantly increased levels of expression; 3406 transcripts were up- whilst 838 were down-regulated. Interestingly, all gene transcripts that have been recently demonstrated to be markers of osteocyte, as well as osteoblast and osteoclast-related genes, were markedly up-regulated in the spine. The transcriptome data is consistent with osteocyte numbers being almost identical at the two anatomical sites, but suggesting a relatively low osteocyte functional activity in the iliac crest. Similarly, osteoblast and osteoclast expression data suggested similar numbers of the cells, but presented with higher activity in the spine than iliac crest. This analysis has also led to the identification of expression of a number of transcripts, previously known and novel, which to our knowledge have never earlier been associated with bone growth and remodelling. This study provides molecular evidence explaining anatomical and micro-architectural site-related changes in bone cell function, which is predominantly attributable to alteration in cell transcriptional activity. A number of novel signaling molecules in critical pathways, which have been hitherto not known to be expressed in bone cells of mature vertebrates, were identified.


Parental decision making regarding consent to randomization on Children's Oncology Group AALL0932.
Within pediatric oncology, parental decision making regarding participation in clinical trials that aim to reduce therapy to mitigate side effects is not well studied. The recently completed Children's Oncology Group trial for standard-risk acute lymphoblastic leukemia (AALL0932) included a reduction in maintenance therapy, and required consent for randomization immediately prior to starting maintenance. At our institution, 40% of children enrolled on AALL0932 were withdrawn from protocol therapy prior to randomization due to parental choice. This study sought to identify factors that impacted parental decision making regarding randomization on AALL0932. Parents of children enrolled on AALL0932 at our institution were eligible if their child met criteria for the average-risk randomization. Parents were invited to participate in a 30-50-minute phone interview. Questions focused on factors that shaped parental decision making about randomization, as well as their perspectives about the clinical trial experience more generally. Fear of receiving less therapy and subsequent relapse was the predominant reason to decline randomization. Reasons given for consenting to randomization included trust in the physician, altruism, hope for less therapy, and potential for fewer side effects. Parents also reflected on ways to support future families making decisions about clinical trial participation. While many parents recognize the importance of clinical trials aiming to mitigate side effects, the fear of their own child relapsing with less than standard therapy may dissuade them from study participation. Recognizing and addressing these concerns will be important for enrollment and retention in future clinical trials.


5-Hydroxytryptamine metabolism in the damselfly, Ischnura graellsii, in relation to sex and larval-adult period.
Changes in total serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were investigated by HPLC EC in Ischnura graellsii over a larval-adult period including both sexes. Variationsof tryptophan (Trp) and protein levels were also studied. Significant higher levels of 5-HT were found in head portion for both sexes over the period studied, with mean values (in ng/mg protein) of 12.19-27.46 (head) and 2.63-6.06 (body) for males, and mean values of 3.13-26.48 (head) and 1.84-4.03 (body) for females. 5-HIAA concentration was also significantly higher in head portion for both sexes; mean values (in ng/mg protein) of 4.45-24.19 (head) and 0.87-8.63 (body) were observed for males, and mean values of 0.76-16.87 (head) and 1.18-7.12 (body) for females. The levels of the four compounds studied were significantly affected by the factor Instar. It is noticeable that significant differences between sexes for head Trp, 5-HT and 5-HIAA were observed in the last larval instar (F0), males showing higher values of 5-HT and 5-HIAA, and females higher values of Trp. In all cases, 5-HIAA/5-HT ratio decreased down to F0 and increased in adult stage. A positive correlation between 5-HT and 5-HIAA in both males (P < 0.0005) and females (P < 0.0001) was also observed. Our data suggest that oxidative deamination of serotonin in Ischnura may have higher importance than in other insects.


[Plasma kallikrein: new functions].
The literature data on some new functions of human plasma kallikrein have been discussed. The role of kallikrein as an enzymatic activator of Hageman factor in fluid-phase was emphasized, and the description of this effect, brought about by a feedback mechanism was given. These new findings stress the importance of plasma kallikrein in the initiation of kinin-forming, intrinsing clotting and fibrinolysis. The chemotactic activity of the kallikrein molecule for human neurophiles was considered. New data were given concerning Hageman factor as proteinase and its substrates in human plasma-coagulation factor XI (PTA), plasminogen proectivator and prekallikrein.


Sociopolitical effects of bow and arrow technology in prehistoric coastal California.
Bow and arrow technology spread across California between ∼AD 250 and 1200, first appearing in the intermountain deserts of the Great Basin and later spreading to the coast. We critically evaluate the available data for the initial spread in bow and arrow technology and examine its societal effects on the well-studied Northern Channel Islands off the coast of Southern California. The introduction of this technology to these islands between AD 650 and 900 appears to predate the appearance of hereditary inequality between AD 900 and 1300. We conclude, based on the available data, that this technology did not immediately trigger intergroup warfare. We argue that the introduction of the bow and arrow contributed to sociopolitical instabilities that were on the rise within the context of increasing population levels and unstable climatic conditions, which stimulated intergroup conflict and favored the development of hereditary inequality. Population aggregation and economic intensification did occur with the introduction of the bow and arrow. This observation is consistent with the hypothesis that social coercion via intra-group "law enforcement" contributed to changes in societal scale that ultimately resulted in larger groups that were favored in inter-group conflict. We argue that the interplay between intra-group "law enforcement" and inter-group warfare were both essential for the ultimate emergence of social inequality between AD 900 and 1300.


Activated PAR-2 regulates pancreatic cancer progression through ILK/HIF-α-induced TGF-α expression and MEK/VEGF-A-mediated angiogenesis.
Tissue factor initiates the process of thrombosis and activates cell signaling through protease-activated receptor-2 (PAR-2). The aim of this study was to investigate the pathological role of PAR-2 signaling in pancreatic cancer. We first demonstrated that activated PAR-2 up-regulated the protein expression of both hypoxia-inducible factor-1α (HIF-1α) and HIF-2α, resulting in enhanced transcription of transforming growth factor-α (TGF-α). Down-regulation of HIFs-α by siRNA or YC-1, an HIF inhibitor, resulted in depleted levels of TGF-α protein. Furthermore, PAR-2, through integrin-linked kinase (ILK) signaling, including the p-AKT, promoted HIF protein expression. Diminishing ILK by siRNA decreased the levels of PAR-2-induced p-AKT, HIFs-α, and TGF-α; our results suggest that ILK is involved in the PAR-2-mediated TGF-α via an HIF-α-dependent pathway. Furthermore, the culture medium from PAR-2-treated pancreatic cancer cells enhanced human umbilical vein endothelial cell proliferation and tube formation, which was blocked by the MEK inhibitor, PD98059. We also found that activated PAR-2 enhanced tumor angiogenesis through the release of vascular endothelial growth factor-A (VEGF-A) from cancer cells, independent of the ILK/HIFs-α pathways. Consistent with microarray analysis, activated PAR-2 induced TGF-A and VEGF-A gene expression. In conclusion, the activation of PAR-2 signaling induced human pancreatic cancer progression through the induction of TGF-α expression by ILK/HIFs-α, as well as through MEK/VEGF-A-mediated angiogenesis, and it plays a role in the interaction between cancer progression and cancer-related thrombosis.


Microplastics could alter invasive plant community performance and the dominance of Amaranthus palmeri.
The increase in alien plant invasions poses a major threat to global biodiversity and ecosystem stability. However, the presence of microplastics (MPs) as an environmental stressor could impact the interactions between invasive and native species in an invasive plant community. Nevertheless, the community alterations and underlying mechanisms resulting from these interactions remain unclear. Herein, we systematically investigated the impacts of polyethylene (PE) and polypropylene (PP) on invasive plant communities invaded by Amaranthus palmeri through soil seed bank. The results illustrated that MPs markedly declined community height and biomass, and altered community structure, low-dose MPs could prominently increase community invasion resistance, but reduced community stability. The niche width and niche overlap of A. palmeri and S. viridis declined when exposed to high-dose MPs, but MPs elicited a significant rise in the niche width of S. salsa. PP had the potential to reduce the diversity of invasive plant community. Structural equation model revealed that PP addition could change soil total phosphorus content, thereby leading to a reduction of the community stability. Our study helps to fill the knowledge gap regarding the effects of MPs on invasive plant communities and provide new perspectives for invasive plant management.


Two-dimensional simulation of a high-gain, generalized self-filtering, unstable resonator.
The performance of a high-power excimer laser, generalized self-filtering, unstable resonator has been modeled by means of a numerical code. The spectral method and the Rigrod equations are basic to the numerical procedure, which is quite general because it results from an appropriate combination of independent propagation algorithms. The code can be applied to arbitrary resonator geometry and can be used to take account of gain medium inhomogeneities and instability phenomena.


Lipiodol lOcalization for Ground-glass opacity mInimal Surgery: Rationale and design of the LOGIS trial.
The diagnosis and treatment of ground-glass opacity (GGO) lesions have become important issues because subsolid nodules including GGO are known to frequently represent the histologic spectrum of lung adenocarcinoma. Because small GGO lesions cannot usually be palpated or visualized during surgery, several marking techniques have been reported for localization during thoracoscopic surgery, such as lipiodol and hook-wire localization. This study is designed to demonstrate the usefulness and safety of the lipiodol localization technique for individuals undergoing GGO VATS resection compared to the hook-wire localization technique. Two hundred fifty participants will be prospectively enrolled in a 1:1 manner to the lipiodol or hook-wire group according to the inclusion criteria. All study participants will undergo preoperative lung localization using either the lipiodol or hook-wire method. Thoracoscopic surgery will be performed by experienced thoracoscopic surgeons within several hours after marking under general anesthesia. The primary endpoint is the procedure success rate, and the secondary endpoints are the procedure complication rate, procedure time, surgery time and the margin from the lesion in the resected specimen. Patient enrollment will be completed within 2years. We will analyze the procedure success rate and the presence of complications with regard to the CT results. In addition, the procedure and surgery times, and the safety margin will be also compared between the 2 techniques. If the aims of this study are achieved, then the use of lipiodol localization technique will be widespread in the localization of non-palpable pulmonary lesions that are indicated for surgical resection. (ClinicalTrials.gov: NCT02180568).


Essentials of Theranostics: A Guide for Physicians and Medical Physicists.
Radiopharmaceutical therapies (RPTs) are gaining increased interest with the recent emergence of novel safe and effective theranostic agents, improving outcomes for thousands of patients. The term theranostics refers to the use of diagnostic and therapeutic agents that share the same molecular target; a major step toward precision medicine, especially for oncologic applications. The authors dissect the fundamentals of theranostics in nuclear medicine. First, they explain the radioactive decay schemes and the characteristics of emitted electromagnetic radiation used for imaging, as well as particles used for therapeutic purposes, followed by the interaction of the different types of radiation with tissue. These concepts directly apply to clinical RPTs and play a major role in the efficacy and toxicity profile of different radiopharmaceutical agents. Personalized dosimetry is a powerful tool that can help estimate patient-specific absorbed doses, in tumors as well as normal organs. Dosimetry in RPT is an area of active investigation, as most of what we know about the relationship between delivered dose and tissue damage is extrapolated from external-beam radiation therapy; more research is needed to understand this relationship as it pertains to RPTs. Tumor heterogeneity is increasingly recognized as an important prognostic factor. Novel molecular imaging agents, often in combination with fluorine 18-fluorodeoxyglucose, are crucial for assessment of target expression in the tumor and potential hypermetabolic disease that may lack the molecular target expression. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.


Temporary transverse colostomy vs loop ileostomy in diversion: a case-matched study.
For temporary fecal diversion, transverse colostomy (TC) has superior safety, but loop ileostomy (LI) has superior management qualities. Of patients with TC or LI seen between 1988 and 1997, 63 patients were matched for diagnosis, operative procedure, and date of surgery. The 2 groups were then compared for hospital/postoperative mortality and morbidity and stoma complications. Mortality rates were 6.3% for the TC group and 1.6% for the LI group (P =.25). Morbidity rates for stoma creation and for stoma closure were 47.6% and 10% (P =.19), respectively, for the TC group, and 36.5% and 6.3% (P>.99), respectively, for the LI group. Most morbidity events were minor, and neither procedure-related nor other medical complications showed a significant difference between the groups. However, patients with a TC were significantly more likely to experience skin trouble around the stoma (TC vs LI, 15.9% vs 3.2%) and leakage around the stoma (TC vs LI, 12.7% vs 1.6%). Regarding safety, TC and LI should be considered equivalent options for temporary fecal diversion. We recommend further study comparing the 2 procedures with regard to patient perception and quality of life.


Improving Suicide Prevention in Dutch Regions by Creating Local Suicide Prevention Action Networks (SUPRANET): A Study Protocol.
The European Alliance against Depression (EAAD) program is to be introduced in The Netherlands from 2017 onwards. This program to combat suicide consists of interventions on four levels: (1) increasing the awareness of suicide by local media campaigns; (2) training local gatekeepers, such as teachers or police officers; (3) targeting high-risk persons in the community; and (4) training and support of professionals in primary care settings. The implementation starts in seven Dutch pilot regions. Each region is designated as a Suicide Prevention Action NETwork (SUPRANET). This paper describes the SUPRANET program components and the evaluation of its feasibility and impact. The findings will be used to facilitate the national implementation of EAAD in The Netherlands and to add new findings to the existing literature on EAAD.


Central sympathoinhibition and peripheral neuronal uptake blockade after desipramine in rabbits.
Peripheral- and central nervous system (CNS)-mediated effects of desipramine (Des) on sympathetic nerves and the contribution of alpha 2-adrenoceptors to these effects were studied in conscious rabbits. Blood pressure, renal sympathetic nerve activity (SNA), and norepinephrine (NE) reuptake and spillover into plasma were measured before and after intracisternal (ic) or intravenous (i.v.) administration of Des. In other animals, NE spillover responses to i.v. Des were examined before and after alpha 2-adrenoceptor blockade with i.v. idazoxan. Treatment with i.v. Des blocked neuronal reuptake and decreased renal SNA but did not alter blood pressure or NE spillover. Decreased NE release by sympathetic nerves after i.v. Des was reflected by a decrease in the combined rate of NE reuptake and spillover. Treatment with ic Des (at 1.7% of the i.v. dose) decreased blood pressure and renal SNA and produced equivalent falls in NE reuptake and spillover, indicating little peripheral effect of centrally administered Des on the efficiency of neuronal reuptake. Thus Des had two distinct actions: the drug blocked neuronal reuptake by direct actions on nerve endings and reduced SNA by actions within the CNS. After ic Des, decreased SNA produced parallel falls in NE reuptake, spillover, and blood pressure. After i.v. Des, blockade of neurotransmitter reuptake increased NE concentrations at sympathoeffector junctions offsetting the fall in SNA, so that there was little change in NE spillover or blood pressure. However, after alpha 2-adrenoceptor blockade with i.v. idazoxan, NE spillover increased in response to i.v. Des. Thus the Des-induced decrease in NE release was partly mediated by an action of raised intrasynaptic NE concentrations on inhibitory alpha 2-adrenoceptors.


Multi-model implementation of evidence-based care in the treatment of opioid use disorder in Pennsylvania.
Pennsylvania has the third highest rate of death due to drug overdose (44.3 per 100,000) in the country, which is significantly higher than the national rate. This continues to have drastic societal impact. Medication assisted treatment (MAT), which includes opioid agonist medications, is the gold standard in treatment for OUD; however, a significant gap remains between the number of individuals in need of treatment and the number of MAT providers. Penn State Health established a system to address the opioid epidemic through the Pennsylvania Coordinated Medication Assisted Treatment program utilizing lessons learned from existing validated models. Connecting primary care sites and hospital systems through a combination of Hub and Spoke, bridge clinic services provided at the Hub, peer recovery services, Project Extension for Community Health Outcomes (ECHO), and layered emergency department (ED) initiation of buprenorphine, this model is an innovative approach that addresses many known barriers to MAT treatment initiation. Early results within the first six months indicate significantly shortened wait time for patients seeking treatment, provision of waiver training to 70 local physicians to prescribe buprenorphine, and improved knowledge and ability to provide patient care for providers participating in our first Project ECHO cohort.


Seroprevalence of hepatitis B, hepatitis C, and HIV in pregnant women from Eastern Turkey.
The vertical transmission of hepatitis B virus, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections are essential public health problems. In this study, we aimed to investigate the seroprevalence of the aforementioned infections among pregnant women. This study was done retrospectively on pregnant women who presented for antenatal follow-up and delivery between 2013 and 2016. Data were collected from the hospital's electronic health records and patient files. Blood samples were analyzed at the microbiology laboratory of the hospital. HBsAg, anti-HBs, anti-HCV, and anti-HIV titers were tested using the chemiluminescence enzyme immunoassay method (Architect, Abbott Laboratories, USA). HBsAg and anti-HBs levels were tested in 35,295 pregnant women aged 18-45 years. The HBsAg and anti-HBs levels were positive in 425 (1.2%) and 9583 (27.7%) patients, respectively. From 2013 to 2016, the HBV carrier rates have continuously decreased from 1.4% to 0.8%, whereas the anti-HBs positivity has increased from 25.4% to 30.2%. Anti-HCV was detected in 6 of the 9709 (0.06%) patients. All the 7113 pregnant women screened for HIV showed negative results. Hepatitis B carrier rates among pregnant women gradually decreased with a simultaneous increase in the immunity rates. HCV seroprevalence was low and HIV positivity was not encountered in the study population.


All-terrain vehicle-related nonfatal injuries among young riders in the United States, 2001-2010.
To estimate the numbers and rates of all-terrain vehicle (ATV)-related nonfatal injuries among riders aged ≤ 15 years treated in hospital emergency departments (EDs) in the United States during 2001-2010. National Electronic Injury Surveillance System-All Injury Program data for 2001-2010 were analyzed. Numbers and rates of injuries were examined by age group, gender, primary body part injured, diagnosis, and hospital admission status. During 2001-2010, an estimated 361,161 ATV riders aged ≤ 15 years were treated in EDs for ATV-related injuries. The injury rate peaked at 67 per 100,000 children in 2004 and then declined to 42 per 100,000 children by 2010. The annualized injury rate for boys was double that of girls (73 vs 37 per 100,000). Children aged 11 to 15 years accounted for two-thirds of all ED visits and hospitalizations. Fractures accounted for 28% of ED visits and 45% of hospitalizations. The reasons for the decline in ATV-related injuries among young riders are not well understood but might be related to the economic recession of the mid-2000s and decreased sales of new ATVs. Although many states have regulations governing children's use of ATVs, their effectiveness in reducing injuries is unclear. Broader use of known effective safety measures, including prohibiting children aged ≤ 15 years from riding adult-sized ATVs, always wearing a helmet while riding, not riding on paved roads, and not riding as or carrying a passenger could additionally reduce ATV-related injuries among children. Last, more research to better understand ATV crash dynamics might lead to safer designs for ATVs.


Incidence of uterine post abortion infection at Hospital de Clínicas de Porto Alegre. Is prophylactic antibiotic necessary?
To identify the incidence of pelvic infection after miscarriage undergoing uterine evacuation in a tertiary hospital in southern Brazil and to compare with the international literature. we reviewed electronic medical records of the Hospital de Clinicas de Porto Alegre of all patients who underwent uterine evacuation for miscarriage between August 2008 and January 2012 were reviewed. We included all patients submitted to uterine curettage due to abortion and who had outpatient visits for review after the procedure. We calculated emographic and laboratory data of the study population, number needed for treatment (NNT) and number needed to harm (NNH). of the 857 revised electronic medical records, 377 patients were subjected to uterine evacuation for miscarriage; 55 cases were lost to follow-up, leaving 322 cases that were classified as not infected abortion on admission. The majority of the population was white (79%); HIV prevalence and positive VDRL was 0.3% and 2%, respectively. By following these 322 cases for a minimum of seven days, it was found that the incidence of post-procedure infection was 1.8% (95% CI 0.8 to 4). The NNT and NNH calculated for 42 months were 63 and 39, respectively. The incidence of post-abortion infection between August 2008 to January 2012 was 1.8% (0.8 to 4).


Addressing the inappropriate use of force by police in the United States and beyond: A behavioral and social science perspective.
Recent high-profile incidents involving the deadly application of force in the United States sparked worldwide protests and renewed scrutiny of police practices as well as scrutiny of relations between police officers and minoritized communities. In this report, we consider the inappropriate use of force by police from the perspective of behavioral and social science inquiry related to aggression, violence, and intergroup relations. We examine the inappropriate use of force by police in the context of research on modern policing as well as critical race theory and offer five recommendations suggested by contemporary theory and research. Our recommendations are aimed at policymakers, law enforcement administrators, and scholars and are as follows: (1) Implement public policies that can reduce inappropriate use of force directly and through the reduction of broader burdens on the routine activities of police officers. (2) For officers frequently engaged in use-of-force incidents, ensure that best practice, evidence-based treatments are available and required. (3) Improve and increase the quality and delivery of noncoercive conflict resolution training for all officers, along with police administrative policies and supervision that support alternatives to the use of force, both while scaling back the militarization of police departments. (4) Continue the development and evaluation of multicomponent interventions for police departments, but ensure they incorporate evidence-based, field-tested components. (5) Expand research in the behavioral and social sciences aimed at understanding and managing use-of-force by police and reducing its disproportionate impact on minoritized communities, and expand funding for these lines of inquiry.


A Multi-Layer Classifier Model XR-KS of Human Activity Recognition for the Problem of Similar Human Activity.
Sensor-based human activity recognition is now well developed, but there are still many challenges, such as insufficient accuracy in the identification of similar activities. To overcome this issue, we collect data during similar human activities using three-axis acceleration and gyroscope sensors. We developed a model capable of classifying similar activities of human behavior, and the effectiveness and generalization capabilities of this model are evaluated. Based on the standardization and normalization of data, we consider the inherent similarities of human activity behaviors by introducing the multi-layer classifier model. The first layer of the proposed model is a random forest model based on the XGBoost feature selection algorithm. In the second layer of this model, similar human activities are extracted by applying the kernel Fisher discriminant analysis (KFDA) with feature mapping. Then, the support vector machine (SVM) model is applied to classify similar human activities. Our model is experimentally evaluated, and it is also applied to four benchmark datasets: UCI DSA, UCI HAR, WISDM, and IM-WSHA. The experimental results demonstrate that the proposed approach achieves recognition accuracies of 97.69%, 97.92%, 98.12%, and 90.6%, indicating excellent recognition performance. Additionally, we performed K-fold cross-validation on the random forest model and utilized ROC curves for the SVM classifier to assess the model's generalization ability. The results indicate that our multi-layer classifier model exhibits robust generalization capabilities.


Sulforaphane inhibits pancreatic cancer through disrupting Hsp90-p50(Cdc37) complex and direct interactions with amino acids residues of Hsp90.
Sulforaphane [1-isothiocyanato-4-(methyl-sulfinyl) butane)], an isothiocyanate derived from cruciferous vegetables, has been shown to possess potent chemopreventive activity. We analyzed the effect of sulforaphane on the proliferation of pancreatic cancer cells. Sulforaphane inhibited pancreatic cancer cell growth in vitro with IC(50)s of around 10-15 μM and induced apoptosis. In pancreatic cancer xenograft mouse model, administration of sulforaphane showed remarkable inhibition of tumor growth without apparent toxicity noticed. We found that sulforaphane induced the degradation of heat shock protein 90 (Hsp90) client proteins and blocked the interaction of Hsp90 with its cochaperone p50(Cdc37) in pancreatic cancer cells. Using nuclear magnetic resonance spectroscopy (NMR) with an isoleucine-specific labeling strategy, we overcame the protein size limit of conventional NMR and studied the interaction of sulforaphane with full-length Hsp90 dimer (170 kDa) in solution. NMR revealed multiple chemical shifts in sheet 2 and the adjacent loop in Hsp90 N-terminal domain after incubation of Hsp90 with sulforaphane. Liquid chromatography coupled to mass spectrometry further mapped a short peptide in this region that was tagged with sulforaphane. These data suggest a new mechanism of sulforaphane that disrupts protein-protein interaction in Hsp90 complex for its chemopreventive activity.


Abnormal ion permeation through cystic fibrosis respiratory epithelium.
The epithelium of nasal tissue excised from subjects with cystic fibrosis exhibited higher voltage and lower conductance than tissue from control subjects. Basal sodium ion absorption by cystic fibrosis and normal nasal epithelia equaled the short-circuit current and was amiloride-sensitive. Amiloride induced chloride ion secretion in normal but not cystic fibrosis tissue and consequently was more effective in inhibiting the short-circuit current in cystic fibrosis epithelia. Chloride ion-free solution induced a smaller hyperpolarization of cystic fibrosis tissue. The increased voltage and amiloride efficacy in cystic fibrosis reflect absorption of sodium ions across an epithelium that is relatively impermeable to chloride ions.


[Difficulties in access to treatment for patients undergoing cataract surgery in public and private health systems].
To identify the difficulties in access to diagnosis and treatment of cataract in patients attended during a cataract campaign. A questionnaire was administered to patients selected for cataract surgery. We evaluated, among others, the following variables: prior access to ophthalmologists (public or private), reason(s) for not having surgery early in the initial service, the average cost charged by cataract surgery and intraocular lens (IOL) (private services and agreements). A total of 627 patients was evaluated. Most of them - 595 (95%) had previously attended an ophthalmologist, and in 63% of cases (375 patients) the consultation had been held for less than a year. The last evaluation was performed by the Brazilian Public Health System (SUS) in 52% of the cases (307 patients). Regarding the reason for not having surgery in the initial service, the high cost of the surgery (R$ 2.000 - R$ 4.000) and the cost of IOLs (R$ 1.000 - R$ 1.500) was the main obstacle for most attended services and private covenants. The results of this study suggest that the routine of ophthalmologic care in SUS at São Paulo is not prepared to answer the demand for cataract surgeries and private healthcare system still excludes a portion of the population. It is important to continue the implementation of community campaigns to serve the population that would be unable to access the surgery through conventional ways.


Synergistic induction of apoptosis in a cell model of human leukemia K562 by nitroglycerine and valproic acid.
Nitroglycerin (NG), a nitric oxide donor, and valproic acid (VPA), an inhibitor of histone deacetylases, have impressive effects on numerous cancer cell lines. This study intended to evaluate synergistic effects of NG and VPA on cell viability and apoptosis in K562 cells. K562 cells were cultured in RPMI-1640 supplemented with 10 % heat-inactivated FBS. They were treated with different doses of NG, VPA and cisplatin for 24, 48, and 72 h, and MTT assay was performed to analyze cell viability. Also, Peripheral blood mononuclear cells (PBMC) were cultured in RPMI-1640 media and incubated with NG (200 μM), VAP (100 μM), NG+VPA (150 μM) and cisplatin (8 μM) to evaluate cytotoxicity. IC50 of the drugs, when they were applied separately and in combination, were calculated using the COMPUSYN software. DNA electrophoresis, TUNEL assay, and Hoechst staining were performed to investigate apoptosis induction. RT-PCR was used for the evaluation of apoptotic genes expression. The results of the MTT assay showed that cell viability decreased at all applied doses of NG and VPA. It was noticed that the cytotoxic effects of these drugs were dose- and time-dependent. Based on the COMPUSYN output, the combination of the drugs (VPA and NG) in a certain ratio concentration synergistically decreased cell viability. Cisplatin significantly decreased cell viability of PBMCs and K562 cells. Also, the combination drug had cytotoxic effect and significantly reduced viability of K562 cells compared with PBMCs and control cells. In the target cells treated with this combination, Bax and caspase-3 expression increased but Bcl-2 expression decreased. These results suggest that NG, VPA, and their combination decreased cell viability and induced apoptosis via the intrinsic apoptotic pathway. This study suggests that this combination therapy can be considered for further evaluation as an effective chemotherapeutic strategy for patients with chronic myeloid leukemia.


In-Line Analysis of Diffusion Processes in Micro Channels by Long Distance Raman Photometric Measurement Technology-A Proof of Concept Study.
This work presents a novel method for the non-invasive, in-line monitoring of mixing processes in microchannels using the Raman photometric technique. The measuring set-up distinguishes itself from other works in this field by utilizing recent state-of-the-art customized photon multiplier (CPM) detectors, bypassing the use of a spectrometer. This addresses the limiting factor of integration times by achieving measuring rates of 10 ms. The method was validated using the ternary system of toluene-water-acetone. The optical measuring system consists of two functional units: the coaxial Raman probe optimized for excitation at a laser wavelength of 532 nm and the photometric detector centered around the CPMs. The spot size of the focused laser is a defining factor of the spatial resolution of the set-up. The depth of focus is measured at approx. 85 µm with a spot size of approx. 45 µm, while still maintaining a relatively high numerical aperture of 0.42, the latter of which is also critical for coaxial detection of inelastically scattered photons. The working distance in this set-up is 20 mm. The microchannel is a T-junction mixer with a square cross section of 500 by 500 µm, a hydraulic diameter of 500 µm and 70 mm channel length. The extraction of acetone from toluene into water is tracked at an initial concentration of 25% as a function of flow rate and accordingly residence time. The investigated flow rates ranged from 0.1 mL/min to 0.006 mL/min. The residence times from the T-junction to the measuring point varies from 1.5 to 25 s. At 0.006 mL/min a constant acetone concentration of approx. 12.6% was measured, indicating that the mixing process reached the equilibrium of the system at approx. 12.5%. For prototype benchmarking, comparative measurements were carried out with a commercially available Raman spectrometer (RXN1, Kaiser Optical Systems, Ann Arbor, MI, USA). Count rates of the spectrophotometer surpassed those of the spectrometer by at least one order of magnitude at identical target concentrations and optical power output. The experimental data demonstrate the suitability and potential of the new measuring system to detect locally and time-resolved concentration profiles in moving fluids while avoiding external influence.


[Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection: the clinical, neuroimaging, virological and evolutive characteristics in 35 patients].
The clinical, neuroimaging, virologic and evolutive characteristics of progressive multifocal leukoencephalopathy (PML) in 35 AIDS patients are studied. PML was diagnosed by clinical and neuroimaging criteria in 32 patients and by autopsy in other three. The detection of JC virus (JCV) was done by PCR and further hybridization of the amplified DNA in peripheral blood lymphocytes, urine and CSF. 127 of 930 HIV positive patients were admitted by neuropsychiatric symptoms and of them 35 (SD 27.6%) by PML. The PML patients had a mean CD4 lymphocytes count of 75.3 (82.0)/x 10(6)/l and a HIV viral load of 330,698 (538,971) copies of RNA/ml. Thirty patients did not receive any anti-retroviral therapy or only transcriptase inhibitors monotherapy and five triple anti-retroviral therapy, including a proteases inhibitor. Multiple hypodense lesions on CT (53.1%) and T2 hyperintense lesions on MRI (58.3%) were the most frequent neuroimaging findings. JCV was detected in 20/21 (95.2%) LMP patients: 18/19 detections in lymphocytes, 6/8 in CSF and 4/6 in urine. The mean survival without and with antiretroviral therapy were 3.0 (0.47) and 21.4 (4.4) months (p < 0.001) in 34 patients followed. PML progressed to death in 31/34 patients (91.2%), and remained stable in 3/34 (8.8%). A patient was lost for follow-up. The application of clinical and neuroimaging criteria and the detection of JCV in CSF are useful for high presumption diagnosis of PML without brain biopsies. JCV detection in lymphocytes and in urine have a much lower predictive value. The evolution and survival of this disease can improve with triple anti-retroviral therapy including a protease inhibitor.


The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias.
Myalgias are the most common side effect of statin use and the commonest cause for discontinuing therapy. Vitamin D has known physiologic functions in muscle and vitamin D deficiency is known to cause myalgias, with its correction leading to disappearance of muscle symptoms. The 521T>C SLCO1B1*5 gene polymorphism decreasing function in the gene coding for a liver anion transporter that is responsible for statin uptake has been found to explain the majority of statin-associated muscle symptoms. Patients with statin-associated myalgias have been reported to improve with vitamin D supplementation. We therefore investigated (i) whether repletion of vitamin D in deficient patients with myalgias could lead to tolerance for subsequent statin therapy and (ii) whether vitamin D status modifies the effect of the SLCO1B1*5 genotype on myalgia risk. Using a retrospective cohort of 64 patients in whom 25-hydroxyvitamin D [25(OH)D] had been measured for any reason while on statin therapy, including 46 patients who consented to be genotyped, we found strong evidence showing that repletion of vitamin D in vitamin D deficient patients improved myalgias. Of 21 vitamin D deficient patients with intolerable statin-associated myalgias, 14 of 15 rechallenged with statins were subsequently symptomfree, with one patient experiencing mild and tolerable symptoms, far exceeding expected rates of acquired tolerability with no therapy (p = 0.01). In addition, while the SLCO1B1*5 genotype was associated with a three-fold increased risk of myalgias (p = 0.07), this risk was not found to differ by vitamin D status (p = 0.60).


Sea-ice transport driving Southern Ocean salinity and its recent trends.
Recent salinity changes in the Southern Ocean are among the most prominent signals of climate change in the global ocean, yet their underlying causes have not been firmly established. Here we propose that trends in the northward transport of Antarctic sea ice are a major contributor to these changes. Using satellite observations supplemented by sea-ice reconstructions, we estimate that wind-driven northward freshwater transport by sea ice increased by 20 ± 10 per cent between 1982 and 2008. The strongest and most robust increase occurred in the Pacific sector, coinciding with the largest observed salinity changes. We estimate that the additional freshwater for the entire northern sea-ice edge entails a freshening rate of -0.02 ± 0.01 grams per kilogram per decade in the surface and intermediate waters of the open ocean, similar to the observed freshening. The enhanced rejection of salt near the coast of Antarctica associated with stronger sea-ice export counteracts the freshening of both continental shelf and newly formed bottom waters due to increases in glacial meltwater. Although the data sources underlying our results have substantial uncertainties, regional analyses and independent data from an atmospheric reanalysis support our conclusions. Our finding that northward sea-ice freshwater transport is also a key determinant of the mean salinity distribution in the Southern Ocean further underpins the importance of the sea-ice-induced freshwater flux. Through its influence on the density structure of the ocean, this process has critical consequences for the global climate by affecting the exchange of heat, carbon and nutrients between the deep ocean and surface waters.


Heterogeneity of brain blood flow and permeability during acute hypertension.
The purpose of this study was to examine regional autoregulation of blood flow in the brain during acute hypertension. In anesthetized cats severe hypertension increased blood flow more in cerebrum (159%) and cerebellum (106%) than brain stem (58%). In contrast to the heterogeneous autoregulatory response, hypocapnia produced uniform vasoconstriction in the brain. We also compared vasodilatation during severe hypertension with vasodilatation during hypercapnia. During hypercapnia, blood flow increased as much in brain stem, as in cerebrum and cerebellum. Thus regional differences in autoregulation appear to be specific for autoregulatory stimulus and are not secondary to nonspecific differences in vasoconstrictor or vasodilator capacity. To determine whether the blood-brain barrier is more susceptible to hypertensive disruption in regions with less effective autoregulation, permeability of the barrier was quantitated with 125I-albumin. Severe hypertension produced disruption of the barrier in cerebrum but not in brain stem. Thus there are parallel differences in effectiveness of autoregulation and susceptibility to disruption of the blood-brain barrier in different regions of the brain.


Epigallocatechin Gallate Modulates Microglia Phenotype to Suppress Pro-inflammatory Signalling Cues and Inhibit Phagocytosis.
Microglia are crucial players in the pathogenesis of late-onset Alzheimer's disease (AD), with evidence for both deleterious and beneficial effects. Identifying interventions to modulate microglial responsiveness, promote amyloid β (Aβ) clearance, disrupt plaque formation, or dampen excessive inflammation has therapeutic potential. Bioavailable flavonoids, such as the flavan 3-ols, are of interest due to their antioxidant, metal chelating, signalling, and anti-inflammatory potential. Primary microglia were treated with a series of structurally related flavanol 3-ols to assess effects on phagocytosis, cytokine release, and transcriptional responses by RNA sequencing. Data indicated that the extent of hydroxylation and the presence of the galloyl moiety were strong determinants of flavan 3-ol activity. Epigallocatechin gallate (EGCG) was the most effective flavan-3-ol tested and strongly inhibited phagocytosis of Aβ independent of any metal chelating properties, suggesting a more direct modulation of microglia responsiveness. EGCG was broadly anti-inflammatory, reducing cytokine release and downregulating transcription, particularly of components of the microglia extracellular matrix such as MMP3 and SerpinB2. Collectively, this brings new insight into the actions of flavonoids on microglial responsiveness with potential implications for the therapeutic use of EGCG and structurally related flavanol-3-ols in AD.


Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2.
To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study. We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type. Multicenter population study. This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort. Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease. Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores. The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.


Lungworms and gastrointestinal parasites of domestic cats: a European perspective.
With the exception of Aelurostrongylus abstrusus, feline lungworms have been poorly studied. Information on their distribution is patchy and mostly limited to case reports. In this study, the occurrence of feline lungworms and co-infecting gastrointestinal parasites has been investigated in 12 European countries (i.e. Austria, Belgium, Bulgaria, France, Greece, Hungary, Italy, Portugal, Romania, Spain, Switzerland and the United Kingdom). An average of 10 domestic cats, with regular outdoor access, was sampled each month for 12months, and freshly passed faeces were collected. Stools were processed using a McMaster assay and a quantitative Baermann-Wetzel method. Animals positive for lungworms and/or gastrointestinal parasites were treated with a formulation containing fipronil, (S)-methoprene, eprinomectin, and praziquantel (Broadline®, Merial), and re-sampled 28days post-treatment. The association between lungworm infection and risk factors was analysed using statistical medians/means and the efficacy of the treatment against each lungworm species was assessed. Of 1990 cats sampled, 613 (30.8%) were positive for at least one parasite, while 210 (10.6%) were infected by lungworms. The prevalence of lungworm infection varied between the sampled sites, with the highest recorded in Bulgaria (35.8%) and the lowest in Switzerland (0.8%). None of the cats from Austria or the United Kingdom were infected by lungworms. Aelurostrongylus abstrusus was the species most frequently detected (78.1%), followed by Troglostrongylus brevior (19.5%), Eucoleus aerophilus (14.8%) and Oslerus rostratus (3.8%). The overall efficacy of the treatment was 99% for A. abstrusus and 100% for T. brevior, O. rostratus and E. aerophilus. Data presented provide a comprehensive account of the diagnosis, epidemiology and treatment of feline lungworms in Europe, as well as of the occurrence of co-infections by gastrointestinal parasites.


Detection and molecular characterization of Babesia canis vogeli from naturally infected dogs and Rhipicephalus sanguineus ticks in Tunisia.
Canine babesiosis, caused by intra-erythrocytic Babesia, is a tick-borne disease of worldwide importance. No information on canine babesiosis has been documented in Tunisia. Detection and analysis of Babesia species from naturally infected dogs and ticks recovered from dogs were attempted by reverse line blot hybridization and nucleotide sequence analysis based on 18S rRNA gene. Out of 180 blood samples collected from domestic dogs in 4 villages situated in different bioclimatic zones, 12 were positive for Babesia canis vogeli. In addition, a total of 160 Rhipicephalus sanguineus were analysed; only one male was infected by B. canis vogeli. This is the first report on the detection of DNA belonging to B. canis vogeli in domestic dogs and in R. sanguineus in Tunisia.


The assessment of knowledge and awareness about iron deficiency anemia among the population of Riyadh province.
Iron deficiency anemia (IDA) is considered the most common micronutrient deficiency and the greatest health concern throughout the globe. The main causes of anemia are iron deficiency, parasitic infestations, viral infections (human immunodeficiency virus), hemorrhage, and renal and hepatic diseases. Therefore, it is mandatory to be equipped with the proper knowledge regarding the causes, signs, symptoms, and diets containing iron, which can be a good initiative for the proper treatment and management of the health hazards; also, it will help primary care physicians to differentiate the degree of the disease and further treatment, planning, and management. The recent study was performed to understand the level of knowledge and awareness about IDA and its causes, prevention, and treatment. The study was carried out through an online survey using Google forms, which were distributed to the population residing in Riyadh Province. The responses received about the knowledge regarding IDA and its symptoms indicated weakness [565 (52.9%)], cold hands and feet [593 (55.5%)], and hair loss [663 (62.1)], and the majority (84.3%) of the participants believed that the major cause for IDA is malnutrition. Conclusively, it was believed that the presented study will be helpful to primary care physicians, the patients suffering from IDA, and the general population with a better understanding of the causes, additional signs and symptoms, proper treatment, timely management, sources of iron, and how to avoid the worse outcomes and complications of the disease. It will also help the health agencies in the kingdom to set further planning for the treatment and management of the disease through awareness platforms.


[Recent Advances in Diagnosis and Treatment Strategies for Multiple Primary Lung Cancer].
As the utilization of computed tomography in lung cancer screening becomes more prevalent in the post-pandemic era, the incidence of multiple primary lung cancer (MPLC) has surged in various countries and regions. Despite the continued application of advanced histologic and sequencing technologies in this research field, the differentiation between MPLC and intrapulmonary metastasis (IM) remains challenging. In recent years, the specific mechanisms of genetic and environmental factors in MPLC have gradually come to light. Lobectomy still predominates in the treatment of MPLC, but the observation that tumor-specific sublobar resection has not detrimentally impacted survival appears to be a viable option. With the evolution of paradigms, the amalgamated treatment, primarily surgical, is an emerging trend. Among these, stereotactic ablative radiotherapy (SABR) and lung ablation techniques have emerged as efficacious treatments for early unresectable tumors and control of residual lesions. Furthermore, targeted therapies for driver-positive mutations and immunotherapy have demonstrated promising outcomes in the postoperative adjuvant phase. In this manuscript, we intend to provide an overview of the management of MPLC based on the latest discoveries. .


Greater viral rebound and reduced time to resume antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452).
Evaluate immunogenicity and clinical efficacy of two immunization strategies with the ALVAC-HIV-recombinant canarypox vaccine (vCP1452) in treated HIV-infected patients. Randomized, double-blind, placebo-controlled, phase II study of vCP1452 immunization in chronically HIV-infected patients on therapy with CD4 T-cell count more than 350 cells/microl, CD4 nadir less than 400 cells/microl and pHIV-RNA less than 400 copies/ml. Patients were equally randomized to four injections at weeks 0, 4, 8, 20; three injections at weeks 4, 8, 20; and placebo. The primary endpoint was vaccine immunogenicity at week 24 measured by enzyme-linked immunospot-interferon-gamma against the HIV-gag-reverse transcriptase-nef vaccine sequences. Secondary endpoints included time to treatment resumption and viral quantitation following treatment interruption at week 24. Criteria to resume therapy included CD4 T-cell count decline less than 250 cells/microl or 50% decrease from baseline or pHIV-RNA more than 50,000 copies/ml. Sixty-five patients enrolled. Changes from baseline in HIV-specific T cells in the four injection arms (+480 spot-forming cells/M-peripheral blood mononuclear cell) were significant compared to placebo (+8; P = 0.014), but not in the three injection arms (+322). The week 36 pHIV-RNA (log10 copies/ml) after treatment interruption was higher in the four (4.71; P = 0.023) and three (4.82; P = 0.009) injection arms compared to placebo (4.40). Percentages of patients reaching treatment resumption criteria by week 48 were 74, 55 and 23% in the three respective arms (P = 0.013). Two independent factors influenced time to therapy resumption: immunization (hazards ratio = 2.7, P = 0.048 for three injections; hazards ratio = 4.1, P = 0.003 for four injections) and CD4 nadir (hazards ratio = 0.4, P = 0.002). Significant immunogenicity was induced by vCP1452; however, this strategy was independently associated with a shorter time to resume therapy and higher viral rebound.


Hierarchical Micro- and Mesoporous Zn-Based Metal-Organic Frameworks Templated by Hydrogels: Their Use for Enzyme Immobilization and Catalysis of Knoevenagel Reaction.
Encapsulation of enzymes in metal-organic frameworks (MOFs) is often obstructed by the small size of the orifices typical of most reported MOFs, which prevent the passage of larger-size enzymes. Here, the preparation of hierarchical micro- and mesoporous Zn-based MOFs via the templated emulsification method using hydrogels as a template is presented. Zinc-based hydrogels featuring a 3D interconnecting network are first produced via the formation of hydrogen bonds between melamine and salicylic acid in which zinc ions are well distributed. Further coordination with organic linkers followed by the removal of the hydrogel template produces hierarchical Zn-based MOFs containing both micropores and mesopores. These new MOFs are used for the encapsulation of glucose oxidase and horseradish peroxidase to prove the concept. The immobilized enzymes exhibit a remarkably enhanced increased operational stability and enzymatic activity with a kcat /km value of 85.68 mm s-1 . This value is 7.7-fold higher compared to that found for the free enzymes in solution, and 2.7-fold higher than enzymes adsorbed on conventional microporous MOFs. The much higher catalytic activity of the mesoporous conjugate for Knoevenagel reactions is demonstrated, since the large pores enable easier access to the active sites, and compared with that observed for catalysis using microporous MOFs.


Dual quantitative coronary angiography accurately quantifies intracoronary thrombotic burden in patients with acute coronary syndrome: Comparison with optical coherence tomography imaging.
Dual quantitative coronary angiography (QCA) has been recently tested for assessment of intracoronary thrombus volume in experimental models. The present study aimed to validate dual QCA in vivo for the assessment of thrombus burden by exploring the correlations between dual QCA-thrombus volume and optical coherence tomography (OCT)-derived indices of thrombotic burden. Fifty-one patients with ACS and angiographic evidence of thrombus undergoing OCT of the culprit lesion before stenting were included. Dual QCA-thrombus volume was calculated as difference between edge-detection and video-densitometry area functions along the target segment. Culprit lesion was categorized using the Ambrose's and AHA/ACC angiographic classifications. Thrombus volume (mean thrombus area × thrombus length), thrombus burden [(mean thrombus area/mean lumen area) x100] and Prati thrombus score (number of quadrants with thrombus) were measured by OCT, and the presence of plaque rupture (PR) or intact fibrous cap (IFC) was assessed. Dual QCA-thrombus volume correlated significantly with OCT-thrombus volume (R = 0.791), thrombus burden (R = 0.767) and Prati thrombus score (R = 0.600) (all p < 0.001). Dual-QCA thrombus volume was significantly higher in patients with PR compared with those with IFC (3.48 mm3 [1.45-11.26] vs. 1.69 mm3 [0.09-5.02], p = 0.013). Compared with IFC, PR showed higher prevalence of eccentric type II Ambrose lesion (41.7% vs. 7.4%, p = 0.004), complex B2/C lesion (87.5% vs. 55.6%, p = 0.012), and heavy calcification (29.2% vs. 3.7%, p = 0.013). Dual QCA analysis appears to be a promising tool for quantification of intracoronary thrombus in vivo. This novel methodology may be useful to guide intracoronary thrombus removal during percutaneous coronary intervention and to aid prognostic stratification in patients with ACS.


Chaplaincy, Spiritual Care and Moral Injury: Considerations Regarding Screening and Treatment.
Moral injury is a complex trauma related syndrome involving a correlation of biological, psychological, social, and spiritual symptoms that can have substantial impact upon health and well-being. This paper argues for a holistic bio-psycho-social-spiritual approach to moral injury, by including chaplaincy in the screening and treatment of moral injury among actively serving military members and retired veterans. As part of the moral injury treatment process, and in alignment with the World Health Organization's Spiritual Intervention Codings, a new technique is proposed, "Pastoral Narrative Disclosure" (PND), as a guide for chaplains and others trained in spiritual care to assist those suffering from moral injury.


Experimental infection of domestic cats with passaged genotype I Bartonella henselae.
The influence of in vitro passage on Bartonella henselae pathogenesis in cats has not been thoroughly evaluated. Our objective was to examine the bacterial kinetics and humoral immune responses in cats experimentally infected with three different in vitro passages of B. henselae F1, a genotype I strain of feline origin. The F1 strain was in vitro passaged 20 and 40 times, and each was inoculated into a group of 5 cats. The kinetics of bacteremia and the feline humoral immune response to bacterial antigens were compared to a previous study involving a group of six cats inoculated with the original F1 strain. Among the three groups of cats, the kinetics of bacteremia profiles and the humoral immune responses to B. henselae lysates were similar. The influence of passage on bacterial membrane proteins was examined. In vitro passage altered the expression of 4/17 (23.5%) bacterial membrane proteins and 6/15 (40%) bacterial membrane antigens. An association between poor seroreactivity to three lysate antigens (15-, 18- and 45kDa), prolonged bacteremia and decreased serum bactericidal activity was noted. Our data show that in vitro passage of B. henselae did not alter the kinetics of bacteremia, including the occurrence of relapsing bacteremia, in experimentally infected cats. This suggests that highly passaged strains may not be suitable for future vaccination studies. Furthermore, in vitro passage results in phenotypic and antigenic changes in the bacterial membrane protein profile, which warrants caution in the interpretation of studies involving passaged B. henselae strains.


The effectiveness of a group intervention to facilitate posttraumatic growth among women with breast cancer.
This longitudinal study tested the effectiveness of a group intervention designed to facilitate posttraumatic growth (PTG). Sample consisted of 205 women diagnosed with non-metastatic breast cancer who were either assigned to an intervention group (n = 58) or to a control group (n = 147). PTG, challenge to core beliefs, and rumination (intrusive and deliberate) were assessed at baseline (T1), at 6 months (T2), and at 12 months after baseline (T3). Results from the Latent Growth Modeling suggested that participants from the intervention group have higher levels of PTG. The challenge to core beliefs and the intrusive rumination have a moderator role on PTG, since group intervention is also linked to the enhancement of both variables. Participation in the intervention group increase PTG. Challenge to core beliefs and intrusive rumination are improved by group intervention, which to a certain extent facilitate PTG.


[Focused ultrasound for treatment of uterine myoma: from experimental model to clinical practice].
It is well known that focused ultrasound has a biologic effect on tissue. High intensity focused ultrasound (HIFU) on a small target area raises the temperature of the tissue enough to denaturate proteins and cause irreversible cell damage. The tight focus of the ultrasound energy allows delivery of the intended dose to a very precise location. The resulting coagulation necrosis is relatively painless. The application of this method in the human clinical setting has required pilot studies on an animal model. Although the treatment had a high success rate, there was a significant percentage of complications, mainly attributed to the technical drawbacks of the procedure. Therefore, this method has been modified for use in humans, and the HIFU is now guided, monitored and controlled by magnetic resonance imaging (MRI). In October 2004, Food and Drug Adiministration (FDA) approved MRI guided focused ultrasound treatment of uterine fibroids in humans. Since then, successful treatment of uterine myomas by HIFU has been performed in thousands of women.


CB2 cannabinoid receptors promote mouse neural stem cell proliferation.
Neurospheres are clonal cellular aggregates of neural stem/precursor cells that grow in culture as free-floating clusters. Activation of CB1 cannabinoid receptors, which are expressed by these cells, promotes proliferation. In the present study we investigated the expression of CB2 cannabinoid receptors and the effect of exogenous cannabinoids on neural stem/precursor cell proliferation. Neurospheres containing nestin-positive and sn-1 diacylglycerol lipase alpha-positive cells expressed both CB1 and CB2 receptors, which were maintained through several passages. Application of the non-selective cannabinoid agonist (HU-210, 0.5 microM) stimulated bromodeoxyuridine incorporation and neurosphere formation. This action involved both CB1 and CB2 receptors as neurosphere formation was stimulated by either selective CB1 [arachidonyl-2'chloroethylamide/(all Z)-N-(2-cycloethyl)-5,8,11,14-eicosatetraenamide (ACEA), 200 nM and 1 microM] or CB2 (JWH-056, 0.5 microM) agonists. In addition, CB1 or CB2 antagonists (1 microM SR-141716A and SR-144528, respectively) blocked basal proliferation, suggesting that endogenous cannabinoids are implicated in neurosphere proliferation. In addition, cannabinoid agonist-stimulated proliferation was reduced by the Akt translocation inhibitor BML-257 (12.5 microM), suggesting a role for phosphoinositide-3 kinase signalling. Together, our results suggest that cannabinoids stimulate proliferation of neural stem/precursor cells acting on both CB1 and CB2 cannabinoid receptors through a phosphoinositide-3 kinase/Akt pathway.


Peripherally inserted central catheter-related thrombosis rate in modern vascular access era-when insertion technique matters: A systematic review and meta-analysis.
Technical factors at the moment of catheter insertion might have a role in peripherally inserted central catheter-related thrombotic risk. We performed a systematic review and meta-analysis to define the actual rate of peripherally inserted central catheter-related symptomatic deep vein thrombosis in patients in whom catheter insertion was performed according to ultrasound guidance, appropriate catheter size choice, and proper verification of tip location. We searched Medline, Embase, and Cochrane Library. Only prospective observational studies published in peer-reviewed journals after 2010 up to November 2018 reporting peripherally inserted central catheter-related deep vein thrombosis rate were included. All studies were of adult patients who underwent peripherally inserted central catheter insertion. Results were restricted to those studies which included in their methods ultrasound guidance for venipuncture, catheter tip location, and a catheter size selection strategy. Random-effect meta-analyses and arcsine transformation for binomial data were performed to pool deep vein thrombosis weighted frequencies. Of the 1441 studies identified, 15 studies involving 5420 patients and 5914 peripherally inserted central catheters fulfilled our inclusion criteria. The weighted frequency of peripherally inserted central catheter-related deep vein thrombosis was 2.4% (95% confidence interval = 1.5-3.3) and remained low in oncologic patients (2.2%, 95% confidence interval = 0.6-3.9). Thrombotic rate was higher in onco-hematologic patients (5.9%, 95% confidence interval = 1.2-10). Considerable heterogeneity (I2 = 74.9) was observed and all studies were considered at high risk of attrition bias. A proper technique is crucial at the moment of peripherally inserted central catheter insertion. Peripherally inserted central catheter-related deep vein thrombosis rate appears to be low when evidence-based technical factors are taken into consideration during the insertion procedure.


[Children's health and environmental air pollution with dust containing asbestos].
According to most parameters, children's health in area containing asbestos production is considered as typical one for industrial environment. Dust containing asbestos induces higher incidence of respiratory diseases and immune changes. Frequent respiratory diseases are characteristic for junior age groups of children.


[Therapy of intestinal bleeding by the intra-arterial injection of a synthetic vasopressin derivative].
The synthetic drug Ornipressin was injected through a 3-French catheter introduced into the superior or inferior mesenteric artery by a coaxial method in nine patients with massive bleeding from the colon. In all patients the bleeding was stopped. In one female patient with a tumour, bleeding recurred, but was stopped by embolisation treatment. There were no complications needing treatment. As a method of treatment for bleeding from diverticula, the following procedure is recommended: an attempt should be made to stop bleeding by injecting vasopressin, or one of its derivatives and the use of a 3-French catheter by a co-axial method is advantageous. If vasopressin is contra-indicated, or is unsuccessful, catheter embolisation is recommended.


Retrospective evaluation of the incidence of early periprosthetic infection with silver-treated endoprostheses in high-risk patients: case-control study.
We conducted a case-control study to examine the merit of silver-coated tumour prostheses. We reviewed 85 patients with Agluna-treated (silver-coated) tumour implants treated between 2006 and 2011 and matched them with 85 control patients treated between 2001 and 2011 with identical, but uncoated, tumour prostheses. In all, 106 men and 64 women with a mean age of 42.2 years (18.4 to 90.4) were included in the study. There were 50 primary reconstructions (29.4%); 79 one-stage revisions (46.5%) and 41 two-stage revisions for infection (24.1%). The overall post-operative infection rate of the silver-coated group was 11.8% compared with 22.4% for the control group (p = 0.033, chi-square test). A total of seven of the ten infected prostheses in the silver-coated group were treated successfully with debridement, antibiotics, and implant retention compared with only six of the 19 patients (31.6%) in the control group (p = 0.048, chi-square test). Three patients in the silver-coated group (3.5%) and 13 controls (15.3%) had chronic periprosthetic infection (p = 0.009, chi-square test). The overall success rates in controlling infection by two-stage revision in the silver-coated group was 85% (17/20) compared with 57.1% (12/21) in the control group (p = 0.05, chi-square test). The Agluna-treated endoprostheses were associated with a lower rate of early periprosthetic infection. These silver-treated implants were particularly useful in two-stage revisions for infection and in those patients with incidental positive cultures at the time of implantation of the prosthesis. Debridement with antibiotic treatment and retention of the implant appeared to be more successful with silver-coated implants.


Comparison of pleural pressure measuring instruments.
The objective of this study was to compare the accuracy of a handheld digital manometer (DM) and U-tube (UT) manometer with an electronic transducer (ET) manometer during thoracentesis. Thirty-three consecutive patients undergoing thoracentesis were enrolled in the study. Pleural pressure (Ppl) measurements were made using a handheld DM (Compass; Mirador Biomedical), a UT water manometer, and an ET (reference instrument). End-expiratory Ppl was recorded after catheter insertion, after each aspiration of 240 mL, and prior to catheter removal. Volume of fluid removed, symptoms during thoracentesis, pleural elastance, and pleural fluid chemistry were also evaluated. A total of 594 Ppl measurements were made in 30 patients during their thoracenteses. There was a strong linear correlation coefficient between elastance for the DM and ET (r = 0.9582, P < .001). Correlation was poor between the UT and ET (r = 0.0448, P = .84). Among the 15 patients who developed cough, recorded ET pressures ranged from -9 to +9 cm H2O at the time of symptom development, with a mean (SD) of -2.93 (4.89) cm H2O. ET and DM measurements among those patients with cough had a low correlation between these measurements (R2 = 0.104, P = .24). Nine patients developed chest discomfort and had ET pressures that ranged from -26 to +6 cm H2O, with a mean (SD) of -7.89 (9.97) cm H2O. The handheld DM provided a valid and easy-to-use method to measure Ppl during thoracentesis. Future studies are needed to investigate its usefulness in predicting clinically meaningful outcomes.


Nursing students' expectations regarding effective clinical education: a qualitative study.
This study aimed to describe the expectations of Bachelor of Science nursing students regarding what constitutes an effective clinical education. In this study, a semistructured interview process was utilized with 17 nursing students studying in sophomore, junior and senior years in training units of hospitals affiliated with Tehran University of Medical Sciences. Content analysis was employed to analyse the data. Data analysis led to identification of three main themes: (i) appropriate communication and interaction between instructors and students; (ii) incorporation of both theory and practice in clinical education, with two subthemes, one being the presence of the instructor as a factor for reducing the gap between theory and practice and the other being evaluation based on appropriate criteria; and (iii) having specialized instructors, with a specific emphasis on the instructor's knowledge and motivation as important factors in learning. The findings reveal the significant role of mentors in providing effective educational and clinical experiences. Therefore, mentors must strive to develop their knowledge and clinical behaviours according to students' needs in clinical settings.


Changes in Hole and Electron Injection under Electrical Stress and the Rapid Electroluminescence Loss in Blue Quantum-Dot Light-Emitting Devices.
Blue quantum dot light-emitting devices (QLEDs) suffer from fast electroluminescence (EL) loss when under electrical bias. Here, it is identified that the fast EL loss in blue QLEDs is not due to a deterioration in the photoluminescence quantum yield of the quantum dots (QDs), contrary to what is commonly believed, but rather arises primarily from changes in charge injection overtime under the bias that leads to a deterioration in charge balance. Measurements on hole-only and electron-only devices show that hole injection into blue QDs increases over time whereas electron injection decreases. Results also show that the changes are associated with changes in hole and electron trap densities. The results are further verified using QLEDs with blue and red QDs combinations, capacitance versus voltage, and versus time characteristics of the blue QLEDs. The changes in charge injection are also observed to be partially reversible, and therefore using pulsed current instead of constant current bias for driving the blue QLEDs leads to an almost 2.5× longer lifetime at the same initial luminance. This work systematically investigates the origin of blue QLEDs EL loss and provides insights for designing improved blue QDs paving the way for QLEDs technology commercialization.


Efficacy of everolimus eluting stent implantation in patients with calcified coronary culprit lesions: two-year angiographic and three-year clinical results from the SPIRIT II study.
Little is known about the impact of treatment with drug-eluting stents (DES) on calcified coronary lesions. This analysis sought to assess the safety and efficacy of the XIENCE V everolimus-eluting stent (EES) in patients with calcified or noncalcified culprit lesions. The study population consisted of 212 patients with 247 lesions, who were treated with EES alone. Target lesions were angiographically classified as none/mild, moderate, or severe grades of calcification. The population was divided into two groups: those with at least one target lesion moderately or severely calcified (the calcified group: 68 patients with 75 calcified lesions) and those with all target lesions having mild or no calcification (the noncalcified group: 144 patients). Six-month and 2-year angiographic follow-up and clinical follow-up up to 3 years were completed. The baseline characteristics were not significantly different between both groups. When compared with the noncalcified group, the calcified group had significantly higher rates of 6-month in-stent angiographic binary restenosis (ABR, 4.3% vs. 0%, P = 0.03) and ischemia-driven target lesion revascularization (ID-TLR, 5.9% vs. 0%, P = 0.01), resulting in numerically higher major cardiac adverse events (MACE, 5.9% vs. 1.4%, P = 0.09). At 2 years, when compared with the noncalcified group, the calcified group presented higher in-stent ABR (7.4% vs. 0%, P = 0.08) and ID-TLR (7.8% vs. 1.5%, P = 0.03), resulting in numerically higher MACE (10.9% vs. 4.4%, P = 0.12). At 3 years, ID-TLR tended to be higher in the calcified group than in the noncalcified group (8.6% vs. 2.4%, P = 0.11), resulting in numerically higher MACE (12.1% vs. 4.7%, P = 0.12). The MACE rates in patients treated with EES for calcified lesions were higher than in those for noncalcified lesions, but remained lower than the results of previously reported stent studies. EES implantation in patients with calcified culprit lesions was safe and associated with favorable reduction of restenosis and repeat revascularization. © 2010 Wiley-Liss, Inc.


Acupuncture vs Noninsertive Sham Acupuncture in Aging Patients with Degenerative Lumbar Spinal Stenosis: A Randomized Controlled Trial.
Acupuncture is commonly used to treat degenerative lumbar spinal stenosis in Asian countries. However, rigorous data regarding the efficacy and safety of acupuncture for aging patients are currently lacking. Eighty patients older than 50 years were assigned randomly to the acupuncture group or the noninsertive sham acupuncture for 24 treatments over an 8-week period. Measurements were obtained at baseline and 4 and 8 weeks of treatment; and 3 and 6 months after completion of treatment. The primary outcome was a change in the 24-point Roland Morris Disability Questionnaire scores at the end of treatment. The secondary outcomes included disability, pain intensity, symptoms, and dysfunction. At the end of treatment, mean changes in the Roland Morris Disability Questionnaire were -4.1 (95% CI, -4.9 to -3.3) in the acupuncture group and -1.5 (95% CI, -2.3 to -0.7) in the sham group, with a statistically significant between-group difference: -2.6 (95% CI, -3.7 to -1.4). Acupuncture was superior to sham acupuncture in reducing pain intensity (between-group difference: -2.9 [95% CI, -3.8 to -2.0] in leg and buttock pain, vs -2.3 [95% CI, -3.0 to -1.5] in back pain), symptoms and dysfunction (between-group difference: -0.9 [95% CI, -1.2 to -0.6] in symptom subscale, and -0.8 [95% CI, -1.1 to -0.5] in dysfunction subscale). Acupuncture provides immediate functional recovery and pain relief for degenerative lumbar spinal stenosis. However, current evidence is insufficient to support the suggestion that acupuncture could offer clinical benefits as compared with noninsertive sham acupuncture for degenerative lumbar spinal stenosis.


Population Pharmacokinetics and Dosing Optimization of Linezolid in Pediatric Patients.
Linezolid is a synthetic antibiotic very effective in the treatment of infections caused by Gram-positive pathogens. Although the clinical application of linezolid in children has increased progressively, data on linezolid pharmacokinetics in pediatric patients are very limited. The aim of this study was to develop a population pharmacokinetic model for linezolid in children and optimize the dosing strategy in order to improve therapeutic efficacy. We performed a prospective pharmacokinetic study of pediatric patients aged 0 to 12 years. The population pharmacokinetic model was developed using the NONMEM program. Goodness-of-fit plots, nonparametric bootstrap analysis, normalized prediction distribution errors, and a visual predictive check were employed to evaluate the final model. The dosing regimen was optimized based on the final model. The pharmacokinetic data from 112 pediatric patients ages 0.03 to 11.9 years were analyzed. The pharmacokinetics could best be described by a one-compartment model with first-order elimination along with body weight and the estimated glomerular filtration rate as significant covariates. Simulations demonstrated that the currently approved dosage of 10 mg/kg of body weight every 8 h (q8h) would lead to a high risk of underdosing for children in the presence of bacteria with MICs of ≥2 mg/liter. To reach the pharmacokinetic target, an elevated dosage of 15 or 20 mg/kg q8h may be required for them. The population pharmacokinetics of linezolid were characterized in pediatric patients, and simulations provide an evidence-based approach for linezolid dosage individualization.


Adult male circumcision in Nyanza, Kenya at scale: the cost and efficiency of alternative service delivery modes.
Adult male circumcision (MC) services in Kenya are provided through both horizontal and vertical programs, and via facility-based, mobile and outreach service delivery. This study assesses the costs and composition of unit costs for each program approach and service delivery mode and assess the cost-effectiveness of each. This study was conducted on the unit costs of adult MC delivery in 222 purposively-selected MC delivery sites in Nyanza Province, Kenya from November 2008 through April 2010 using program data from the AIDS, Population, and Health Integrated Assistance Project II (APHIA II) and from the Nyanza Reproductive Health Society (NRHS). The former program can be characterized as horizontal or integrated; the latter as 'diagonal'; containing both horizontal and vertical elements. Expenditure and services data were collected from project financial and monitoring documents and via discussions with program officials. In addition, per-case, direct service delivery costs were calculated using time and motion observations of 246 adult MC procedures performed during May and June, 2010. We calculated the cost per HIV infections averted for each of the service delivery modalities. Unit cost per adult MC was $38.62 and $44.24 for APHIA II and NRHS respectively, ranging from $29.32 (APHIA II mobile) to $46.20 (NRHS outreach/mobile). Unit costs at base facilities was similar for the two approaches. Time and motion data revealed that the opportunity cost of the elapsed time between the arrival of the surgical team and the time the first MC procedure begins varies between $2.08 and $6.27 per case. The cost per HIV infection (HIA) averted ranged from $117.29 for mobile service via the horizontal APHIA-II program to $184.84 per HIA for the diagonal NRHS program. This study provides evidence for the similar efficiency of a horizontal approach (APHIA II) and a combination of horizontal and vertical approaches (NRHS) to support scale-up of adult MC services in Nyanza. Differences in unit cost are modest, not consistently in the same direction, and largely explained by differences in compensation levels.