Factors associated to quality of life in patients with leprosy.
To evaluate quality of life and associated factors in patients with leprosy. A cross-sectional study with 63 people diagnosed as leprosy, seen at a reference service for the disease in the southeastern region of Mato Grosso, Brazil. The questionnaire World Health Organization Quality of Life Bref was used to evaluate quality of life. Simple and multiple linear regressions evaluated the association between sociodemographic variables and quality of life domains. The highest mean of quality of life was observed in the psychological domain (16.28±2.30), and the lowest in the environmental domain (13.86±2.21). Females, individuals with no partners, and people who owned their own house had the lowest quality of life means within the psychological domain. People who did not receive visits by Community Health Workers had the lowest means in quality of life within the environmental domain. Multivariate analysis revealed that the best quality of life was associated to self-reported white skin color within the environmental domain, and the worst quality of life was associated to less schooling within the physical domain. This study showed the influence of sociodemographic factors on the quality of life of patients with leprosy, and indicated the need for comprehensive health care, considering the social determinants of health.


Cancer and dementia: Two sides of the same coin?
Noncentral nervous system cancer and the brain share an interesting and complex relation, with an emerging body of evidence showing that cancer patients are at an increased risk of developing cognitive problems. In contrast, population-based studies consistently find an inverse link between cancer and dementia, that is patients with dementia having a lower risk of subsequently developing cancer, and cancer patients being less often diagnosed with dementia. Different biological processes such as inversely activated cell proliferation and survival pathways have been suggested to have an important role underlying this inverse association. However, the effect of methodological biases including surveillance or survival bias has not been completely ruled out, calling into question the inverse direction of the association between cancer and dementia. In fact, emerging evidence now suggests that cancer and dementia might share a positive association. This narrative review summarises the current literature on cancer, cognitive problems and dementia. Moreover, different strategies will be discussed to reduce the impact of potential methodological biases on the association between cancer and dementia, trying to reveal the true direction of this link.


Comprehensive review of micro/nanostructured ZnSnO3: characteristics, synthesis, and diverse applications.
Generally, zinc stannate (ZnSnO3) is a fascinating ternary oxide compound, which has attracted significant attention in the field of materials science due to its unique properties such high sensitivity, large specific area, non-toxic nature, and good compatibility. Furthermore, in terms of both its structure and properties, it is the most appealing category of nanoparticles. The chemical stability of ZnSnO3 under normal conditions contributes to its applicability in various fields. To date, its potential as a luminescent and photovoltaic material and application in supercapacitors, batteries, solar cells, biosensors, gas sensors, and catalysts have been extensively studied. Additionally, the efficient energy storage capacity of ZnSnO3 makes it a promising candidate for the development of energy storage systems. This review focuses on the notable progress in the structural features of ZnSnO3 nanocomposites, including the synthetic processes employed for the fabrication of various ZnSnO3 nanocomposites, their intrinsic characteristics, and their present-day uses. Specifically, we highlight the recent progress in ZnSnO3-based nanomaterials, composites, and doped materials for their utilization in Li-ion batteries, photocatalysis, gas sensors, and energy storage and conversion devices. The further exploration and understanding of the properties of ZnSnO3 will undoubtedly lead to its broader implementation and contribute to the advancement of next-generation materials and devices.


Poly[(μ(3)-4-carb-oxy-pyridine-3-carboxyl-ato-κN:O:O)(triphenyl-phosphine-κP)silver(I)].
In the title 1:1 silver(I) 4-carb-oxy-pyridine-3-carboxyl-ate adduct with triphenyl-phosphine, [Ag(C(7)H(4)NO(4))(C(18)H(15)P)](n), the carboxyl-ate anion bridges the phosphine-coordinated Ag atoms through its N and O atoms, generating a coordination polymer forming layers in the bc plane. The Ag atom exists in a distorted tetra-hedral geometry. The H atom of the carboxyl-ate is midway between two O atoms of the two carboxyl groups, thus forming a strong intra-molecular hydrogen bond.


Deep sequencing of the murine IgH repertoire reveals complex regulation of nonrandom V gene rearrangement frequencies.
A diverse Ab repertoire is formed through the rearrangement of V, D, and J segments at the IgH (Igh) loci. The C57BL/6 murine Igh locus has >100 functional VH gene segments that can recombine to a rearranged DJH. Although the nonrandom usage of VH genes is well documented, it is not clear what elements determine recombination frequency. To answer this question, we conducted deep sequencing of 5'-RACE products of the Igh repertoire in pro-B cells, amplified in an unbiased manner. Chromatin immunoprecipitation-sequencing results for several histone modifications and RNA polymerase II binding, RNA-sequencing for sense and antisense noncoding germline transcripts, and proximity to CCCTC-binding factor (CTCF) and Rad21 sites were compared with the usage of individual V genes. Computational analyses assessed the relative importance of these various accessibility elements. These elements divide the Igh locus into four epigenetically and transcriptionally distinct domains, and our computational analyses reveal different regulatory mechanisms for each region. Proximal V genes are relatively devoid of active histone marks and noncoding RNA in general, but having a CTCF site near their recombination signal sequence is critical, suggesting that being positioned near the base of the chromatin loops is important for rearrangement. In contrast, distal V genes have higher levels of histone marks and noncoding RNA, which may compensate for their poorer recombination signal sequences and for being distant from CTCF sites. Thus, the Igh locus has evolved a complex system for the regulation of V(D)J rearrangement that is different for each of the four domains that comprise this locus.


An examination of the causes and solutions to eyewitness error.
Eyewitness error is one of the leading causes of wrongful convictions. In fact, the American Psychological Association estimates that one in three eyewitnesses make an erroneous identification. In this review, we look briefly at some of the causes of eyewitness error. We examine what jurors, judges, attorneys, law officers, and experts from various countries know about eyewitness testimony and memory, and if they have the requisite knowledge and skills to accurately assess eyewitness testimony. We evaluate whether legal safeguards such as voir dire, motion-to-suppress an identification, cross-examination, jury instructions, and eyewitness expert testimony are effective in identifying eyewitness errors. Lastly, we discuss solutions to eyewitness error.


Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet light.
The mdm2 (murine double minute 2) oncogene encodes several proteins, the largest of which (p90) binds to and inactivates the p53 tumor suppressor protein. Multiple MDM2 proteins have been detected in tumors and in cell lines expressing high levels of mdm2 mRNAs. Here we show that one of these proteins (p76) is expressed, along with p90, in wild-type and p53-null mouse embryo fibroblasts, indicating that it may have an important physiological role in normal cells. Expression of this protein is induced, as is that of p90, by UV light in a p53-dependent manner. The p76 protein is synthesized via translational initiation at AUG codon 50 and thus lacks the N terminus of p90 and does not bind p53. In cells, p90 and p76 can be synthesized from mdm2 mRNAs transcribed from both the P1 (constitutive) and P2 (p53-responsive) promoters. Site-directed mutagenesis reveals that these RNAs give rise to p76 via internal initiation of translation. In addition, mdm2 mRNAs lacking exon 3 give rise to p76 exclusively, and such mRNAs are induced by p53 in response to UV light. These data indicate that p76 may be an important product of the mdm2 gene and a downstream effector of p53.


Improving the ability to detect the impact of labor on patient outcomes.
A key part of resource allocation decisions is determining the impact of staffing on clinical outcomes. A national study involving eight hospitals and 77 units lends support for a previously identified labor assignment phenomena that may contribute to an underestimation of the impact of nursing labor on outcomes if only traditional labor measurement methods are used. The authors suggest actions for nurse administrators and researchers who must address frequent queries as to the adequacy of nursing staffing.


Endoscopic Conduit Harvest in Coronary Artery Bypass Grafting Surgery: An ISMICS Systematic Review and Consensus Conference Statements.
The purpose of this consensus conference was to develop and update evidence-informed consensus statements and recommendations on harvesting saphenous vein and radial artery via an open as compared with endoscopic technique by systematically reviewing and performing a meta-analysis of randomized and nonrandomized clinical trials. All randomized controlled trials and nonrandomized controlled trials included in the first the International Society for Minimally Invasive Cardiothoracic Surgery Consensus Conference and Statements, in 2005 up to November 30, 2015, were included in a systematic review and meta-analysis. Based on the resultant, 76 studies (23 randomized controlled trials and 53 nonrandomized controlled trials) on 281,459 patients analyzed, consensus statements, and recommendations were generated comparing the risks and benefits of endoscopic versus open conduit harvesting for patients undergoing coronary artery bypass grafting. Compared with open vein harvest, it is reasonable to perform endoscopic vein harvest of saphenous vein to reduce wound-related complications, postoperative length of stay, and outpatient wound management resources and to increase patient satisfaction (class I, level A). Based on the quality of the conduit and major adverse cardiac events as well as 6-month angiographic patency, endoscopic vein harvest was noninferior to open harvest. It is reasonable to perform endoscopic radial artery harvest to reduce wound-related complication and to increase patient satisfaction (class I, level B-R and B-NR, respectively) with reduction in major adverse cardiac events and noninferior patency rate at 1 and 3 to 5 years (class III, level B-R). Based on the consensus statements, the consensus panel recommends (class I, level B) that endoscopic saphenous vein and radial artery harvesting should be the standard of care for patients who require these conduits for coronary revascularization.


Role of key regulators of the cell cycle in maintenance of hematopoietic stem cells.
Hematopoietic stem cells (HSCs) are characterized by pluripotentiality and self-renewal ability. To maintain a supply of mature blood cells and to avoid HSC exhaustion during the life span of an organism, most HSCs remain quiescent, with only a limited number entering the cell cycle. The molecular mechanisms by which quiescence is maintained in HSCs are addressed, with recent genetic studies having provided important insight into the relation between the cell cycle activity and stemness of HSCs. The cell cycle is tightly regulated in HSCs by complex factors. Key regulators of the cell cycle in other cell types-including cyclins, cyclin-dependent kinases (CDKs), the retinoblastoma protein family, the transcription factor E2F, and CDK inhibitors-also contribute to such regulation in HSCs. Most, but not all, of these regulators are necessary for maintenance of HSCs, with abnormal activation or suppression of the cell cycle resulting in HSC exhaustion. The cell cycle in HSCs is also regulated by external factors such as cytokines produced by niche cells as well as by the ubiquitin-proteasome pathway. Studies of the cell cycle in HSCs may shed light on the pathogenesis of hematopoietic disorders, serve as a basis for the development of new therapeutic strategies for such disorders, prove useful for the expansion of HSCs in vitro as a possible replacement for blood transfusion, and provide insight into stem cell biology in general. This article is part of a Special Issue entitled Biochemistry of Stem Cells.


[Quality of life, loneliness and social contacts among persons with long-term mental illness].
Chronic long-term patients who were residents in psychiatric nursing homes at a given point in time were traced six years later. Over this period, there had been deep cuts in the number of psychiatric beds in the county in question; we wanted to assess how the patients now perceived their quality of life. All 107 patients were traced; of the 75 who were still alive, 74 took part in the study and were visited at their place of residence. 42 patients, mean age 56.9 years, were able to respond to personal questions regarding social contact, loneliness and quality of life. Health care providers were the most important persons in the patients' networks. Most patients reported a satisfactory quality of life; those who lived outside institutions (N = 21) tended to be more satisfied than those in residential care, they were more socially active and had better contact with their families. The variables loneliness, satisfaction with neighbourhood and leisure activities explained 63% of the variance in quality of life.


Barriers and facilitators of HIV vaccine and prevention study participation among Young Black MSM and transwomen in New York City.
Black men who have sex with men (MSM), and Transwomen (TW) shoulder disproportionate burden of HIV. However, they are unrepresented in HIV vaccine trials. We investigated the perceptions of that factors associated with HIV vaccine trials participation among Black MSM and TW in New York. Self-administered online questionnaires were administered to 18-29 years of NYC residents who identified as Black MSM and TW, assessing demographics, awareness and willingness to participate in HIV vaccine trials, barriers and facilitators associated with willingness, and sexual behaviors. Frequency summation was performed to determine barriers and facilitators, and logistic regression analysis was performed to determine factors association with expressed willingness. Black MSM and TW who reported engaging in risk behaviors had a 61% lower likelihood of participating in HIV vaccine trials when compared to those who did not report engaging in any risk behavior. Facilitators associated with trial participation were: cash compensation, confidentiality regarding participation, public transportation vouchers, gift cards, and food or grocery vouchers as potential facilitators for trial participation. Conversely, fear of side effects from the vaccine, concerns about testing positive on routine HIV testing due to an HIV vaccine, limited knowledge of research trials, and fear of being judged as HIV-positive were perceived as barriers. These findings provided insights into the considerations and perceptions of Black MSM and TW towards HIV vaccine trials. However, further studies are needed to delineate the complex mechanisms underlying the decision-making process and establish approaches to increase study participation in this population.


Medication reconciliation and hypertension control.
Discrepancies between the medical record and patient medication list are common. The relationship of discrepancies to chronic disease control has not been established. To determine the frequency and type of antihypertensive medication discrepancies between patient-named antihypertensive medications and the medical record, we performed a cross-sectional study of 315 adults with medically treated hypertension from 6 safety-net clinics in 3 states. We determined the association between medication discrepancies and uncontrolled blood pressure (> or =140/90 mm Hg or > or =130/80 mm Hg if diabetes) using multivariate logistic regression models. Discrepancies were present for 75.2% of patients; 25.7% of patients could not provide the name of any antihypertensive medication they took; 49.5% could name 1 or more antihypertensive medications but had discrepancies between patient-reported antihypertensive medications and those listed in the medical record. Both patients who were unable to name any of their antihypertensive medications and patients with discrepancies between patient-named medications and the medical record were significantly more likely to have uncontrolled blood pressure than patients who named the same medications as the medical record in adjusted analyses, adjusted risk ratios 1.66 (95% confidence interval, 1.31-2.10) and 1.51 (95% confidence interval, 1.11-2.07), respectively. Twelve percent of patients reporting medications took antihypertensive medication that altered potassium metabolism that was not in their medical record. Among patients at safety-net clinics, inability to name one's antihypertensive medications and discrepancies between patient-reported medications and the medical record were very common. Both were strongly associated with inadequate hypertension control. Performing medication reconciliation at the point of care may be an important way to identify patients at high risk for inadequate disease control or safety problems.


Strong anisotropy of ferroelectricity in lead-free bismuth silicate.
Bismuth silicate (Bi2SiO5) was recently suggested as a potential silicate based lead-free ferroelectric material. Here, we show the existence of ferroelectricity and explore the strong anisotropy of local ferroelectricity using piezoresponse force microscopy (PFM). Domain structures are reconstructed using angle-resolved PFM. Furthermore, piezoresponse hysteresis loops and piezoelectric coefficients are spatially investigated at the nanoscale. The obtained results confirm the existence of ferroelectricity with strong c-axis polarization. These results could provide basic information on the anisotropic ferroelectricity in Bi2SiO5 and furthermore suggest its considerable potential for lead-free ferroelectric applications with silicon technologies.


Nonfixed duplication containing the Adh gene and a truncated form of the Adhr gene in the Drosophila funebris species group: different modes of evolution of Adh relative to Adhr in Drosophila.
The sequence of the genomic region that contains the Adh and Adhr genes of Drosophila funebris was used to demonstrate that both genes are present in species of the funebris group. The sequence of this genomic region reveals a 2.9-kb tandem duplication which encompasses 1.6 kb of the 5' flanking region, the entire Adh gene, and two thirds of the first exon of the Adhr gene in D. funebris. This duplication is not fixed in this species since some strains do not carry the duplication. The Adh duplication has also been found in another species of the funebris group, Drosophila macrospina macrospina. The sequence analysis of the 5'-flanking region of the Adh gene indicates a single promoter and shows stretches of high similarity with cis-acting elements responsible for the expression of Adh in Drosophila melanogaster. In confirmation of this indication, the larval and adult transcripts have the same length, which corresponds to the transcription from the promoter proximal to the coding region. The codon bias of the Adh gene of D. funebris is among the lowest reported for any Adh gene in the Drosophilidae species and is very similar to that of the Adhr gene. The Adhr gene evolves slightly faster than Adh at synonymous positions. At nonsynonymous positions, the Adh gene evolves 2.5 times faster than Adhr in the species pair D. funebris-Drosophila immigrans, while in other interspecific comparisons the average is about 1.25. However, in comparisons between some species within the melanogaster and obscura groups, Adh evolves at half the rate of Adhr. The phylogenetic trees constructed with the coding region of the Adh gene cluster D. funebris and D. immigrans and clearly separate them from the clade in which virilis, repleta, and Hawaiian species are grouped. Using the evolutionary synonymous rate estimated for Hawaiian species, the divergence time of D. funebris from the virilis-repleta-Hawaiian clade was estimated as 34.3 Myr, and the divergence time of D. funebris and D. immigrans was estimated as 23.5 Myr.


Acylceramide head group architecture affects lipid organization in synthetic ceramide mixtures.
The lipid organization in the upper layer of the skin, the stratum corneum (SC), is important for the skin barrier function. This lipid organization, including the characteristic 13 nm lamellar phase, can be reproduced in vitro with mixtures based on cholesterol, free fatty acids and natural as well as synthetic ceramides (CER). In human SC, nine CER classes have been identified (CER1-CER9). Detailed studies on the effect of molecular structure of individual ceramides on the SC lipid organization are only possible with synthetic lipid mixtures, as their composition can be accurately chosen and systematically modified. In the present study, small-angle X-ray diffraction was used to examine the organization in synthetic lipid mixtures of which the synthetic ceramide fraction was prepared with sphingosine-based CER1 or phytosphingosine-based CER9. The latter acylceramide contains an additional hydroxyl group at the sphingoid backbone. The results show that a gradual increase in CER1 level consistently promotes the formation of the 13 nm lamellar phase and that partial replacement of CER1 by CER9 does not affect the phase behavior. Interestingly, complete substitution of CER1 with CER9 reduces the formation of the long periodicity phase and results in phase separation of CER9.


Knockdown of KIF15 promotes cell apoptosis by activating crosstalk of multiple pathways in ovarian cancer: bioinformatic and experimental analysis.
Ovarian cancer (OC) is the most lethal malignancy of women. Unlimited proliferation is a fundamental feature of OC cells. The genes associated with cell proliferation may be histopathologic biomarkers and targets of anti-tumor therapeutic strategies. The present study aimed to identify proliferation-associated biomarkers with prognostic, diagnostic, and therapeutic value and reveal the underlying molecular mechanism of candidate genes involved in OC by a combination of bioinformatic and experimental methods. KIF15 was upregulated in early-stage OC tissues and could predict poor prognosis of patients of Stage I and II. The knockdown of KIF15 significantly inhibited cell proliferation, tumor formation, and growth as well as promoting apoptosis of OC cells. A combination of experimental and bioinformatic analyses revealed KIF15 knockdown promoted cell apoptosis by activating crosstalk of multiple pathways in OC. KIF15, an early-stage prognostic gene, was identified as a candidate histopathologic biomarker and therapeutic target of OC.


Evaluation of a SARS-CoV-2 spike protein ectodomain subunit vaccine with a squalene emulsion adjuvant in rodents and rhesus macaques.
COVID-19 vaccines have played an important role in reducing the impact of the current pandemic. Previously, we developed NARUVAX-C19 vaccine based on a recombinant Wuhan spike protein extracellular domain expressed in insect cells and formulated with a squalene emulsion adjuvant (Sepivac SWE™). The current study assessed the immunogenicity, efficacy, and safety of NARUVAX-C19 vaccine in rhesus macaques and hamsters. Macaques immunized intramuscularly with two doses of NARUVAX-C19 vaccine showed no adverse effects and demonstrated cellular immunity as assessed by T cell IFN-γ responses against spike protein, in addition to inducing a humoral response. Serum from immunized animals neutralized the homologous wild-type SARS-CoV-2 virus as well as the Alpha and Delta variants. In hamsters, immunization with NARUVAX-C19 vaccine protected against a heterologous challenge with the Delta virus, as reflected by reduced lung and nasal viral loads and lung pathology in immunized animals. Nevertheless, some NARUVAX-C19 vaccinated animals were still shown to transmit infection to naïve sentinel animals. Overall, NARUVAX-C19 vaccine induced broadly cross-neutralizing antibody and T cell IFN-γ responses in rhesus macaques and provided heterologous protection of hamsters against infection by the Delta virus variant. This data supports the utility of squalene emulsion-based adjuvanted recombinant vaccine in protection against SARS-CoV-2 and supports their continued clinical development.


Exercise in gestational diabetes. An optional therapeutic approach?
Forty-one patients with gestational diabetes requiring insulin were enrolled in a randomized study to investigate the efficacy of an exercise program in normalizing glucose tolerance. Seventeen of 21 patients completed the exercise program while maintaining normoglycemia and obviating insulin therapy. Maternal and neonatal complications did not differ between the study and control groups. The type of program described appears to be safe and can serve as a model for exercise prescription for pregnant diabetic women to attain improved glucose tolerance.


Effective dose of peri-operative oral pregabalin as an adjunct to multimodal analgesic regimen in lumbar spinal fusion surgery.
A prospective, randomized, controlled, and double-blind trial. To evaluate the effects of 2 different doses of perioperative pregabalin administration, twice on the day of surgery, on acute postoperative pain after spinal surgery. Besides its well-established role on neuropathic pain, pregabalin seems to be a promising adjunct to multimodal analgesic regimen following surgery. No comprehensive data exist regarding the optimal dosage of pregabalin on reducing postoperative pain and opioid consumption in spinal surgery. Patients were randomly assigned to 1 of 3 groups. The placebo group (n = 28) received placebo capsules 1 hour before the anesthetic induction and 12 hours after surgery. The pregabalin groups received pregabalin 75 mg (P75 group, n = 28) or 150 mg (P150 group, n = 28), respectively at the same points. Assessed variables were total amount of administered fentanyl-based intravenous patient-controlled analgesia, pain intensity, and the frequency of rescue analgesic administered during the first 48 hours after surgery, subdivided into the following 4 periods: on arrival of patient to the postanesthesia care unit, 1 to 6 hours, 6 to 24 hours, and 24 to 48 hours. RESULTS.: The amount of patient-controlled analgesia volume infused until 24 hours (P 5 0.025) and 48 hours (P 5 0.028) after surgery was significantly less in the P150 group compared with the control group. The frequency of additional anodynes administered until 6 hours (P 5 0.049) and 24 hours (P 5 0.045) after surgery was significantly less in the P150 group compared with the control group. Perioperative administration of pregabalin 150 mg before and 12 hours after surgery, but not 75 mg, significantly reduced opioid consumption and the use of additional pain rescue for 48 hours after surgery without significant side effects in patients undergoing spinal fusion surgery.


Evidence-based practice guidelines for instructing individuals with neurogenic memory impairments: what have we learned in the past 20 years?
This article examines the instructional research literature pertinent to teaching procedures or information to individuals with acquired memory impairments due to brain injury or related conditions. The purpose is to evaluate the available evidence in order to generate practice guidelines for clinicians working in the field of cognitive rehabilitation. A systematic review of the instructional literature from 1986 to 2006 revealed 51 studies meeting search criteria. Studies were analysed and coded within the following four key domains: Population Sample, Intervention, Study Design, and Treatment Outcomes. Coding included 17 characteristics of the population sample; seven intervention parameters; five study design features; and five treatment outcome parameters. Interventions that were evaluated included systematic instructional techniques such as method of vanishing cues and errorless learning. The majority of the studies reported positive outcomes in favour of systematic instruction. However, issues related to the design and execution of effective instruction lack clarity and require further study. The interaction between the target learning objective and the individual learner profile is not well understood. The evidence review concludes with clinical recommendations based on the instructional literature and a call to clinicians to incorporate these methods into their practice to maximise patient outcomes.


Activation of the signal transducer and activator of transcription 3 pathway up-regulates estrogen receptor-beta expression in lung adenocarcinoma cells.
Estrogens contribute to the pathogenesis of female lung cancer and function mainly through estrogen receptor-β (ERβ). However, the way in which ERβ expression is regulated in lung cancer cells remains to be explored. We have found that signal transducer and activator of transcription 3 (Stat3) activation up-regulates ERβ expression in PC14PE6/AS2 lung cancer cells in a preliminary Affymetrix oligonucleotide array study, and we sought to confirm the findings. In this study, we show that IL-6 induced ERβ mRNA and protein expression in lung cancer cells. The induction of ERβ in response to IL-6 was abolished by Janus kinase 2 inhibitor-AG490, dominant-negative mutant of Stat3, and Stat3-targeting short interfering RNA. The luciferase reporter assay and chromatin immunoprecipitation assay confirmed that IL-6-activated Stat3 binds to the ERβ promoter. Besides the Janus kinase 2/Stat3 pathway, the MEK/Erk pathway contributes to ERβ up-regulation induced by IL-6; however, the phosphoinositide 3'-kinase/Akt pathway does not. We also found that epidermal growth factor (EGF) stimulation or L858R mutation in EGF receptor (EGFR) induced Stat3 activation as well as ERβ expression in lung cancer cells. Inhibiting Stat3 activity by pharmacological or genetic approaches reduced EGF- and L858R mutant EGFR-induced ERβ expression, indicating that Stat3 activation is required for EGFR signaling-mediated ERβ up-regulation. Silencing ERβ decreased cell proliferation in lung cancer cells that overexpress L858R mutant EGFR. In conclusion, we have identified that Stat3 activation is essential for ERβ induction by IL-6, EGF, and the presence of EGFR mutation. The findings shed light on new therapeutic targets for female lung cancer, especially for those with EGFR mutations.


[Monitoring of the misuse of prescription drugs by clients of outpatient addiction treatment centres (PHAR-MON, formerly: Ebis-med). Monitoring of medication misuse].
The monitoring system PHAR-MON (formerly: ebis-med) documents the misuse of pharmaceuticals in addiction counseling centres as an early warning system. It is described as a diagnostic instrument according to its aims and tasks, implementation and assessing procedures and is evaluated according to the main quality criteria of diagnostic instruments. In addition, selected results are reported about the misuse of medicaments in the year 2004. In analogy to diagnostic instruments, the main quality criteria objectivity, reliability and validity are applied to evaluate PHAR-MON, they are extended, however, by the validity of the sample of reference outpatient centers. Statistical methods for proving results are applied and discussed concerning their appropriateness for cross-sectional and longitudinal analyses of PHAR-MON data. The selected results are based on the survey data for 2004 of 32 counseling centers with 629 medicaments abused by 500 clients. The representativity was checked by comparison with the outpatient addiction statistics. The sample of counseling centers is representative for all addiction counseling centers in Germany. The dominant influence factor on the abuse of medicaments is the main diagnosis of the clients. Therefore, the analysis is separated for the main diagnoses as to alcohol, illegal drugs and medicaments. The statistical methods of confidence intervals and other statistical procedures are useful in proving data for cross-sectional and longitudinal analyses. In 2004 there was an increase of abused buprenorphine by 5.7% compared to the previous year. The rate of misuse of hypnotics, which is the largest group of abused medicaments, only slightly increased by 2.4%. The monitoring system PHAR-MON is a sensitive and valid monitoring system for the abuse of medicaments in addiction counseling centres. By documenting individual criteria of abuse in the new version of the documentation sheet, the results of medicament abuse can be analyzed in a more valid way. To improve the PHAR-MON system a study about reliability is planned. Because of the health risks associated with the abuse of medicaments, continuous information for physicians about the risks of medicament abuse is helpful to prevent negative consequences.


Transplantation of the major salivary glands.
In absolute aqueous-deficient dry eye, severe signs and symptoms may persist despite punctal occlusion and frequent application of artificial tear substitutes. In this group of patients the three major salivary glands, the parotid, the submandibular and the sublingual gland, have been used to lubricate the ocular surface. A PubMed search was performed using the keywords 'dry eye, major salivary glands, parotid gland, parotid duct, sublingual gland, submandibular gland (SMG), transposition, transplantation' to identify the current literature on major salivary gland transplantation. The surgical procedures are described, their principle advantages and disadvantages and the published results are analyzed. To use the parotid gland as a source of substitute lubrication its secretory duct is transposed to the lower conjunctival fornix. The procedure results in a purely serous secretion and severe gustatory reflex epiphora. Parts of the sublingual gland, which produces a mucoserous secretion, have been transplanted into the subconjunctival space. Since the graft is left without a direct vascularisation, it frequently becomes non-functional. The SMG finally produces a more tear-like, seromucinous secretion. It is transferred as a free, denervated graft to the temporal fossa, where a microvascular anastomosis with the temporal artery and vein is established. Graft survival in the long term is 72%. Graft viability is associated with a significant improvement of Schirmer's test, break-up time, rose bengal staining and symptoms. In 38% of eyes with a viable graft, salivary epiphora results, which is independent of gustatory stimuli. Since the salivary tear film is substantially hypoosmolar, microcystic epithelial oedema can result and subsequent corneal transplantation remains unsuccessful. Of the three major salivary glands, the parotid and the SMG have been used successfully to provide substitute lubrication in severely dry eyes. The surgical technique varies significantly in terms of complexity and reversibility. While the procedures are capable of improving comfort, due to the salivary character of the new tear film subsequent ocular surface reconstruction remains unsuccessful.


Breast imaging in the young: the role of magnetic resonance imaging in breast cancer screening, diagnosis and follow-up.
Diagnosis of breast cancer in young individuals (younger than 40 years old) poses a real challenge to breast radiologists because their breast tissue is often denser than the breast tissue of older women. Magnetic Resonance Imaging (MRI) may be particularly helpful in such situations. The American Cancer Society (ACS) recommended breast MRI screening as an adjunct to mammography for: BRCA mutation carriers and their first-degree relatives; women with a lifetime breast cancer risk ≥20% to 25%; women with a history of chest radiation between ages of 10 and 30 years; and women with predisposing genetic syndromes. Currently, breast MRI demonstrates a high sensitivity in the range of 93-100%. As many benign lesions also show enhancement or other atypical features on MRI, the primary weakness of contrast enhanced MRI remains in its low specificity, reported to be in the range of 37-97%. Breast MRI is helpful in demonstrating the true tumor size initially, as well as identifying residual tumor following the completion of neo-adjuvant therapy. In general, sensitivities ranging from 61% to 86% for detecting residual disease have been reported. The absence of enhancement virtually excludes a recurrence and the presence of enhancement is very specific for tumor even in the radiated breast. MRI is also the preferred modality for assessment of the breast after re- constructive surgery. The role of Magnetic Resonance Imaging (MRI) in breast diagnosis will continue to evolve as technology improves and clinical experience with new techniques expands.


Dual transcriptional profiling of a bacterial/fungal confrontation: Collimonas fungivorans versus Aspergillus niger.
Interactions between bacteria and fungi cover a wide range of incentives, mechanisms and outcomes. The genus Collimonas consists of soil bacteria that are known for their antifungal activity and ability to grow at the expense of living fungi. In non-contact confrontation assays with the fungus Aspergillus niger, Collimonas fungivorans showed accumulation of biomass concomitant with inhibition of hyphal spread. Through microarray analysis of bacterial and fungal mRNA from the confrontation arena, we gained new insights into the mechanisms underlying the fungistatic effect and mycophagous phenotype of collimonads. Collimonas responded to the fungus by activating genes for the utilization of fungal-derived compounds and for production of a putative antifungal compound. In A. niger, differentially expressed genes included those involved in lipid and cell wall metabolism and cell defense, which correlated well with the hyphal deformations that were observed microscopically. Transcriptional profiles revealed distress in both partners: downregulation of ribosomal proteins and upregulation of mobile genetic elements in the bacteria and expression of endoplasmic reticulum stress and conidia-related genes in the fungus. Both partners experienced nitrogen shortage in each other's presence. Overall, our results indicate that the Collimonas/Aspergillus interaction is a complex interplay between trophism, antibiosis and competition for nutrients.


[Typing of herpes simplex virus in patients with uveitis].
To examine the type of herpes simplex virus (HSV) in cases with uveitis. Intraocular fluid specimens obtained from 3 cases with herpetic iridocyclitis and 6 cases with acute retinal necrosis (ARN) were examined by polymerase chain reaction (PCR). HSV typing was performed by the restriction patterns of the PCR products. Serum samples obtained from these cases and 33 cases with uveitis were examined by neutralization test (NT) for the availability of the typing of HSV. The restriction patterns of the PCR products amplified from 3 specimens of iridocyclitis revealed HSV type 1 DNA. HSV type 2 DNA was identified in 5 of 6 cases of ARN and HSV type 1 DNA was found in only one case. The results of serum NT titers correlated with the typing of the amplicons. In the cases studied, HSV type 1 was the dominant etiological agent in herpetic iridocyclitis, while HSV type 2 played a similar role in HSV-associated ARN. The examination of the serum NT may be helpful for the identification of the etiological types of HSV in patients with uveitis.


A community-based collaborative approach to improve breast cancer screening in underserved African American women.
Although African American women in the United States have a lower incidence of breast cancer compared with white women, those younger than 40 years actually have a higher incidence rate; additionally, African American women are more likely to die from breast cancer at every age compared with white women. Racial disparities in breast cancer mortality rates are especially significant in Maryland, which ranks fifth in the nation for breast cancer mortality, and in Baltimore City, which has the second highest annual death rate for African American women in Maryland. To address this disparity in care, Med-IQ, an accredited provider of CME, collaborated with Sisters Network Baltimore Metropolitan, Affiliate Chapter of Sisters Network® Inc., the only national African American breast cancer survivorship organization, to sponsor their community-based educational outreach initiative. The collaborative mission was to engage at-risk African American women, their families, local organizations, healthcare professionals, and clinics, with the goals of increasing awareness, addressing fears that affect timely care and diagnosis, and encouraging women to obtain regular mammograms. Intervention strategies included (1) a "Survivor Stories" video, (2) patient outreach consisting of neighborhood walks and an educational luncheon, and (3) a community outreach utilizing direct mailings to local businesses, community groups, and healthcare professionals. Trusted and well-known community resources were presented as mediums to promote the initiative, yielding achievement of broader and more effective outcomes. As a result of this patient-friendly initiative, two (2) of the women who sought screening were diagnosed with breast cancer and underwent treatment.


Calcium binding is essential for plastin 3 function in Smn-deficient motoneurons.
The actin-binding and bundling protein, plastin 3 (PLS3), was identified as a protective modifier of spinal muscular atrophy (SMA) in some patient populations and as a disease modifier in animal models of SMA. How it functions in this process, however, is not known. Because PLS3 is an actin-binding/bundling protein, we hypothesized it would likely act via modification of the actin cytoskeleton in axons and neuromuscular junctions to protect motoneurons in SMA. To test this, we examined the ability of other known actin cytoskeleton organizing proteins to modify motor axon outgrowth phenotypes in an smn morphant zebrafish model of SMA. While PLS3 can fully compensate for low levels of smn, cofilin 1, profilin 2 and α-actinin 1 did not affect smn morphant motor axon outgrowth. To determine how PLS3 functions in SMA, we generated deletion constructs of conserved PLS3 structural domains. The EF hands were essential for PLS3 rescue of smn morphant phenotypes, and mutation of the Ca(2+)-binding residues within the EF hands resulted in a complete loss of PLS3 rescue. These results indicate that Ca(2+) regulation is essential for the function of PLS3 in motor axons. Remarkably, PLS3 mutants lacking both actin-binding domains were still able to rescue motor axons in smn morphants, although not as well as full-length PLS3. Therefore, PLS3 function in this process may have an actin-independent component.


Results of a Regional Effort to Improve Warfarin Management.
Improved anticoagulation control with warfarin reduces adverse events and represents a target for quality improvement. No previous study has described an effort to improve anticoagulation control across a health system. To describe the results of an effort to improve anticoagulation control in the New England region of the Veterans Health Administration (VA). Our intervention encompassed 8 VA sites managing warfarin for more than 5000 patients in New England (Veterans Integrated Service Network 1 [VISN 1]). We provided sites with a system to measure processes of care, along with targeted audit and feedback. We focused on processes of care associated with site-level anticoagulation control, including prompt follow-up after out-of-range international normalized ratio (INR) values, minimizing loss to follow-up, and use of guideline-concordant INR target ranges. We used a difference-in-differences (DID) model to examine changes in anticoagulation control, measured as percentage time in therapeutic range (TTR), as well as process measures and compared VISN 1 sites with 116 VA sites located outside VISN 1. VISN 1 sites improved on TTR, our main indicator of quality, from 66.4% to 69.2%, whereas sites outside VISN 1 improved from 65.9% to 66.4% (DID 2.3%, P < 0.001). Improvement in TTR correlated strongly with the extent of improvement on process-of-care measures, which varied widely across VISN 1 sites. A regional quality improvement initiative, using performance measurement with audit and feedback, improved TTR by 2.3% more than control sites, which is a clinically important difference. Improving relevant processes of care can improve outcomes for patients receiving warfarin.


Effects of soy polysaccharide on gastrointestinal functions, nutrient balance, steroid excretions, glucose tolerance, serum lipids, and other parameters in humans.
A diet-controlled study with a cross-over design was conducted to determine the effect of soy polysaccharide on gastrointestinal functions, nutrient balance, steroid excretion, blood lipid levels, postprandial serum glucose response, and other blood parameters in healthy male human subjects. A total of 14 college students was selected to participate in the study on a voluntary basis and each served as his own control. The study had two 17-day feeding periods. During the first feeding period, half of the subjects served as controls, the other as experimentals. During the second feeding period, treatments were crossed. When serving as controls, subjects consumed a low-fiber basal diet; when serving as experimentals, the same diet was supplemented with 25 g/day of soy polysaccharide. Blood samples taken at the beginning (days -1 and 1) and at the end (days 17 and 18) of each period revealed no changes in serum lipid levels or other blood parameters by soy polysaccharide supplementation. Nutrient balance and fecal transit studies revealed a significant increase in fecal wet weight and fecal water content, but no changes in total dry weight, fecal neutral steroid, bile salt, protein, and mineral contents. Glucose tolerance tests conducted during each period revealed that addition of soy polysaccharide to the glucose solution significantly reduced the reactive hypoglycemia at 180 min. Results of the present study suggest that in healthy male subjects, supplementation of soy polysaccharide can result in an increase in wet fecal content and possibly some improvement in glucose tolerance response.


Investigation on the properties of a laminar grating as a soft x-ray beam splitter.
Laminar-type gratings as soft x-ray beam splitters for interferometry are presented. Gold-coated grating beam splitters with 1000 lines/mm are designed for grazing incidence operation at 13.9 nm. They are routinely fabricated using electron beam lithography and ion etching techniques. The laminar grating is measured to have almost equal absolute efficiencies of about 20% in the zeroth and -1st orders, which enables a fringe visibility up to 0.99 in the interferometer. The discrepancy of the grating profiles between the optimized theoretical and the experimental results is analyzed according to the comparison of the optimized simulation results and the measurement realization of the grating efficiencies. By a precise control of the grating profile, the grating efficiency in the -1st order and the fringe visibility could be improved to 25% and 1, respectively.


The hidden costs of accounts receivable.
To maintain and expand their missions, hospitals must make the best use of their assets. Knowing the true cost of accounts receivable is important for efficient operations. Knowing how to reduce this cost is critical for liquidity. This article offers a guide to ensuring these assets are used most productively.


Role of parafovea in blur perception.
The blur experienced by our visual system is not uniform across the visual field. Additionally, lens designs with variable power profile such as contact lenses used in presbyopia correction and to control myopia progression create variable blur from the fovea to the periphery. The perceptual changes associated with varying blur profile across the visual field are unclear. We therefore measured the perceived neutral focus with images of different angular subtense (from 4° to 20°) and found that the amount of blur, for which focus is perceived as neutral, increases when the stimulus was extended to cover the parafovea. We also studied the changes in central perceived neutral focus after adaptation to images with similar magnitude of optical blur across the image or varying blur from center to the periphery. Altering the blur in the periphery had little or no effect on the shift of perceived neutral focus following adaptation to normal/blurred central images. These perceptual outcomes should be considered while designing bifocal optical solutions for myopia or presbyopia.


Capitellocondylar total elbow replacement. A long-term follow-up study.
Fifty-one capitellocondylar elbow replacements were inserted in forty-one patients between 1976 and 1986. Thirty-nine patients had rheumatoid arthritis and two had traumatic osteoarthrosis. The average age of the patients at the time of the operation was fifty-six years (range, twenty-one to seventy-seven years). Thirty-one patients who had thirty-nine retained elbow prostheses had an average length of follow-up of 6.5 years (range, two to thirteen years). Flexion improved an average of 20 degrees; extension, 4 degrees; pronation, 22 degrees; and supination, 36 degrees. Relief of pain was complete in 85 per cent of the thirty-nine elbows, and in 15 per cent there was only mild pain. Noteworthy postoperative complications in the original fifty-one elbows included infection in four elbows (8 per cent), dislocation in three (6 per cent), and ulnar neuropathy in sixteen (31 per cent). Three elbows were revised: one for a humeral fracture, one for recurrent dislocation, and one for aseptic loosening. Aseptic loosening was evident on radiographs of two elbows; one patient was completely asymptomatic, and one had mild pain with deformity. The Souter zonal radiographic assessment system for identification of radiolucencies at the bone-cement interface was utilized; there was no significant difference in radiolucencies between ulnar components backed with metal and those that were not backed with metal. Kaplan-Meier cumulative survivorship analysis demonstrated that a functional prosthesis was retained in 88 per cent of the elbows at 1.4 years postoperatively and in 83 per cent at 5.5 years.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of adaptive capacity on the outcome of climate change vulnerability assessment.
Climate change vulnerability assessment (CCVA) has become a mainstay conservation decision support tool. CCVAs are recommended to incorporate three elements of vulnerability - exposure, sensitivity and adaptive capacity - yet, lack of data frequently leads to the latter being excluded. Further, weighted or unweighted scoring schemes, based on expert opinion, may be applied. Comparisons of these approaches are rare. In a CCVA for 17 Australian lizard species, we show that membership within three vulnerability categories (low, medium and high) generally remained similar regardless of the framework or scoring scheme. There was one exception however, where, under the warm/dry scenario for 2070, including adaptive capacity lead to five fewer species being classified as highly vulnerable. Two species, Eulamprus leuraensis and E. kosciuskoi, were consistently ranked the most vulnerable, primarily due to projected losses in climatically suitable habitat, narrow thermal tolerance and specialist habitat requirements. Our findings provide relevant information for prioritizing target species for conservation and choosing appropriate conservation actions. We conclude that for the species included in this study, the framework and scoring scheme used had little impact on the identification of the most vulnerable species. We caution, however, that this outcome may not apply to other taxa or regions.


Influence of glycerol on the structure and redox properties of horse heart cytochrome c. A circular dichroism and electrochemical study.
The effect of glycerol on the structure and redox properties of horse heart cytochrome c was investigated by absorption spectroscopy, circular dichroism, and dc cyclic voltammetry techniques. The results show that the organic solvent increases the alpha-helix structure of the protein and induces slight changes at the active-site environment: however, the overall tertiary structure does not appear to be significantly perturbed. Glycerol stabilizes cytochrome c, the free energy of denaturation (delta G0) being approximately 0.7 kcal/mol larger than that determined in phosphate buffer under the same conditions, and influences the heterogeneous electron transfer kinetics at a chemically modified gold electrode: on the other hand, the redox potential of the protein is unaltered. On the whole, the results obtained indicate that glycerol acts as a suitable stabilizing agent of cytochrome c, which is of interest for application in biotechnology: the organic solvent does not alter the tertiary structure significantly or the redox properties of the protein. This has to be interpreted not only in terms of the glycerol-induced solvent ordering around the protein surface, but also as due to the specific features of the protein matrix.


Increased glomerular capillary pressure and size mediate glomerulosclerosis in SHR juxtamedullary cortex.
To gain insight into the mechanisms in the development of glomerulosclerosis in juxtamedullary cortex, the degree of glomerulosclerosis, glomerular tuft diameter, glomerular capillary pressure (Pgc), and local renal blood flow (RBF) autoregulation were measured in superficial and juxtamedullary cortex of 10- and 70-wk-old spontaneously hypertensive rat (SHR), using aged matched Wistar-Kyoto (WKY) rats as controls. Pgc was measured after corticotomy by direct micropuncture of glomeruli in superficial and juxtamedullary cortex. Total RBF was measured by a transit-time flowmeter (Transonic) and local blood flow by use of laser-Doppler flowmetry. The degree of glomerulosclerosis measured by a semiquantitative histological technique was significantly increased in juxtamedullary compared with superficial cortex in all groups. The difference was most pronounced in the juxtamedullary cortex of 70-wk-old SHR. Pgc was significantly increased in juxtamedullary cortex compared with superficial cortex in 70-wk SHR (57.1 +/- 2.7 vs. 46.5 +/- 0.5 mmHg, P < 0.01). The corresponding data set from 70-wk WKY was 45.5 +/- 0.43 vs. 41.6 +/- 1.5 (P < 0.05). The Pgc in juxtamedullary cortex of 10-wk SHR was slightly higher than in superficial cortex (45.1 +/- 2.3 vs. 50.1 +/- 1.2 mmHg, P = 0.05), whereas there was no difference in 10-wk WKY. Glomerular diameter was larger in juxtamedullary cortex in old animals but not significantly different in 10-wk WKY rats and 10-wk SHR. Total RBF was reset to higher perfusion pressures in hypertensive rats. Juxtamedullary and superficial blood flow autoregulation were not significantly different from total RBF autoregulation in all groups. These results suggest that hypertrophy as well as increased Pgc might contribute to the development of manifest glomerulosclerosis. Changes in local blood flow autoregulation do not seem to play a major role in the development of glomerulosclerosis.


The role of policy in improving diets: experiences from the Pacific Obesity Prevention in Communities food policy project.
There is global interest in using multisectoral policy approaches to improve diets, and reduce obesity and non-communicable disease. However, there has been ad hoc implementation, which in some sectors such as the economic sector has been very limited, because of the lack of quality evidence on potential costs and impacts, and the inherent challenges associated with cross-sectoral policy development and implementation. The Pacific Obesity Prevention in Communities food policy project aimed to inform relevant policy development and implementation in Pacific Island countries. The project developed an innovative participatory approach to identifying and assessing potential policy options in terms of their effectiveness and feasibility. It also used policy analysis methodology to assess three policy initiatives to reduce fatty meat availability and four soft drink taxes in the region, in order to identify strategies for supporting effective policy implementation.


Genomic landscape and evolutionary trajectories of ovarian cancer precursor lesions.
The clonal relationship between ovarian high-grade serous carcinoma (HGSC) and its presumed precursor lesion, serous tubal intraepithelial carcinoma (STIC), has been reported. However, when analyzing patients with concurrent ovarian carcinoma and tubal lesion, the extensive carcinoma tissues present at diagnosis may have effaced the natural habitat of precursor clone(s), obscuring tumor clonal evolutionary history, or may have disseminated to anatomically adjacent fimbriae ends, masquerading as precursor lesions. To circumvent these limitations, we analyzed the genomic landscape of incidental tubal precursor lesions including p53 signature, dormant STIC or serous tubal intraepithelial lesion (STIL) and proliferative STIC in women without ovarian carcinoma or any cancer diagnosis using whole-exome sequencing and amplicon sequencing. In three of the four cancer-free women with multiple discrete tubal lesions we observed non-identical TP53 mutations between precursor lesions from the same individual. In one of the four women with co-existing ovarian HGSC and tubal precursor lesion we found non-identical TP53 mutations and a lack of common mutations shared between her precursor lesion and carcinoma. Analyzing the evolutionary history of multiple tubal lesions in the same four patients with concurrent ovarian carcinoma indicated distinct evolution trajectories. Collectively, the results support diverse clonal origins of tubal precursor lesions at the very early stages of tumorigenesis. Mathematical modeling based on lesion-specific proliferation rates indicated that p53 signature and dormant STIC may take a prolonged time (two decades or more) to develop into STIC, whereas STIC may progress to carcinoma in a much shorter time (6 years). The above findings may have implications for future research aimed at prevention and early detection of ovarian cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Molecular communication: modeling noise effects on information rate.
Molecular communication is a new paradigm for communication between biological nanomachines over a nano- and microscale range. As biological nanomachines (or nanomachines in short) are too small and simple to communicate through traditional communication mechanisms (e.g., through sending and receiving of radio or infrared signals), molecular communication provides a mechanism for a nanomachine (i.e., a sender) to communicate information by propagating molecules (i.e., information molecules) that represent the information to a nanomachine (i.e., a receiver). This paper describes the design of an in vitro molecular communication system and evaluates various approaches to maximize the probability of information molecules reaching a receiver(s) and the rate of information reaching the receiver(s). The approaches considered in this paper include propagating information molecules (diffusion or directional transport along protein filaments), removing excessive information molecules (natural decay or receiver removal of excessive information molecules), and encoding and decoding approaches (redundant information molecules to represent information and to decode information). Two types of molecular communication systems are considered: a unicast system in which a sender communicates with a single receiver and a broadcast system in which a sender communicates with multiple receivers. Through exploring tradeoffs among the various approaches on the two types of molecular communication systems, this paper identifies promising approaches and shows the feasibility of an in vitro molecular communication system.


Physical therapists should play a greater role in managing patients with opioid use and opioid misuse.
The U.S. opioid crisis necessitates that health care providers of all types work collaboratively to manage patients taking prescription opioid medications and manage those who may be misusing prescription opioids. Musculoskeletal conditions are the most common diagnoses associated with an opioid prescription. Physical therapists commonly manage patients with musculoskeletal conditions and chronic pain. Some patients who attend physical therapy for pain management take prescription opioid medications for pain and some of these patients may be misusing prescription opioids. Physical therapists who manage patients with musculoskeletal conditions are well-positioned to help address the opioid crisis. Historically, physical therapists have not been adequately engaged in efforts to manage persons with co-occurring musculoskeletal pain and opioid misuse or OUD. The American Physical Therapy Association (APTA) has emphasized physical therapy over the use of prescription opioids for the management of painful conditions. The APTA, however, does not highlight the important role that physical therapists could play in monitoring opioid use among patients receiving treatment for pain, nor the role that physical therapists should play in screening for opioid misuse. Such screening could facilitate referral of patients suspected misuse to an appropriate provider for formal assessment and treatment. This commentary presents simulated musculoskeletal patient presentations depicting 2 common opioid use states; chronic opioid use and opioid misuse. The cases highlight and interactions that physical therapists could have with these patients and actions that the physical therapist could take when working inter-disciplinarily. Recommendations are provided that aim to increase physical therapists' knowledge and skills related to managing patients taking prescription opioid medications for pain.


Stoichiometry of soil enzyme activity at global scale.
Extracellular enzymes are the proximate agents of organic matter decomposition and measures of these activities can be used as indicators of microbial nutrient demand. We conducted a global-scale meta-analysis of the seven-most widely measured soil enzyme activities, using data from 40 ecosystems. The activities of beta-1,4-glucosidase, cellobiohydrolase, beta-1,4-N-acetylglucosaminidase and phosphatase g(-1) soil increased with organic matter concentration; leucine aminopeptidase, phenol oxidase and peroxidase activities showed no relationship. All activities were significantly related to soil pH. Specific activities, i.e. activity g(-1) soil organic matter, also varied in relation to soil pH for all enzymes. Relationships with mean annual temperature (MAT) and precipitation (MAP) were generally weak. For hydrolases, ratios of specific C, N and P acquisition activities converged on 1 : 1 : 1 but across ecosystems, the ratio of C : P acquisition was inversely related to MAP and MAT while the ratio of C : N acquisition increased with MAP. Oxidative activities were more variable than hydrolytic activities and increased with soil pH. Our analyses indicate that the enzymatic potential for hydrolyzing the labile components of soil organic matter is tied to substrate availability, soil pH and the stoichiometry of microbial nutrient demand. The enzymatic potential for oxidizing the recalcitrant fractions of soil organic material, which is a proximate control on soil organic matter accumulation, is most strongly related to soil pH. These trends provide insight into the biogeochemical processes that create global patterns in ecological stoichiometry and organic matter storage.


Phase II study of irinotecan plus cisplatin with concurrent radiotherapy for the patients with limited-disease small-cell lung cancer.
A recently conducted randomized, phase III study that compared irinotecan plus cisplatin (IP) with etoposide plus cisplatin for the patients with extensive disease SCLC revealed a superior median survival rate and a superior 2-year survival rate for the IP combination therapy. Yet there have been few such reports on the patients suffering with limited disease SCLC (LD-SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of administering IP with concurrent radiotherapy for the patients with LD-SCLC. Twenty chemotherapy-naïve patients with LD-SCLC were enrolled in our study. The patients were treated with 40 mg/m(2) irinotecan on days 1, 8 and 15 and with 60 mg/m(2) cisplatin on day 1 every 4 weeks until a maximum of six cycles was delivered. Once-daily radiotherapy included the administration of 50.4 Gy in 28 fractions. After completion of the radiation therapy, the dose of irinotecan was increased to 60 mg/m(2). The response rate was 85% (CR: 6; partial response, PR: 11). The median survival was 20.0 months (95% CI: 15.6-24.4 months) with 1-year and 2-year overall survival rates of 85 and 35%, respectively. The median progression free survival (PFS) was 12 months (95% CI: 6.2-18.1 months) with a 1-year PFS of 36%. The major hematologic toxicities of this regimen were neutropenia (60%), leukopenia (55%), anemia (20%) and thrombocytopenia (10%). The non-hematologic toxicities were nausea/vomiting (55%), diarrhea (35%) and dysphagia (15%). Our data show that IP with concurrent radiotherapy is an effective and tolerable regimen for the treatment of LD-SCLC and these findings warrant further investigation.


Older adults. An 11-year longitudinal study of adult protective service use.
Little is known about the epidemiology of adult protective services agency (APS) utilization, the state entities charged with assessment and advocacy for disenfranchised older adults. To determine the prevalence of utilization by older adults and risk factors for APS. A longitudinal study using the New Haven Established Population for Epidemiologic Studies in the Elderly population, a cohort of 2812 community-dwelling adults who were older than 65 years in 1982. The main outcome measure was referral to the state ombudsman on aging for protective services. Over the 11-year follow-up period, 209 cohort members (7.4%) were referred to the ombudsman 302 times as protective service cases for a community prevalence of 6.4% after adjusting for the sampling strategy of the cohort. Self-neglect was the most common indication for referral (73% of the cases). While in bivariate analyses a variety of baseline sociodemographic features, functional impairments, medical conditions, and social network factors were associated with APS use, in multivariable analysis only sociodemographic variables remained independent risk factors including low income (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8 to 3.9), nonwhite race (OR, 2.2; 95% CI, 1.3 to 3.7), and age older than 75 years at cohort inception (OR, 1.9; 95% CI, 1.1 to 3.0). Prevalence of APS use by older adults is substantial, and sociodemographic features were the most compelling risk factors in our cohort. As the population ages, the number of older adults at risk for abuse, neglect, self-neglect, exploitation, and abandonment will increase; physicians will need to become familiar with APS referral pathways and mandatory reporting laws in their states.


Relaxation rate in the assessment of masseter muscle fatigue.
The aim of this study was to assess a simple method of measuring relaxation rate in the jaw-closing system for the purpose of quantifying jaw muscle fatigue. A summary of the various different methods of measuring relaxation rate is also provided. The rates of twitch contraction and relaxation were measured in 30 symptom-free subjects following bilateral direct electrical stimulation of the masseter muscles. The resulting twitch force was recorded via a force transducer placed between the anterior teeth. The transducer was held between the teeth with as little force as possible while four single stimuli were delivered at 5-s intervals. The stimulating electrodes were then removed and replaced and the experiment was repeated. The force records of the resulting twitches were averaged and the half-contraction time, twitch amplitude and half-relaxation time were measured. There was a significant difference in half-relaxation time between males and females, being faster in females (P=0.0045, independent t-test). No significant difference was found in twitch amplitude and half-contraction time between males and females. Half-relaxation time and half-contraction time were independent of twitch amplitude. This method of measuring the relaxation rate of the masseter muscles was found to be practical and the results were reproducible between sessions.


Immunohistochemical evaluation of experimental Vagococcus salmoninarum infection in rainbow trout (Oncorhynchus mykiss, Walbaum 1792).
The aim of this study was to investigate the pathogenesis and histopathological and immunohistochemical findings in rainbow trout (Oncorhynchus mykiss) following experimental vagococcosis. For this purpose, 60 rainbow trout were used. The experimental study used the pathogen Vagococcus salmoninarum. The fish were intraperitoneally (IP) administered with an inoculate containing 0.1 mL of the bacteria, resulting in a dose of 1.2 × 10(9) cfu mL(-1) per fish. For histopathological observations, tissue samples were taken from fish that died during the experiment and fish that survived until the end of the trial (60th day). All the tissue samples were immunohistochemically stained by the avidin-biotin-peroxidase complex and immunofluorescence methods using polyclonal antibody to detect V. salmoninarum antigens. In immunoperoxidase staining, positive reactions to bacterial antigens were most commonly seen in the kidney, heart and liver. In the immunofluorescence analysis, the distribution of antigens in the tissue and organs was similar to that observed with the immunoperoxidase staining. The results reveal an important correlation between histochemical and immunohistochemical staining in demonstrating the distribution of V. salmoninarum antigens in the affected tissues.


[Clinical and laboratory characteristics of the acetonemia syndrome in children with severe acute intestinal infection].
A total of 55 children suffering from acute intestinal infection severe in age from 3 months to 7 years; of these, 37 patients with atsetonemicheskim syndrome (AS). Found that the development AS in children with acute intestinal infections severe, aggravate the disease. In children with acute intestinal infection with the syndrome, the duration of atsetonemicheskim main symptoms of intoxication in the 1,2-1,5 times longer than those of children suffering from acute intestinal infection without atsetonemicheskogo syndrome.


The Usability of the Preliminary ICF Core Set for Hospitalized Patients After a Hematopoietic Stem Cell Transplantation From the Perspective of Nurses: A Feasibility Study.
Background: A hematopoietic stem cell transplantation (HSCT) has a major impact on the functioning and perceived quality of life of patients. To describe the functioning of patients, a preliminary set of 53 categories of the International Classification of Functioning, Disability and Health (ICF) as relevant for HSCT patients has been selected earlier by a Delphi study. For the implementation of this preliminary ICF core set for patients after HSCT in clinical practice, a feasibility study was requested. Methods: A feasibility study was conducted in an explanatory mixed-methods research design. Qualitative data were collected cross-sectionally by semi-structured interviews based on specific topics related to feasibility regarding the use of the preliminary ICF core set for HSCT patients from the perspective of nurses (five in ICF-trained nurses and five regular, untrained, nurses). Quantitative data, were collected longitudinally by using a mobile health application based on ICF in which the ICF trained nurses registered HSCT patients' functioning. Results: Qualitative analysis indicated that using the preliminary ICF core set is practical and acceptable for providing information about the functioning of HSCT patients from the perspective of nurses. In addition, nurses indicated a demand for this information due to its impact on multidisciplinary meetings and clinical decision-making by involving relevant aspects of the functioning of patients. Management support, trained staff, and designated time to focus on functioning are mentioned as requirements for successful implementation. Quantitative analysis demonstrated that the most used 30% (n = 17) ICF categories are included in the preliminary ICF core set for HSCT patients (n = 24). Energy (b130) was the most used ICF category. Family relationships (d760) was the most frequently and highly positively associated ICF category. Conclusions: From the perspective of nurses, the preliminary ICF core set for HSCT patients is feasible and relevant in gaining information regarding functioning. Applying this preliminary ICF core set for HSCT patients in the anamnesis and the nursing consultations contributes to this information. Further research is needed to look at the perspective of other professionals and HSCT patients themselves.


A unifying model of concurrent spatial and temporal modularity in muscle activity.
Modularity in the central nervous system (CNS), i.e., the brain capability to generate a wide repertoire of movements by combining a small number of building blocks ("modules"), is thought to underlie the control of movement. Numerous studies reported evidence for such a modular organization by identifying invariant muscle activation patterns across various tasks. However, previous studies relied on decompositions differing in both the nature and dimensionality of the identified modules. Here, we derive a single framework that encompasses all influential models of muscle activation modularity. We introduce a new model (named space-by-time decomposition) that factorizes muscle activations into concurrent spatial and temporal modules. To infer these modules, we develop an algorithm, referred to as sample-based nonnegative matrix trifactorization (sNM3F). We test the space-by-time decomposition on a comprehensive electromyographic dataset recorded during execution of arm pointing movements and show that it provides a low-dimensional yet accurate, highly flexible and task-relevant representation of muscle patterns. The extracted modules have a well characterized functional meaning and implement an efficient trade-off between replication of the original muscle patterns and task discriminability. Furthermore, they are compatible with the modules extracted from existing models, such as synchronous synergies and temporal primitives, and generalize time-varying synergies. Our results indicate the effectiveness of a simultaneous but separate condensation of spatial and temporal dimensions of muscle patterns. The space-by-time decomposition accommodates a unified view of the hierarchical mapping from task parameters to coordinated muscle activations, which could be employed as a reference framework for studying compositional motor control.


Flow-through microfluidic photoionization detectors for rapid and highly sensitive vapor detection.
A photoionization detector (PID) is well known for its high sensitivity, large dynamic range, and non-destructive vapor detection capability. However, due to its tardy response, which results from the relatively large ionization chamber and dead volume, the application of the PID in gas chromatography (GC) has been limited. Here, we developed a rapid, flow-through, and highly sensitive microfluidic PID that was microfabricated directly on a conductive silicon wafer. The microfluidic PID has a significantly reduced ionization chamber volume of only 1.3 μL, nearly 10 times smaller than that of state-of-the-art PIDs and over 100 times smaller than that of commercial PIDs. Moreover, it has virtually zero dead volume due to its flow-through design. Consequently, the response time of the microfluidic PID can be considerably shortened, ultimately limited by its residence time (7.8 ms for 10 mL min(-1) and 78 ms for 1 mL min(-1)). Experimentally, the response of the microfluidic PID was measured to be the same as that of the standard flame ionization detector with peak full-widths-at-half-maximum of 0.25 s and 0.085 s for flow rates of 2.3 mL min(-1) and 10 mL min(-1), respectively. Our studies further show that the microfluidic PID was able to detect analytes down to the picogram level (at 3σ of noise) and had a linear dynamic range of six orders of magnitude. Finally, because of the very short distance between the electrodes, low voltage (<10 VDC, over 10 times lower than that in a regular PID) can be used for microfluidic PID operation. This work will open a door to broad applications of PIDs in gas analyzers, in particular, micro-GC and multi-dimensional GC.


Mycotoxin analysis: an update.
Mycotoxin contamination of cereals and related products used for feed can cause intoxication, especially in farm animals. Therefore, efficient analytical tools for the qualitative and quantitative analysis of toxic fungal metabolites in feed are required. Current methods usually include an extraction step, a clean-up step to reduce or eliminate unwanted co-extracted matrix components and a separation step with suitably specific detection ability. Quantitative methods of analysis for most mycotoxins use immunoaffinity clean-up with high-performance liquid chromatography (HPLC) separation in combination with UV and/or fluorescence detection. Screening of samples contaminated with mycotoxins is frequently performed by thin layer chromatography (TLC), which yields qualitative or semi-quantitative results. Nowadays, enzyme-linked immunosorbent assays (ELISA) are often used for rapid screening. A number of promising methods, such as fluorescence polarization immunoassays, dipsticks, and even newer methods such as biosensors and non-invasive techniques based on infrared spectroscopy, have shown great potential for mycotoxin analysis. Currently, there is a strong trend towards the use of multi-mycotoxin methods for the simultaneous analysis of several of the important Fusarium mycotoxins, which is best achieved by LC-MS/MS (liquid chromatography with tandem mass spectrometry). This review focuses on recent developments in the determination of mycotoxins with a special emphasis on LC-MS/MS and emerging rapid methods.


Session 6: Infant nutrition: future research developments in Europe EARNEST, the early nutrition programming project: EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research.
Increasing evidence from lifetime experimental studies in animals and observational and experimental studies in human subjects suggests that pre- and postnatal nutrition programme long-term health. However, key unanswered questions remain on the extent of early-life programming in contemporary European populations, relevant nutritional exposures, critical time periods, mechanisms and the effectiveness of interventions to prevent or reverse programming effects. The EARly Nutrition programming - long-term Efficacy and Safety Trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST) consortium brings together a multi-disciplinary team of scientists from European research institutions in an integrated programme of work that includes experimental studies in human subjects, modern prospective observational studies and mechanistic animal work including physiological studies, cell-culture models and molecular techniques. Theme 1 tests early nutritional programming of disease in human subjects, measuring disease markers in childhood and early adulthood in nineteen randomised controlled trials of nutritional interventions in pregnancy and infancy. Theme 2 examines associations between early nutrition and later outcomes in large modern European population-based prospective studies, with detailed measures of diet in pregnancy and early life. Theme 3 uses animal, cellular and molecular techniques to study lifetime effects of early nutrition. Biomedical studies are complemented by studies of the social and economic importance of programming (themes 4 and 5), and themes encouraging integration, communication, training and wealth creation. The project aims to: help formulate policies on the composition and testing of infant foods; improve the nutritional value of infant formulas; identify interventions to prevent and reverse adverse early nutritional programming. In addition, it has the potential to develop new products through industrial partnerships, generate information on the social and economic cost of programming in Europe and help maintain Europe's lead in this critical area of research.


On the Applicability of Elastic Network Models for the Study of RNA CUG Trinucleotide Repeat Overexpansion.
Non-coding RNAs play a pivotal role in a number of diseases promoting an aberrant sequestration of nuclear RNA-binding proteins. In the particular case of myotonic dystrophy type 1 (DM1), a multisystemic autosomal dominant disease, the formation of large non-coding CUG repeats set up long-tract hairpins able to bind muscleblind-like proteins (MBNL), which trigger the deregulation of several splicing events such as cardiac troponin T (cTNT) and insulin receptor's, among others. Evidence suggests that conformational changes in RNA are determinant for the recognition and binding of splicing proteins, molecular modeling simulations can attempt to shed light on the structural diversity of CUG repeats and to understand their pathogenic mechanisms. Molecular dynamics (MD) are widely used to obtain accurate results at atomistic level, despite being very time consuming, and they contrast with fast but simplified coarse-grained methods such as Elastic Network Model (ENM). In this paper, we assess the application of ENM (traditionally applied on proteins) for studying the conformational space of CUG repeats and compare it to conventional and accelerated MD conformational sampling. Overall, the results provided here reveal that ANM can provide useful insights into dynamic rCUG structures at a global level, and that their dynamics depend on both backbone and nucleobase fluctuations. On the other hand, ANM fail to describe local U-U dynamics of the rCUG system, which require more computationally expensive methods such as MD. Given that several limitations are inherent to both methods, we discuss here the usefulness of the current theoretical approaches for studying highly dynamic RNA systems such as CUG trinucleotide repeat overexpansions.


CircHIPK3 Promotes Gemcitabine (GEM) Resistance in Pancreatic Cancer Cells by Sponging miR-330-5p and Targets RASSF1.
Pancreatic cancer is one of the most common malignant diseases in the world. Gemcitabine chemotherapy remains the most important clinical treatment. However, research found that pancreatic cancer cells have chemoresistance to gemcitabine and the effect is not satisfactory. Therefore, it is urgent to find an effective early diagnosis and treatment strategy. Circular RNA is one of the most popular prognostic biomarkers in GEM-resistant PC. The present study was designed to evaluate the role of circHIPK3 in PC. The expression of circHIPK3 in PC tissues and cells and its effect on proliferation, migration, invasion, EMT, and apoptosis were investigated in vitro; its effect on tumor xenografts was assessed in vivo. Used bioinformation analysis to predict which miRNAs could potentially interact with circHIPK3, mRNA, and miR-330-5p. RT-PCR showed that the level of circHIPK3 was increased in PC tumor tissues; moreover, circHIPK3 was also increased in GEM-resistant PC tumors tissues and GEM-resistant PC cells. Sh-circHIPK3 could knockdown circHIPK3 in PANC-1-GEM and SW-1990-GEM and could significantly inhibit cell proliferation, invasion, migration, EMT and enhance cell apoptosis, compare with control group, the tumor xenografts of circHIPK3 knockdown group were significantly smaller. CircHIPK3 served as a sponge for miR-330-5p, and miR-330-5p directly bound to the 3' UTR of RASSF1 were revealed by dual luciferase assay and RIP in PC cells. CircHIPK3 knockdown of RASSF1 expression could neutralize the cytological function of PC cells by miR-330-5p inhibitor mediated GEM-resistance. CircHIPK3 promotes gemcitabine (GEM) resistance in pancreatic cancer cells by targeting RASSF1 via miR-330-5p and regulates proliferation, invasive, migration, EMT, and apoptosis. Our research revealed that circHIPK3 may be a novel biomarker in GEM-resistant PC and could be used as a prognostic target.


Efficacy and safety of tapentadol prolonged release for moderate-to-severe chronic osteoarthritis knee pain: a pooled analysis of two double-blind, randomized, placebo- and oxycodone controlled release-controlled studies.
To compare efficacy and safety of tapentadol prolonged-release (PR) and oxycodone-controlled release (CR) in moderate-to-severe chronic osteoarthritis knee pain. Data from two double-blind, randomized, placebo- and oxycodone CR-controlled phase 3 studies with a 3-week titration period and 12-week controlled dose adjustment maintenance period were pooled. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point). A total of 2,010 patients were assessed. For both primary end-points, tapentadol PR was significantly more effective than oxycodone CR (LS mean difference of -0.41 [95% CI = -0.65, -0.16; p = 0.001] at week 12 and -0.35 [95% CI = -0.58, -0.12; p = 0.003] over 12 weeks of maintenance [last observation carried forward]). Significantly better outcomes than for oxycodone CR were also observed for patient global impression of change, both Short Form-36 component scores, and EuroQoL-5Dimensions health status index (all p < 0.001). Relative risk for vomiting, constipation, nausea, somnolence, and pruritus was lower for tapentadol PR than for oxycodone CR. A higher proportion of oxycodone CR patients discontinued treatment (64% vs 42.2% for tapentadol PR); time to treatment discontinuation due to an adverse event was significantly shorter for oxycodone CR (p < 0.001). The analyses suggest that tapentadol PR provided superior pain relief and a more improved overall health status than oxycodone CR in a large patient population with moderate-to-severe chronic osteoarthritis pain. Compared to oxycodone CR, tapentadol PR showed a more favorable tolerability profile with better gastrointestinal tolerability.


Correlation between lordosis distribution index, lordosis tilt, and occurrence of proximal junctional kyphosis following surgery for adult degenerative scoliosis.
This study aimed to evaluate the effect of postoperative reciprocal progression of Lordosis tilt (LT), Lordosis distribution index (LDI) and occurrence of Proximal junctional kyphosis (PJK) following surgery for Degenerative lumbar scoliosis (DLS). A total of 122 consecutive patients with ADS were treated with correction of deformity and followed up for a minimum of 2 years. Spinopelvic parameters were measured preoperatively, postoperatively, and at the latest follow-up. The Japanese Orthopaedic Association score, Oswestry Disability Index, and visual analog scale scores were measured at the latest follow-up. Associations between LT, LDI, and PJK were analyzed using receiver operating characteristic analyses. The prevalence of PJK in the present study was 24.6%. The outcomes of patients with PJK were significantly worse than those of patients without PJK. Postoperative reciprocal progression in LT and LDI with lumbar lordosis restorative surgery was observed. Preoperative risk factors for PJK were older age, larger LT, and larger Cobb angle of the curves. Postoperative risk factors for PJK included postoperative LT and postoperative Cobb angle of the curves, which were smaller than those preoperatively. We found a strong correlation between postoperative LT and Cobb angle of the curves resulting in PJK. Patients with LT < - 8° were at a higher risk of PJK. LT can be used to predict the occurrence of PJK in patients undergoing surgery for DLS. Appropriate postoperative LT is crucial for preventing the progression of PJK.


Tropicimonas aquimaris sp. nov., isolated from seawater, and emended description of the genus Tropicimonas Harwati et al. 2009.
A Gram-staining-negative, aerobic, non-motile and rod-shaped bacterial strain, designated DPG-21(T), was isolated from seawater from the South Sea in Korea, and investigated using a polyphasic taxonomic approach. Strain DPG-21(T) grew optimally at pH 7.0-8.0, at 30 °C and in the presence of 2% (w/v) NaCl. In a neighbour-joining phylogenetic tree based on 16S rRNA gene sequences, strain DPG-21(T) clustered with Tropicimonas isoalkanivorans B51(T) (with a sequence similarity of 97.1%); the novel strain showed lower 16S rRNA gene sequence similarities (<95.4%) with the other species included in the tree. The mean DNA-DNA relatedness value between strain DPG-21(T) and T. isoalkanivorans DSM 19548(T) was 12%. The predominant ubiquinones of strain DPG-21(T) were Q-10 and Q-9 while C(18:1)ω7c was the strain's major fatty acid. The polar lipid profile of strain DPG-21(T) was similar to that of T. isoalkanivorans DSM 19548(T). The genomic DNA G+C content of the novel strain was 69.6 mol%. Some phenotypic properties and the phylogenetic and genetic data indicated that strain DPG-21(T) was distinct from T. isoalkanivorans and represents a novel species of the genus Tropicimonas, for which the name Tropicimonas aquimaris sp. nov. is proposed. The type strain is DPG-21(T) (=KCTC 23424(T)=CCUG 60524(T)).


[Mesenchymal chondrosarcoma of the lung].
The authors present the data available in the literature and their observation of mesenchymal chondrosarcoma of the lung a 68-year-old female patient. Histologically, the tumor is exhibited by the fields of monomorphic round and oval cells with hyperchromic muclei and a scanty cytoplasm, with the hemangiopericytoma-like structures being formed here and there. There are foci of chondroid cells, portions of necrosis, and an ample quantity of mitoses. Immunohistochemical study has revealed that the tumor cells show the expression of vimentin, S-100 protein, neuron-specific enolase and the cytoplasmic expression of CD 99. The tests using CD 31, CD 34, factor VIII, desmin, total cytokeratin, or synaptophysin are negative.


Epilepsy in families: Age at onset is a familial trait, independent of syndrome.
We tested 2 hypotheses regarding age at onset within familial epilepsies: (1) family members with epilepsy tend to have similar ages at onset, independent of epilepsy syndrome; and (2) age at onset is younger in successive generations after controlling for sampling bias. We analyzed clinical data collected by the Epi4K Consortium (303 multiplex families, 1,120 individuals). To test hypothesis 1, we used both linear mixed models commonly used for heritability analysis and Cox regression models with frailty terms to assess clustering of onset within families after controlling for other predictors. To test hypothesis 2, we used mixed effects models, pairwise analyses, and survival analysis to address sampling-related bias that may mimic anticipation. Regarding hypothesis 1, age at seizure onset was significantly heritable (intraclass correlation coefficient = 0.17, p < 0.001) after adjusting for epilepsy type, sex, site, history of febrile seizure, and age at last observation. This finding remained significant after adjusting for epilepsy syndromes, and was robust across statistical methods in all families and in generalized families. Regarding hypothesis 2, the mean age at onset decreased in successive generations (p < 0.001). After adjusting for age at last observation, this effect was not significant in mixed effects models (p = 0.14), but remained significant in pairwise (p = 0.0003) and survival analyses (p = 0.02). Age at seizure onset is an independent familial trait, and may have genetic determinants distinct from the determinants of particular epilepsy syndromes. Younger onsets in successive generations can be explained in part by sampling bias, but the presence of genetic anticipation cannot be excluded. ANN NEUROL 2019.


The discovery of the placental growth factor and its role in angiogenesis: a historical review.
The placental growth factor (PlGF) is an angiogenic protein belonging to the vascular endothelial growth factor (VEGF) family, which was discovered in 1991 by an Italian scientist, Maria Graziella Persico. Dr Persico cloned and purified PlGF and determined its structure by crystallography resolution. Furthermore, she identified VEGF receptor-1 (VEGFR-1) as the receptor for PlGF, and in collaboration with Dr Peter Carmeliet in Leuven, she generated evidence that loss of PlGF does not affect development, reproduction, or postnatal life. PlGF is expressed primarily in the placenta and is up-regulated in several pathological conditions, although its role is still controversial. Some data in literature reported that PlGF enhances pathological angiogenesis by initiating a cross-talk between VEGFR-1 and VEGFR-2, whereas other studies did not confirm these findings. Regarding the potential therapeutic employment of PlGF, recent evidence has shown that an anti-PlGF antibody may act as a potent antiangiogenic agent, and that it has the advantage of minor toxicity when combined with anti-VEGF strategies.


Compound heterozygosity for an out-of-frame deletion and a splice site mutation in the LAMB3 gene causes nonlethal junctional epidermolysis bullosa.
Laminin-5 is the major adhesion ligand of epithelial cells. Mutations in the genes encoding laminin-5 cause junctional epidermolysis bullosa (JEB), a clinically and genetically heterogeneous group of recessively inherited blistering disease of skin and mucous membranes. In this report, we describe a patient with a non-lethal variant of JEB who is a compound heterozygous for mutations affecting the LAMB3 gene. The paternally inherited mutation is a deletion of a single base (T) leading to a frameshift and premature termination codon. It results in mRNA decay. The maternally inherited mutation is a G-->A transition at the last base of exon 7 (628G-->A) which converts a codon for glutamic acid in a codon for lysine (E210K). The mutation 628G-->A alters the correct splicing of LAMB3 pre-mRNA giving rise to two aberrant mRNA, in addition to the RNA transcript carrying the G-->A substitution. This result is compatible with the reduced expression of mutated laminin 5 molecules with altered biological activity, and the mild JEB phenotype observed in the patient.


Boosting the circularly polarized luminescence of small organic molecules via multi-dimensional morphology control.
Achieving a higher dissymmetry factor is a crucial issue in developing circularly polarized luminescence (CPL) materials. Here, by tailoring the solvent composition and the morphology of the same chiral emissive small molecules (R- or S-SPAn), circularly polarized emission with a boosted dissymmetry factor (two orders) was realized. It was found that by regulating the water fraction in the mixed THF/H2O, we were able to achieve kinetic control over association of chiral emissive R- or S-SPAn into various nanostructures with 0D nanospheres, 2D nanoflakes and 3D stacked nanoflakes. These nanostructures are all CPL active. Remarkably, the dissymmetry factors of the nanostructures were significantly enhanced compared to those of the molecules and further boosted in different morphologies, from ∼10-4 (0D nanospheres) to 10-3 (2D flake) to ∼10-2 (3D nanoflakes). The enlarged g lum value could be assigned to a good packing induced strong luminescence of an excimer. This strategy provides an efficient way to fabricate higher dissymmetry factor CPL organic nanomaterials by only changing the supramolecular architectures while using the same chiral small molecules.


Imaging Barrett's oesophagus.
Eight patients who had Barrett's oesophagus confirmed by histology are presented. All had barium swallow examinations and technetium-99m sodium pertechnetate (99Tcm-pertechnetate) scintigraphy, the findings of which are reviewed and discussed. The most valuable diagnostic signs on barium swallow examination related to the site of the stricture and the presence of mucosal outpouchings. Scintigraphy was positive in all eight cases. Patients suspected of having Barrett's oesophagus on barium swallow examination should undergo scintigraphy. When the latter is positive, the endoscopist should be alerted to obtain biopsies not only at the site of stricture but serially as far as the gastrooesophageal junction.