Headaches and sleep problems in US adolescents: Findings from the National Comorbidity Survey - Adolescent Supplement (NCS-A).
There is limited research on the association of sleep problems with International Classification of Headache Disorders (ICHD-II)-defined headache subtypes in youth, particularly from community-based samples. This cross-sectional study examines the associations of sleep patterns, symptoms and disorders with specific headache subtypes among adolescents from the general population of the United States. The sample includes 10,123 adolescents in the National Comorbidity Survey - Adolescent Supplement, a face-to-face survey of adolescents aged 13-18 years in the continental USA. Headache subtype diagnoses were based on modified ICHD-III criteria, and mood and anxiety disorders were based on Diagnostic and Statistical Manual of Mental Disorders criteria. The associations of self-reported sleep patterns and insomnia symptoms and headache status were estimated with multivariate regression models that adjust for demographic characteristics and comorbid anxiety and mood disorders. There was no significant difference in bedtime between youth with and without headache. However, adolescents with migraine headache reported significantly shorter sleep duration (p = .022) and earlier wakeup time (p = .002) than those without headache. Youth with any headache, particularly migraine, had significantly more sleep disturbances than those without headache. With respect to headache subtypes, youth with migraine with aura were more likely to report difficulty maintaining sleep, early morning awakening, daytime fatigue, and persistent insomnia symptoms than those with migraine without aura. However, these associations were largely accounted for by comorbid anxiety and mood disorders. There was a monotonic increase in the number of insomnia symptoms with increasingly restrictive definitions of migraine. Pervasive sleep disturbances in adolescents with headache have important implications for the evaluation, treatment and etiology of pediatric headache.


Towards a multilingual morpheme thesaurus for medical free-text retrieval.
We introduce a methodology for the segmentation of complex compounds into medically plausible morphemes. A tool for thesaurus compilation and management is presented, and design principles for a multilingual morpheme thesaurus are outlined. Our goal is to enhance the quality of medical free-text retrieval by replacing lexically based through morpheme-based search procedures.


Synthesis of some new 2,5-disubstituted 1,3,4-thiadiazoles containing isomeric pyridyl as potent antimicrobial agents.
Several new 2,5-disubstituted derivatives of 1,3,4-thiadiazoles containing isomeric pyridyl were obtained from cyclization of corresponding thiosemicarbazides under acidic conditions. The newly synthesized compounds were characterized using different methods of spectroscopy such as IR, 1H-NMR, 13C-NMR, MS and elemental analysis. The minimal inhibitory concentration (MIC) results of screening of some of the synthesized compounds were also reported. Most of the synthesized compounds have been found to be active against both Gram-positive and Gram-negative bacteria at less than 3.6 mg/ml. The compound (10b) is most active against all seventeen used gram-positive and gram-negative bacteria.


The prognostic value of histology in ulcerative colitis in clinical remission with mesalazine.
The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC). Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI). Endoscopic activity was scored using the Mayo endoscopic subscore (MES). The clinical course was evaluated measuring relapses needing steroids during a follow up of 3 years. A total of 52 patients were enrolled into the study and followed up for 3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17 patients (32.69%) showed no histological alteration. At 3 years of follow up, overall, 26 patients (50%) were still in steroid-free remission. Using univariate logistic regression analysis, both histological (HAI ⩾ 1) and endoscopic activity (MES ⩾ 1) were significantly associated with outcome, showing, respectively, a relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI 0) (96% confidence interval [CI]: 3.2-84.3) and 6.3 times higher with respect to endoscopic remission (MES 0) (96% CI: 1.9-21.3). After multivariate logistic regression analysis, histological activity was the only factor significantly associated with outcome (OR 10.2; 95% CI: 1.7-59.4). Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.


Ceftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations.
The large variability in drug pharmacokinetic disposition has already been described in ICU patients leading to important variations in drugs concentrations. The usual recommended dosage of ceftazidime is not adapted for all ICU situations and ceftazidime should be monitored closely. New recommendations have to be given for some specific cases. Our results propose individual therapeutic drug monitoring taking into account: For the patient: the reason of admission in the ICU, the mechanical ventilation status and the creatinine clearance calculated by the modified diet in renal disease (MDRD). • For the antibiotics: the lung distribution, the minimal inhibitory concentration (MIC) of the strain to eradicate and the potential toxicity. AIM To predict the ceftazidime dosage regimen as a function of the glomerular filtration rate expressed by the modification of the diet in renal disease (MDRD), reason for admission and mechanical ventilation in intensive care unit (ICU) patients to treat Pseudomonas aeruginosa pneumonia. A published and qualified population pharmacokinetic model was used to perform Monte Carlo simulations of ceftazidime concentrations. The serum target of 40-100 mg l(-1) was defined based on the minimal inhibitory concentration (MIC), the European break point (EBP), the pulmonary drug diffusion and toxicity. The recommended dosage regimens were based on the maximum percentile of the patients with simulated steady state concentrations reaching the target. Steady-state was reached at 72 h whatever the MDRD. The simulations of serum concentrations generated higher percentiles of the population reaching the target after continuous administration. We recommend a 4 g continuous dose after the usual 2 g loading dose for patients with MDRD from 10 to 30 ml min(-1) , 6 g for MDRD between 40 and 80 ml min(-1) , 8 g for MDRD from 90 to 110 ml min(-1) , 10 g for MDRD from 120 to 190 ml min(-1) and 12 g day(-1) for patients with MDRD higher than 200 ml min(-1) . Our study demonstrated that in ICU patients for a given MDRD, steady-state takes longer to reach in polytrauma patients than in patients with medical or post surgery reasons for admission. Continuous infusion ensures that a higher percentage of patients reaches the target than the same dose given by discontinuous administration and this only depends on MDRD.


Factors in contraceptive method choice in Bangladesh: goals, competence, evaluation and access.
In this study, we have extended Bulatao's conceptual framework for selecting the determinants of method choice. Attempts have been made to capture Bulatao's dimensions directly rather than through proxies. The results of logistic regression analysis using the 1996-97 BDHS indicate that as the number of living children increases, women prefer non-terminal efficient methods such as the pill and injectable/IUD/implant and depend less on inefficient methods such as condom and permanent methods such as sterilization. With an increase in marital duration and age, women increasingly prefer sterilization as compared with other modern methods. The results may indicate a strong preference for male children among those in the sample, as women increasingly use permanent methods to prevent pregnancy as the number of living male children increases. Condom use increases with education of both women and their husbands, compared with other modern methods, indicating that more educated couples possibly have the greater understanding necessary to use the method. The better educated are significantly less likely to use sterilization. The two indicators of contraceptive evaluation, side effect and convenience of current modern method, are very important considerations in selecting the pill, injectable/IUD/implant, and condom over other modern methods. On the basis of convenience, women are most likely to use the pill over other modern methods, while they are least likely to use sterilization. Condom is the most preferred method on the basis of side effect. On the other hand, sterilization is the least preferred of other modern methods for the same reason. Sterilization is significantly less common among the Muslims, which is likely due to religious reasons, while condom use is significantly less common among non-Muslims. The two indicators of contraceptive access, accessibility/availability of current modern method and cost of current modern method, are very important considerations in pill use, while sterilization is less preferred over other modern methods on the basis of both accessibility/availability and cost. The programmatic factor visit of family planning workers/FWAs significantly increases the likelihood of using the pill compared to other modern methods.


Inhibition of Pancreatic Lipase and Triacylglycerol Intestinal Absorption by a Pinhão Coat (Araucaria angustifolia) Extract Rich in Condensed Tannin.
The purpose of the present work was to characterize the possible inhibition of pancreatic lipase by a tannin-rich extract obtained from the pinhão (Araucaria angustifolia seed) coat, based on the previous observation that this preparation inhibits α-amylases. Kinetic measurements of pancreatic lipase revealed that the pinhão coat tannin is an effective inhibitor. Inhibition was of the parabolic non-competitive type. The inhibition constants, Ki1 and Ki2, were equal to 332.7 ± 146.1 μg/mL and 321.2 ± 93.0 μg/mL, respectively, corresponding roughly to the inhibitor concentration producing 50% inhibition ([I]50). Consistently, the pinhão coat extract was also effective at diminishing the plasma triglyceride levels in mice after an olive oil load; 50% diminution of the area under the plasma concentration versus the time curve occurred at a dose of 250 mg/kg. This observation is most probably the consequence of an indirect inhibition of triglyceride absorption via inhibition of pancreatic lipase. For the pinhão coat tannin, this is the second report of a biological activity, the first one being a similar inhibition of the absorption of glucose derived from starch as a consequence of an inhibitory action on α-amylases. Taken together, these effects represent a potential anti-obesity action, as suggested for other polyphenol or tannin-rich preparations.


Health Care in the United States: Individual Right or Government Duty?
The authors discuss the notion of health care as a governmental duty rather than a right of individuals. The notion of individual rights was proposed by political philosophers of the 17th and 18th centuries, who posited that people existed in a state of nature before coming together to form communities. Members of communities relinquish certain freedoms in exchange for services provided by government, including protection of the natural rights of "life, liberty, and the pursuit of happiness." In this tradition, there are natural rights that exist before government and must be protected from government infringement. The U.S. Constitution almost exclusively enshrines negative rights, which protect natural rights from government interference. Rights belong to individuals, whereas the government has duties to provide services, such as basic education, that society deems to be important. The discussion of health care as a positive right, one requiring government to provide citizens with services, runs counter to this tradition of natural rights.The authors propose that reframing the discussion to see universal access to health care as an obligation of government, rather than a right of individuals, will center the discussion more accurately within U.S. political tradition. This may drain the emotional charge associated with claims to "rights" from public debate and allow for productive negotiations over the extent of health care appropriate for government to provide, within the context of the other obligations that form the social contract between the citizenry and its government.


A recombinase polymerase amplification-based assay for rapid detection of African swine fever virus.
A recombinase polymerase amplification (RPA)-based method was developed for rapid and specific detection of African swine fever virus (ASFV), the etiologic agent of African swine fever, a devastating disease of swine. Primers and the exo probe targeting the conserved region of the P72 gene of ASFV were designed and the reaction was run on the Genie III scanner device. Using recombinant plasmid DNA containing the P72 gene as template, we showed that the amplified product could be detected in less than 10 min and that the detection limit was 102 copies DNA/reaction [same detection limit as real-time polymerase chain reaction (PCR)]. The RPA assay did not cross-detect CSFV, PCV-2, PRV, PRRSV, or FMDV, common viruses seen in pigs. Tests of recombinant plasmid-spiked serum samples revealed that RPA and real-time PCR had the same diagnostic rate. The RPA assay, which is simple, cost-effective, and fast, is a promising alternative to real-time PCR for ASFV detection.


[Retrieval and failure analysis of surgical implants in Brazil: the need for proper regulation].
This paper summarizes several cases of metallurgical failure analysis of surgical implants conducted at the Laboratory of Failure Analysis, Instituto de Pesquisas Tecnológicas (IPT), in Brazil. Failures with two stainless steel femoral compression plates, one stainless steel femoral nail plate, one Ti-6Al-4V alloy maxillary reconstruction plate, and five Nitinol wires were investigated. The results showed that the implants were not in accordance with ISO standards and presented evidence of corrosion-assisted fracture. Furthermore, some of the implants presented manufacturing/processing defects which also contributed to their premature failure. Implantation of materials that are not biocompatible may cause several types of adverse effects in the human body and lead to premature implant failure. A review of prevailing health legislation is needed in Brazil, along with the adoption of regulatory mechanisms to assure the quality of surgical implants on the market, providing for compulsory procedures in the reporting and investigation of surgical implants which have failed in service.


A practical overview and decision tool for analyzing recurrent events in mental illness: A review.
Mental illnesses are chronic conditions in which an individual will often experience recurrent outcomes such as hospitalization, symptomatic relapse or self-harm behaviours. Most clinical research in psychiatry considers only the first event, and does not analyze subsequent recurrent events. Methods exist to analyze recurrent events; however, these methods are underused in the psychiatric research literature. This review identifies that recurrent events can be analyzed using a time homogenous or time-to-recurrent-event (TTRE) framework. The TTRE framework is underutilized in psychiatric research; however, this framework allows for longitudinal observations that are more congruent with the chronic nature of psychiatric illness than typical first event analyses. There are several readily available statistical models using the TTRE framework extending the standard Cox proportional hazards model. Our decision tool outlines four aspects of a research question to consider when selecting a TTRE model: (1) importance of event timing, (2) explanatory vs predictive, (3) common vs event-specific hazard, and (4) correlation of events within an individual. Analyzing recurrent events in psychiatric research provides an opportunity to address research questions aimed at understanding the longitudinal course of a chronic condition. These approaches may provide novel insights into risk factors or interventions for psychiatric illness, and ultimately improved outcomes for these chronic conditions.


Recent advances of dendrimers in delivery of genes and drugs.
Dendrimers as a new kind of polymer have been studied for medical applications mainly in two aspects: drug delivery and gene delivery. The unique characteristics, such as uniformity, monodispersity and the ability to functionalize their terminal groups with various targeting agents distinguish them as versatile carriers. In the paper the recent advances of dendrimer in gene transfer vehicles and drug delivery are separately reviewed. These advances illustrate the direction of the future development of dendrimers.


Anaesthetic Management in Mucopolysaccharidoses Patients: Clinical Experience in a Tertiary Hospital.
Mucopolysaccharidoses (MPS) are a group of rare inherited metabolic diseases caused by the deficiency of enzymes required to degrade glycosaminoglycans (GAGs) in the lysosome with progressive and multiorgan involvement. Due to its progressive nature, a large number of patients need surgical intervention, which is associated with higher perioperative morbidity. We retrospectively reviewed 29 medical records regarding the peri and post-operative anaesthetic care of 10 children with mucopolysaccharidoses at a tertiary hospital in Northern Portugal between 2010 and 2021. A comprehensive review of the literature is also included. Twenty-nine medical records of 10 patients with a mean age of 8.8 years old were included. At the time of the procedure, 65.5% of patients were under enzymatic replacement and all had some type of organ involvement.Each patient was subjected to 2.9 elective procedures on average, with the lowest age of two years at the first procedure. Regarding surgical specialties, 41.4% of interventions were orthopaedic. Balanced anaesthesia with inhalational induction and spontaneous breathing was performed in 48.3% of cases, with no reports of difficult bag-mask ventilation. Endotracheal intubation in the operating room was performed in nine cases. Direct laryngoscopy with a Macintosh blade was the first option in seven patients. Success was achieved only in three cases. Failed intubation was managed with a paediatric C-MAC® video laryngoscope (VLG; one case) and fiberoptic bronchoscopy (two cases). Video laryngoscopy and fibroscopy were the first choices in one case each. Post-operative complications were registered in 10 procedures (34.5%), with airway and pulmonary complications in 17.2%. All complications occurred in different patients except for post-operative nausea and vomiting, which were registered in three cases, two of them in the same patient at different orthopaedic surgical interventions. The high percentage of direct laryngoscopy could be related to the greater number of interventions performed in a period when indirect methods were not so widely used in anaesthetic practice, and the high rate of failure highlights the importance of transitioning to indirect techniques upon the first attempt. The high percentage of patients under enzymatic treatment can explain the low number of adverse airway events. High-quality evidence regarding MPS is lacking in the literature. Prospective studies would improve the perioperative care of this particular subset of patients. Patients with MPS represent a huge challenge for the anaesthesiologist, mainly in view of airway management. The integration of all available data in clinical practice is essential to optimize perioperative management of mucopolysaccharidoses patients' management and improve clinical outcomes.


Does chemotherapy prior to liver resection increase the potential for cure in patients with metastatic colorectal cancer? A report from the European Colorectal Metastases Treatment Group.
Liver resection offers the only chance of cure for patients with advanced colorectal cancer (CRC). Typically, the 5-year survival rates following liver resection range from 25% to 40%. Unfortunately, approximately 85% of patients with stage IV CRC have liver disease which is considered unresectable at presentation. However, the rapid expansion in the use of improved combination therapy regimens has increased the percentage of patients eligible for potentially curative surgery. Despite this, the selection criteria for patients potentially suitable for resection are not well documented and patient management by multidisciplinary teams, although essential, is still evolving. The goal of the European Colorectal Metastases Treatment Group is to establish pan-European guidelines for the treatment of patients with CRC liver metastases that can be adopted more widely by established treatment centres and to develop more accurate staging systems and evaluation criteria.


DC Electric Fields Induce Perpendicular Alignment and Enhanced Migration in Schwann Cell Cultures.
Schwann cells (SCs) are PNS glia that play numerous support functions including myelination of axons. After PNS injury, SCs facilitate regeneration by phagocytosing cellular debris and providing physical and biochemical cues to guide axon growth. This reparative phenotype suggests SCs could be critical cellular targets for enhancing nerve regeneration. One method for altering cell morphology and motility is the application of direct current (DC) electric fields (EFs). Endogenous EFs have physiologic relevance during embryogenesis and serve as guidance and polarization cues. While much literature exists on EFs and CNS and PNS neurons, the effects of EFs on SCs have not been extensively studied. In this work, cell alignment, migration, and morphology of rat SCs were measured in response to several EF stimulation regimes including constant DC, 50% duty cycle DC and oscillating DC. SCs were found to re-orient perpendicular to field lines and respond to DC EFs as low as 75 mV/mm. EF exposure promoted directed migration, with travel towards the cathode at a mean rate of 7.5 µm/h. The data highlight the utility of EFs in modulating SC morphology, alignment and migration. Results may have implications for using EFs to attract and realign SCs at the site of PNS trauma.


Docosahexaenoic acid potentiates interleukin-1beta induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells.
The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)-1beta, and whether the effect of DHA is related to its effect on mitogen-activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle cells (VSMCs). DHA and eicosapentaenoic acid (EPA), although less potent, increased the NO production induced by IL-1beta (3 ng ml(-1)) in a concentration-dependent manner (3 - 30 microM) Arachidonic acid had no significant effect. The stimulatory effect of DHA (30 microM) on the NO production was more obvious at lower concentrations of IL-1beta. IL-1beta induced iNOS protein and mRNA expressions, which were significantly potentiated by DHA. EPA (30 microM) had a tendency to increase the iNOS protein and mRNA expressions, but arachidonic acid had no effect. IL-1beta-induced iNOS protein expression was significantly inhibited by PD 98059 (10 microM), a selective inhibitor of p44/42 MAPK kinase, both in the absence and the presence of DHA. SB 203580 (10 microM), a selective inhibitor of p38 MAPK activity, had no significant effect, although had a tendency to inhibit slightly. IL-1beta increased the phosphorylation of p44/42 MAPK, while it did not apparently increase the phosphorylation of p38 MAPK. DHA significantly potentiated the IL-1beta-induced phosphorylation of p44/42 MAPK, while it had no significant effect on the phosphorylation of p38 MAPK. These results suggest that DHA increases NO production by potentiating iNOS expression induced by IL-1beta through mechanism involving p44/42 MAPK signalling cascade in rat VSMCs. The present study may contribute to the understanding of basic mechanisms underlying the beneficial effects of DHA on various cardiovascular disorders.


Implementation of patient-reported outcome measures into health care for men with localized prostate cancer.
Measuring treatment-related quality of life (QOL) has become an increasingly requisite component of delivering high-quality care for patients with prostate cancer. Patient-reported outcome measures (PROMs) have, therefore, become an important tool for understanding the adverse effects of radical prostate cancer treatment and have been widely integrated into clinical practice. By providing real-time symptom monitoring and improved clinical feedback to patients and providers, PRO assessment has led to meaningful gains in prostate cancer care delivery and quality improvement worldwide. By providing an avenue for benchmarking, collaboration and population health monitoring, PROMs have delivered substantial improvements beyond providing individual symptom feedback. However, multilevel barriers exist that need to be addressed before the routine implementation of PROMs is achieved. Improvements in collection, interpretation, standardization and reporting will be crucial for the continued implementation of PROM instruments in prostate cancer pathways.


T Cells Are Required for Orthodontic Tooth Movement.
The immune system plays a pivotal role during bone remodeling process. Orthodontic tooth movement (OTM) induces local inflammation in periodontium, but whether systemic immune response is involved in OTM remains unknown. In this study, we show that tooth movement distance was significantly reduced in T-cell-deficient immunocompromised mice compared with wild-type (WT) mice. Intravenous infusion of allogeneic T cells to the immunocompromised mice rescued the OTM distance. Correspondingly, increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts were detected around the alveolar bone after OTM in WT mice but were barely detected in immunocompromised mice. Moreover, intravenous infusion of T cells rescued the number of TRAP-positive osteoclasts in the OTM area of the immunocompromised mice, thus suggesting T cells are required for OTM. We then reveal that OTM induced a significant elevation of type 1 T helper cell (Th1) cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) around periodontal tissue in WT but not in immunocompromised mice. Infusion of T cells could increase the levels of TNF-α and IFN-γ in periodontal tissues of immunocompromised mice. More interestingly, intraperitoneal injection of TNF-α inhibitor etanercept significantly reduced the distance of OTM in T-cell-infused immunocompromised mice. In summary, this study demonstrates a previously unrecognized mechanism that T cells are required for OTM depending on Th1-associated cytokines.


Anteroposterior hippocampal metabolic heterogeneity: three-dimensional multivoxel proton 1H MR spectroscopic imaging--initial findings.
To quantify proton magnetic resonance (MR) spectroscopy-detectable metabolite concentrations along anteroposterior axis of hippocampus in healthy young and elderly subjects. Young (three women, three men; age range, 25-35 years) and elderly (four women, two men; age range, 68-72 years) groups underwent MR imaging and proton MR spectroscopic imaging at 3 T in this HIPAA-compliant prospective study and gave institutional review board-approved written consent. Volume of interest was centered on and tilted parallel to hippocampal anteroposterior plane. Absolute N-acetylaspartate (NAA), choline, and creatine levels were obtained in each voxel, with phantom replacement. Mean NAA, creatine, and choline concentrations in the young group were higher in posterior hippocampus (12.9 mmol/L +/- 2.0 [standard deviation], 7.8 mmol/L +/- 1.2, 2.3 mmol/L +/- 0.4, respectively) than anterior hippocampus (8.0 mmol/L +/- 1.1, 6.0 mmol/L +/- 1.4, 1.5 mmol/L +/- 0.2; P = .005, .02, and .0002, respectively). In the elderly group, mean concentrations were higher in posterior hippocampus (8.6 mmol/L +/- 0.9, 5.6 mmol/L +/- 0.6, 1.5 mmol/L +/- 0.2, respectively) than anterior hippocampus (7.2 mmol/L +/- 1.0, 2.4 mmol/L +/- 0.3, 1.0 mmol/L +/- 0.2; P = .006, .0001, .04, respectively). Mean concentrations were significantly higher in the young group (13.2 mmol/L +/- 1.0, 7.4 mmol/L +/- 0.8, 2.1 mmol/L +/- 0.3, respectively) than in the elderly group (9.0 mmol/L +/- 1.0, 5.8 mmol/L +/- 0.8, 1.8 mmol/L +/- 0.3; P = .0001, .01, .05, respectively). Posteroanterior metabolic gradients differed: NAA decreased faster in the young group (-1.0 mmol/L x cm(-1)) than the elderly group (-0.7 mmol/L x cm(-1)); creatine and choline concentrations decreased faster in the elderly group (-0.8 and -0.058 mmol/L x cm(-1), respectively) than the young group (-0.16 and -0.008 mmol/L x cm(-1), respectively). No left-right metabolic differences were found. Significant metabolic heterogeneity was observed between groups and along anteroposterior axis of healthy hippocampus in both groups. Age matching and consistent voxel placement are important for correct comparisons of both absolute metabolic levels and metabolite ratios in longitudinal intra- and intersubject cross-sectional studies.


Primary mucosal malignant melanoma of the larynx: case report and review of the literature.
We report a case of primary melanoma of the larynx in a patient who died of disseminated disease 13 months later. It is a rare malignant tumor in the head and neck, accounting for 0.4-10% of all melanomas of this site. Histologically, the presence of in situ changes within the laryngeal mucosa strongly supports our diagnosis of primary melanoma of the larynx.


Separation of two closely related serine protease analogues using HPCE/MECC with SDS in a dynamic mode.
HPCE was evaluated for the identification of different serine protease analogues. This work represents a separation of two serine proteases, Savinase (SAV) (Novo Nordisk A/S, Bagsvaerd, Denmark) and a Savinase analogue, both consisting of 269 amino acids and having identical isoelectric points. The only difference between the two protease variants is that a methionine is substituted with a serine, M222S. The separation was only made feasible by the HPCE/micellar electrokinetic capillary chromatography (MECC) technique using sodium dodecyl sulfate (SDS) dynamically as the surfactant. This paper shows that it is possible to employ HPCE/MECC to separate Savinase and a Savinase variant with no alteration in net charge.


Association of khellin and 308-nm excimer lamp in the treatment of severe alopecia areata in a child.
Alopecia areata (AA) is an autoimmune inflammatory disorder of hair, characterized by non-scarring hair loss. A 308-nm excimer lamp (EL) has been reported as one effective modality in the treatment of AA. Khellin is a furanochromone photosensitizer whose chemical structure is close to psoralens and has previously proven its efficacy in vitiligo in association with ultraviolet A. We evaluated the efficacy and safety of a combination of topical khellin and 308-nm EL in the treatment of a refractory ophiasic AA, of 1-year evolution, in a 5-year-old boy. Treatment consisted in topical application of khellin 45 mn before irradiation with EL (starting dose 50 mJ/cm2) twice a week for 3 months. The result was a complete regrowth of hair with no recurrence 1 year later. Further studies should be carried out to confirm this promising result and to propose khellin-excimer as a new alternative treatment for resistant cases of AA in children.


Regional metastases in patients with advanced laryngeal cancer. Department of Veterans Affairs Laryngeal Cancer Study Group.
To determine patterns of regional metastases in patients with advanced squamous cell carcinoma of the larynx and the effect of these patterns on regional and distant tumor recurrence and disease-free and overall survival. One hundred fifty-nine patients treated with conventional surgery and radiation in the Veterans Affairs Cooperative Study were studied. Ninety-three of the patients underwent modified or classic radical neck dissection. Median follow-up was 5 years. Patient data collected included age, gender, alcohol consumption, tobacco use, and performance status. Tumor variables evaluated included TNM classification, tumor site, surface area, presence of ulceration and invasion, and histologic growth pattern. Histologically positive regional lymph nodes were examined for level, number, site, and extracapsular spread. Outcome variables included time and location of recurrence, distant metastases, and survival. Regional metastases were more common in supraglottic than glottic or subglottic tumors (P < .001) and in tumors with larger surface dimensions (P = .004). Cervical metastases were associated with decreased disease-free interval (P < .001) and survival (P = .001) and increased distant metastases (P < .001). Presence of 3 or more positive nodes predicted distant recurrence (P < .001) and decreased survival (P < .001, multivariate analysis). An analysis of lymph node involvement (levels I-V) indicated that level 1 and 5 involvement was a significant prognostic factor. Age, sex, race, and tobacco or alcohol use were not associated with number or extent of regional metastases. These findings confirm the prognostic importance of number and level of lymph nodes in advanced laryngeal cancer. The association of distant metastases with number and level of regional nodes indicates a use for these variables in considering adjuvant chemotherapy.


Vaccination Serology Status and Cardiovascular Mortality: Insight from NHANES III and Continuous NHANES.
Prior studies have described a negative relationship between influenza vaccination and recurrence of cardiovascular (CV) events. However, due to lack of any prior studies, we evaluated and attempted to define the relationship between non-influenza vaccines and CV mortality. We used the National Health and Nutrition Examination Survey III (NHANES III-1988-1994, n = 19,215) and Continuous NHANES (1999-2004, n > 17,000), which includes oral surveys and general examination. It was designed to assess the demographic, socioeconomic, dietary, and overall health status of a nationally representative sample in non-institutionalized patients from all 50 states in the USA. Cox proportional hazard regression modeling was used to calculate the hazard ratio of CV mortality, and multivariate models were built for the individual seropositive vaccination titers as well as after creating a combined vaccination variable. A total of >35,000 subjects (>18 years old) have been identified for analysis. Multivariate analysis from NHANES III and continuous NHANES did not show any influence of individual seroprotective titers of routine vaccinations on CV mortality. The combined effect of vaccination in NHANES III data did not show any protective effect of three or more positive vaccination titers (odds ratio = 0.94, p = 0.6) or all four positive vaccination titers (odds ratio = 0.93, p = 0.6) with two or less positive vaccination titers as the referent group. Effect on non-influenza vaccinations in preventing CV mortality seems to be unclear.


Occurrence of polar organic compounds in atmospheric particulate matter: a system review in South America.
Particulate matter (PM) is one of the existing air pollutants, which can cause damages to human health, public property, and the environment. The chemical composition of this pollutant greatly varies, mainly its organic fraction. Thus, our objective was to carry out a literature review based on articles, considering studies conducted in South America, whose authors address the characterization of the polar organic fraction of PM. We performed the review using the Scopus, SciELO, and Web of Science databases, considering publications dated from the years 2010 to 2019. A total of 14,575 articles were found, of which only 12 met the predefined selection criteria. According to our research, the most studied compound is levoglucosan, a biomass burning marker belonging to the group of anhydrous sugars. Besides, nitro-PAHs, which usually originate from vehicular sources and are compounds with mutagenic and carcinogenic characteristics, have also been found. Moreover, we concluded that, currently, there are few studies on the subject in South America, requiring more research on polar organic compounds present in PM in countries of this region. These studies are of great importance because some compounds can cause great damage to human health, such as the nitro-PAHs; furthermore, PM may still have unknown compounds that need identification and elucidation of their toxicity.


21st century paradigm of tissue banking: the Clinical Breast Care Project.
The Clinical Breast Care Project (CBCP) is a congressionally mandated program that began in the year 2000. The military-civilian collaboration was founded on five pillars: (1) center of excellence in clinical care, (2) risk reduction for women at risk for developing breast cancer, (3) tissue banking to develop and maintain the world's finest repository of human biospecimens of breast diseases, (4) targeted research into the molecular signatures of breast diseases and cancer, and (5) biomedical informatics core to support the data warehouse needs of the project. Now in its eighth year of operation, these efforts have resulted in more than 300 peer-reviewed scientific publications and dozens of collaborations with world leaders in cancer research. In this short time, CBCP has created what is believed to be the world's largest breast tissue biorepository.


Cytogenetic heterogeneity in t(11;19) acute leukemia: clinical, hematological and cytogenetic analyses of 48 patients--updated published cases and 16 new observations.
We report on 16 cases of t(11;19) acute leukemia and review data of published observations: altogether updated data of 48 patients are analyzed. Four hematological groups could be distinguished: (i) 13 cases of acute lymphoblastic leukemia (ALL) of B lineage, mostly CD19+; (ii) eight cases of biphenotypic leukemia: CD19+ (most often) ALL but with simultaneous or inducible expression of differentiation marker of monocytic lineage. The B lineage and biphenotypic leukemias were predominantly found in female infants; (iii) four cases of T-ALL in children; and (iv) 23 acute non-lymphocytic leukemia (ANLL) cases generally of M4 or M5 subtype, predominantly in males. Cytogenetically, at least two subtypes were observed with possibly an identical breakpoint on 11q23 but discrete breakpoints on 19p: lymphoid, biphenotypic, and most congenital myeloid cases showed a distal breakpoint on 19p13 producing 11q- and 19p+ derivatives, while most older myeloid cases showed 11q+ and 19p- derivatives as a result of a more proximal breakpoint on 19p12 or p13.1. The latter type was clearly detected using R bands but barely visible using Q or G bands while the other translocation was easy to detect with G bands but could be missed with R bands. The white blood cell count is usually high in these t(11;19) acute leukemias and prognosis is poor, except for T-ALL cases.


Volatile compounds emitted by sclerotia of Sclerotinia minor, Sclerotinia sclerotiorum, and Sclerotium rolfsii.
Volatile compounds emitted by sclerotia of Sclerotinia minor, Sclerotinia sclerotiorum, and Sclerotium rolfsii were identified by solid phase microextraction followed by gas chromatography and mass spectometry. Both S. minor and S. sclerotiorum emitted 2-methylenebornane and 2-methylisoborneol. In addition, S. minor emitted mesityl oxide, gamma-butyrolactone, cis- and trans-linalool oxide, linalool, and trans-nerolidol. S. sclerotiorum emitted 2-methyl-2-bornene, 1-methylcamphene, and a diterpene with a molecular weight of 272. Sclerotium rolfsii did not emit any of these compounds but did emit delta-cadinene and cis-calamenene. Chemicals emitted by S. minor and S. sclerotiorum were tested to determine if they could stimulate germination of conidia of Sporidesmium sclerotivorum, a mycoparasite on sclerotia of Sclerotinia spp. Chemicals were tested at 1 part per billion to 100 parts per million, both in direct contact with conidia and near, but not in, physical contact. None of the chemicals alone nor a combination of all chemicals induced germination of conidia of S. sclerotivorum.


The Generalized Anxiety Disorder 7-item scale in adolescents with generalized anxiety disorder: Signal detection and validation.
In pediatric patients with anxiety disorders, existing symptom inventories are either not freely available or require extensive time and effort to administer. We sought to evaluate a brief self-report scale-the Generalized Anxiety Disorder 7-item scale (GAD-7)-in adolescents with generalized anxiety disorder (GAD). The Pediatric Anxiety Rating Scale (PARS) and the GAD-7 were administered to youth with GAD (confirmed by structured interview). Relationships between the measures were assessed, and sensitivity and specificity was determined with regard to a global symptom severity measure (Clinical Global Impression-Severity). In adolescents with GAD (N = 40; mean age, 14.8 ± 2.8), PARS and GAD-7 scores strongly correlated (R = 0.65, P ≤ .001) and a main effect for symptom severity was observed (P ≤ .001). GAD-7 scores ≥11 and ≥17 represented the optimum specificity and sensitivity for detecting moderate and severe anxiety, respectively. The PARS and GAD-7 similarly reflect symptom severity. The GAD-7 is associated with acceptable specificity and sensitivity for detecting clinically significant anxiety symptoms. GAD-7 scores may be used to assess anxiety symptoms and to differentiate between mild and moderate GAD in adolescents, and may be more efficient than the PARS.


Children's Diet during the Early Stages of the Nutritional Transition. The Foundlings in the Hospital of Valencia (Spain), 1852-1931.
The nutritional transition brought about profound changes in the nutrition of the European population in the 19th and 20th centuries. The predominant consumption of cereals gave way to kilocalorie-, protein-, vitamin- and mineral-rich diets that involved a greater intake of animal products. However, not all population groups underwent this transition at the same pace; socio-economic conditions, sex and age led to important inequalities. This article uses institutional sources to analyse the nutrition of children during the early stages of the nutritional transition and to compare it with that of other age groups (adult psychiatric patients). The study examines the average diets and nutritional balance of foundlings in the Hospital General de Valencia from 1852 to 1931. The main conclusion of the study is that, throughout the period under study, foundlings were exposed to a poor, traditional diet, characterized by structural deficits and imbalances. This may have affected their physical growth, health and biological wellbeing in adulthood, and demonstrates that the nutritional transition was anything but a homogeneous process.


Incorporation of alpha-chymotrypsin into the 3D channels of bicontinuous cubic lipid mesophases.
The effects of protein entrapment on the structure and phase behavior of periodically curved lipid mesostructures have been examined by synchrotron small-angle X-ray diffraction and FT-IR spectroscopy. The study was directed towards a better understanding of the effect of confinement in a lipid environment on the stability and unfolding behavior of alpha-chymotrypsin, and, vice versa, the effect of the entrapped protein on the lipid's mesophase structure and temperature- and pressure-dependent phase behavior. We compare the interaction of protein molecules of two different sizes (cytochrome c, 12.4 kDa, and alpha-chymotrypsin, 25.8 kDa) with the cubic Ia3d phase of monoolein (MO), which forms spontaneously in water. The cubic structure changes significantly when cyt c is incorporated: above a protein concentration of 0.2 wt.%, the interaction between the positively charged protein and the lipid headgroups leads to an increase in interfacial curvature which promotes the formation of a new micellar cubic phase, presumably of crystallographic space group P4(3)32, which the lipid system does not form on its own. The larger alpha-chymotrypsin leads to a different scenario. On the basis of an examination of the calculated geometric parameters and water volume fractions, it is concluded that the alpha-chymotrypsin molecules cannot be located exclusively in the water channels of the cubic Ia3d or P4(3)32 phases, but rather form new, less ordered (presumably cubic Pn3m) structures. The new structure disappears above the unfolding temperature of chymotrypsin and exhibits a pressure stability, which-- in contrast to cyt c in MO-- decreases with increasing chymotrypsin concentration in the system. While the secondary structure of cyt c remains unaffected in the confining lipid environment, the structure of alpha-chymotrypsin gets destabilized slightly, and the protein tends to aggregate even at relatively low concentrations.


Factors of the psychopathic personality inventory: criterion-related validity and relationship to the BIS/BAS and five-factor models of personality.
Psychopathy is a personality disorder that includes interpersonal-affective and antisocial deviance features. The Psychopathic Personality Inventory (PPI) contains two underlying factors (fearless dominance and impulsive antisociality) that may differentially tap these two sets of features. In a mixed-gender sample of undergraduates and prisoners, we found that PPI fearless dominance was related to low Behavioral Inhibition System activity, high Behavioral Activation System (BAS) activity, expert prototype psychopathy scores, and primary psychopathy. Impulsive antisociality was related to high BAS activity and all psychopathy measures. High Extraversion and Openness and low Neuroticism and Agreeableness predicted fearless dominance, whereas high Neuroticism and low Agreeableness and Conscientiousness predicted impulsive antisociality. Although low levels of Agreeableness predicted both PPI factors, their differential relations with other five-factor model traits highlight differences in the way psychopathy manifests itself. Consistent with movements toward assessing personality disorder using the five-factor model, the authors report regression-based equations for the clinical assessment of these psychopathy dimensions using the NEO Personality Inventory-Revised (NEO-PI-R).


'Translational formative evaluation': critical in up-scaling public health programmes.
The process of generating evidence-based public health interventions is understood to include steps that define the issue, generate and test solutions in controlled settings, replicate and then disseminate more widely. However, to date models have not considered the types and scale of formative evaluation tasks that are needed to up-scale interventions, from efficacy to population-wide dissemination in the real world. In this paper, we propose that an additional stage of 'translational formative evaluation' is necessary for the translation of effectiveness evidence into wide-scale public health practice. We illustrate the utility of translational formative evaluation, through a case study of the Get Healthy Information and Coaching Service(®) (GHS), a population-based telephone service designed to assist adults change lifestyle-related behaviours. The additional translational formative evaluation steps comprised synthesis of efficacy studies, qualitative research with the wider target audience, environmental analysis and stakeholder consultation. They produced precise recommendations to refine GHS design and implementation. Translational formative evaluation is a necessary intermediate step, following efficacy studies and a precursor to population-wide implementation of public health programmes.


Mesenteric fibromatosis: a rare cause of acute abdominal pain.
A 45-year-old man, with a previous history of astrocytoma, presented with diffuse abdominal pain. A CT scan was non-specific and the pain worsened; his abdomen became peritonitic on examination. An exploratory laparotomy was performed, and a large small bowel mesenteric mass was found together with an associated haematoma. Subsequent histology showed the tumour to be a benign fibromatosis, and the patient recovered uneventfully. There were no reports in the literature of any association between astrocytomas and fibromatosis. Mesenteric fibromatosis is a rare tumour often associated with Gardner's syndrome. It can present in a multitude of ways and the only definite treatment is surgical resection.


Histological and genotypical characterization of feline cutaneous mycobacteriosis: a retrospective study of formalin-fixed paraffin-embedded tissues.
Twenty-nine cases presumptively diagnosed as feline cutaneous mycobacteriosis were evaluated microscopically with haematoxylin and eosin and modified Fite's stained sections using archived formalin-fixed paraffin-embedded tissue specimens. Lesions were characterized histologically as feline leprosy (7 cases lepromatous and 16 cases tuberculoid) or atypical mycobacteriosis (3 cases); three cases did not fit these criteria and were classified as 'miscellaneous'. Actinomycetales-specific polymerase chain reaction (PCR) of variable regions 1, 2 and 3 of the 16S ribosomal RNA (rRNA) gene and subsequent sequence analysis of the amplicons were performed to identify the species of mycobacteria associated with each case. Together, this study identified 10 different Actinomycetales organisms with greater than 98% nucleotide sequence identity to named species, nine were of the genus Mycobacterium and eight were associated with feline leprosy (both lepromatous and tuberculoid). Based on this study, we conclude that feline cutaneous mycobacteriosis should be considered as a syndrome with varied clinical and histological presentations associated with a variety of different Mycobacterium species, organisms other than Mycobacterium sp. may be associated with feline cutaneous mycobacteriosis lesions, and molecular diagnostic techniques can be an important tool for identifying agents associated with lesions of feline cutaneous mycobacteriosis.


Fourier transform infrared imaging analysis in discrimination studies of bladder cancer.
Bladder carcinoma represents more than 4% of all cancer diseases in Austria. The histomorphological evaluation is invasive and remains a subjective and time consuming technique. On account of this it is necessary to find novel non-invasive approaches which support the pathologists for histological recognition to identify malignancy at an early stage. In the present study, Fourier transform infrared (FTIR) microscopic imaging was combined with univariate and multivariate data analysis methods to study bladder carcinoma tissue sections in detail. The possibility to collect IR spectra of bladder carcinoma tissue sections employing an optimized analytical protocol is demonstrated. The correlation between FTIR microscopic imaging and the morphological tissue features obtained by histological staining of the sections demonstrated that many histomorphological tissue patterns can be visualized in the colour images. The routine generation of high quality imaging data is enabled because of the combination of FTIR technology and optimized sample preparation techniques. This opens a new quality of spectroscopic analyses of cancerous tissue, allowing exploration of molecular changes associated with the histopathological morphology.


[Relationship between the expressions of indoleamine 2, 3-dioxygenase in hepatocellular carcinoma and clinicopathological parameters].
To explore the expressions of indoleamine 2, 3-dioxygenase (IDO) in hepatocellular carcinoma and analyze its relationship with clinicopathological parameters. Quantitative real-time polymerase chain reaction (PCR), fluorogenic quantitative PCR, immunohistochemical and immunofluorescence were used to detect the expression of indoleamine 2, 3-dioxygenase in hepatocellular carcinoma. The IDO mRNA expression in cancerous tissues increased markedly than that in the corresponding non-cancerous tissues (2(-ΔΔCT) = 1.71, P = 0.001) . The immunohistochemical and immunofluorescence results showed that IDO protein was expressed in cytoplasm of hepatocellular carcinoma and tumor-surrounding tissues. But there was no expression in normal liver tissues from benign hepatic lesions and corresponding non-cancerous tissues. An over-expression of IDO protein was detected in 43 patients (48.3%) , a low expression in 25 (28.1%) and no expression in 21 (23.6%). Relationship between IDO expression and clinicopathological parameters: an over-expression of IDO in HCC was associated with recurrence, survival time, metastasis and TNM stage (P < 0.05), but not associated with patient's cirrhosis, AFP level, histological differentiation type, Barcelona clinic liver cancer stage, gender, age, HbsAg positivity, number of tumors and tumor size (P > 0.05). An over-expression of IDO in HCC patients may affect patient prognosis.


Skin toxicity after Filgrastim treatment for an Ewing's sarcoma patient.
Filgrastim is a granulocyte colony-stimulating factor (GSCF) used in some chemotherapy regimen to prevent febrile neutropenia. Most common reaction of filgrastim are aches and pain including headaches, nausea and skin rash. We report the case of a patient who developed unusual, non-commonly reported adverse toxidermy to filgrastim. At first the eruption was limited to the lower members and genetics organs. Then it slowly spread across the whole body presenting as a polymorphic exanthematous-pustulosis lesions. A cutaneous biopsy was done, identifying a toxidermy modified by systemic treatment. A pharmacological study linked the role of filgrastim to these lesions. After switching from filgrastim to lénograstim, his lesions are completely gone and haven't flared up again. Thus, clearly imputing the use of filgrastim. The cutaneous reaction that has reported with use of GSCF are sweet syndrome, erythema nodosum, pyoderma nodosum and pyoderma gangrenosum. As far as we know, no acute generalized exanthematous pustulosis due to GSCF has been reported.


Asymmetric programming: a highly reliable metadata allocation strategy for MLC NAND flash memory-based sensor systems.
While the NAND flash memory is widely used as the storage medium in modern sensor systems, the aggressive shrinking of process geometry and an increase in the number of bits stored in each memory cell will inevitably degrade the reliability of NAND flash memory. In particular, it's critical to enhance metadata reliability, which occupies only a small portion of the storage space, but maintains the critical information of the file system and the address translations of the storage system. Metadata damage will cause the system to crash or a large amount of data to be lost. This paper presents Asymmetric Programming, a highly reliable metadata allocation strategy for MLC NAND flash memory storage systems. Our technique exploits for the first time the property of the multi-page architecture of MLC NAND flash memory to improve the reliability of metadata. The basic idea is to keep metadata in most significant bit (MSB) pages which are more reliable than least significant bit (LSB) pages. Thus, we can achieve relatively low bit error rates for metadata. Based on this idea, we propose two strategies to optimize address mapping and garbage collection. We have implemented Asymmetric Programming on a real hardware platform. The experimental results show that Asymmetric Programming can achieve a reduction in the number of page errors of up to 99.05% with the baseline error correction scheme.


Electronic effects in the acylation of alpha-chymotrypsin by substituted N-benzoylimidazoles.
Rate constants for the acylation of alpha-chymotrypsin by a series of acyl-substituted N-benzoylimidazoles have been determined by proflavin displacement from the active site. The second-order acylation rate constants k2/Km are large [e.g., that for N-(m-nitrobenzoyl)imidazole is 1.7 X 10(4) M-1 s-1 at pH 7.5], even though Km must be quite large (plots of k vs. k/[S]0 have infinite slopes). The values of k2/Km are nearly independent of pH in the range 5.0-9.0 when the substituent group is electron donating. Electron-withdrawing substituents produce an increase in k2/Km with increasing pH until a maximum is reached near pH 7. This is also the case in acylation by the N-[p-(dimethylamino)benzoyl]-N'-methylimidazolium ion (pKapp = 6.5). While the reaction of the N'-methylated derivative is via a positively charged species at all pH values, the unmethylated compounds react through both the neutral species and the conjugate acids, with the observed pH dependence depending on the relative values of the rate constants. The limiting value of k2/Km for the N-[p-(dimethylamino)benzoyl]-N'-methylimidazolium ion is 2.1 times less in D2O than in H2O. Thus, His-57 must be participating in the acylation reaction as a general base. The limiting values of k2/Km for the corresponding N'-methylated and unmethylated derivatives differ by a factor of only 150, which is similar to the difference in the second-order rate constants for nonenzymatic OH- -catalyzed hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)


Abdominal aortic dissection with acute mesenteric ischemia in a patient with Marfan syndrome.
Marfan syndrome is an autosomal dominant inherited disorder of connective tissue, with various complications manifested primarily in the cardiovascular system. It potentially leads to aortic dissection and rupture, these being the major causes of death. We report a patient who complained of acute abdominal pain, which presented as acute mesenteric ischemia combined with abdominal aortic dissection. Echocardiography showed enlargement of the aortic root and mitral valve prolapse. Abdominal computed tomography scan revealed acute mesenteric ischemia due to abdominal aortic dissection. Finally, the patient underwent surgery of aortic root replacement and had a successful outcome. Therefore, we suggest that for optimal risk assessment and monitoring of patients with Marfan syndrome, both aortic stiffness and the diameter of the superior mesenteric vein compared with that of the superior mesenteric artery are useful screening methods to detect acute mesenteric ischemia secondary to abdominal aortic dissection. Early diagnosis and early treatment can decrease the high mortality rate of patients with Marfan syndrome.


Psychotic ideation and receipt of government entitlements among homeless persons in New York City.
This study compared changes in receipt of government entitlements by homeless persons with and without psychotic ideation in New York City between January 1997 and July 1998, a period characterized by changing state government policies and greater bureaucratic monitoring of eligibility. In conjunction with an experimental study of the efficacy of social work services provided to homeless persons in Manhattan by a mobile medical van, 25 persons who were assessed as having experienced psychotic ideation in the previous year and 134 nonpsychotic persons were followed up after four months to identify changes in their receipt of Medicaid benefits, Supplemental Security Income (SSI) or Social Security Disability Insurance (SSDI), food stamps, and home relief (state welfare for single persons). The social work intervention was designed to help eligible clients gain access to entitlements and substance abuse treatment. The proportion of clients with psychotic ideation who received Medicaid, food stamps, or home relief decreased during the study period, while the proportion of nonpsychotic clients who received these entitlements increased. Little change was observed in receipt of SSI or SSDI by either group. Psychotic ideation among homeless persons may be a significant factor in access to and maintenance of government entitlements. In the context of an increasingly restrictive and bureaucratic welfare system, providing assistance to homeless persons who have severe psychopathology presents new challenges to service providers.


Laser diode thermal desorption/atmospheric pressure chemical ionization tandem mass spectrometry analysis of selected steroid hormones in wastewater: method optimization and application.
A rapid and reliable method enabling high-throughput sample analysis for quicker data generation, detection, and monitoring of eight selected steroid hormones in water matrixes was developed and validated. Our approach is based on a novel sample introduction method, the laser diode thermal desorption/atmospheric pressure chemical ionization (LDTD/APCI) coupled to tandem mass spectrometry (MS/MS). The optimization of instrumental parameters and a method application are presented. Our method was successfully applied to spiked effluent wastewater in the low-nanogram per liter concentrations with total analysis time reduced to seconds (15 s) using LDTD/APCI-MS/MS compared to minutes with traditional liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS) following solid-phase extraction (SPE). The instrumental detection limits for LDTD/APCI-MS/MS ranged from 5 to 24 microg L(-1) and from 13 to 43 ng L(-1) for the method detection limits. Calibration curves in wastewater matrix showed good linearity (R(2) > 0.99), and precision (intraday and interday) was below 20%. This work demonstrates that LDTD/APCI-MS/MS could be used for fast and effective quantitative analysis of emerging contaminants in different water matrixes with reduced cost by eliminating the chromatography step used in traditional LC-MS/MS.


Boards want leadership and decisiveness.
Regardless of whether they aspire to the top executive spot, physician managers are likely to benefit from insights into what hospital boards want in their chief executive officers. Many of the attributes board chairs desire in hospital CEOs involve how they handle medical staff matters. In general, board chairs want leadership and decisiveness--attributes they likely would covetin any physician manager who has hospital management responsibilities.


Biological significance of human endogenous retroviral sequences.
Endogenous retroviruses (ERVs) have been known for many years to exist in numerous natural and laboratory animal species. In humans it has been demonstrated that at least 1% of the genome consists of retrovirus-related sequences. Involvement of ERVs in the development of neoplastic and autoimmune diseases in the mouse model implicated a potentially pathogenic role of ERVs for humans, too. The research in this field led to a number of results strongly suggesting that human endogenous retroviral sequences (HERVs) are biologically active, on the RNA and even on the protein level. Particle formation, regulation or dysregulation of cellular gene expression, and synthesis of potentially pathogenic viral proteins indicate the broad spectrum of mechanisms by which HERVs may obtain biological significance.


High mobility group A1 (HMGA1) protein and gene expression correlate with ER-negativity and poor outcomes in breast cancer.
The high mobility group A1 (HMGA1) chromatin remodeling protein is required for metastatic progression and cancer stem cell properties in preclinical breast cancer models, although its role in breast carcinogenesis has remained unclear. To investigate HMGA1 in primary breast cancer, we evaluated immunoreactivity score (IRS) in tumors from a large cohort of Asian women; HMGA1 gene expression was queried from two independent Western cohorts. HMGA1 IRS was generated from breast tumors in Korean women as the product of staining intensity (weak = 1, moderate = 2, strong = 3) and percent positive cells (< 5% = 0, 5-30% = 1, 30-60% = 2, > 60% = 3), and stratified into three groups: low (< 3), intermediate (3-6), high (> 6). We assessed HMGA1 and estrogen receptor (ESR1) gene expression from two large databases (TCGA, METABRIC). Overall survival was ascertained from the METABRIC cohort. Among 540 primary tumors from Korean women (181 ER-negative, 359 ER-positive), HMGA1 IRS was < 3 in 89 (16.5%), 3-6 in 215 (39.8%), and > 6 in 236 (43.7%). High HMGA1 IRS was associated with estrogen receptor (ER)-negativity (χ2 = 12.07; P = 0.002) and advanced nuclear grade (χ2 = 12.83; P = 0.012). In two large Western cohorts, the HMGA1 gene was overexpressed in breast cancers compared to non-malignant breast tissue (P < 0.0001), including Asian, African American, and Caucasian subgroups. HMGA1 was highest in ER-negative tumors and there was a strong inverse correlation between HMGA1 and ESR1 gene expression (Pearson r = - 0.60, P < 0.0001). Most importantly, high HMGA1 predicted decreased overall survival (P < 0.0001) for all women with breast cancer and further stratified ER-positive tumors into those with inferior outcomes. Together, our results suggest that HMGA1 contributes to estrogen-independence, tumor progression, and poor outcomes. Moreover, further studies are warranted to determine whether HMGA1 could serve as a prognostic marker and therapeutic target for women with breast cancer.


Antioxidative flavan-3-ol glycosides from stems of Rhizophora stylosa.
Two flavan-3-ol glycosides together with seven flavan-3-ols were isolated from stems of the mangrove plant, Rhizophora stylosa. Their structures were established as glabraoside A (7) and glabraoside B (8) by spectroscopic and chemical methods. The antioxidative activity of these isolated compounds evaluated by the diphenylpicrylhydrazyl (DPPH) radical scavenging reaction was higher than that of L-ascorbic acid.


How Environmental Leadership Boosts Employees' Green Innovation Behavior? A Moderated Mediation Model.
We examined employees' green organizational identity as a mediator and green organizational climate as a moderator in the relationship between environmental leadership and follower green innovation behavior. Through collecting data (N = 313) from public organizations in China at different times, we found that environmental leadership is positively related to employees' green innovation behavior through increasing their green organizational identity. Meanwhile, the mediating relationship is conditional on the moderator of green organizational climate. The current study aims to clarify the mechanism and boundary condition in the relationship between environmental leadership and employees' green innovation behaviors.


A Major Population of Functional KLRG1- ILC2s in Female Lungs Contributes to a Sex Bias in ILC2 Numbers.
Humans show significant sex differences in the incidence and severity of respiratory diseases, including asthma and virus infection. Sex hormones contribute to the female sex bias in type 2 inflammation associated with respiratory diseases, consistent with recent reports that female lungs harbor greater numbers of GATA-3-dependent group 2 innate lymphoid cells (ILC2s). In this study, we determined whether sex hormone levels govern sex differences in the numbers, phenotype, and function of ILC2s in the murine lung and bone marrow (BM). Our data show that lungs of female mice harbor significantly greater ILC2 numbers in homeostasis, in part due to a major subset of ILC2s lacking killer-cell lectin like receptor G1 (KLRG1), a population largely absent in male lungs. The KLRG1- ILC2s were capable of type 2 cytokine production and increased with age after sexual maturity, suggesting that a unique functional subset exists in females. Experiments with gonadectomized mice or mice bearing either global or lymphocyte restricted estrogen receptor α (Esr1) deficiency showed that androgens rather than estrogens regulated numbers of the KLRG1- ILC2 subset and ILC2 functional capacity in the lung and BM, as well as levels of GATA-3 expression in BM ILC2s. Furthermore, the frequency of BM PLZF+ ILC precursors was higher in males and increased by excess androgens, suggesting that androgens act to inhibit the transition of ILC precursors to ILC2s. Taken together, these data show that a functional subset of KLRG1- ILC2s in females contributes to the sex bias in lung ILC2s that is observed after reproductive age.


The effect of activin A on signal transduction pathways in PC12 cells subjected to oxygen and glucose deprivation.
The processes and mechanisms underlying brain injuries due to ischemia and anoxia have yet to be determined. Additionally, few clinical treatements are currently available. Activins have a protective role in the restoration, differentiation, and survival of injured cells, including Activin A (ActA), which acts as a neuroprotectant. However, its exact mechanism of action remains to be determined. ActA has been shown to protect neurons following ischemic brain injury. In this study, PC12 cells were differentiated into neuron-like cells after stimulation with nerve growth factor to prepare an oxygen/glucose deprivation (OGD) model in neurons. The differentiated PC12 cells, subjected to the OGD model, were exposed to ActA. Results showed that the PC12 survival rate decreased after OGD, leading to an increase in caspase-3 expression in these cells. Pretreatment with ActA was able to partially prevent OGD-induced apoptosis, likely through the downregulation of caspase-3. Futhermore, ActA pretreatment increased the expression of key proteins in the ActA/Smads signal transduction pathway, which may promote neuroprotection after OGD. Therefore, exogenous ActA may function as a neuroprotectant and provide a novel therapeutic treatment for ischemic brain injury.


[Sertraline in the treatment of mixed anxiety and depression disorder].
Mixed anxiety and depression disorder (MAD) has been recognized in ICD-10 as a diagnostic group including those anxious and depressed patients who do not fit criteria for any major axis 1 disorders. Mad is usually treated with a combination on AD and BZD although recent reports suggest that SSRI might have both anxiolytic and AD intrinsic properties. 36 patients diagnosed of MAD (ICD-10 criteria) underwent treatment with a flexible dose of sertraline for 8 weeks. No BDZ werre allowed during the trial. Efficacy was tested with the Clinical Global Improvement Scale and with changes in Hamilton Depression and Anxiety Scales. Personality scales, including the Cloninger's TCI and the Eysenck's EPQ were used to test the predictive value of personality traits in treatment. Anxiety was reduced in 55% and depression in 60%. At the 8th week, 27 patients were responder (CGI 1-2). 2 patients discontinued the trial and only one due to adverse events. Sertraline demonstrated excellent tolerability in these MAD patients, despite the high levels of baseline anxiety in the group. Efficacy was as high as described in patients with major depression. These results warrant further placebo controlled pharmacological trials of SSRI in MAD.


A single amino acid substitution in the enzymatic domain of cytotoxic necrotizing factor type 1 of Escherichia coli alters the tissue culture phenotype to that of the dermonecrotic toxin of Bordetella spp.
Cytotoxic necrotizing factor type 1 (CNF1) and dermonecrotic toxin (DNT) share homology within their catalytic domains and possess deamidase and transglutaminase activities. Although each toxin has a preferred enzymatic activity (i.e. deamidation for CNF1 and transglutamination for DNT) as well as target substrates, both modify a specific glutamine residue in RhoA, Rac1 and Cdc42, which renders these GTPases constitutively active. Here we show that despite their similar mechanisms of action CNF1 and DNT induced unique phenotypes on HEp-2 and Swiss 3T3 cells. CNF1 induced multinucleation of HEp-2 cells and was cytotoxic for Swiss 3T3 cells (with binucleation of the few surviving cells) while DNT showed no morphological effects on HEp-2 cells but did induce binucleation of Swiss 3T3 cells. To determine if the enzymatic domain of each toxin dictated the induced phenotype, we constructed enzymatically active chimeric toxins and mutant toxins that contained single amino acid substitutions within the catalytic site and tested these molecules in tissue culture and enzymatic assays. Moreover, both site-directed mutant toxins showed reduced time to maximum transglutamination of RhoA compared with the parent toxins. Nevertheless, the substitution of threonine for Lys(1310) in the DNT-based mutant, while affecting transglutamination efficiency of the toxin, did not abrogate that enzymatic activity.


ASIC1a Promotes Acid-Induced Autophagy in Rat Articular Chondrocytes through the AMPK/FoxO3a Pathway.
Acid-sensing ion channel 1a (ASIC1a) is a member of the extracellular H⁺-activated cation channels family. Our previous studies suggested that ASIC1a contributed to acid-induced rat articular chondrocytes autophagy. However, its potential mechanisms remain unclear. The present study demonstrated the effect of ASIC1a on rat articular chondrocytes autophagy and explored the underlying molecular mechanisms. The results demonstrated that ASIC1a contributed to acid-induced autophagy in rat articular chondrocytes, and which was associated with an increase in (Ca2+)i, as indicated that acid-induced increases in mRNA and protein expression of LC3B-II and other autophagy-related markers were inhibited by ASIC1a-specific blocker, PcTx1 and calcium chelating agent, BAPTA-AM. Furthermore, the results showed that extracellular acid increased level of Forkhead box O (FoxO) 3a, but was reversed by inhibition of ASIC1a and Ca2+ influx. Moreover, gene ablation of FoxO3a prevented acid-induced increases in mRNA and protein expression of LC3B-II, Beclin1 and the formation of autophagosome. Finally, it also showed that ASIC1a activated adenine nucleotide (AMP)-activated protein kinase (AMPK). In addition, suppression of AMPK by Compound C and its small interfering RNA (siRNA) prevented acid-induced upregulation of total and nuclear FoxO3a and increases in mRNA and protein expression of LC3B-II, Beclin1, and ATG5. Taken together, these findings suggested that AMPK/FoxO3a axis plays an important role in ASIC1a-mediated autophagy in rat articular chondrocytes, which may provide novel mechanistic insight into ASIC1a effects on autophagy.


Non-dysraphic intramedullary spinal cord lipoma. A case report.
Non-dysraphic spinal cord lipomas are rare benign lesions, accounting for approximately 1% of all spinal cord tumors. Patients usually present with long histories of disability followed by rapid progression of their symptoms. Presenting symptoms include spinal pain, dysesthesic sensory changes, gait difficulties, weakness, and incontinence. Magnetic resonance imaging is the examination of choice. The T1- and T2-weighted images show increased and decreased signal intensity, respectively. The goal of intervention is decompression and generous debulking following by duraplasty. Early diagnosis of spinal cord lipomas and early surgery is advanced prior to irreversible disease progression. One new case of true non-dysraphic cervicodorsal spinal cord lipoma is reported.


Synthesis and Atomic Structure of the Yb-Ga-Au 1/1 Quasicrystal Approximant.
The Yb-Ga-Au 1/1 quasicrystal approximant (AP) composition ranges from Yb14.0Ga20.6Au65.4 to Yb14.8Ga46.3Au38.9, and single crystals of the 1/1 AP having the composition Yb13.8Ga26.1Au60.1 were obtained by the self-flux technique. X-ray structural analysis demonstrated that the atomic structure [space group Im3; a = 14.6889(9) Å] can be described by the body-centered packing of Tsai-type rhombic triacontahedron (RTH) clusters. The positional disorder in these clusters, interpreted as the average of an orientationally disordered tetrahedron and triangle, results in positional disorder in the outer shells. The elemental distributions and positions of mixtures of Au and Ga atoms in the RTH clusters correspond to those in the isostructural Yb15Al36Au49 1/1 AP.


Chemical-Modified Nucleotide-Based Elemental Tags for High-Sensitive Immunoassay.
Multiplex biomolecular analysis with inductively coupled plasma mass spectrometry (ICP-MS) becomes increasingly important in clinical diagnosis and single cell analysis. However, the sensitivity of ICP-MS-based immunoassay is only comparable or lower than those of fluorescence methods at the present stage. Therefore, designing elemental tags with a large number of metal atoms is necessary to achieve high-sensitive detection. In this work, we proposed a new strategy to build up elemental tag loading with hundreds of rare earth ions by coupling alkyne-DNA chains with rare earth element (REE)-DOTA complexes a click chemistry reaction. There are about 2 orders of magnitude improvement in sensitivity compared with single metal-ion tags. DNA chains with multialkynyl groups were facilely prepared by PCR synthesis. Moreover, the DNA-based elemental tags own excellent water-solubility and biocompatibility. The tags would be potentially applied to mass cytometry and clinical diagnosis.


Boundary slip of superoleophilic, oleophobic, and superoleophobic surfaces immersed in deionized water, hexadecane, and ethylene glycol.
The boundary slip condition is an important property, and its existence can reduce fluid drag in micro/nanofluidic systems. The boundary slip on various surfaces immersed in water and various electrolytes has been widely studied. For the surfaces immersed in oil, the boundary slip on superoleophilic and oleophilic surfaces has been studied, but there is no data on oleophobic and superoleophobic surfaces. In this paper, experiments are carried out to study electrostatic force and boundary slip on superoleophilic, oleophobic, and superoleophobic surfaces immersed in deionized (DI) water, hexadecane, and ethylene glycol. In addition, the surface charge density of the samples immersed in DI water is quantified. Results show that the electrostatic force and the absolute value of the surface charge density of an octadecyltrichlorosilane surface are larger than that of a polystyrene surface, and the electrostatic force and the absolute value of surface charge density of a superoleophilic surface are larger than that of oleophobic and superoleophobic surfaces. For the same liquid, the larger contact angle leads to a larger slip length at the solid-liquid interface. For the same surface, the larger liquid viscosity leads to a larger slip length. The relevant mechanisms are discussed in this paper.


Chronic kidney disease and the severity of coronary artery disease and retinal microvasculature changes: a cross-sectional study.
Prior studies have suggested the association between incidence of coronary artery disease (CAD) with chronic kidney disease (CKD) and poor glomerular filtration function. However to the best of our knowledge, few studies have specifically assessed this relationship based on the severity of CAD as quantified using Extent and Gensini scores. Between June 2009 and January 2012, data were collected from 1,680 participants as part of the Australian Heart Eye Study (AHES) cohort. Coronary angiograms were scored according to Gensini (severity) and Extent scores. Retinal vessel calibres were measured using validated semi-automated software. Potential confounders were adjusted for using multivariate analysis. There were no significant associations found between CKD status with Extent and Gensini scores for CAD severity, both unadjusted and when adjusted for confounding factors. In unadjusted analyses, a significant association between CKD and narrower retinal arteriolar diameter was observed (P=0.0072). After multivariate adjustment, the association between CKD and retinal arteriolar diameter was attenuated and was no longer significant (P=0.1466). No associations were observed between retinal venular calibre and prevalent CKD. The present study demonstrated no independent associations between CKD and CAD severity. These results warrant validation by future large, prospective longitudinal studies.


Pancreatic morphogenesis and extracellular matrix organization during rat development.
We investigated the rat pancreatic morphology at various developmental stages ranging from 12 days of gestation to the neonatal stage, with special emphasis on alterations in extracellular matrix organization in vivo. The rat pancreatic development in utero could be divided into four representative stages as follows: (1) initial epithelial buds (12 days of gestation), (2) elongated and branching epithelium (13-14 days), (3) tubular structure (15-16 days), and (4) acinar structure (17 days or more). Ultrastructurally, the fetal and neonatal pancreata were almost constantly encompassed by continuous basal lamina, except for the earliest stage, in which minute disruptions of basal lamina were observed. Through the disruption, the direct epithelial-mesenchymal contact was formed between an endocrine cell and an adjacent mesenchymal cell, which implied epithelial-mesenchymal interactions in processes of endocrine cell differentiation. Collagen fibrils were frequently accumulated at the cleft (branchpoint) of the branching epithelium during the second and third stages mentioned above. Immunohistochemically, fibronectin and collagen type-I were localized particularly beside the neck (narrow part) or cleft of the pancreatic epithelium at these stages, although continuous linear localization of these matrices was noted around the initial pancreatic bud. This was in contrast to invariable linear localization of laminin and collagen type-IV at the epithelial/mesenchymal interface throughout the pancreatic development. Diffuse fibrillar localization of fibronectin and collagen type-I in the mesenchyme was pronounced at the later stages and after birth. Collagen type-III was only focally detectable around the pancreatic epithelium from the second stage, and its distinct localization was noted in the interlobular connective tissue after birth. Thus, chronological changes in extracellular matrix organization seemed to be closely related to morphogenetic processes of the rat pancreas, especially in the branching epithelial morphogenesis, and the major alterations appeared prior to distinct acinar cell differentiation.


[Neuropeptide-mediated transmission of nociceptive information and its regulation. Novel mechanisms of analgesics].
Substance P and somatostatin may be transmitters of nociceptive information, which are involved in the transmission of pressure and heat nociceptive information, respectively, in the spinal dorsal horn. Calcitonin gene-related peptide, which is present in the primary sensory neurons having substance P or somatostatin, may function as a pain-promoting substance and be involved in the production of inflammation-induced hyperalgesia. The descending noradrenergic system plays a role in inhibiting nociceptive transmission in the spinal dorsal horn, and inhibits the release of substance P evoked by noxious mechanical stimulation. Persistent noxious stimuli increase the release of Met-enkephalin from the nucleus reticularis gigantocellularis, which promotes the activity of the descending noradrenergic system. Morphine activates the descending noradrenergic system, acting on the nucleus reticularis gigantocellularis. Morphine also activates the descending serotonergic system, which inhibits the release of somatostatin evoked by thermal noxious stimulation.


Supervisor Narcissism and Time Theft: Investigating the Mediating Roles of Emotional Exhaustion and the Moderating Roles of Attachment Style.
Although some studies have begun to explore the factors influencing employees' time theft, it has not been uncommon to link employee time theft to leader personality traits. Based on the conservation of resources theory, this paper examines the influence of supervisor narcissism on employee time theft. It is found that supervisor narcissism positively affects employee time theft via the emotional exhaustion of employees. Further, employee's attachment styles moderate the mediation effect of emotional exhaustion between supervisor narcissism and employee time theft. This study adds important insights into employee time theft, leader negative traits and the theory and practice of organizational management.


Location of the ankle center for total knee arthroplasty.
The purpose of this study was to investigate the ankle center position as determined from the malleoli for total knee arthroplasty (TKA). We retrospectively analyzed computed tomography data from 102 patients with osteoarthritic knees. The tibial anteroposterior (AP) axis and transmalleolar axis (TMA) were used as rotational reference axes of the knee and ankle joint, respectively. With these axes, we regarded the offset distance from the intermalleolar midpoint as the position of the ankle center and investigated any angular osteotomy errors on the proximal tibia when the ankle center was assumed to the intermalleolar midpoint. The mean offset distances relative to the tibial AP axis were 1.8±0.9mm medial and 4.2±1.2mm anterior, and the distances relative to the TMA were 3.0±0.9 and 3.6±1.1mm in the coronal and sagittal planes, respectively. Mean angular osteotomy errors were 0.3±0.2° in the coronal plane and 0.8±0.2° in the sagittal plane. The ankle center was located around the intermalleolar midpoint. The position of the ankle center observed along the knee reference axis further approached the intermalleolar midpoint than when observed along the ankle reference axis in the coronal plane, but not in the sagittal plane. And the coronal angular osteotomy error was smaller than the sagittal error. Therefore, the intermalleolar midpoint in the coronal plane is a reliable landmark for the ankle center during TKA. However, surgeons should be cognizant of this sagittal angular error.


Bartholin cyst presenting as inguinal hernia.
The clinical diagnosis of Bartholin cysts is usually very simple. This paper, however, reports a very unusual presentation, a Bartholin cyst originally thought to be an inguinal hernia. The history, anatomy, and clinical findings of Bartholin cysts are discussed, as well as a case history of this interesting presentation.


Mechanisms of transport of polymeric and lipidic nanoparticles across the intestinal barrier.
Unraveling the mechanisms of nanoparticle transport across the intestinal barrier is essential for designing more efficient nanoparticles for oral administration. The physicochemical parameters of the nanoparticles (e.g., size, surface charge, chemical composition) dictate nanoparticle fate across the intestinal barrier. This review aims to address the most important findings regarding polymeric and lipidic nanoparticle transport across the intestinal barrier, including the evaluation of critical physicochemical parameters of nanoparticles that affect nanocarrier interactions with the intestinal barrier.


Microbial production of virus-like particle vaccine protein at gram-per-litre levels.
This study demonstrates the feasibility of large-scale production of murine polyomavirus VP1 protein in recombinant Escherichia coli as pentamers which are able to subsequently self-assemble in vitro into virus-like particles (VLPs). High-cell-density pH-stat fed-batch cultivation was employed to produce glutathione-S-transferase (GST)-VP1 fusion protein in soluble form. The expression of recombinant VP1 was induced with IPTG at different cell optical densities (OD at 600 nm of 20, 60 or 100). GST-VP1 production was highest when the culture was induced at a cell density of OD 60, with volumetric yield reaching 4.38 gL⁻¹ in 31h, which we believe is the highest volumetric productivity for viral capsid protein reported to date. The induction cell density is shown to have a significant effect on the overall volumetric yield of recombinant VP1 and on final cell density, but not on VLP quality. VP1 yield was enhanced 15-fold by scaling-up from shake flask to pH-stat fed-batch cultivation in a bioreactor. Although numerous studies have expressed structural viral protein in E. coli, we believe this is the first report of translation to bioreactors yielding gram-per-litre levels. This VLP production technology overcomes major drawbacks associated with eukaryotic cell-based vaccine production technologies, and propounds the scope for large-scale commercially viable E. coli based VLP production by significantly reducing vaccine production time and cost.


shRNA Depletion of cIAP1 Sensitizes Human Ovarian Cancer Cells to Anticancer Agent-Induced Apoptosis.
Emerging evidence suggests a potential role of cellular inhibitor of apoptosis protein 1 (cIAP1) in the development of human ovarian cancer. However, its function in the progression of ovarian cancer has not been clearly determined. Our study aimed to investigate the effect of cIAP1 gene depletion on the chemosensitivity of ovarian cancer cells. We developed a novel short hairpin RNA (shRNA) plasmid specifically targeting cIAP1. Cell proliferation, invasion, and apoptosis of the shRNA-transfected cells were evaluated using MTT, Transwell chamber, and flow cytometric assays, respectively. The concentration of MMP-9 in the supernatant was detected by ELISA. Targeted depletion of cIAP1 by shRNA significantly reduced expression levels of cIAP1 mRNA and protein, leading to inhibition of cell proliferation and invasion capability in SKOV3 cells. At the same time, cIAP1 downregulation decreased the secretion of MMP-9. shRNA depletion of cIAP1 enhanced chemosensitivity of ovarian cancer cells to Taxol and carboplatin-induced apoptosis. cIAP1 is associated with tumor progression in human ovarian cancer. Therefore, cIAP1 might be a potential target for therapeutic anticancer drugs.


Stepwise structure of Lyapunov spectra for many-particle systems using a random matrix dynamics.
The structure of the Lyapunov spectra for the many-particle systems with a random interaction between the particles is discussed. The dynamics of the tangent space is expressed as a master equation, which leads to a formula that connects the positive Lyapunov exponents and the time correlations of the particle interaction matrix. Applying this formula to one- and two-dimensional models we investigate the stepwise structure of the Lyapunov spectra that appear in the region of small positive Lyapunov exponents. Long range interactions lead to a clear separation of the Lyapunov spectra into a part exhibiting stepwise structure and a part changing smoothly. The part of the Lyapunov spectrum containing the stepwise structure is clearly distinguished by a wave-like structure in the eigenstates of the particle interaction matrix. The two-dimensional model has the same step widths as found numerically in a deterministic chaotic system of many hard disks.


A Genomic Snapshot of the SARS-CoV-2 Pandemic in the Balearic Islands.
Objective: To analyze the SARS-CoV-2 genomic epidemiology in the Balearic Islands, a unique setting in which the course of the pandemic has been influenced by a complex interplay between insularity, severe social restrictions and tourism travels. Methods: Since the onset of the pandemic, more than 2,700 SARS-CoV-2 positive respiratory samples have been randomly selected and sequenced in the Balearic Islands. Genetic diversity of circulating variants was assessed by lineage assignment of consensus whole genome sequences with PANGOLIN and investigation of additional spike mutations. Results: Consensus sequences were assigned to 46 different PANGO lineages and 75% of genomes were classified within a VOC, VUI, or VUM variant according to the WHO definitions. Highest genetic diversity was documented in the island of Majorca (42 different lineages detected). Globally, lineages B.1.1.7 and B.1.617.2/AY.X were identified as the 2 major lineages circulating in the Balearic Islands during the pandemic, distantly followed by lineages B.1.177/B.1.177.X. However, in Ibiza/Formentera lineage distribution was slightly different and lineage B.1.221 was the third most prevalent. Temporal distribution analysis showed that B.1 and B.1.5 lineages dominated the first epidemic wave, lineage B.1.177 dominated the second and third, and lineage B.1.617.2 the fourth. Of note, lineage B.1.1.7 became the most prevalent circulating lineage during first half of 2021; however, it was not associated with an increased in COVID-19 cases likely due to severe social restrictions and limited travels. Additional spike mutations were rarely documented with the exception of mutation S:Q613H which has been detected in several genomes (n = 25) since July 2021. Conclusion: Virus evolution, mainly driven by the acquisition and selection of spike substitutions conferring biological advantages, social restrictions, and size population are apparently key factors for explaining the epidemic patterns registered in the Balearic Islands.


Male breast carcinoma. II. A study of the total material reported to the Swedish Cancer Registry 1958-1967 with respect to treatment, prognostic factors and survival.
The complete material of male breast cancer, 166 cases, reported to the Swedish Cancer Registry in 1958-1967 is described and analyzed concerning different prognostic parameters, treatment methods and survival. Age at diagnosis, axillary lymph node status and tumour size all had significant prognostic importance in a multivariate analysis with axillary lymph node status as the strongest factor. Histologic malignancy grade was strongly correlated to axillary lymph node status and tumour size and thus to prognosis, but did not seem to be an independent prognostic factor. The primary treatment methods were quite heterogeneous and were obviously influenced by both age of the patient and clinical tumour status. No significant correlation was found between type of primary treatment and survival, but due to the retrospective nature of the study no definite conclusion could be drawn. Radical mastectomy seemed, however, to give fewer loco-regional recurrences than both modified radical mastectomy and simple mastectomy. Very few patients in the present series had received radiation therapy in adequate doses. The material gave some indications that orchiectomy might prolong survival in patients with recurrent or generalized disease.


A unique type of a dicobalt cage templated by a weakly coordinated hexafluorophosphate anion: design, structure and solid-state NMR investigations.
A dinuclear cobalt capsule [PF(6) subset(CH(3)CN)(2)(Co(2)L(4))][PF(6)](3) (2), (L = bis-benzimidazole-1,3-phenylene) has been prepared using a self-assembly approach. This unique class of cage is perfectly designed to encapsulate weakly coordinated anions, i.e. BF(4)(-) and PF(6)(-)via an Manion weak interaction as illustrated by X-ray and solid-state NMR investigations. Selective anion binding for BF(4)(-) over PF(6)(-) is also observed.


Technology-Enabled Mental Health Service Reform for Open Arms - Veterans and Families Counselling: Participatory Design Study.
The impact of mental ill-health on every aspect of the lives of a large number of Australian Defence Force (ADF) personnel, their partners, and their families is widely recognized. Recent Senate inquiries have highlighted gaps in service delivery as well as the need for service reform to ensure appropriate care options for individuals who are currently engaged with mental health and support services as well as for those who, for a variety of reasons, have not sought help. To that end, successive Australian governments generally and the Department of Veterans' Affairs specifically have prioritized veteran-centric reform. Open Arms is an Australia-wide service that provides counseling and support to current and former ADF personnel, and their family members, for mental health conditions. The aim of this study was to develop and configure a prototypic Web-based platform for Open Arms - Veterans & Families Counselling (formerly Veterans and Veterans Families Counselling Service) with the Open Arms community to enhance the quality of mental health services provided by Open Arms. The study aimed to recruit up to 100 people from the Open Arms community (current and former ADF personnel and their families, health professionals, service managers, and administrators) in regions of New South Wales, including Sydney, Canberra, Maitland, Singleton, and Port Stephens. Participants were invited to participate in 4-hour participatory design workshops. A variety of methods were used within the workshops, including prompted discussion, review of working prototypes, creation of descriptive artifacts, and group-based development of user journeys. Seven participatory design workshops were held, including a total of 49 participants. Participants highlighted that the prototype has the potential to (1) provide the opportunity for greater and better-informed personal choice in relation to options for care based on the level of need and personal preferences; (2) ensure transparency in care by providing the individual with access to all of their personal health information; and (3) improve collaborative care and care continuity by allowing information to be shared securely with current and future providers. Our findings highlight the value of actively engaging stakeholders in participatory design processes for the development and configuration of new technologies.