Sequence and rate of bone marrow conversion in the femora of children as seen on MR imaging: are accepted standards accurate?
The purpose of this study was to reassess the normal sequence and rate of marrow conversion in the femora of children as depicted on MR imaging. We retrospectively analyzed 81 T1-weighted MR images of the femur for the appearance and distribution of hematopoietic (red) and fatty (yellow) marrow. Eighty-one children 2 days to 15 years old with no known bone marrow abnormalities were divided into four age groups. The signal intensity and homogeneity of the marrow in the proximal epiphysis, proximal metaphysis, diaphysis, distal metaphysis, distal epiphysis, and greater trochanter were compared with the signal intensity and homogeneity of surrounding muscle and fat and graded by two observers. In select cases, region-of-interest measurements of marrow, subcutaneous fat, and muscle were obtained to validate the visual grading system. Conversion of hematopoietic to fatty marrow in the femur followed a well-defined sequence, occurring first in the proximal and distal epiphyses, followed by the diaphysis, distal metaphysis, and then the proximal metaphysis. Although high-signal-intensity fatty marrow could be seen within the femoral diaphysis as early as 3 months of age, fatty marrow with various degrees of heterogeneity was routinely seen in this region by 12 months of age. After 5 years of age, the femoral diaphysis showed homogeneous high signal intensity. These findings are in contrast to previously published data that describe homogeneous red marrow within the femoral diaphysis during the first year of life and homogeneous yellow marrow visualized by 10 years of age. The normal age-related sequence of femoral marrow conversion we saw on MR images conforms to the sequence described in previously published reports, but this transformation, particularly in the diaphysis, occurs significantly earlier in life than has been previously reported. This discrepancy might be explained partially by the sensitivity of signal intensity in the femoral marrow to alterations in window and level settings.


No safe haven. II: The effects of violence exposure on urban youth.
To examine the moderating effects of gender, grade level, and ethnicity on the associations between violence exposure and adolescents' internalizing symptoms and externalizing behavior and to explore whether such relationships persist over time. A survey of adolescents' exposure to violence, internalizing symptoms, and externalizing behavior was administered to 2 cross-sectional samples of 6th, 8th, and 10th graders (N = 2,748 in 1994 and 2,600 in 1996) in an urban school system. Approximately 1,100 adolescents participated in both surveys and served as the longitudinal sample. Structural equation models indicated that violence exposure was closely associated with both externalizing behavior (r = 0.74-0.79) and internalizing symptoms (r = 0.36-0.38). The strength of association was similar across gender and ethnic groups. However, violence exposure was more closely related with internalizing symptoms for younger adolescents than their older counterparts. The longitudinal analysis suggested that exposure to violence reported at time 1 was related to adolescents' internalizing symptoms and externalizing behavior 2 years later. These results document high levels of violence exposure for urban youths and indicate links to a range of psychiatric symptoms and indicators of poor adjustment. Such findings carry implications for direct clinical work with young people, as well as for program development and public policy.


Bik/NBK accumulation correlates with apoptosis-induction by bortezomib (PS-341, Velcade) and other proteasome inhibitors.
Proteasome inhibitors have emerged as promising anticancer therapeutic agents. Bortezomib (PS-341), a specific proteasome inhibitor, exhibits antitumor activity against a wide range of malignancies and has been approved by the US Food and Drug Administration for the treatment of relapsed or refractory multiple myeloma. However, the molecular mechanisms of bortezomib-mediated apoptosis remain unclear. To characterize the mechanisms of apoptosis induction by proteasome inhibitors, we examined levels of Bcl-2 protein family members (Bik/NBK, Bax, Bak, Bcl-2, and Bcl-XL), release of cytochrome c, and activation of caspase-9 and -3 in human colon cancer cell lines DLD1, LOVO, SW620, and HCT116; human lung cancer cell line H1299; and human ovarian cancer cell line SKOV3 after they were treated with bortezomib. The result showed that bortezomib induced rapid accumulation of Bik/NBK but not other Bcl-2 family members in all six cell lines. Bortezomib-mediated Bik/NBK accumulation and apoptosis were also observed in human embryonic kidney cells 293 and normal human bronchial epithelial cells. Moreover, dramatic Bik/NBK accumulation and apoptosis induction were observed when cells were treated with proteasome inhibitor MG132 and calpain inhibitor I (ALLN). Furthermore, no detectable changes in IkappaBalpha levels or in NFkappaB functionality were found after treatment with bortezomib. Finally, Bik/NBK accumulation was caused by stabilization of the protein from degradation and was associated with bortezomib cytotoxicity and apoptosis induction. Pretreatment of DLD1 cells with Bik/NBK siRNA reduced bortezomib-mediated Bik/NBK accumulation and cell death. Our results suggested that Bik/NBK is one of the mediators of proteasome inhibitor-induced apoptosis.


Asian international psychotherapist's experiences of client's microaggression in therapy.
Much of the multicultural counseling literature focuses on how White or U.S.-born therapists can work effectively with clients of color. However, with the increasing number of racial minority and international therapists and trainees, there is a need to expand the multicultural counseling literature to acknowledge and center the experiences of therapists and trainees of color, particularly the experiences of Asian international therapists. Specifically, a greater understanding and guidelines are needed regarding how Asian international therapists handle clients' xenophobia, racism, and microaggressions in therapy. This qualitative study interviewed 11 licensed practicing Asian international psychotherapists within the United States about their experiences of client-initiated microaggressions in therapy. Consensual qualitative research was used to analyze interview data. Results indicated four domains pertaining to Asian international psychotherapists' experiences in therapy: xenophobia, microaggression, impact, and strategy. Participants reported complex negative impacts of xenophobia and microaggressions on their well-being as well as the therapeutic relationship and treatment outcomes. Additionally, participants identified the difficulty and complexity of addressing client-initiated microaggressions in session. Implications for training and practice as well as suggestions for future research are provided. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


[Structure of over lapping region of ICP18.5 and gB genes of type 1 bovine herpesvirus strain TK-A].
Nucleotide sequence of DNA fragment coding 3'-terminal of ICO 18.5 gene that overlaps the regulatory region and 5'-terminal of open reading frame of gB gene of bovine herpesvirus (BHV-1, subtype 1.3), strain TK-A, was determined. Comparative analysis of the sequence with the corresponding DNA regions of BHV-1, subtype 1.1, equine herpesviruses of the first and fourth types, and porcine pseudorabies virus was performed.


[Twin pregnancy in uterus didelphys].
A case of twin pregnancy in uterus didelphys is reported. This rare event is discussed from obstetric aspects as well as that of dizygotic twins.


Expression of type 1 plasminogen activator inhibitor in chronic pulmonary thromboemboli.
Chronic thromboembolic pulmonary hypertension is the result of nonresolving pulmonary emboli that lead to chronic obstruction of the central pulmonary arteries. To determine if the failure to lyse pulmonary thromboemboli is caused by the local expression of the primary inhibitor of tissue-type plasminogen activator (type 1 plasminogen activator inhibitor, PAI-1), levels of PAI-1 antigen and mRNA were analyzed by immunohistochemistry and in situ hybridization in specimens harvested from a series of patients during pulmonary thromboendarterectomies. Red, fibrin-rich thrombi within the thromboendarterectomy specimens were lined with a single layer of endothelial cells exhibiting high levels of PAI-1 antigen. Quantitation of the in situ hybridization signal revealed that a significant increase in PAI-1 mRNA was present in the endothelial cells lining the fresh thrombi in comparison to the signal present in the endothelial cells from noninvolved areas of patients' pulmonary arteries (n = 16, P < .001). In contrast, tissue-type plasminogen activator antigen levels were low in all samples. Yellowish-white thrombi were composed of smooth muscle cells and endothelial cells in numerous vessels that stained prominently for PAI-1 antigen. Both types of cells within the highly organized tissues also exhibited elevated PAI-1 mRNA levels in comparison to patient pulmonary artery specimens that were free of thrombus (n = 16, P < .02). The prevalence of PAI-1 expression within pulmonary thromboemboli suggests that this inhibitory may play a role in the stabilization of vascular thrombi.


On Between Death and Life: Intensive Care Nurses.
The aim of this study is to explore intensive care nurses' perceptions and experiences about death and dying patient. This study included 15 nurses from a university hospital's intensive care units (paediatric and internal medicine). Data were collected through face-to-face, in-depth and individual interviews using the "Nurse Information Form" and "Semi-Structured Interview Form". Six major themes and sixteen sub-themes were identified on the nurses' perceptions and experiences with death. After the nurses described their perceptions of death, their responses, approaches, coping mechanisms, and effects on the dead and dying patient in care and factors affecting perceptions of death were defined. Our findings suggest that nurses, particularly those working in intensive care, should be educated/trained on death, and dying patient care. Thus, orderly psychological support should be provided to nurses.


Fatty acid transport protein 4 is the principal very long chain fatty acyl-CoA synthetase in skin fibroblasts.
Fatty acid transport protein 4 (FATP4) is a fatty acyl-CoA synthetase that preferentially activates very long chain fatty acid substrates, such as C24:0, to their CoA derivatives. To gain better insight into the physiological functions of FATP4, we established dermal fibroblast cell lines from FATP4-deficient wrinkle-free mice and wild type (w.t.) mice. FATP4 -/- fibroblasts had no detectable FATP4 protein by Western blot. Compared with w.t. fibroblasts, cells lacking FATP4 had an 83% decrease in C24:0 activation. Peroxisomal degradation of C24:0 was reduced by 58%, and rates of C24:0 incorporation into major phospholipid species (54-64% decrease), triacylglycerol (64% decrease), and cholesterol esters (58% decrease) were significantly diminished. Because these lipid metabolic processes take place in different subcellular organelles, we used immunofluorescence and Western blotting of subcellular fractions to investigate the distribution of FATP4 protein and measured enzyme activity in fractions from w.t. and FATP4 -/- fibroblasts. FATP4 protein and acyl-CoA synthetase activity localized to multiple organelles, including mitochondria, peroxisomes, endoplasmic reticulum, and the mitochondria-associated membrane fraction. We conclude that in murine skin fibroblasts, FATP4 is the major enzyme producing very long chain fatty acid-CoA for lipid metabolic pathways. Although FATP4 deficiency primarily affected very long chain fatty acid metabolism, mutant fibroblasts also showed reduced uptake of a fluorescent long chain fatty acid and reduced levels of long chain polyunsaturated fatty acids. FATP4-deficient cells also contained abnormal neutral lipid droplets. These additional defects indicate that metabolic abnormalities in these cells are not limited to very long chain fatty acids.


Pyrrolidine dithiocarbamate inhibits herpes simplex virus 1 and 2 replication, and its activity may be mediated through dysregulation of the ubiquitin-proteasome system.
Pyrrolidine dithiocarbamate (PDTC) is widely used as an antioxidant or an NF-κB inhibitor. It has been reported to inhibit the replication of human rhinoviruses, poliovirus, coxsackievirus, and influenza virus. In this paper, we report that PDTC could inhibit the replication of herpes simplex virus 1 and 2 (HSV-1 and HSV-2). PDTC suppressed the expression of HSV-1 and HSV-2 viral immediate early (IE) and late (membrane protein gD) genes and the production of viral progeny. This antiviral property was mediated by the dithiocarbamate moiety of PDTC and required the presence of Zn(2+). Although PDTC could potently block reactive oxygen species (ROS) generation, it was found that this property did not contribute to its anti-HSV activity. PDTC showed no activity in disrupting the mitogen-activated protein kinase (MAPK) pathway activation induced by viral infection that was vital for the virus's propagation. We found that PDTC modulated cellular ubiquitination and, furthermore, influenced HSV-2-induced IκB-α degradation to inhibit NF-κB activation and enhanced PML stability in the nucleus, resulting in the inhibition of viral gene expression. These results suggested that the antiviral activity of PDTC might be mediated by its dysregulation of the cellular ubiquitin-proteasome system (UPS).


Studies on host-virus interactions in the chick embryo-influenza virus system. IV. The role of inhibitors of hemagglutination in the evaluation of viral multiplication.
The role of inhibitors of hemagglutination in the evaluation of host-virus interactions in the chick embryo-influenza virus system has been analyzed. Comparisons were made between materials (allantoic fluids and membrane suspensions) derived from in vivo (growth curve) experiments at hourly intervals after inoculation, and from in vitro tests in which normal allantoic fluids and membrane suspensions were incubated with virus at 37 degrees C. for various periods of time. In both instances large amounts of virus were added to the systems, resulting in comparable concentrations of the agent. The seeds employed were either fully active or irradiated by ultraviolet light to the extent that the virus lost its capacity to increase but kept its interfering and hemagglutinating properties. The various materials were assayed for (a) the hemagglutinating titers of the virus present in the systems before and after heating to 56 degrees C.; (b) the concentration of inhibitor in the materials at various stages of incubation after heating to 70 degrees C. for 30 minutes as measured by the hemagglutination-inhibition reaction with native or heated test virus (30 minutes 56 degrees C.); and (c) the degree of adsorption of the hemagglutinins present in the materials onto chicken red cells at 0 degrees C. and their subsequent elution at 37 degrees C. The effects of receptor-destroying enzyme (RDE), treatment with sodium periodate, or high speed centrifugation on the inhibitory activities were studied in some of the tests. The essential results which indicate certain sources of error in the evaluation of host-virus interactions as well as means for studying virus activity at the early stages of the infectious process, were as follows: 1. Though some inhibitory effects on hemagglutination were noticeable in the allantoic fluid during the 1st hour after inoculation they were, as a rule, no longer apparent after this interval, and treatment with RDE did not increase the hemagglutinin titers. Thus, the interpretation of growth curve data concerning allantoic fluids hardly seems to be affected by inhibitor. On the other hand, striking effects were noted with the membrane suspensions of growth curve experiments in that RDE shortened the latent period to 2 hours and the titers in the first few positive samples (4 to 5 hours) increased) whereas in later harvests no such effect was noted. Under these conditions complement-fixation antigens and hemagglutinins made their appearance in the tissues simultaneously and not as previously reported the former prior to the latter. However, the infectivity showed increments only several hours after these two activities had become measurable. Thus the hypothesis of the stagewise development of influenza virus is still supported by these data. 2. Using the inhibition of hemagglutination technic it was found that the inhibitor in allantoic fluid rapidly decreased as a result of the action of active and irradiated virus, but destruction was never complete. In the membranes of the in vivo series only active seed led to loss of inhibitor, again without complete destruction, beginning at the time complement-fixing antigen and hemagglutinins became measurable. Irradiated seed was without effect in vivo whereas, in the in vitro tests it equalled the activity of the active virus. The implications of this difference in the effectiveness of active and irradiated seed in vivo with regard to the understanding of the mode of viral multiplication are discussed. 3. Although many factors may influence the shape of adsorption-elution curves it is felt that at 0 degrees C. the extent of adsorption is directly related to the amount of inhibitor present in the systems. In the early hours after inoculation the degree of adsorption was relatively small but it increased gradually with the time of incubation. The inhibitor of adsorption was destroyed by RDE and NaIO(4) and was only partially sedimentable by high speed centrifugation. In every respect studied its properties corresponded with the findings obtained with inhibitors in the hemagglutination-inhibition technic. Although the difference in the rapidity of inhibitor destruction as measured by the various technics might suggest a multiplicity of inhibitors it is felt that it rather denotes a greater sensitivity of the adsorption technic as compared to the others.


Sucrose ingestion following exercise: selected cardiovascular, hormonal, renal, and metabolic effects.
Carbohydrates, frequently consumed following exercise for glycogen resynthesis, have been shown to have other systemic effects in resting men. We examined the effects of postexercise sucrose (a disaccharide carbohydrate) ingestion on the renal, cardiovascular, and sympathetic nervous systems. Eight men consumed 1 l of water (W) or 1 l of a 200 g sucrose solution (S) following 1 hour of bicycle exercise at 70% heart rate reserve. Measurements were made during 2 hours of recovery. Heart rate and systolic blood pressure were elevated following S as compared to W (p < 0.009, p < 0.04, respectively). Diastolic blood pressure was lower after S (p < 0.04) and mean blood pressure did not differ between beverages. Plasma and urinary catecholamines decreased similarly after exercise regardless of treatment. After S insulin (p = 0.0019) and glucose (p = 0.0036) were increased but serum aldosterone (p = 0.0083) and potassium (p = 0.0285) responses were lower. No differences were observed for plasma renin activity. Urine volume and kaliuresis were less after S (p = 0.03, p = 0.03). A 24% increase in metabolic rate (p = 0.002) and increased respiratory exchange ratio (p = 0.02) after S were observed. Systemic effects of sucrose ingestion following exercise include cardiovascular, renal, endocrine, and metabolic changes.


New‑onset neuropsychiatric sequelae and 'long‑COVID' syndrome (Review).
The ongoing coronavirus disease 2019 (COVID-19) pandemic has had a widespread impact on individuals' mental health through indirect psychological and social mechanisms, related to factors such as fear of infection or death, social isolation, lack of social support and financial instability. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has also been associated with the development or recurrence of neuropsychiatric symptoms, both during the acute phase, as well as during the post-acute 'long-COVID' phase. In addition to the COVID-19 survivors with a mental health history that are at a high risk of experiencing a range of neuropsychiatric symptoms following resolution of acute COVID-19, there is accumulating evidence that a diagnosis of COVID-19 may also be associated with new-onset neuropsychiatric morbidity among survivors without pre-existing mental health disorders. In particular, studies investigating the incidence of post-acute neuropsychiatric sequelae, based mostly on retrospective cohort study designs and data from national health registries, have reported the development of new-onset manifestations, including depression, anxiety, psychotic symptoms, sleep disturbances and fatigue. Nevertheless, when COVID-19 survivors were compared with SARS-CoV-2-negative controls and especially survivors of other disorders (such as influenza), the findings regarding the risk of incident neuropsychiatric manifestations varied among studies. While there is evidence of an association between SARS-CoV-2 infection and the subsequent occurrence of new-onset neuropsychiatric symptoms, especially among patients with increased disease severity, further research using methodological approaches less susceptible to confounding bias is required to establish causal relationships.


Selective association of protein kinase C with 14-3-3 zeta in neuronally differentiated PC12 Cells. Stimulatory and inhibitory effect of 14-3-3 zeta in vivo.
The 14-3-3 protein is a family of highly conserved acidic proteins found in a wide range of eukaryotes from yeast to mammals. 14-3-3 acts as an adapter protein and interacts with signaling molecules including protein kinase C (PKC). Although 14-3-3 zeta was originally characterized as an endogenous PKC inhibitor, it was reported to activate PKC in vitro, but the in vivo regulation of PKC by 14-3-3 is still not well understood. To examine the regulation of PKC by 14-3-3 in the cell, we have generated a sub-cell line, PC12-B3, that stably expresses FLAG epitope-tagged 14-3-3 zeta isoform in PC12 cells. Here we show that PKC-alpha and PKC-epsilon become associated with 14-3-3 zeta when the cells are neuronally differentiated by nerve growth factor. We found that the immunoprecipitate by anti-FLAG antibody contains constitutive and autonomous Ca(2+)-independent non-classical PKC activity. In contrast, the FLAG immunoprecipitate has no Ca(2+)-dependent classical PKC activity despite the fact that PKC-alpha is present in the FLAG immunoprecipitate from differentiated PC12-B3 cells. Our results show that the association with 14-3-3 zeta has distinct effects on classical PKC and non-classical PKC activity.


[Preoperative care and anesthesia in surgical treatment of thyrotoxicosis].
The authors made an analysis of clinical materials pertaining to 1234 patients with thyrotoxicosis, who were given different preoperative management and operated upon under local and general anesthesia. It is noted, that there is less number of postoperative thyrotoxic crises after mercosolyl administration in combination with reserpine and nonspecific drugs than after Plummer preoperative preparation (0.1% versus 1.2%).


A novel growth process of calcium carbonate crystals in silk fibroin hydrogel system.
We report an interesting finding of calcium carbonate (CaCO3) crystal growth in the silk fibroin (SF) hydrogel with different concentrations by a simple ion diffusion method. The experimental results indicate that the CaCO3 crystals obtained from silk fibroin gels with low and high concentrations are all calcites with unusual morphologies. Time-dependent growth study was carried out to investigate the crystallization process. It is believed that silk fibroin hydrogel plays an important role in the process of crystallization. The possible formation mechanism of CaCO3 crystals is proposed. This study provides a better explanation of the influence of silk fibroin concentration and its structure on CaCO3 crystals growth.


Synoviocytes-derived Interleukin 35 Potentiates B Cell Response in Patients with Osteoarthritis and Rheumatoid Arthritis.
Elevated expression of interleukin 35 (IL-35) is associated with autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the functional interaction among IL-35, B cells, and stromal cells residing in the synovium of patients with RA and osteoarthritis (OA). IL-35 (EBI-3/p35) expression was investigated in RA and OA synovium using quantitative real-time PCR (qRT-PCR) and immunohistochemistry. IL-35 receptor (IL-35R) expression on B cells dissociated from synovium and periphery of patients with RA, OA, and healthy donor controls (HC) was determined by flow cytometry. The degree of B cells activation after IL-4 and/or IL-35 stimulation was measured by flow cytometry and qRT-PCR. Synovial fibroblasts (SF) purified from RA and OA synovium were cocultured with peripheral HC B cells in the presence/absence of tumor necrosis factor-α (TNF-α) and with/without anti-IL-35-blocking antibodies. EBI-3/p35 transcripts were expressed in close proximity to B cells residing in RA and OA synovium. IL-35R subunits, gp130 and IL-27Rα, but not IL-12Rβ2, were expressed in B cells extracted from the synovium and periphery of patients with RA/OA. Notably, RA synovium expressed the highest level of IL-27Rα on their cell surface. IL-35 induced proliferation and IgG production in HC B cells. Cocultures of HC B cells with RASF, but not OASF, exhibited significantly elevated B cells activation. TNF-α-induced, RASF-dependent secretion of IgG in B cells is partly IL-35-dependent. To our knowledge, for the first time we demonstrated that synovial/peripheral B cells expressed IL-35R and were responsive to IL-35 stimulation. SF residing in RA synovium can be linked to B cell activation and maintenance in RA synovium through IL-35.


Decoding the genome with an integrative analysis tool: combinatorial CRM Decoder.
The identification of genome-wide cis-regulatory modules (CRMs) and characterization of their associated epigenetic features are fundamental steps toward the understanding of gene regulatory networks. Although integrative analysis of available genome-wide information can provide new biological insights, the lack of novel methodologies has become a major bottleneck. Here, we present a comprehensive analysis tool called combinatorial CRM decoder (CCD), which utilizes the publicly available information to identify and characterize genome-wide CRMs in a species of interest. CCD first defines a set of the epigenetic features which is significantly associated with a set of known CRMs as a code called 'trace code', and subsequently uses the trace code to pinpoint putative CRMs throughout the genome. Using 61 genome-wide data sets obtained from 17 independent mouse studies, CCD successfully catalogued ∼12 600 CRMs (five distinct classes) including polycomb repressive complex 2 target sites as well as imprinting control regions. Interestingly, we discovered that ∼4% of the identified CRMs belong to at least two different classes named 'multi-functional CRM', suggesting their functional importance for regulating spatiotemporal gene expression. From these examples, we show that CCD can be applied to any potential genome-wide datasets and therefore will shed light on unveiling genome-wide CRMs in various species.


Health Literacy and Exercise to Treat Frailty in Community-Dwelling Older Adults: A National Survey Study.
Aging is a major challenge facing modern society and has attracted global attention. Studies have provided some initial evidence that health literacy plays a role in determining frailty; however, most of these studies have used small convenience samples of individuals recruited from geographically limited areas, thus limiting the generalizability of their findings. The present study explored the relationships among health literacy, exercise, and frailty in Taiwanese older adults by using the data of a national population-based survey. We retrieved data from the Taiwan Longitudinal Study on Aging, a population-based survey. We gathered the 2015 data on the age, sex, education level, marital status, exercise habits, and activities of daily living (ADLs) of each eligible respondent. We evaluated the respondents' health literacy by using a nine-item health literacy scale and categorized their health literacy level as low, medium, or high. Frailty was diagnosed according the Fried criteria. Our final sample consisted of 7702 community-dwelling older adults (3630 men and 4072 adults). Of these, 25.3% had low health literacy. The proportion of respondents who had two or more disabilities in terms of ADLs or instrumental ADLs was higher among the women (36.4% and 12.6%, respectively), and regular exercise was more common among the men (19.6%). Frailty was more prevalent among the women; the prevalence of frailty among the male and female respondents was 4.5% and 8.1%, respectively. High health literacy and regular exercise were protective factors for frailty. According to our results, poor health literacy is a risk factor for prefrailty and frailty, and regular exercise is significantly negatively associated with prefrailty and frailty. Additional studies are necessary to define practical strategies for reducing the risks of disability and death for older adults with low health literacy who do not exercise regularly, thereby improving their quality of life.


[Correlation of the behavioral characteristics of animals with varying levels of alcohol motivation: motor activity, taste and electrical pain sensitivities].
It is shown that rats with a high degree of orienting-investigatory behaviour, low thresholds of emotional and pain sensitivity consume considerably more ethanol and rejected substances--urea and mustard--in comparison with low-active, less electrical pain-sensitive animals with a low degree of alcohol motivation. It is suggested that studying of characteristics of specialized appetite can be an important factor for prognostication of behaviour and role of individual in population.


Stapedotomy in Congenital Fixation with Cochlear Hypoplasia: A New Concept Among the Treatment Options for Cochlear Hypoplasia.
To introduce the concept of stapedotomy as a new treatment alternative in cochlear hypoplasia (CH) and propose a new guideline for its management. Forty-two primary cases out of 355 presented with congenital stapes fixation between January 2003 and September 2015 were included in the study. Computed tomography scans of all cases with congenital stapes fixation were reviewed, and cases with inner ear anomalies were taken into account. Eleven cases had various inner ear anomalies, and 9 cases had various types of CH. In the present paper, only the CH cases with stapes fixation, all of whom underwent stapedotomy, are reviewed regarding preoperative audiological and radiological characteristics as well as surgical findings and postoperative audiological results. The patients were aged between 4 and 22. There were 2 males (3 ears) and 4 females (6 ears). Three cases had bilateral stapedotomy. The remaining 3 cases had unilateral surgery. The average preoperative air-bone gap (ABG) was 50.3 dB. Postoperative hearing: preoperative ABG was 50.3 dB. Postoperative ABG was calculated as 20.1 dB hearing. Hearing loss (HL) in hypoplastic cochlea demonstrates the full spectrum of HL types. CH is a unique inner ear anomaly that can be treated with all of the available rehabilitation modalities. As a result of current findings, a new treatment algorithm for CH is proposed.


KRAS mutant allele-specific imbalance (MASI) assessment in routine samples of patients with metastatic colorectal cancer.
Patients with colorectal cancer harbouring KRAS mutations do not respond to antiepidermal growth factor receptor (anti-EGFR) therapy. Community screening for KRAS mutation selects patients for treatment. When a KRAS mutation is identified by direct sequencing, mutant and wild type alleles are seen on the sequencing electropherograms. KRAS mutant allele-specific imbalance (MASI) occurs when the mutant allele peak is higher than the wild type one. The aims of this study were to verify the rate and tissue distribution of KRAS MASI as well as its clinical relevance. A total of 437 sequencing electropherograms showing KRAS exon 2 mutation was reviewed and in 30 cases next generation sequencing (NGS) was also carried out. Five primary tumours were extensively laser capture microdissected to investigated KRAS MASI tissue spatial distribution. KRAS MASI influence on the overall survival was evaluated in 58 patients. In vitro response to anti-EGFR therapy in relation to different G13D KRAS MASI status was also evaluated. On the overall, KRAS MASI occurred in 58/436 cases (12.8%), being more frequently associated with G13D mutation (p=0.05) and having a heterogeneous tissue distribution. KRAS MASI detection by Sanger Sequencing and NGS showed 94% (28/30) concordance. The longer overall survival of KRAS MASI negative patients did not reach statistical significance (p=0.08). In cell line model G13D KRAS MASI conferred resistance to cetuximab treatment. KRAS MASI is a significant event in colorectal cancer, specifically associated with G13D mutation, and featuring a heterogeneous spatial distribution, that may have a role to predict the response to EGFR inhibitors. The foreseen implementation of NGS in community KRAS testing may help to define KRAS MASI prognostic and predictive significance.


Improving Dementia Long-Term Care: A Policy Blueprint.
In 2010, 15 percent of Americans older than age 70 had dementia, and the number of new dementia cases among those 65 and older is expected to double by the year 2050. As the baby boomer generation ages, many older adults will require dementia-related long-term services and supports (LTSS). This blueprint is the only national document to date that engages local, state, and national stakeholders to specifically focus on policy options at the intersection of dementia and LTSS. The authors undertook five major tasks that resulted in a prioritized list of policy options and research directions to help decisionmakers improve the dementia LTSS delivery system, workforce, and financing. These were to (1) identify weaknesses in the LTSS system that may be particularly severe for persons with dementia; (2) review national and state strategies addressing dementia or LTSS policy; (3) identify policy options from the perspective of a diverse group of stakeholders; (4) evaluate the policy options; and (5) prioritize policy options by impact and feasibility. Stakeholders identified 38 policy options. RAND researchers independently evaluated these options against prespecified criteria, settling on 25 priority options. These policy options can be summarized into five objectives for the dementia LTSS system: (1) increase public awareness of dementia to reduce stigma and promote earlier detection; (2) improve access to and use of LTSS; (3) promote high-quality, person- and caregiver-centered care; (4) provide better support for family caregivers of people with dementia; and (5) reduce the burden of dementia LTSS costs on individuals and families. This policy blueprint provides a foundation upon which to build consensus among a larger set of stakeholders to set priorities and the sequencing of policy recommendations.


[Endolaser photocoagulation in vitrectomy surgery].
To verify the usefulness and effectiveness of endolaser photocoagulation in vitrectomy. Endolaser photocoagulation was applied in 40 cases (45 eyes) of vitrectomy surgery. Indications for vitrectomy included vitreous hemorrhage 31 eyes (proliferative diabetic retinopathy 13, Eales's disease 13, retinal vein occlusion 4, and scleral penetrating injury with intraocular foreign body removal 1), complex retinal detachment 12 eyes, intraocular nonmagnetic foreign body removal and postoperative silicone oil tamponade 1 eye respectively. Treatment involved pan-retinal scatter therapy in 7 eyes, focal therapy in 22 eyes, sealing primary or iatrogenic retinal breaks in 14 eyes, draining retinotomy in 2 eyes, and encircling scleral buckle photocoagulation in 3 eyes. The follow-up times ranged from 2 to 18 months (average 9 months). Whitening of laser spots was not apparent in 6 eyes with retinal breaks following incomplete gas-fluid exchange. Recurrent retinal detachments occurred in 5 eyes postoperatively. Endolaser photocoagulation facilitates the performance and reduces the complications of vitrectomy surgery.


Induction of food craving experience: the role of mental imagery, dietary restraint, mood and coping strategies.
Food craving consists of a strong motivational state whereby a person is driven to seek and ingest a specifically desired food. To explore the influence of mental imagery on the food craving experience as well as to analyse the role of different psychological variables. Participants consisted of 65 normal weight undergraduate students. An experimental induction of food craving was analysed considering the actual previous craving and the induced one as a state food craving. Measures of trait food craving, imaging ability, dietary restraint, anxiety, depression, and coping strategies were considered. Sweet foods in general and chocolate in particular were the most craved foods. During the induction thoughts and images were the most highly rated triggers, and all the different sensory modalities were involved. Anxiety, depression, and negative coping strategies influenced the results with regards to the food craving. This study confirms the role of mental imagery, the correlation between state and trait food craving, and the influence of different psychological variables on the food craving.


[The role of the intestine microbiota in the development of obesity].
Medical societies all around the world have been alarmed by the problem of obesity and the diseases related to it. You can call it pandemic. Nowadays, obesity is viewed as a chronic condition that requires proper treatment. People suffering from it typically consume a larger amount of food, which in turn leads to changes in intestinal microbiome. Furthermore, obese people possess a specific kind of microflora, which might influence on the structure of human genome. Changes of intestine microflora depend on age, point of residence, culture specifics, lifestyle and socio-economic status. Currently, we can adjust intestinal micloflora by presenting pro- and prebiotics, which we believe might help in improving obesity level.


Amphetamine in human plasma: a sensitive and specific enzymatic assay.
A sensitive and specific enzymatic-isotopic method of determining plasma amphetamine concentrations in man is described. The assay is based on the transfer of the tritiated methyl group of S-adenosyl-L-[methyl-(3)H]methionine to amphetamine in the presence of a partially purified N-methyltransferase from rabbit lung. With this assay as little as 10 nanograms of amphetamine per milliliter of plasma can be accurately determined. The concentrations of d- and 1-amphetamine in the plasma after 20 to 30 milligrams of the drug had been ingested by human subjects are reported.


A multi-informant and multi-polygenic approach to understanding predictors of peer victimisation in childhood and adolescence.
Peer victimisation is a prevalent occurrence in childhood and adolescence and can often have long-lasting consequences. Previous research using polygenic scores (PGSs) have revealed various genetic vulnerabilities as predictive of victimisation in childhood. However, findings were based on self-report and may therefore be influenced by varying self-perceptions. Previous investigations also focused on average victimisation across childhood, and thus do not capture variability in polygenic predictability over time. The present study, therefore, aimed to investigate associations between PGSs and victimisation using separate and combined reports from teachers and peers in childhood, as well as self-reports in later adolescence to explore trajectories of victimisation. Data were derived from the Quebec Newborn Twin Study. Participants were assessed for victimisation using self-reports from 7 to 17 years and using teacher ratings and peer nominations between 7 and 10 years (n = 536). Ten PGSs related to mental health, cognitive abilities and physical traits were examined as possible predictors of victimisation using linear regressions and growth curve models. Findings revealed that PGSs associated with victimisation are consistent across informants, but to varying extent according to estimated effect sizes. Self-reported victimisation was predicted by PGSs related to mental health, while PGSs related to cognitive and physical traits had larger effect estimates when predicting teacher- and peer-reported victimisation. The PGS for educational attainment was consistently negatively associated with victimisation across informants, producing the largest effect estimates (β = -.104, 95% CI = -.169 to -.039) when predicting a multi-informant measure of victimisation. No PGS predicted changes in victimisation over time. While the PGS for educational attainment is a robust predictor of victimisation, many PGSs are differentially associated with victimisation depending on the informant. Such findings highlight the need to pay close attention to the phenotypic assessment of victimisation, and show that using multiple informants can both strengthen and provide unique insight into how associations may occur.


Purification and properties of a vanadate- and N-ethylmaleimide-sensitive ATPase from chromaffin granule membranes.
A vanadate- and N-ethylmaleimide-sensitive ATPase was purified about 500-fold from chromaffin granule membranes. The purified preparation contained a single major polypeptide with an apparent molecular mass of about 115 kDa, which was copurified with the ATPase activity. Immunological studies revealed that this polypeptide has no relation to subunit I (115 kDa) of the H+-ATPase from chromaffin granules. The ATPase activity of the enzyme is inhibited about 50% by 100 microM N-ethylmaleimide or 5 microM vanadate. The enzyme is not sensitive to dicyclohexylcarbodiimide, ouabain, SCH28080, and omeprazole, which distinguishes it from Na+/K+-ATPase and the gastric K+/H+-ATPase. ATP and 2-deoxy ATP are equally effective substrates for the enzyme. However, the enzyme exhibited only 10% activity with GTP as a substrate. UV illumination of the purified enzyme in the presence of [alpha-32P]ATP exclusively labeled the 115 kDa protein. This labeling was increased by Mg2+ and strongly inhibited by Ca2+ ions. Similarly, the ATPase activity was dependent on Mg2+ and inhibited by the presence of Ca2+ ions. The ATPase activity of the enzyme was largely insensitive to monovalent anions and cations, except for F-, which inhibited the vanadate-sensitive ATPase. Incubation of the enzyme in the presence of [14C]N-ethylmaleimide labeled the 115-kDa polypeptide, and this labeling could be prevented by the addition of ATP during the incubation. A reciprocal experiment showed that preincubation with N-ethylmaleimide inhibited the labeling of the 115-kDa polypeptide by [alpha-32P]ATP by UV illumination. This suggests a close proximity between the ATP-binding site and an essential sulfhydryl group. A possible connection between the isolated ATPase and organelle movement is discussed.


Preventive effect of silymarin in cerebral ischemia-reperfusion-induced brain injury in rats possibly through impairing NF-κB and STAT-1 activation.
Silymarin and silibinin are bioactive components isolated from Silybum marianum. They have been reported to exhibit anti-oxidative and anti-inflammatory effects. Many studies revealed that drugs with potent anti-inflammatory potential can protect animals against inflammation-associated neurodegenerative disease, e.g., stroke. In this current work we established an animal model of acute ischemic stroke injury by inducing cerebral ischemic/reperfusion (CI/R) in rats to elucidate whether silymarin or silibinin can protect animals from CI/R injury. Pretreatment with silymarin, but not silibinin, dose-dependently (1-10μg/kg, i.v.) reduced CI/R-induced brain infarction by 16-40% and improved neurological deficits in rats with a stroke. Elevated pathophysiological biomarkers for CI/R-induced brain injury, including lipid peroxidation, protein nitrosylation, and oxidative stress, were all reduced by silymarin. In addition, expression of inflammation-associated proteins (e.g., inducible nitric oxide synthase, cyclooxygenase-2 and myeloperoxidase), and transcriptional factors (e.g., nuclear factor (NF)-kappa B and signal transducer and activator of transcription (STAT)-1), as well as production of proinflammatory cytokine (e.g., interleukin-1β and tumor necrosis factor-α) was all significantly prevented by silymarin. Furthermore, an in vitro study on microglial BV2 cells showed that silymarin could inhibit nitric oxide and superoxide anion production, possibly by interfering with NF-κB nuclear translocation/activation. Likewise, silymarin pretreatment also inhibited IκB-α degradation and NF-κB nuclear translocation in brain tissues of ischemic rats. Our results reveal that silymarin, but not its active component silibinin, protected rats against CI/R-induced stroke injury by amelioration of the oxidative and nitrosative stresses and inflammation-mediated tissue injury through impeding the activation of proinflammatory transcription factors (e.g., NF-κB and STAT-1) in the upregulation of proinflammatory proteins and cytokines in stroke-damaged sites. In conclusion, silymarin displays beneficial effects of preventing inflammation-related neurodegenerative disease, e.g., stroke, which needs further investigation and clinical evidences.


Friction induced structural transformations of water monolayers at graphene/Cu interfaces.
Tribological and structural properties of water monolayers confined at interfaces between graphene and Cu substrates at cryogenic and room temperatures are extensively studied using molecular dynamics simulations and first-principles calculations. The frictions caused by the sliding of graphene sheets and increasing temperature will reduce the interfacial density of water molecules and lead to structural transformations of water monolayers and direct contacts of graphene with the underlying Cu substrates. Such changes in water structures give rise to higher friction forces and shear strengths at the graphene/Cu interfaces. Depending on the water coverage density and temperature, the motions of graphene on monolayer water covered Cu exhibit stick-slip and continuous slipping behaviors. The strong association of friction characteristics with structural transformations of water molecules could be used to unveil interfacial information of graphene on water adsorbed metal surfaces.


Patient-Specific iPSC-Derived RPE for Modeling of Retinal Diseases.
Inherited retinal diseases, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world. Currently, treatments for these conditions are limited. Recently, considerable attention has been given to the possibility of using patient-specific induced pluripotent stem cells (iPSCs) as a treatment for these conditions. iPSCs reprogrammed from adult somatic cells offer the possibility of generating patient-specific cell lines in vitro. In this review, we will discuss the current literature pertaining to iPSC modeling of retinal disease, gene therapy of iPSC-derived retinal pigmented epithelium (RPE) cells, and retinal transplantation. We will focus on the use of iPSCs created from patients with inherited eye diseases for testing the efficacy of gene or drug-based therapies, elucidating previously unknown mechanisms and pathways of disease, and as a source of autologous cells for cell replacement.


Are senior high school students in Ghana meeting WHO's recommended level of physical activity? Evidence from the 2012 Global School-based Student Health Survey Data.
Physical activity (PA) has both short- and long-term importance. In this study we sought to assess the prevalence and correlates of PA among 1,542 Senior High School (SHS) students. A cross-sectional study was conducted in Ghana among SHS students using the 2012 version of the Ghana Global School-based Student Health Survey (GSHS) data, which utilised two-stage cluster sampling technique. The population for the study comprised SHS students. The outcome variable was physical activity. The data were analysed using STATA version 14.2 for Mac OS. Both bivariate and multivariate analyses were employed. At the bivariate level, Pearson chi-square test between each independent variable and PA was conducted and the level of statistical significance was set at 5%. All the significant variables from the chi-square test were selected for the multivariate analysis. In the multivariate analysis, Poisson regression with robust variance was performed to estimate crude and adjusted prevalence ratios (APR). It was found that 25.0% (29.0% males and 21.9% females) of SHS students were physically active. Female students (APR = 0.78, 95% CI = 0.65, 0.94), students in SHS 2 (APR = 0.76, 95% CI = 0.577, 0.941) and SHS3 (APR = 0.79, 95% CI = 0.63, 0.93), and those who went hungry (APR = 0.77, 95% CI = 0.65, 0.92) were less likely to be physically active compared to males, those in SHS1 and those who did not go hungry respectively. On the other hand, students who actively commuted to school (APR = 2.40, 95% CI = 1.72, 2.42) and got support from their peers were more likely to be physically active (APR = 1.62, 95% CI = 1.09-2.41). Only a quarter of SHS students who participated in the 2012 version of the GSHS met the WHO's recommended level of physical activity. Sex, grade/form and experience of hunger are associated with physical activity. Physical activity is a major component of any health promotion program. Policies and programmes targeting improvement in physical activity among SHS students should take these associated factors into consideration.


Molecular analysis of C1 alleles in Zea mays defines regions involved in the expression of this regulatory gene.
The structure and function of several C1 alleles have been investigated molecularly and the importance of C1 promoter sequences for gene expression was studied using transient transformation assays. The C1 mutants analyzed were the overexpressing allele C1-S, the light-inducible allele c1-p, the null recessive allele c1-n, and the Ds element-induced allele c1-m1. Nucleotide sequence analysis of the alleles revealed a number of differences, predominantly located at the 3' end of the gene. The promoter sequences of the C1 alleles investigated so far (including wild-type and the dominant inhibitor C1-I allele) are almost identical except for two short footprint-like sequences (Box I and Box II) close to the putative CAAT box. Northern blot experiments and transient expression in particle gun experiments indicate that these sequences may be correlated with the different expression patterns of the alleles in the aleurone of maturing and germinating kernels.


Systematic review and meta-analysis of the effects of foot and ankle physical therapy, including mobilisations and exercises, in people with diabetic peripheral neuropathy on range of motion, peak plantar pressures and balance.
To evaluate the effects of foot and ankle physical therapy on ankle and first metatarsophalangeal joint range of motion (ROM), peak plantar pressures (PPPs) and balance in people with diabetes. MEDLINE, EBSCO, Cochrane Database of Systematic Reviews, Joanna Briggs Institute Database of Systematic Reviews, PROSPERO, EThOS, Web of Science and Google Scholar were searched in April 2022. Randomised Controlled Trials (RCT), quasi-experimental, pre-post experimental design and prospective cohort studies were included. Participants were people with diabetes, neuropathy and joint stiffness. Interventions included physical therapy such as mobilisations, ROM exercises and stretches. Outcome measures focused on ROM, PPPs and balance. Methodological quality was assessed with Critical Appraisal Skills Programme RCT and Risk-of-Bias 2 tool. Meta-analyses used random-effects models and data was analysed using the inverse variance method. In total, 9 studies were included. Across all studies, participant characteristics were similar; however, type and exercise dosage varied greatly. Meta-analysis was performed with four studies. Meta-analysis showed significant effects of combined exercise interventions in increasing total ankle ROM (3 studies: MD, 1.76; 95% CI, 0.78-2.74; p = 0; I2 = 0%); and reducing PPPs in the forefoot area (3 studies; MD, -23.34; 95% CI, -59.80 to 13.13; p = 0.21, I2 = 51%). Combined exercise interventions can increase ROM in the ankle and reduce PPPs in the forefoot. Standardisation of exercise programmes with or without the addition of mobilisations in the foot and ankle joints needs further research.


Molecular phylogenies reveal host-specific divergence of Ophiocordyceps unilateralis sensu lato following its host ants.
Ophiocordyceps unilateralis (Hypocreales, Ascomycetes) is an entomopathogenic fungus specific to formicine ants (Formicinae, Hymenoptera). Previous works have shown that the carpenter ant Camponotus leonardi acts as the principal host with occasional infections of ants from the genus Polyrhachis (sister genus of Camponotus). Observations were made on the permanent plots of Mo Singto, Khao Yai National Park of Thailand according to which O. unilateralis was found to occur predominantly on three host species: C. leonardi, C. saundersi and P. furcata. Molecular phylogenies of the elongation factor 1-α and β-Tubulin genes indicate a separation of O. unilateralis samples into three clades, reflecting specificity to each of the three different ant species. Samples collected from P. furcata and from C. leonardi were found to form sister groups with samples from C. saundersi forming an outgroup to the latter. Additional samples collected from unidentified ant species of Camponotus and Polyrhachis were positioned as outgroups to those samples on identified species. These results demonstrate that O. unilateralis is clearly not a single phylogenetic species and comprises at least three species that are specific to different host ant species. These cryptic species may arise through recent events of speciation driven by their specificity to host ant species.


Dysfunctional personality traits: relationship with Five Factor Model, adaptation and symptomatology in a community sample from Buenos Aires.
The paper introduces an analysis of the dimensional maladaptive personality traits model stated in the section III of Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), conducted on a community sample composed of 906 adults from Buenos Aires, Argentina. Data were gathered using a socio-demographic survey as well as the Personality Inventory for DSM-5 (PID-5), the Big Five Inventory (BFI), the Symptom Check List 90-R (SCL-90-R), and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). A joint exploratory factor analysis was carried out including the PID-5's 25 facets along with BFI's 5 factors as input variables. Findings showed a 5-factor structure mostly coincident with DSM-5's hypotheses as well as with previous research. Besides, correlations calculated between PID-5 and BFI scores behaved according to theoretical hypotheses. By means of a two-stage cluster analysis which used WHODAS 2.0 score and the Global Severity Index index from SCL-90-R as segmentation criteria, two groups were differentiated: The High-Adaptation/Low-Symptomatology group vs the Low- Adaptation/High-Symptomatology one. The second group obtained significantly higher means in the five domains, and in 24 of the 25 facets of PID-5.


An interventional study for improving the manual dexterity of dentistry students.
Traditionally, the acquisition of manual skills in most dental schools worldwide is based on exercises on plastic teeth placed in a "phantom head simulator". No manual trainings are done at home. Studies revealed that preliminary training of one motoric task leads to significant improvement in performance of the required motoric task that has similar components. Performing tasks indirectly via a dental mirror are complicated for the young dental students. We hypothesized that instructed training of basic skills required in dentistry at home on a tool simulating the phantom laboratory will improve the capabilities of the students and will be reflected by their clinical grades. We developed a portable tool PhantHome which is composed of jaws, gingival tissue, rubber cover and a compatible stand. Specific teeth produced by a 3D printer with drills in different directions were placed in both jaws. Students were requested to insert pins by using tweezers and dental mirror according to instructions initiating with easy tasks and continue to ones that are more complicated. 106 first clinical year dental students participated in the study; 65 trained only in the traditional phantom lab (control). 41 trained at home by the PhantHome tool two weeks before and 2 months during the initial stage of phantom lab. The students grades routinely provided in the phantom laboratory at different stages were compared. Students who trained with the portable tool performed better than the control group in the first direct and second indirect preparations (p<0.05). These exams were taken when the PhantHome was available to the students. Then, the tool was returned and the phantom course continued regularly. We believe that this is why no differences between the grades of the groups were observed further on. Training by the PhantHome improves motor skills and consequently the clinical performances.


Dielectric behavior of lysozyme and ferricytochrome-c in water/ethylene-glycol solutions.
This work deals with a dielectric study at radio frequencies of the influence at room temperature of two organic molecules, known as cryo-protectants, ethylene-glycol and glycerol, on conformational and dynamic properties of two model proteins, lysozyme (lys) from chicken egg-white and ferricytochrome-c (cyt-c) from horse heart. Cyt-c is a compact globular protein whereas lys is composed of two structural domains, separated by the active site cleft. Measurements were carried out at the fixed temperature of 20 degrees C varying the concentration of the cosolvent up to 90% w/w. From the analysis of the dielectric relaxation of the protein solution, the effective hydrodynamic radius and the electric dipole moment of the protein were calculated as a function of the cosolvent concentration. The data show that glycerol does not modify significantly the conformation of both proteins and cyt-c is also stable in the presence of ethylene-glycol. On the contrary ethylene-glycol strongly affects the dielectric response of lysozyme denoting a specific effect on its conformation and dynamics. The data are coherently interpreted hypothesizing that glycol molecule wedges between and separates the two domains of lys making them rotationally independent.


Interventions for smoking cessation in hospitalised patients: a systematic review.
An admission to hospital provides an opportunity to help people stop smoking. Individuals may be more open to help at a time of perceived vulnerability, and may find it easier to quit in an environment where smoking is restricted or prohibited. Providing smoking cessation services during hospitalisation may help more people to attempt and sustain an attempt to quit. The purpose of this paper is to systematically review the effectiveness of interventions for smoking cessation in hospitalised patients. We searched the Cochrane Tobacco Addiction Group register, CINAHL, and the Smoking and Health database for studies of interventions for smoking cessation in hospitalised patients. Randomised and quasi-randomised trials of behavioural, pharmacological, or multi-component interventions to help patients stop smoking conducted with hospitalised patients who were current smokers or recent quitters were included. Studies of patients admitted for psychiatric disorders or substance abuse, those that did not report abstinence rates, and those with follow up of less than 6 months were excluded. Two of the authors extracted data independently for each paper, with assistance from others. Intensive intervention (inpatient contact plus follow up for at least 1 month) was associated with a significantly higher cessation rate compared with controls (Peto odds ratio (OR) 1.82, 95% CI 1.49 to 2.22). Any contact during hospitalisation followed by minimal follow up failed to detect a statistically significant effect on cessation rate, but did not rule out a 30% increase in smoking cessation (Peto OR 1.09, 95% CI 0.91 to 1.31). There was insufficient evidence to judge the effect of interventions delivered only during the hospital stay. Although the interventions increased quit rates irrespective of whether nicotine replacement therapy (NRT) was used, the results for NRT were compatible with other data indicating that it increases quit rates. There was no strong evidence that clinical diagnosis affected the likelihood of quitting. High intensity behavioural interventions that include at least 1 month of follow up contact are effective in promoting smoking cessation in hospitalised patients.


Human immunodeficiency virus related reactive arthritis in Zambia.
To characterize the clinical, radiological, and diagnostic features of reactive arthritis (ReA) in indigenous Black Zambians with human immunodeficiency virus (HIV) infection. Consecutive patients attending an arthritis clinic over a 5-year period were studied prospectively. Those who satisfied diagnostic criteria for ReA were analyzed. In total, 170 patients satisfied the ESSG criteria for ReA; 71 (45 men, 26 women) had one or more extraarticular manifestations; 30% had enteroreactive and 14% uroreactive disease. Only 59% of patients had the diagnostic features of ReA at presentation. The initial diagnosis was undifferentiated spondyloarthropathy (uSpa) in 20%, other ReA in 14%, and "arthritis alone" in 7%. Of 65 (42 men, 23 women) patients tested, 94% were HIV-positive (91% men, 100% women). In those with HIV, the arthritis was predominantly polyarticular, lower limb-predominant, and progressive; 58% of 33 with persistent disease had erosions of foot and/or hand joints (average disease duration, 24.4 mo); 6 of 10 showed early radiological spine or sacroiliac joint changes (average duration 47.7 mo). Anterior uveitis occurred in 33% of patients, while keratoderma blenorrhagicum and stomatitis occurred in 14.3% and 9.5%, respectively, of patients with enteroreactive ReA. Uroreactive ReA was more common in women. There were no significant differences in the clinical, diagnostic, or radiographic features between men and women or between those with or without a known preceding trigger. HIV associated ReA in Black Zambians frequently follows an accelerated course with a strong tendency to relapse, develop early erosions and joint deformity, and become chronic. The clinical, diagnostic, and radiographic features are indistinguishable from those described in the conventional (HLA-B27 related) disease, although our HIV-positive patients have a high overall frequency of uveitis, keratoderma, and onycholysis.


Hemorrhagic upper extremity complications from tissue plasminogen activator.
Five patients, ages 63 to 79, had hemorrhagic complications involving the upper extremity from fibrinolytic therapy using intravenous tissue plasminogen activator (tPA) for acute myocardial infarction. The hemorrhages varied in severity. Three patients were treated for superficial hematomas, one with a deep subcutaneous hematoma producing skin necrosis, and one compartment syndrome with posterior interosseous nerve palsy and marked intramuscular bleeding. tPA is currently being used in the treatment of acute myocardial infarction and acute nonhemorrhagic stroke. Caution should be used particularly for IV sites, central lines, arterial catheterization, and pneumatic tourniquets, to avoid upper extremity hemorrhage.


Effects of clipping of flight feathers on resource use in Gallus gallus domesticus.
Ground-dwelling species of birds, such as domestic chickens (Gallus gallus domesticus), experience difficulties sustaining flight due to high wing loading. This limited flight ability may be exacerbated by loss of flight feathers that is prevalent among egg-laying chickens. Despite this, chickens housed in aviary style systems need to use flight to access essential resources stacked in vertical tiers. To understand the impact of flight feather loss on chickens' ability to access elevated resources, we clipped primary and secondary flight feathers for two hen strains (brown-feathered and white-feathered, n = 120), and recorded the time hens spent at elevated resources (feeders, nest-boxes). Results showed that flight feather clipping significantly reduced the percentage of time that hens spent at elevated resources compared to ground resources. When clipping both primary and secondary flight feathers, all hens exhibited greater than or equal to 38% reduction in time spent at elevated resources. When clipping only primary flight feathers, brown-feathered hens saw a greater than 50% reduction in time spent at elevated nest-boxes. Additionally, brown-feathered hens scarcely used the elevated feeder regardless of treatment. Clipping of flight feathers altered the amount of time hens spent at elevated resources, highlighting that distribution and accessibility of resources is an important consideration in commercial housing.


Dynamic hydrolase labelling as a marker for seed quality in Arabidopsis seeds.
Seed quality is affected by different constituents of the seed. In general, seed lots are considered to be of high quality when they exhibit fast and homogeneous germination. When seeds are stored, they undergo different degrees of damage that have detrimental effects on their quality. Therefore, accurate prediction of the seed quality and viability levels of a seed lot is of high importance in the seed-producing industry. Here, we describe the use of activity-based protein profiling of proteases to evaluate the quality of artificially and naturally aged seeds of Arabidopsis thaliana Using this approach, we have identified two protease activities with opposite behaviours in aged seeds of Arabidopsis that correlate with the quality status of the seeds. We show that vacuolar processing enzymes (VPEs) become more active during the ageing process, in both artificial and natural ageing treatments. Secondly, we demonstrate that serine hydrolases are active at the beginning of our artificial ageing treatment, but their labelling decreases along with seed viability. We present a list of candidate hydrolases active during seed germination and propose that these protease activities can be used in combination with VPEs to develop novel markers of seed quality.


Pulmonary densities during anesthesia with muscular relaxation--a proposal of atelectasis.
Twenty patients (23-76 yr) were studied with regard to lung tissue changes prior to and following induction of general anesthesia with muscular relaxation, and another four subjects were studied for a longer period awake. The transverse thoracic area and the structure of the lung tissue were determined by computerized tomography. No abnormalities in the lung tissue were noted before anesthesia. Within 5 min after induction, including muscular relaxation, all subjects had developed crest-shaped changes of increased density in the dependent regions of both lungs. They were largest in the most caudal segment (4.8 +/- 0.8% of the transverse lung area, mean +/- SE) and smaller in the cephalad exposures (3.4 +/- 0.7% of the transverse area). The size of the densities showed no correlation to age. The densities did not increase after a further 20 min of anesthesia and were not affected by the inspiratory oxygen fraction. When the subjects were moved from the supine to the lateral position, the crest-shaped densities disappeared in the nondependent lung and remained in the dorsal part of the dependent lung. The application of positive end-expiratory pressure of 10 cmH2O eliminated or reduced the densities. The four awake subjects showed no lung densities after 90 min in the supine position. It is suggested that these crest-shaped densities represent atelectases, which develop by compression of lung tissue rather than by resorption of gas.


Signaling cascades in thyroid cancer: Increasing the armory of archers to hit bullseye.
Thyroid cancer is a multifaceted and therapeutically challenging disease and rapidly accumulating experimentally verified findings have considerably improve our understanding of the molecular mechanisms which underlie its development. Substantial fraction of information has been added into existing landscape of molecular oncology and we have started to develop a sharper understanding of the underlying mechanisms of thyroid cancer. Wealth of information demystified different intracellular signaling cascades which are frequently deregulated in thyroid cancer. In vitro assays and xenografted mice based studies have helped us to identify drug targets and different synthetic and natural products are currently being tested to effectively treat thyroid cancer. Cabozantinib and vandetanib have been approved to treat medullary thyroid cancer (MTC) and two agents (lenvatinib and sorafenib) are also being used to treat radioactive-iodine refractory differentiated thyroid cancer. This review comprehensively summarizes most recent advancements in our knowledge related to dysregulated intracellular signaling cascades in thyroid cancer and how different proteins can be therapeutically exploited. (1) We discuss how loss of TRAIL mediated apoptosis occurred in thyroid cancer cells and how different strategies can be used to restore apoptosis in resistant cancer cells; (2) We provide detailed account of seemingly opposite roles of NOTCH signaling in thyroid cancers; (3) TGF/SMAD mediated signaling also needs detailed research because of context dependent role in thyroid cancer. Researchers have only begun to scratch the surface of how TGF signaling works in thyroid cancer and metastasis; and (4) Role of SHH signaling in thyroid cancer stem cells is also well appreciated and targeting of SHH pathway will be an important aspect in treatment of thyroid cancer. Better concepts and improved knowledge will be helpful for clinicians in getting a step closer to individualized medicine.


Myeloma: Patient accounts of their pathways to diagnosis.
Pathways to myeloma diagnosis can be prolonged, and are often preceded by multiple GP consultations and emergency presentation. This is the first qualitative study to examine events leading to diagnosis by asking patients about their experiences during this time. Set within a UK population-based cohort, semi-structured interviews were conducted with 20 myeloma patients with varying characteristics and pathways, 12 of whom invited their relatives to take part. Interviews were audio-recorded and qualitative analysis undertaken. Pre-diagnostic awareness of myeloma was minimal. Disease onset was typically described as gradual, and health changes vague but progressive, with increasing loss of function. A wide range of symptoms was reported, with the similarity of these to self-limiting conditions failing to raise suspicion of myeloma among patients and GPs. Patients tended to normalise symptoms at first, although all eventually sought GP advice. GPs often initially suggested benign diagnoses, which were sometimes only revised after multiple consultations with persistent/worsening symptoms. Referrals were made to various hospital specialities, and haematology if associated with abnormal blood tests suggestive of myeloma. Once in secondary care, progress towards diagnosis was generally rapid. Accounts confirmed that pathways to diagnosis could be difficult, largely due to the way myeloma presents, and how symptoms are interpreted and managed by patients and GPs. Recognition of 'normal' health and consultation patterns for the individual could promote appropriate help-seeking and timely referral when changes occur, and may be more effective than raising awareness about the myriad of potential symptoms associated with this disease.


Emerging microbiota during cold storage and temperature abuse of ready-to-eat salad.
Introduction: Ready-to-eat (RTE) leafy vegetables have a natural leaf microbiota that changes during different processing and handling steps from farm to fork. The objectives of this study were (i) to compare the microbiota of RTE baby spinach and mixed-ingredient salad before and after seven days of storage at 8°C or 15°C; (ii) to explore associations between bacterial communities and the foodborne pathogens Listeria monocytogenes, pathogenic Yersinia enterocolitica, and pathogen model organism Escherichia coli O157:H7 gfp+ when experimentally inoculated into the salads before storage; and (iii) to investigate if bacterial pathogens may be detected in the 16S rRNA amplicon dataset. Material and methods: The microbiota was studied by means of Illumina 16S rRNA amplicon sequencing. Subsets of samples were inoculated with low numbers (50-100 CFU g-1) of E. coli O157:H7 gfp+, pathogenic Y. enterocolitica or L. monocytogenes before storage. Results and discussion: The composition of bacterial communities changed during storage of RTE baby spinach and mixed-ingredient salad, with Pseudomonadales as the most abundant order across all samples. Although pathogens were present at high viable counts in some samples, they were only detected in the community-wide dataset in samples where they represented approximately 10% of total viable counts. Positive correlations were identified between viable counts of inoculated strains and the abundance of Lactobacillales, Enterobacteriales, and Bacillales, pointing to positive interactions or similar environmental driver variables that may make it feasible to use such bacterial lineages as indicators of microbial health hazards in leafy vegetables. The data from this study contribute to a better understanding of the bacteria present in RTE salads and may help when developing new types of biocontrol agents..


Supporting a sugar tax in New Zealand: Sugar sweetened beverage ('fizzy drink') consumption as a normal behaviour within the obesogenic environment.
Excessive intake of sugar sweetened beverages (SSBs) is a preventable cause of death. While some countries have implemented a tax on SSBs, other countries, such as New Zealand, rely on industry self-regulation and individual responsibility, such as referring to labels, to control one's own sugar intake from SSBs. The present study examines whether SSB consumers consciously control their diet and therefore interventions such as better labelling might be effective, or alternatively, whether SSB consumers engage in a general pattern of unhealthy eating, and in which case government regulation would be advisable. To explore self-reported dietary consumption and conscious healthy eating behaviours of New Zealand consumers who had consumed SSBs over a 24 hour period. A cross-sectional survey of a representative sample of 2007 New Zealanders, measuring their food and beverage intake over a 24 hour period and self-reported intentions to eat healthily. Within this was a measurement of SSB consumption in the 24 hour period. Multivariable logistic regression revealed that compared to non-SSB consumers, SSB consumers were more likely to have eaten the following: confectionery; fast food; pre-prepared food; biscuits, cakes or pastries; takeaways; ice-cream/dessert. SSB consumption was also associated with a lower likelihood of referring to food labels, less conscious effort to eat healthily, and to less likely to avoid: sugar; fat; calories; food additives; pre-prepared food. SSB consumers were also less likely to have eaten breakfast, or made a meal at home made from scratch. SSB consumers were more likely than non-SSB consumers to demonstrate a general pattern of unhealthy eating and were less likely to report consciously controlling their diet. The findings raise significant concerns regarding the efficacy of individual and industry self-regulation and lend support to stronger government targeted interventions.


Effect of Saccharomyces boulardii in dog with chronic enteropathies: double-blinded, placebo-controlled study.
Saccharomyces boulardii is used to treat acute and chronic enteropathies in humans, but to date, no studies have evaluated the use of this yeast in dogs. The current study, a prospective non-randomised, double-blinded, placebo-controlled study, evaluated the effects of S boulardii in healthy dogs and dogs with chronic enteropathies (CE). Four healthy dogs and 20 dogs with CE were included. In healthy dogs, S boulardii was administered for 10 days. Possible short-term adverse effects were recorded, and quantitative stool cultures for yeasts were performed. In dogs with CE, S boulardii or a placebo was administered in addition to standard treatment protocols. Canine Chronic Enteropathy Clinical Activity Index, abdominal ultrasonography, gastroenteroscopy and histology were performed at the time of diagnosis and after 60 days of treatment. In healthy dogs, S boulardii reached a steady state in five days and was completely eliminated on day 4 after administration. No short-term side effects were seen. Clinical activity index, stool frequency, stool consistency and body condition score improved significantly in dogs with CE receiving S boulardii versus the placebo. In conclusion, S boulardii can be safely used in dogs with CE and seems to achieve better control of clinical signs than standard therapy alone.


Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis.
The aim of this meta-analysis was to assess the risks and incidence of nephrotoxicity and electrolyte abnormalities in patients receiving programmed cell death protein 1 (PD-1) inhibitors. We conducted a meta-analysis of clinical trials that monitored electrolyte levels and kidney functions during treatment with nivolumab or pembrolizumab by searching MEDLINE, EMBASE and the Cochrane Database from inception through April 2017. Our protocol is registered with International Prospective Register of Systematic Reviews; no.CRD42017060579. A total of 48 clinical trials with a total of 11 482 patients were included. The overall pooled risk ratios (RR) of all acute kidney injury (AKI) and all electrolyte abnormalities in patients treated with PD-1 inhibitors were 1.86 [95% confidence interval (CI) 0.95-3.64] and 1.67 (95% CI 0.89-3.12), respectively. Compared with non-nephrotoxic controls, the pooled RR of AKI in patients treated with PD-1 inhibitors was 4.19 (95% CI 1.57-11.18). Prespecified subgroup analyses demonstrated a significant association between PD-1 inhibitors and hypocalcemia with a pooled RR of 10.87 (95% CI 1.40-84.16). The pooled estimated incidence rates of AKI and hypocalcemia in patients treated with PD-1 inhibitors were 2.2% (95% CI 1.5-3.0%) and 1.0% (95% CI 0.6-1.8%), respectively. Among patients who developed AKI with PD-1 inhibitors, the pooled estimated rate of interstitial nephritis was 16.6% (95% CI 10.2-26.0%). Treatment with PD-1 inhibitors is associated with a higher risk of AKI compared with non-nephrotoxic agents. It will be important to characterize the AKI patients to better understand the etiology behind the event. In addition, treatment with PD-1 inhibitors is associated with an increased risk of hypocalcemia. This study highlights a rare but serious adverse event of anti-PD-1 antibodies and we recommend, in addition to electrolytes panel, routine calcium monitoring.


Semantic Congruence Drives Long-Term Memory and Similarly Affects Neural Retrieval Dynamics in Young and Older Adults.
Learning novel information can be promoted if it is congruent with already stored knowledge. This so-called semantic congruence effect has been broadly studied in healthy young adults with a focus on neural encoding mechanisms. However, the impacts on retrieval, and possible impairments during healthy aging, which is typically associated with changes in declarative long-term memory, remain unclear. To investigate these issues, we used a previously established paradigm in healthy young and older humans with a focus on the neural activity at a final retrieval stage as measured with electroencephalography (EEG). In both age groups, semantic congruence at encoding enhanced subsequent long-term recognition memory of words. Compatible with this observation, semantic congruence led to differences in event-related potentials (ERPs) at retrieval, and this effect was not modulated by age. Specifically, congruence modulated old/new ERPs at a fronto-central (Fz) and left parietal (P3) electrode in a late (400-600 ms) time window, which has previously been associated with recognition memory processes. Importantly, ERPs to old items also correlated with the positive effect of semantic congruence on long-term memory independent of age. Together, our findings suggest that semantic congruence drives subsequent recognition memory across the lifespan through changes in neural retrieval processes.


A Systematic Review of the Effects of Hyperoxia in Acutely Ill Patients: Should We Aim for Less?
Despite widespread and liberal use of oxygen supplementation, guidelines about rational use of oxygen are scarce. Recent data demonstrates that current protocols lead to hyperoxemia in the majority of the patients and most health care professionals are not aware of the negative effects of hyperoxemia. To investigate the effects of hyperoxemia in acutely ill patients on clinically relevant outcomes, such as neurological and functional status as well as mortality, we performed a literature review using Medline (PubMed) and Embase. We used the following terms: hyperoxemia OR hyperoxemia OR ["oxygen inhalation therapy" AND (mortality OR death OR outcome OR survival)] OR [oxygen AND (mortality OR death OR outcome OR survival)]. Original studies about the clinical effects of hyperoxemia in adult patients suffering from acute or emergency illnesses were included. 37 articles were included, of which 31 could be divided into four large groups: cardiac arrest, traumatic brain injury (TBI), stroke, and sepsis. Although a single study demonstrated a transient protective effect of hyperoxemia after TBI, other studies revealed higher mortality rates after cardiac arrest, stroke, and TBI treated with oxygen supplementation leading to hyperoxemia. Approximately half of the studies showed no association between hyperoxemia and clinically relevant outcomes. Liberal oxygen therapy leads to hyperoxemia in a majority of patients and hyperoxemia may negatively affect survival after acute illness. As a clinical consequence, aiming for normoxemia may limit negative effects of hyperoxemia in patients with acute illness.


Effects of 3' untranslated and intergenic regions on gene expression in Trypanosoma cruzi.
The effects of 3' untranslated regions (UTR) and intergenic regions (INT), from various Trypanosoma cruzi stage-specific and constitutive genes, on the expression of the reporter firefly luciferase gene (luc), were studied using stable episomal transformation. The 3' UTR influenced luciferase expression by changing the steady-state level and/or the translation efficiency of luc mRNA. Glycoprotein 72 gene (gp72), glycoprotein 85 gene (gp85) or amastin gene (ama) 3' UTR decreased the luc mRNA level 6- to 14-fold, compared to the glyceraldehyde 1-phosphate dehydrogenase gene (gapdh) 3' UTR, in epimastigotes. Luciferase activity decreased in parallel with the luc mRNA level in transformants utilizing the gp85 or ama 3' UTR, whereas luc mRNA containing the gp72 3' UTR showed approximately 5-fold higher translation efficiency than luc mRNA containing a minimal 3' UTR. In amastigotes, the inhibitory effect of the ama 3' UTR observed in other life cycle stages was abolished and luciferase expression was stimulated 16-fold. The overall stage-specific difference mediated by the ama 3' UTR, between epimastigotes and amastigotes, was approximately 100-fold. INT, which was expected to influence polyadenylation efficiency, of gapdh, gp72, or heat shock protein 60 gene inserted after gapdh 3' UTR increased luc mRNA 2- to 8-fold, whereas gp85 INT slightly decreased luc mRNA. By separating effects attributable to the 3' UTR and INT, this study shows the effects of 3' UTR on RNA levels and translational efficiency in T. cruzi.


The speciation of copper (II)/ethylenediamine/oxalate system by evolving factor analysis.
Principal component analysis and evolving factor analysis were applied to the study of the speciation of Cu (II)/ethylenediamine/ oxalate. Two programs were designed, based on mathematical algorithms. Error functions were calculated for evaluating the number of species. Submatrix analysis plots were constructed to estimate the species present in the system. The method should prove useful in studies of complex systems in environmental samples.


Catalytic site-specific inhibition of the 20S proteasome by 4-hydroxynonenal.
The proteasome is responsible for most intracellular protein degradation and is essential for cell survival. Previous research has shown that the proteasome can be inhibited by a number of oxidants, including 4-hydroxynonenal (HNE). The present study demonstrates that HNE rapidly inhibits the chymotrypsin-like activity of the 20S proteasome purified from liver. Subunits containing HNE-adducts were identified following 2D gel electrophoresis, Western immunoblotting, and analysis by MALDI-TOF MS. At a time when only the chymotrypsin-like activity was inhibited, the alpha 6/C2 subunit was uniquely modified. These results provide important molecular details regarding the catalytic site-specific inhibition of proteasome by HNE.


Impact of a livelihood intervention on gender roles and relationship power among people with HIV.
To evaluate the impact of an agricultural livelihood intervention on gender role conflict and sexual relationship power among people with HIV (PWH) in western Kenya. Study participants were enrolled in Shamba Maisha , a cluster randomized controlled trial of an agricultural intervention conducted among PWH across 16 health facilities during 2016-2020. Intervention participants received a water pump, seeds, and agricultural and financial training; control participants received standard of HIV care. We assessed men's views on masculinity and gender roles via the validated gender role conflict score (GRCS; range 18-78, higher = greater gender role conflict). We measured gender power imbalances among women via the validated Sexual Relationship Power Scale (SRPS), which combines subscales of relationship control and decision-making dominance (range 1-4, higher = female holds more power). We compared changes over the study period by arm using longitudinal multilevel difference-in-difference linear regression models accounting for clustering of facilities using the intention-to-treat cohort. We enrolled 720 participants (366 intervention, 354 control); 2-year retention was 94%. Median age was 40 and approximately 55% of participants were female. Among men, after 24-months the decrease in GRCS scores was 4.3 points greater in the intervention than the control arm ( P < 0.001). Among women, the intervention resulted in 0.25 points greater increase in the SRPS compared to the control arm ( P < 0.001). Shamba Maisha resulted in less gender role conflict in men and greater sexual relationship power for women. Agricultural livelihood interventions may be a powerful tool to improve gender power imbalances, which may subsequently mitigate poverty and food insecurity.


DNA ploidy in curettage specimens identifies high-risk patients and lymph node metastasis in endometrial cancer.
Preoperative risk stratification is essential in tailoring endometrial cancer treatment, and biomarkers predicting lymph node metastasis and aggressive disease are aspired in clinical practice. DNA ploidy assessment in hysterectomy specimens is a well-established prognostic marker. DNA ploidy assessment in preoperative curettage specimens is less studied, and in particular in relation to the occurrence of lymph node metastasis. Curettage image cytometry DNA ploidy in relation to established clinicopathological variables and outcome was investigated in 785 endometrial carcinoma patients prospectively included in the MoMaTEC multicentre trial. Diploid curettage status was found in 72.0%, whereas 28.0% were non-diploid. Non-diploid status significantly correlated with traditional aggressive postoperative clinicopathological features, and was an independent predictor of lymph node metastasis among FIGO stage I-III patients in multivariate analysis (OR 1.94, P=0.033). Non-diploid status was related to shorter disease-specific survival (5-year DSS of 74.4% vs 88.8% for diploid curettage, P<0.001). When stratifying by FIGO stage and lymph node status, the prognostic effect remained. However, in multivariate regression analysis, preoperative histological risk classification was a stronger predictor of DSS than DNA ploidy. Non-diploid curettage is significantly associated with aggressive clinicopathological phenotype, lymph node metastasis, and poor survival in endometrial cancer. The prognostic effect was also observed among subgroups with (presumably) less aggressive traits, such as low FIGO stage and negative lymph node status. Our results indicate curettage DNA ploidy as a possible supplement to existing parameters used to tailor surgical treatment.


Extreme features of the Galdieria sulphuraria organellar genomes: a consequence of polyextremophily?
Nuclear genome sequencing from extremophilic eukaryotes has revealed clues about the mechanisms of adaptation to extreme environments, but the functional consequences of extremophily on organellar genomes are unknown. To address this issue, we assembled the mitochondrial and plastid genomes from a polyextremophilic red alga, Galdieria sulphuraria strain 074 W, and performed a comparative genomic analysis with other red algae and more broadly across eukaryotes. The mitogenome is highly reduced in size and genetic content and exhibits the highest guanine-cytosine skew of any known genome and the fastest substitution rate among all red algae. The plastid genome contains a large number of intergenic stem-loop structures but is otherwise rather typical in size, structure, and content in comparison with other red algae. We suggest that these unique genomic modifications result not only from the harsh conditions in which Galdieria lives but also from its unusual capability to grow heterotrophically, endolithically, and in the dark. These conditions place additional mutational pressures on the mitogenome due to the increased reliance on the mitochondrion for energy production, whereas the decreased reliance on photosynthesis and the presence of numerous stem-loop structures may shield the plastome from similar genomic stress.


Safety of Diazepam Nasal Spray in Pediatric Patients With Developmental Epileptic Encephalopathies: Results From a Long-term Phase 3 Safety Study.
Pediatric developmental epileptic encephalopathies are often refractory to treatment despite stable antiseizure therapy. The safety profile of diazepam nasal spray (Valtoco) as rescue therapy for seizure clusters was described in a long-term safety study. This post hoc analysis assessed safety and effectiveness within a subpopulation of patients with developmental epileptic encephalopathies. Of 163 treated patients, 64 were diagnosed with ≥1 pediatric developmental epileptic encephalopathy. Among the most common developmental epileptic encephalopathies were Rett syndrome (n = 16), Lennox-Gastaut syndrome (n = 9), and Dravet syndrome (n = 7). In the broad pediatric developmental epileptic encephalopathy group, 10.6% of seizure clusters were treated with a second dose, with similar proportions in the 3 individual encephalopathies. Across groups, treatment-emergent adverse event rates ranged from 66.7% to 100%. Only epistaxis (n = 2) was treatment-related and reported in >1 patient. In this long-term safety analysis in patients with developmental epileptic encephalopathies, diazepam nasal spray demonstrated a consistent safety profile, supporting its use in these hard-to-treat patients (ClinicalTrials.gov NCT02721069).


Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism.
Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance for the identification of pharmacological targets for the treatment of obesity and its associated metabolic diseases.


Examining the health and health service utilization of heterosexual men with HIV: a community-informed scoping review.
The prevalence of HIV infection among heterosexual men has increased. Consequently, the need for health and support services for this group is likely to increase. We conducted a scoping review of studies regarding the health and health service use of heterosexual men with HIV that was informed by research priorities identified by this community. We searched six databases from inception to August 2014. We included all English-language qualitative and quantitative studies examining the health and health service use of heterosexual men with HIV. Our search strategy yielded 2665 references, of which 70 were included in the scoping review. We summarized the research into the following domains identified by summit participants: treatment of HIV and its complications (n = 9), health and social support services utilization (n = 27), social determinants of health (n = 20), prevention (n = 11), family planning (n = 4) and psychosocial research (n = 33). Key findings from the review included poor mental health-related well-being, over-representation among "late presenters" to care and greater fear of disclosure of HIV status relative to men who have sex with men. In general, research conducted to date was not well aligned with the priorities identified by the community.


Comparison of Yuzpe regimen, danazol, and mifepristone (RU486) in oral postcoital contraception.
To compare the effectiveness and acceptability of three regimens of postcoital contraception. Randomised group comparison of ethinyloestradiol 100 micrograms plus levonorgestrel 500 micrograms repeated after 12 hours (Yuzpe method); danazol 600 mg repeated after 12 hours; and mifepristone 600 mg single dose. Community family planning clinic. 616 consecutive women with regular cycles aged 16 to 45 years. Number of pregnancies, incidence of side effects, and timing of next period. The raw pregnancy rates (with 95% confidence intervals) for the Yuzpe, danazol, and mifepristone groups were 2.62% (0.86% to 6.00%), 4.66% (2.15% to 8.67%), and 0% (0% to 1.87%) respectively. Overall, these rates differed significantly (chi 2 = 8.988, df = 2; p = 0.011). The differences between the mifepristone and Yuzpe groups and between the mifepristone and danazol groups were also significant. Side effects were more common and more severe in the Yuzpe group (133 women (70%)) than in either the danazol group (58 (30%)) or the mifepristone group (72 (37%)). The Yuzpe regimen tended to induce bleeding early but mifepristone prolonged the cycle. Three women bled more than seven days late in the Yuzpe group compared with 49 in the mifepristone group. Mifepristone was effective in reducing expected pregnancy rates and the Yuzpe method also had a clinical effect. Danazol had little or no effect. A further multicentre trial is needed.