Poorer mental well-being and prior unmet need for mental healthcare: a longitudinal population-based study on men in Sweden.
Depression and anxiety disorder contribute to a significant part of the disease burden among men, yet many men refrain from seeking care or receive insufficient care when they do seek it. This is plausibly associated with poorer mental well-being, but there is a lack of population-based research. This study investigated 1) if men who had refrained from seeking mental healthcare at any time in life had poorer mental well-being than those who sought care, 2) if those who had sought care but perceived it as insufficient had poorer mental well-being than those who had perceived care as sufficient, and 3) if these differences persisted after 1 year. This longitudinal study used questionnaire data from a population-based sample of 1240 men, aged 19-64 years, in Sweden. Having refrained from seeking mental healthcare, or perceiving the care as insufficient, at any time in life, was assessed in a questionnaire, 2008. Current mental well-being was assessed in 2008 and 2009 using mean scores on the WHO (Ten) Well-being Index. Lower scores indicate poorer mental well-being. Group differences were calculated using t-tests and multivariable linear regression analysis. Of the men who had perceived a need for mental healthcare, 37% had refrained from seeking such care. They had lower mental well-being scores in 2008, compared to those who sought care. Of those seeking care, 29% had perceived it as insufficient. They had lower mental well-being scores in 2008, compared to those who perceived the care as sufficient, but this was not statistically significant when controlling for potential confounders. There were no differences in mental well-being scores based on care-seeking or perceived care-sufficiency in 2009. This population-based study indicates that men who have previously refrained from seeking mental healthcare, or perceived the care as insufficient, have poorer mental well-being. However, the lack of differences at the one-year follow-up contradicts these results. The results highlight the need for larger longitudinal studies, measuring care-seeking within a more specified time frame. This should be combined with efforts to increase men's mental healthcare-seeking and to provide mental healthcare that is perceived as sufficient.


Construction and validation of a prognostic model for stage IIIC endometrial cancer patients after surgery.
To explore the most predictive lymph node (LN) scheme for stage IIIC endometrial cancer (EC) patients after hysterectomy and develop a scheme-based nomogram. Data from 2626 stage IIIC EC patients, diagnosed between 2010 and 2014, were extracted from the Surveillance, Epidemiology, and End Results (SEER) registry. The predictive ability of four LN schemes was assessed using C-index and Akaike information criterion (AIC). A nomogram based on the most predictive LN scheme was constructed and validated. The comparison of the predictive ability between nomogram and FIGO stage was conducted using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). FIGO stage (stage IIIC1/stage IIIC2) was not an independent risk factor for OS in stage IIIC EC patients (P = 0.672) and log odds of positive lymph nodes (LODDS) had the best predictive ability (C-index: 0.742; AIC: 8228.95). A nomogram based on LODDS was constructed and validated, which had a decent C-index of 0.742 (0.723-0.762). The nomogram showed a better predictive ability than that of the FIGO staging system. FIGO IIIC1/FIGO IIIC2 could not differentiate the prognosis for stage IIIC EC patients. We developed and validated a nomogram based on LODDS to predict OS for post-operative patients with stage IIIC EC.


Longitudinal association of PTSD symptoms and self-reported physical functioning among Veterans.
Few longitudinal studies have investigated the potentially dynamic relationship between Posttraumatic Stress Disorder (PTSD) and physical functioning, and the number of follow-up timepoints have been limited. We evaluated whether PTSD symptoms predicted future physical functioning and vice versa using five assessments over four years. Data was used from a longitudinal cohort of 695 participants recruited from Veteran Affairs medical outpatient clinics who experienced a traumatic event. PTSD symptom severity was assessed annually with the PTSD Checklist (PCL). Physical functioning was measured with the 10-item subscale of the SF-36. An autoregressive cross-lagged panel model was used to determine the temporal associations between PTSD and physical functioning, adjusting for age, sex, ethnicity, education and employment. Comorbidities and health behaviors were added to assess their roles in the relationship. Greater PTSD symptom severity predicted worse physical functioning the following year (average β = -0.10, P <0.001), where a 10-point increase in PCL score predicted a 0.3-point decline in physical function score over one year. Similarly, better physical functioning also predicted reduced PTSD severity the following year, but to a smaller magnitude (average β = -0.04, P = .003). The pattern of effects was similar after controlling for comorbidities and health behaviors. Both primary variables relied on self-report, and generalizability may be limited by the mostly male Veteran sample. Our results support a bidirectional, but unequal, relationship between PTSD and physical functioning over time. They also highlight the importance of long-term control of PTSD symptoms in preventing functional decline.


Shanghai Time Outside to Reduce Myopia trial: design and baseline data.
Myopia is a major public health concern worldwide, while outdoor time is indicated to be protective against the onset of myopia. To describe the methodology and baseline data of the Shanghai Time Outside to Reduce Myopia (STORM) trial. A 2-year, school-based, prospective, cluster randomized trial. Children from grade I and II classes of 24 schools from eight districts in Shanghai, China, were randomized to either a control group, a test group I (40-min outdoor time/day) or test group II (80-min outdoor time/day). At baseline and annual intervals, cycloplegic autorefraction and axial length measurement will be performed. Time outdoors and light exposure will be monitored via parent/carer questionnaires and a wearable device. Spherical equivalent, prevalence of myopia and time outdoors in each group. A total of 6295 eligible children (age 7.2 ± 0.7 y [6-9 y]) were randomized to control (n = 2037), test group I (n = 2329) and test group II (n = 1929). At baseline, spherical equivalent was +0.98 ± 1.02D, +1.02 ± 1.02D and +1.00 ± 0.99D (P = 0.708), myopia prevalence was 8.9, 7.7 and 7.8% (P = 0.270) and time outdoors was 58.5 ± 35.8, 59.8 ± 34.7 and 58.5 ± 35.3 min/d (P = 0.886) for control, test groups I and II, respectively. Myopia prevalence was high at nearly 8 to 9% in school children aged 7 years in Shanghai, China. The current trial will help evaluate if increased time outdoors has a role to play in reducing the incidence of myopia and/or slow the progression of myopia.


In-silico characterization of ECE-1 inhibitors.
Atherosclerosis is the primary cause of CAD and cerebrovascular disease. Endothelin (ET)-1 is a vasoconstrictive peptide implicated in Atherosclerosis pathology. Endothelin-converting enzyme (ECE) is a membrane metalloprotease that generates endothelin. Reported inhibitors of ECE-1 and their IC(50) values were retrieved from literature and their structures were docked with the parent protein using the Molegro virtual docker. The obtained MolDock scores of each of the compounds are hereby reported and are subject to graphical analysis in conjunction with their respective IC(50) values to characterize potent inhibitors. A search was then run in the ZINC database for compounds with similar properties. Potent inhibitors with higher Dock scores and better Ranking were isolated and are reported.


Reconstitution of CHIP E3 ubiquitin ligase activity.
CHIP, the carboxyl-terminus of Hsp70 interacting protein, is both an E3 ubiquitin ligase and an Hsp70 co-chaperone and is implicated in the degradation of cytosolic quality control and numerous disease substrates. CHIP has been shown to monitor the folding status of the CFTR protein, and we have successfully reconstituted this activity using a recombinant CFTR fragment consisting of the cytosolic NBD1 and R domains. We have found that efficient ubiquitination of substrates requires chaperone activity to either deliver the substrate to CHIP or to maintain the substrate in a ubiquitination-competent conformation. This chaperone activity can be provided by the Hsp70/Hsp40 molecular chaperone system as seen in the NBD1-R ubiquitination assay. Alternatively, heat treatment of CHIP can activate its own innate substrate-binding activity and allow for efficient ubiquitination of model substrates, such as denatured luciferase. Here, we describe methods for purifying the recombinant proteins necessary for in vitro reconstitution of CHIP ubiquitin ligase activity, as well as two methods used to monitor CHIP ligase activity. One method allows for the measurement of the Hsp70- and Hsp40-dependent CHIP activity while the other measures the Hsp40- and Hsp70-independent activity of heat-activated CHIP.


Essential Light Chains of Myosin and Their Role in Functioning of the Myosin Motor.
This review summarizes current data on the structure and functions of myosin essential light chains (ELCs) and on their role in functioning of the myosin head as a molecular motor. The data on structural and functional features of the N-terminal extension of myosin ELC from skeletal and cardiac muscles are analyzed; the role of this extension in the ATP-dependent interaction of myosin heads with actin in the molecular mechanism of muscle contraction is discussed. The data on possible interactions of the ELC N-terminal extension with the myosin head motor domain in the myosin ATPase cycle are presented, including the results of the authors' studies that are in favor of such interactions.


Relationship between collagen fibril diameters and body size. Study of fish derma.
Suspensions of collagen fibrils obtained from derma of Elasmobranchia and Actinopterygia of different body sizes and developmental stages were examined by transmission electron microscopy. Fibril diameters were measured and classified into groups comprising a 20 nm diameter interval. Diagrams showing fibril populations of each fish were made. The measurements were averaged and their confidence intervals and standard errors determined. For each species other diagrams were plotted in which the mean diameters were correlated to the body length of each sample. The results show that: 1) a correlation exists between an increase in diameter of collagen fibrils and somatic growth until sexual maturity is reached; 2) fibril populations are subsequently spread over a wider range due to the presence in the derma of classes of newly formed and therefore thinner fibrils. The deposition of new fibrils is possibly influenced by individual factors; 3) no relationship exists between mean fibril diameter and body size; 4) no relationship exists between phylogenetic position and pattern of diameter distribution.


Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes.
Nivolumab is a monoclonal antibody that blocks the activation of programmed death-1 receptor, promoting T-cell activation against cancer cells. Thyroid dysfunction (TD) is a common immune-related adverse event (irAE) induced by nivolumab. We report the prevalence, patterns and outcomes of nivolumab-induced TD among cancer patients in our center. All patients treated with nivolumab during 2016 were included. We assessed thyroid function tests, thyroid autoimmunity, thyroid imaging, and clinical outcome during nivolumab therapy as well as overall survival (OS). Seventy-three patients (55 with non-small-cell lung cancer [NSCLC], 9 with melanoma and 9 with Hodgkin lymphoma) were included. Median of follow up: 390.5 days. Seventeen patients (23.3%) developed TD during treatment. Thyrotoxicosis was reported in seven patients. Serum thyroid-stimulating hormone (TSH) nadir occurred after a median of 51 days (95% CI: 35-71). Thyroid antibodies were positive in three of the seven patients. Five of the seven hyperthyroid patients became hypothyroid later, and four of them required levothyroxine treatment. Primary hypothyroidism occurred in ten patients. Serum TSH peak occurred after a median of 110 days [95% CI: 85.2-197]. Thyroid autoimmunity was positive in one patient. In patients with NSCLC, TD was associated with better OS (HR = 0.4 [95% CI: 0.17-0.94]; p = 0.035). TD induced by nivolumab is a common and heterogeneous irAE. Thyrotoxicosis develops earlier than hypothyroidism. A pattern consistent with a transient thyroiditis followed by hypothyroidism was observed in one-third of patients. Our results suggest that patients with NSCLC and nivolumab-induced TD might have better survival.


A survey of non-expert surgeons using the open tension-free mesh patch repair for primary inguinal hernias.
The aim of this study was to learn if general surgeons with no special interest in hernia repairs, using the open tension free repair, could achieve a degree of success comparable to that of the experts. A survey was undertaken of 72 surgeons who were known to be performing an open tension-free onlay mesh patch repair for primary inguinal hernias with no attempt to suture together the edges of the hernia defect. While several European surgeons were included, most were from the United States. There was a minimal amount of wound infection, an absence of mesh rejection when Marlex mesh was used, and a recurrence rate under 0.5% in 16,068 operations. The experience of the non-experts demonstrated that excellent results were attained by surgeons who had no special interest in hernia surgery and testifies to the simplicity and reliability of the method.


Sleep Deficiency: Epidemiology and Effects.
Adequate sleep is an important pillar of physical and mental health. Sleep deficiency, resulting from short sleep or suboptimal sleep quality, is highly prevalent in modern society. Occupation, social demands, psychiatric disorders, physical disorders, and sleep disorders are some of the contributing factors to sleep deficiency. Some populations are at increased risk of sleep deficiency based on ethnicity, age, marital status, sex, and hospitalization. Sleep deficiency influences cognition, alertness, mood, behavior, diabetes, cardiovascular health, renal function, immune system, and respiratory physiology. This review summarizes the epidemiology and effects of sleep deficiency.


Optic nerve sheath diameter sonography during the acute stage of intracerebral hemorrhage: a potential role in monitoring neurocritical patients.
Optic nerve sheath diameter (ONSD) sonography has been proposed as a reliable bedside tool for the detection of increased intracranial pressure (ICP). ONSD reacts almost simultaneously to oscillations in ICP. The aim of this study was to investigate the ONSD dynamics in the acute stage of intracerebral hemorrhage (ICH) and to compare ONSD dynamics to the clinical outcome. We enrolled 35 acute ICH patients and 20 healthy volunteers in this prospective study. At the admission, all patients underwent brain CT scan and ONSD sonography. We repeated the ONSD on the second and the third day in all patients while CT scan was repeated if a patient condition deteriorated. The changes in serial ONSD measurements were termed as stable or unstable ONSD trend. ONSD trend was considered as unstable if variations of average ONSD were above 5%. The outcome of the patient was assessed with the Modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS). In healthy volunteers serial ONSD recordings for 3 days revealed a stable trend in 100%. However, in the study group, 23 patients had unstable and 12 had stable ONSD trend during the acute stage of ICH. The patients with unstable ONSD trend were more likely to have worse outcomes (p value 0.003). In patients with ICH, the acute-phase ONSD dynamics can help in predicting the clinical outcome.


Transcriptomic analysis reveals novel molecular signaling networks involved in low voluntary running behavior after AP-1 inhibition.
Understanding the neuro-molecular mechanisms that mediate the quantity of daily physical activity (PA) level is of medical significance, given the tremendous health benefits associated with greater physical activity. Here, we examined the effects of intra-nucleus accumbens (NAc) inhibition of activator protein-1 (AP-1), an important transcriptional factor downstream of cAMP response element binding protein (CREB; a reward-related transcriptional regulator), on voluntary wheel running behavior in wild-type (WT) and low voluntary running (LVR) female rats. Transcriptome analysis of the nucleus accumbens (NAc; a brain region critical for PA reward and motivation) was performed to further determine molecular responses to intra-NAc AP-1 inhibition in these rat lines. Within WT rats, intra-NAc AP-1 inhibition caused a significant decrease in overnight running distance in comparison to control rats (p = 0.009). Transcriptomic and bioinformatic analysis in WT rats identified involvement of gene products that regulate cellular proliferation and development, which were cellular processes regulated by AP-1. In contrast to above decreased WT distances, intra-NAc AP-1 inhibition in LVR rats increased nightly running distance in comparison to LVR control rats (p = 0.0008). Further analysis identified gene products that are associated with regulating intracellular Ca2+ homeostasis, calcium ion binding and neuronal excitability. In short, our study aims to gain a comprehensive understanding of transcriptional profile that was due to AP-1 inhibition in NAc, in which it could not only enhance the knowledge regarding molecular regulatory loops within NAc for modulating voluntary running behavior, but also provide further insights into molecular targets for future investigations.


Treatment of ornithine transcarbamylase deficiency in girls by auxiliary liver transplantation: conceptual changes in a living-donor program.
Ornithine transcarbamylase (OTC) deficiency is an X-chromosome-linked genetic disorder resulting in hyperammonemia hepatic dysfunction, coma, and serious neurological sequelae. This report describes an experience in treating this condition with living-related liver transplantation. Three children with OTC were treated with a living-related liver transplantation. Potential donors were evaluated with the allopurinol loading test to exclude heterozygotes. FK506 and low-dose steroids were used for immunosuppression. Auxiliary partial orthotopic transplantation (APOLT) was used in two of the cases. All three children survived and are doing well without protein restriction. These observations suggest that in OTC removal of the native liver is not necessary because (1) a partial liver segment with normal enzyme activity corrects the hyperammonemia, (2) in case of graft failure the native liver is an available backup, and (3) the native liver has the ability to recover function. As long as living-related donors serve as the main source of donor organs, APOLT is a safer approach to liver transplantation in OTC.


Pediatric End-of-Life Care in Rural America: A Systematic Review.
Families increasingly desire to bring their children home from the acute care setting at end of life. This transition includes home to rural or remote areas. Little is known about the end-of-life care for children who reside in rural areas. The purpose of this study was to comprehensively review and summarize the evidence regarding end-of-life care for children living in rural areas, identify key findings and gaps in the literature, and make recommendations for future research. A systematic review was conducted from 2011 to 2021 using MEDLINE and CINAHL databases. Nine studies met inclusion criteria. Key themes from the literature included: barriers, facilitators, and needs. Three articles identified barriers to end-of-life care for children in rural communities, which included access to end-of-life care and clinicians trained to provide pediatric care. Three studies identified and evaluated the facilitators of end-of-life care for rural children. The articles identified technology and additional training as facilitators. Four studies reported on the needs of rural children for end-of-life care with serious illness. We found major barriers and unmet needs in the delivery of rural pediatric end-of-life care. A few facilitators in delivery of this type of care were explored. Overall research in this area was sparse. Future studies should focus on understanding the complexities associated with delivery of pediatric end-of-life care in rural areas.


Recent progresses in marine microbial-derived antiviral natural products.
Viruses have always been a class of pathogenic microorganisms that threaten the health and safety of human life worldwide. However, for a long time, the treatment of viral infections has been slow to develop, and only a few antiviral drugs have been using clinically. Compared with these from terrestrial environments, marine-derived microorganisms can produce active substances with more novel structures and unique functions. From 2015 to 2019, 89 antiviral compounds of 8 structural classes have been isolated from marine microorganisms, of which 35 exhibit anti-H1N1 activity. This review surveys systematically marine microbial-derived natural products with antiviral activity and illustrates the impact of these compounds on antiviral drug discovery research.


A quantitative study of cell proliferation in ependyma and choroid plexus in the postnatal rat brain.
Profliferative activity in forebrain ependyma aand choroid plexus epithelium was studied in rats aged up to 42 days by means of autoradiography after injection of [3H]-thymidine. Labelling indices were higher in the lateral than in the third ventricle, while values for choroid plexus epithelium were lower than those for ependyma. In all areas examined, labelling indices showed a similar pattern of decline in the first two postnatal weeks reaching by day 12 a level about 20-30% of that on day 1. This low level, corresponding to a turnover time of 130 days for ependyma, was maintained tereafter up to day 42, indicating the persistence of proliferation in the young adult.


The corneal endothelium after laser therapy for glaucoma.
Using computer assisted morphologic analysis of central corneal endothelial specular micrographs, we prospectively examined the effects of glaucoma laser procedures on the corneal endothelium. Argon laser trabeculoplasty was performed in 22 eyes of 17 patients. Argon laser iridotomy was performed in 14 eyes of seven patients. Untreated fellow eyes in ten patients undergoing laser trabeculoplasty were used as controls. After one year, no statistically significant difference in cell area, percent hexagonal cells, or shape factor was observed. Our results suggest that argon laser procedures do not pose any long-term hazard to the corneal endothelium.


Synthesis and biological evaluation of new benzo-thieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives as potential selective cyclooxygenase-2 inhibitors.
The aim of this work was to evaluate the potential anti-inflammatory activity of eleven (5-15) new synthesized derivatives of benzo-thieno[3,2-d]pyrimidine on two cell models, namely human keratinocytes NCTC 2544 and mouse monocyte-macrophages J774. For the synthesis of test compounds an efficient approach was developed: the key isothiocyanate was prepared through a simple and ecological method using di-2-pyridyl thionocarbonate (DPT) in substitution of thiophosgene, a highly toxic agent, and the cyclization reaction of benzo-thiosemicarbazide derivates was performed through Wamhoff methods. This procedure can be a new alternative method economically and environmentally advantageous by the simplicity of procedure, reduction of isolation and purification steps, time, costs, and waste production. The potential anti-inflammatory activity of 5-15 was evaluated by determining the expression of cyclooxygenase (COX)-2, inducible NO synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1), and the release of prostaglandins (PG)E[Formula: see text] and interleukin-8 (IL-8). Our results demonstrate that the compounds 7, 10, 12, 13, 14, and 15 act as a potent inhibitor of COX-2, iNOS, ICAM-1 expression while also suppressing the production of PGE[Formula: see text] and IL-8 in human keratinocytes NCTC 2544 exposed to interferon-gamma (IFN-[Formula: see text]) and histamine and monocyte-macrophages J774 cells treated with lipopolysaccharides (LPS). In conclusion, some derivatives of benzo-thieno[3,2-d]pyrimidine could be developed as a novel class of anti-inflammatory agents.


Osteoprotective effect of green tea polyphenols and annatto-extracted tocotrienol in obese mice is associated with enhanced microbiome vitamin K2 biosynthetic pathways.
The role of the gut microbiome in bone health has received significant attention in the past decade. We investigated the effects of green tea polyphenols (GTP) and annatto-extracted tocotrienols (AT) on bone properties and gut microbiome in obese mice. Male mice were assigned to a two (no AT vs. 400 mg/kg diet AT) × two (no GTP vs. 0.5% w/v GTP) factorial design, namely control, G, T, and G+T group respectively, for 14 weeks. The 4th lumbar vertebra (LV-4) and femur were harvested for bone microstructural analysis using μ-CT. Microbiome analysis using 16S rRNA gene sequencing of cecal feces was performed. AT increased bone volume at distal femur. GTP increased serum procollagen type 1 N-terminal propeptide concentration, bone volume at the distal femur and the LV-4, and trabecular number at distal femur; whereas GTP decreased trabecular separation at distal femur. Interactions between GTP and AT were observed in serum C-terminal telopeptide of type I collagen level (control>G=T=G+T) as well as the cortical bone area (control<G=T=G+T) and thickness (T≥G+T≥G≥control) at femur mid-diaphysis. Redundancy analysis showed a significant difference in the gut microbiome profile among different groups and the relative abundance of Akkermansia muciniphila, Clostridum saccharogumia, and Subdoligranulum variabile was increased in the GTP- and AT-supplemented groups. Functional profiling of the gut microbiome showed the combination of GTP and AT induced biosynthetic pathways for vitamin K2. Our results suggest that GTP and AT supplementation benefits bone properties in obese mice through modifying gut microbiome composition and function.


Prevalence of Iron Deficiency and Iron Deficiency Anaemia in Adolescent Girls in a Tertiary Care Hospital.
Iron Deficiency Anaemia (IDA) is a global health problem. It involves population of all age group and sex. But adolescent girls are more vulnerable to it. The reasons may be increased iron demand, menstrual blood loss, infection, worm infestation etc. To find the prevalence of iron deficiency and IDA in adolescent girls in a Tertiary Care Hospital. This cross-sectional study was done in the biochemistry clinical laboratory of Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India for a period of six months (April 2015-October 2015). Haemoglobin estimation was done by Sahli's method. Total iron and Total Iron Binding Capacity (TIBC) estimation was done by Ferrozine method on fully automated chemistry analyzer Olympus AU 400 with the reagent kit available in the market. Ferritin estimation was done by chemiluminesence immunoassay method, using Access 2 (Beckman Coulter). Out of 200 girls, 50% adolescent girls were found to be anaemic. Of the total, 43.3% were mildly, 3.3% were moderately and 3.3% were severely affected by anaemia. As prevalence of anaemia is 50%, it needs intervention for its prevention and control. This study will help in planning and implementation of the policy for prevention of iron deficiency and IDA.


Flow cytometric S-phase fraction contributes to diagnosis of diploid malignant salivary gland tumours.
DNA ploidy studies on salivary gland tumours have shown that the proportion of aneuploid cases, although confined to the malignant entities, is considerably lower than for other solid malignancies. To analyse whether the S-phase fraction (SPF) may contribute to discrimination of diploid malignant from benign tumours, DNA flow cytometric data from 45 different malignant salivary gland tumours was compared with that of 121 pleomorphic adenomas. All benign tumours were diploid. Twelve malignant tumours contained aneuploid cell populations. The SPF values for diploid malignancies ranged between 0.9% and 11.0% (mean 3.9%), and between 0.5% and 7.9% (mean 2.7%) for pleomorphic adenomas. A 4% cut-off value gained statistical significance for discriminating diploid malignant tumours from pleomorphic adenomas (P<0.01). The sensitivity for SPF>4% was 46% and the positive predictive value was 40%. A sensitivity of 60% and a positive predictive value of 54% was achieved by combining aneuploidy and SPF>4%. These results show that DNA flow cytometry may contribute to diagnostic assessment in salivary gland tumours.


Malaria in 2002.
The burden of malaria is increasing, especially in sub-Saharan Africa, because of drug and insecticide resistance and social and environmental changes. Thus, there is an urgent need for vaccines, new drugs and insecticides. Parasite, mosquito and human genome projects are helping in the search for new control tools and international donors are developing new funding mechanisms that could make them available to poor countries. But these new tools will achieve their maximum impact only if additional resources are deployed to strengthen malaria research and control communities in countries where the new tools will be used.


In vivo guidance of regenerating nerve by laminin-coated filaments.
Laminin is reportedly an extremely potent neurite-promoting agent in vitro. We investigated the effect of laminin on regeneration of axons in vivo, using a cord of polyester filaments coated with laminin as a guide, replacing a 10-mm segment of the rat sciatic nerve. After 4 weeks the cross section of the nerve guide at its midportion was examined under an electron microscope. Many regenerated axons were seen in the laminin-coated group, whereas no axon was observed in the controls. We conclude that laminin guides the regeneration of axons in vivo.


"This group… I felt like I was medicating myself from this cyberscam illness that was living with me." A qualitative evaluation of co-designing cybersafety training resources with and for people with acquired brain injury.
Whilst anyone can be scammed, individuals with acquired brain injury (ABI) may have unique risk factors to cyberscams for which tailored interventions are required. To address this, a co-design approach was utilised to develop cybersafety resources with people with living experience of ABI and scams. This study aimed to evaluate the co-design experience to inform future utilisation of co-design methods. Semi-structured qualitative interviews explored perceived benefits and challenges, level of support and the co-design process for people with ABI (n= 7) and an attendant care worker (ACW) (n= 1). Transcripts were analysed using a six-stage reflexive thematic analysis. Five themes were identified: "An Intervention Addressing Shame"; "Feeling Validated and Valued"; "Experiencing a 'Profound Change Amongst a Group of Peers'"; 'Gaining Stronger Scam Awareness'; and 'Taking Ownership'. Adjustments to support communication, memory impairments and fatigue in the co-design process were recommended. Participant reflections on the co-design process extended beyond resource design and highlighted therapeutic benefits of increased insight and emotional recovery from shame. Likely mechanisms underpinning these benefits were the peer group format and opportunities to make meaningful contributions. Despite identified challenges in facilitating co-design projects, the practical and emotional benefits reported by participants underscore the value of co-design with people with ABI. Implications for rehabilitationIndividuals with acquired brain injury (ABI) may be at increased risk of cyberscams due to cognitive impairments, for which tailored cyberscam interventions are required.Using a co-design approach maximises the relevance of training resources for individuals with ABI.Using a collaborative co-design approach to developing cybersafety training resources may facilitate scam awareness and peer support.Support for communication, memory impairments and fatigue may be necessary in co-design efforts with people with ABI.


ATPase activity of RecD is essential for growth of the Antarctic Pseudomonas syringae Lz4W at low temperature.
RecD is essential for growth at low temperature in the Antarctic psychrotrophic bacterium Pseudomonas syringae Lz4W. To examine the essential nature of its activity, we analyzed wild-type and mutant RecD proteins with substitutions of important residues in each of the seven conserved helicase motifs. The wild-type RecD displayed DNA-dependent ATPase and helicase activity in vitro, with the ability to unwind short DNA duplexes containing only 5' overhangs or forked ends. Five of the mutant proteins, K229Q (in motif I), D323N and E324Q (in motif II), Q354E (in motif III) and R660A (in motif VI) completely lost both ATPase and helicase activities. Three other mutants, T259A in motif Ia, R419A in motif IV and E633Q in motif V exhibited various degrees of reduction in ATPase activity, but had no helicase activity. While all RecD proteins had DNA-binding activity, the mutants of motifs IV and V displayed reduced binding, and the motif II mutant showed a higher degree of binding to ssDNA. Significantly, only RecD variants with in vitro ATPase activity could complement the cold-sensitive growth of a recD-inactivated strain of P. syringae at 4 degrees C. These results suggest that the requirement for RecD at lower temperatures lies in its ATP-hydrolyzing activity.


Debonding of cast metal-based cantilever and fixed-fixed resin-retained bridgework: A review of the literature.
Cast metal-based resin-retained bridgework (RRB) offers a practical, conservative approach when restoring edentulous spaces. This review examines the debonding of cast metal-based RRB, comparing cantilever resin-retained bridgework (CRRB) and fixed-fixed resin-retained bridgework (FRRB) designs taking into context developments in RRB design, construction, and cementation over time. An electronic search was conducted through Medline and Embase with the aid of Boolean operators to combine the following key words: "adhesive bridges", "resin-bonded bridges", "resin-retained bridges", "resin-bonded fixed partial dentures", "cantilever", "debond", "fixed-fixed", "decementation", "failure", "success", "outcome", "longevity" and "survival". The search was limited to peer-reviewed articles written in English and published from 1995 through to 2019. Thirty-one studies were included. Five studies compared the longevity of CRRB versus FRRB, five assessed the clinical performance of CRRBs alone, and 21 studies assessed the clinical performance of FRRBs. There was great variability in study design and the reporting of clinical outcomes, and an analysis and critique of the included papers is provided. Overall, CRRB tend to debond less and hence provide longer-term and more reliable clinical service when compared to FRRB. More high-level, long-term, prospective and clinical controlled trials are required to further analyse and evaluate the long-term outcomes of cast metal-based RRB.


Age-related periosteal expansion at femoral neck among elderly women may maintain bending stiffness, but not femoral strength.
Periosteal expansion and bone loss have opposite effects on femur strength. Their combined effect has not been fully understood. Our investigation using a recently developed beam model suggested that periosteal expansion may maintain femur bending stiffness among elderly women, but not help preserve femoral strength and reduce hip fracture risk. Periosteal expansion and bone loss are two accompanying biological phenomena in old population. Their combined effect on bone stiffness, strength, and fracture risk is still not clear, because previous studies have reported contradictory results. A recently developed DXA (dual-energy X-ray absorptiometry)-based beam model was applied to study the effect at the femoral neck. We first made a theoretical analysis. Then, a clinical cohort consisting of 961 women (316 hip fractures and 645 controls, age of 75.9 ± 7.1) was used to investigate the associations quantitatively. We investigated (1) correlations of femoral-neck width and bone mineral density with femoral stiffness and strength; (2) correlations of femoral stiffness, strength, and hip fracture risk index with age; (3) associations of femoral stiffness, strength and fracture risk index with actual fracture status, measured by the area under the curve (AUC) and odds ratio (OR). The investigation results showed that (i) femoral-neck width had stronger correlation with femoral bending stiffness (r = 0.61-0.82, p < 0.001) than with the other stiffness components, while bone mineral density had stronger correlation with axial/shearing stiffness (r = 0.84-0.97, p < 0.001), strength (r = 0.85-0.92, p < 0.001), and fracture risk index (r = -0.61-0.62, p < 0.001) than with bending stiffness. (ii) The association between femoral bending stiffness and age was insignificant (r = - 0.06-0.05, r > 0.05); The associations of axial/shearing stiffness (r = - 0.27--0.20, p < 0.001), strength (r = - 0.28, p < 0.001), and fracture risk index (r = 0.38, p < 0.001) with age were significant. (iii) Fracture risk index had the strongest association with actual fracture status (AUC = 0.75, OR = 3.19), followed by strength (AUC = 0.74, OR = 2.84) and axial/shearing stiffness (AUC = 0.56-0.65, OR = 2.39-2.49). Femoral bending stiffness had the weakest association (AUC = 0.48-0.69, OR = 1.42-2.09). We concluded that periosteal expansion may be adequate to maintain femoral bending stiffness among elderly women, but it may not help preserve strength and reduce hip fracture risk.


Nifedipine and its indications in obstetrics and gynecology.
To review studies and investigations regarding the safety and efficacy of nifedipine. We reviewed the published literature on calcium channel blockers and their pharmacology and therapeutic applications in obstetrics and gynecology. We paid particular attention to methods of animal research and recent clinical evaluations. The dihydropyridine group of calcium channel blockers (type II calcium blockers) and, specifically, nifedipine are safe for use in pregnancy. They have little teratogenic or fetotoxic potential. Nifedipine's mechanism of action is through smooth-muscle relaxation secondary to blockage of the slow calcium channels into the cells. In vivo, there is minimal effect on the cardiac conducting system. Multiple studies in women have demonstrated the effectiveness and safety of nifedipine as an antihypertensive. Therapeutic doses range from 10-30 mg orally every 6-8 hours. For acute control of hypertension, 10 mg of sublingual nifedipine may be used. Nifedipine is as effective as beta-mimetics in decreasing uterine activity. As a tocolytic agent, it is more effective as there are fewer patients who have to discontinue nifedipine because of side effects. The side effects of nifedipine include flushing, headache, or, rarely, hypotension in the hypovolemic patient. Nifedipine has potential and theoretical indications for dysmenorrhea and bladder irritability.


Electrical and metabolic activity of suprachiasmatic nucleus neurons in hamster hypothalamic slices.
Single unit neuronal activity and glucose utilization were studied in the suprachiasmatic nucleus (SCN) in hypothalamic slices from the golden hamster brain in vitro. An apparent circadian rhythm was observed both in SCN single unit activity and in glucose utilization. These observations indicate that the brain slice method is useful for the analysis of pacemaker function in hamster SCN.


Bis(1-methyl-imidazole)[meso-α,α,α,α-tetra-kis(o-nicotinamido-phen-yl)porphinato]iron(II)-1-methyl-imidazole-tetra-hydro-furan (1/1/1.5).
In the title compound, [FeII(C68H44N12O4)(C4H6N2)2]·C4H6N2·1.5C4H8O, the central FeII ion is coordinated by four pyrrole N atoms of the porphyrin core and two N atoms of the 1-methyl-imidazole ligands in the axial sites. One 1-methyl-imidazole and one and a half tetra-hydro-furan solvent mol-ecules are also present in the asymmetric unit. The complex exhibits a near planar porphyrin core conformation, in which the iron centre is slightly displaced towards the hindered porphyrin side (0.01 Å). The average Fe-Np (Np refers to the pyrrole nitro-gen atoms in the porphyrin) bond length is 1.990 (9) Å, and the axial Fe-NIm (NIm refers to the imidazole nitro-gen atoms) bond lengths are 1.993 (3) and 2.004 (3) Å. The dihedral angle between the two coordinated 1-methyl-imidazole planes is 56.6 (2)°. The dihedral angles between the 1-methyl-imidazole planes and the planes of the closest Fe-Np vector are 16.8 (2) and 39.8 (2)°. N-H⋯N and N-H⋯O inter-actions are observed in the crystal structure.


The emerging role of real-world data in advanced breast cancer therapy: Recommendations for collaborative decision-making.
Among stakeholders and decision-makers in advanced breast cancer, the demand for insights from real-world data (RWD) is increasing. Although RWD can be used to support decisions throughout different stages of a breast cancer drug's life cycle, barriers exist to its use and acceptance. We propose a collaborative approach to generating and using RWD that is meaningful to multiple stakeholders, and encourage frameworks toward international guidelines to help standardize RWD methodologies to achieve more efficient use of RWD insights.


Novel method of breaking down barriers in the provision of menopause care in Ireland.
A novel method of providing education and support to GP's was developed. The goal was to create a rapidly accessed peer advisory community to empower GP HRT prescribing. A core group of doctors with special expertise in HRT were assembled on a GP interest group on the Telegram messaging platform. It is called 'HRT prescribers', an educational community with entrance by peer invitation. Most are GPs and number between 800 and 1000. Members post clinical questions and receive evidence-based responses to their dilemmas. A survey of members was overwhelmingly positive. 98% agreed the group empowered them to be confident and feel supported in their HRT prescribing. 90% agreed the group helped improve access to HRT for women who needed it in their practice. This project developed, with the cooperation of specialists, a cost-effective rapid method of educating and empowering GP's to be supported to safely treat their patients in their menopause transition. With further support and development, we believe it is the model that could be adopted in many countries.


Mechanical Ventilation During Resuscitation: How Manual Chest Compressions Affect a Ventilator's Function.
Guidelines for resuscitation recommend positive-pressure ventilation with a fixed ventilation rate as provided by an automated transport ventilator during cardiopulmonary resuscitation (CPR) with a secured airway. We investigated the influence of manual chest compressions (CC) on the accuracy of ventilator presets and the quality of CC with intermittent positive-pressure ventilation (IPPV), bilevel ventilation (BiLevel), and the novel ventilation mode chest compression synchronized ventilation (CCSV) in a simulation model. Ninety paramedics performed continuous CC for 2 min on a modified advanced life support mannequin with a realistic lung model. IPPV, BiLevel, and CCSV were applied in a randomized order. CCSV is a novel type of pressure-controlled ventilation with short insufflations synchronized with CC, which are stopped before decompression begins. The ventilator presets (tolerance range) were IPPV Vt = 450 (400-500) ml, PEEP = 0 hPa, f = 10/min; BiLevel Pinsp = 19 (17.1-20.9) hPa, PEEP = 5 hPa, f = 10/min; CCSV Pinsp = 60 (54-66) hPa, PEEP = 0 hPa, Tinsp = 205 ms, f = CC rate. Preset values were compared with the measured results. Values were defined as correct within a tolerance range. Quality of CC was evaluated using ERC guidelines (depth >50 mm, CC rate 100-120/min). Median (25th/75th percentiles) IPPV V t = 399 (386/411) ml, BiLevel Pinsp = 22.0 (19.7/25.6) hPa, and CCSV Pinsp = 55.2 (52.6/56.7) hPa. Relative frequency of delivering correct ventilation parameters according to ventilation mode: IPPV = 40 (0/100)% vs. BiLevel = 20 (0/100)%, p = 0.37 and vs. CCSV = 71 (50/83)%, p < 0.02. Pinsp was too high in BiLevel = 80 (0/100)% vs. CCSV = 0(0/0)%, p < 0.001. CC depth: IPPV 56 (48/63) mm, BiLevel 57 (48/63) mm, CCSV 60 (52/67) mm; CC rate: IPPV 117 (105/124)/min, BiLevel 116 (107/123)/min, CCSV 117 (107/125)/min. When compared to IPPV and BiLevel, CCSV works best with preset values, without exceeding the upper pressure preset during simulated CPR. Quality of CC is not negatively affected by any of the ventilation patterns. Parts of this study were supported by Weinmann Emergency Medical Technology GmbH + Co.KG.


"A square peg into a round hole": a modified rhomboid flap and its clinical application.
Two modifications to the classic design of the rhomboid flap are described. Firstly, no attempt is made to engineer a rhomboid defect and, secondly, the flap is made smaller than the defect to be reconstructed. The advantages of these modifications are discussed and their application in 175 reconstructions is reported.


Are specific learning disorders truly specific, and are they disorders?
Specific learning disorders, such as dyslexia and dyscalculia, are frequently studied to inform our understanding of cognitive development, genetic mechanisms and brain function. In this Opinion Paper, we discuss limitations of this research approach, including the use of arbitrary criteria to select groups of children, heterogeneity within groups and overlap between domains of learning. By drawing on evidence from cognitive science, neuroscience and genetics, we propose an alternative, dimensional framework. We argue that we need to overcome the problems associated with a categorical approach by taking into account interacting factors at multiple levels of analysis that are associated with overlapping rather than entirely distinct domains of learning. We conclude that this research strategy will allow for a richer understanding of learning and development.


Erratum: Perinatal Management and Outcomes of Pregnancy Following Sheehan Syndrome: A Case Report and Literature Review: Erratum.
[This corrects the article DOI: 10.1097/FM9.0000000000000092.].


Evaluation of 169Yb decay data.
This evaluation of the complete decay scheme of 169Yb sums up the recent measurements carried out during an international exercise in which 11 laboratories were involved, and also takes into account other independent experiments. As a result of the numerous high-quality measurements available, the decay scheme is shown to be highly consistent. The half-life is determined to be 32.018 (5)d, and the emission probabilities of the two reference gamma lines of 198 and 307 keV are recommended to be 35.93 (12)% and 10.046 (45)%, respectively.


Immunocytochemical localization of GABA in neurons projecting to the ventrolateral nucleus of the solitary tract.
To determine the origin of gamma-aminobutyric acidergic (GABAergic) input to the ventrolateral solitary tract nucleus (vlnTS), we used a double-labeling procedure for retrogradely transported horseradish peroxidase (HRP) and the immunocytochemical localization of GABA. Following HRP injections into the vlnTS, double-labeled neurons were found within the Bötzinger Complex. We conclude that these double-labeled cells are the inhibitory Bötzinger neurons and that GABA is a likely transmitter in this respiratory nucleus.


Determination of feed forces to improve process understanding of Fused Deposition Modeling 3D printing and to ensure mass conformity of printed solid oral dosage forms.
Fused Deposition Modeling is a suitable technique for the production of personalized solid oral dosage forms. For widespread application, it is necessary to be able to print a wide range of different formulations to address individual therapeutic needs. Due to the complexity of formulation composition (e.g., due to different compounds, excipients for enhancement of release and mechanical properties) and limited mechanical understanding, determination of suitable printing parameters is challenging. To address this challenge, we have developed a feed force tester using a Texture Analyser setup that mimics the actual printing process. Feed force data were compared to the mass of tablets printed from technical materials as well as pharmaceutical filaments containing ketoconazole at high drug loads of 20% and 40% and polyvinyl alcohol. By determining a feed force limit for the 3D printer from feed force data of several formulations printed, it was possible to specify the operable printing range, where printing is reproducible and printed mass corresponds the target mass. Based on these results, rational optimization of the printing process in terms of speed, time and temperature for different materials and formulations is possible.


Determination of lonazolac and its hydroxy and O-sulfated metabolites by on-line sample preparation liquid chromatography with fluorescence detection.
A reliable method, which can be used for the determination of lonazolac and its hydroxylated and O-sulfated metabolites in cell culture media with methyllonazolac as the internal standard is described. The procedure employs on-line sample enrichment using a BioTrap 500 MS (20 x 4 mm I.D.) extraction pre-column and subsequent gradient separation on an Xterra MS C18-HT (100 x 3 mm I.D., 3.5 microm particles) analytical column in the back-flush mode. Signal monitoring was done by measurement of fluorescence responses at 273 nm for excitation and 385 nm for emission. Structural identity of analyte peaks was confirmed by liquid chromatography coupled to mass spectroscopy (LC-MS-MS) using an electrospray ionization (ESI) source in the selected reaction monitoring (SRM) mode. Mean recoveries of lonazolac, hydroxylonazolac and lonazolac sulfate, respectively, from the biological matrix were 104.2 +/- 3.5, 96.7 +/- 2.2, and 100.9 +/- 3.5%. The limit of detection (LOD) for the three compounds was about 5 ng/ml using a total sample volume of only 50 microl. Linearity of signal responses versus concentration for all three analytes was accomplished in the range 10-600 ng/ml. The mean values of the coefficients of variation (CV) for quality control samples measured in duplicate at three different days at the 10, 40, 100, and 400 ng/ml level were 4.46 +/- 1.15, 3.94 +/- 2.13 and 4.79 +/- 2.07% for lonazolac, hydroxylonazolac and lonazolac sulfate. The target analytes were sufficiently stable at both storage and sample preparation conditions because no substantial deviations between analyte concentrations measured before and after subsequently performed freeze and thaw cycles were observed.


Proteinchemical characterization of three structurally distinct domains along the protofilament unit of desmin 10 nm filaments.
Limited chymotryptic cleavage of soluble chicken gizzard desmin protofilaments allows the characterization of three structurally distinct domains. A surface-exposed very basic amino-terminal region (the headpiece) with an amino acid sequence excluding alpha-helical organization (7.5 kd) is separated from the perhaps globular carboxy-terminal 48 residues (the tailpiece) by a distinctly different middle domain of approximately 330 residues. This 38 kd domain is very rich in alpha-helix (at least 83%), and electron microscopy reveals a thin rod with a length of 500 +/- 50 A. Amino acid sequence data also show that the rod domain is interrupted by a nonhelical portion. An alpha-helical array is able to form a coiled-coil spanning the carboxy-terminal half of the 38 kd domain. The alpha-type diffraction pattern of 10 nm filaments arises from a coiled-coil conformation displayed through most but not all of the middle domain of the protofilaments.


THESEUS 1, FERONIA and relatives: a family of cell wall-sensing receptor kinases?
The plant cell wall provides form and integrity to the cell as well as a dynamic interface between a cell and its environment. Therefore mechanisms capable of policing changes in the cell wall, signaling cellular responses including those that would feedback regulate cell wall properties are expected to play important roles in facilitating growth and ensuring survival. Discoveries in the last few years that the Arabidopsis THESEUS 1 receptor-like kinase (RLK) may function as a sensor for cell wall defects to regulate growth and that its relatives FERONIA and ANXURs regulate pollen tube integrity imply strongly that they play key roles in cell wall-related processes. Furthermore, FERONIA acts as a cell surface regulator for RAC/ROP GTPases and activates production of reactive oxygen species which are, respectively, important molecular switches and mediators for diverse processes. These findings position the THESEUS 1/FERONIA family RLKs as surface regulators and potential cell wall sensors capable of broadly and profoundly impacting cellular pathways in response to diverse signals.


Ent-pimara-8(14), 15-dien-19-oic acid isolated from the roots of Aralia cordata inhibits induction of inflammatory mediators by blocking NF-kappaB activation and mitogen-activated protein kinase pathways.
Macrophages play central roles in the innate immune system. The roots of Aralia cordata are widely used in Oriental medicine as a remedy for arthritis. During our program to screen medicinal plants for potential anti-inflammatory compounds, ent-pimara-8(14), 15-dien-19-oic acid (pimaradienoic acid; PA) was isolated from the roots of A. cordata. We examined the effect of PA on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. PA was found to significantly inhibit the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and interleukin-6 (IL-6), as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and IL-6. Furthermore, we examined whether mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K) signaling pathways are involved in LPS-induced RAW 264.7 cells. We found that a p38 inhibitor (SB203580) and an ERK 1/2 inhibitor (PD98059) significantly affected LPS-induced IL-6 production. In contrast, a JNK 1/2 inhibitor (SP600125) and PI3K inhibitor (wortmannin or LY294002) did not block the induction of IL-6 production by LPS. The LPS-induced phosphorylation of p38 MAPK and extracellular signal-regulated kinase 1/2 (ERK1/2) was inhibited by PA, but not the phosphorylation of JNK 1/2 and AKT (Ser473). Moreover, PA suppressed I kappaB alpha degradation, NF-kappaB activation and luciferase activity. These results suggest that PA isolated from A. cordata has a potential regulatory effect on inflammatory iNOS, COX-2 and IL-6 expression through blockade of the phosphorylation of MAPKs following I kappaB alpha degradation and NF-kappaB activation.


Massive impalement wound of the chest. A case report.
A 29-year-old man sustained an impalement wound of the right side of the chest with a 6 foot long, 4 by 4 inch wooden post during a high-speed automobile accident. The post entered the right side of the chest anteriorly and exited posteriorly. The great vessels of the chest were spared, but the right lung was lacerated and contused. Removal of the post, treatment of pulmonary parenchymal damage, and reconstruction of the two large chest wall defects presented problems in management. Rapid transport of the patient to the hospital, effective emergency treatment, surgical repair of the chest injury, and appropriate supportive measures contributed to his survival.


Effects of parentage, prior fruit set and pollen load on fruit and seed production in Campanula americana L.
We conducted a controlled crossing experiment to examine the effects of maternal and paternal parentage, the size of the pollen load, and prior fruit production on the proportion of flowers that set fruit, seed number per fruit and seed weight in a natural population of Campanula americana. Effects due to the maternal parent were large for all measures of fruit and seed production, while the paternal parent had a significant effect only upon mean seed weight. As the number of prior fruits on the maternal plant increased the probability that a flower would produce a mature fruit, the number of seeds per fruit, and total seed weight per fruit all decreased. We found no effect of the size of the pollen loads used in this study on fruit or seed production. These results are consistent with those of other studies that suggest in natural plant populations maternal effects, especially environmental maternal effects, can have an overwhelming effect on fruit and seed production and on seed characteristics.


Light and electron microscopic analysis of bovine embryos derived by in vitro and in vivo fertilization.
The aim of this study was to examine the morphological features of in vitro fertilization-derived bovine embryos (IVt) and compare them with those of in vivo fertilization-derived (IVv) ones. Light microscopy showed the blastomeres of IVv embryos to have a tendency to be rounder up to the 16-cell stage and to form a more compact mass at the morula stage than in their IVt counterparts. Electron microscopy revealed that as development progressed, some structures (such as microvilli, phagosomes/lysosomes, intercellular junctions and intermediate filaments) appeared or reappeared while others (such as lipid droplets, vesicles with flocculent materials, cortical granules, nuclear annulate lamellae, nuclear envelope blebs) decreased or disappeared. These changes were observed about one cell stage later in IVt than in IVv embryos. Other structures were present in both IVt and IVv embryos, and they morphologically either changed (such as mitochondria, endoplasmic reticulum, Golgi apparatus and nucleoli) or did not change (cytoplasmic annulate lamellae). In contrast to previous reports, vacuolated nucleoli in both IVt and IVv embryos were observed from the two-cell stage. It was concluded that (1) the development of bovine embryos to the blastocyst stage is like that of other mammalian embryos; (2) IVt and IVv embryos did not show consistent differences in morphological features; (3) although IVt embryos appear delayed in development, this may reflect different definition of age in vivo and in vitro.


Pontine Infarct Presenting with Atypical Dental Pain: A Case Report.
Orofacial pain' most commonly occurs due to dental causes like caries, gingivitis or periodontitis. Other common causes of 'orofacial pain' are sinusitis, temporomandibular joint(TMJ) dysfunction, otitis externa, tension headache and migraine. In some patients, the etiology of 'orofacial pain' remains undetected despite optimal evaluation. A few patients in the practice of clinical dentistry presents with dental pain without any identifiable dental etiology. Such patients are classified under the category of 'atypical odontalgia'. 'Atypical odontalgia' is reported to be prevalent in 2.1% of the individuals. 'Atypical orofacial pain' and 'atypical odontalgia' can result from the neurological diseases like multiple sclerosis, trigeminal neuralgia and herpes infection. Trigeminal neuralgia has been frequently documented as a cause of 'atypical orofacial pain' and 'atypical odontalgia'. There are a few isolated case reports of acute pontine stroke resulting in 'atypical orofacial pain' and 'atypical odontalgia'. However, pontine stroke as a cause of atypical odontalgia is limited to only a few cases, hence prevalence is not established. This case is one, where a patient presented with acute onset atypical dental pain with no identifiable dental etiology, further diagnosed as an acute pontine infarct on neuroimaging. A 40 years old male presented with acute onset, diffuse teeth pain on right side. Dental examination was normal. Magnetic resonance imaging(MRI) of the brain had an acute infarct in right pons near the trigeminal root entry zone(REZ). Pontine infarct presenting with dental pain as a manifestation of trigeminal neuropathy, has rarely been reported previously. This stresses on the importance of neuroradiology in evaluation of atypical cases of dental pain.


Declining use of radiotherapy in stage I and II Hodgkin's disease and its effect on survival and secondary malignancies.
Concerns regarding long-term toxicities have led some to withhold radiotherapy (RT) for the treatment of Stage I and II Hodgkin's disease (HD). The present study was undertaken to assess the use of RT for HD and its effect on overall survival and the development of secondary malignancies. The present study included data from the Surveillance, Epidemiology, and End Results database from patients aged ≥ 20 years who had been diagnosed with Stage I or II HD between 1988 and 2006. Overall survival was estimated using the Kaplan-Meier method, and the Cox multivariate regression model was used to analyze trends. A total of 12,247 patients were selected, and 51.5% had received RT. The median follow-up for the present cohort was 4.9 years, with 21% of the cohort having >10 years of follow-up. Between 1988 and 1991, 62.9% had undergone RT, but between 2004 and 2006, only 43.7% had undergone RT (p < .001). The 5-year overall survival rate was 76% for patients who had not received RT and 87% for those who had (p < .001). The hazard ratio adjusted for other variables in the regression model showed that patients who had not undergone RT (hazard ratio, 1.72; 95% confidence interval, 1.72-2.02) was associated with significantly worse survival compared with patients who had received RT. The actuarial rate of developing a second malignancy was 14.6% vs. 15.0% at 15 years for those who had and had not undergone RT, respectively (p = .089). The present study is one of the largest studies to examine the role of RT for Stage I and II HD. Our results revealed a survival benefit with the addition of RT with no increase in the development of secondary malignancies compared with patients who had not received RT. Furthermore, the present nationwide study revealed a >20% absolute decrease in the use of RT from 1988 to 2006.


Effect of Strontium Substituted Tetracalcium Phosphate Cement on Proliferation and Mineralization Potential in Human Dental Pulp Stem Cells.
The aim of this study was to comparatively evaluate the proliferation, differentiation and mineralization inducing potential of strontium incorporated tetracalcium phosphate cement (STTCP) and mineral trioxide aggregate (MTA) on human dental pulp stem cells (hDPSCs). hDPSCs were cultured from freshly extracted human premolar teeth. Cement discs (5mm×3mm) were prepared using MTA and STTCP. hDPSCs were exposed to the test materials and grouped as follows: 1. MTA; 2. STTCP; 3. NC: Media alone (negative control; 4.PC: hDPSCs with osteogenic medium (positive control); Cell viability and proliferation was evaluated using MTT and trypan blue assays for 0, 7 and 14 day intervals. Odontoblastic differentiation potential were evaluated using ALP assay followed by degree of mineralization using Alizarin Red test and Osteopontin expression on day 7,14 and 21. Quantitative analysis were done by evaluating the absorbance and expressed as optical density. Statistical analysis was performed using Kruskal Wallis test followed by Friedman test (P<0.05). MTA showed higher percentage of cell proliferation than STTCP at day 7 and 14. ALP assay revealed higher significant value for STTCP on day 7 and 14. STTCP exhibited intense staining and similar mineralization potential with MTA at all time periods. Osteopontin expression was exhibited by both MTA and STTCP on all days (P<0.05). STTCP promoted cell viability and enhanced mineralization and odontogenic differentiation potential on hDPSCs similar to MTA. STTCP has a potential to be an alternative therapeutic agent for pulp capping procedures.


Self-selection of calcium during pregnancy and lactation in rats.
A modification of the two-choice diet paradigm was used to determine whether female rats would self-select high levels of calcium at different times in a reproductive episode. A 2 X 2 X 5 (reproductive state X diet X time) design was used to compare the relative calcium intake of impregnated and non-impregnated rats given ad lib access to a calcium deficient or calcium sufficient diet together with demineralised water and a 2.4% calcium lactate solution over five weeks. For the impregnated groups, this time period comprised three weeks of pregnancy and two weeks of lactation. The results showed that during lactation the impregnated animals maintained on the calcium deficient diet consumed a greater amount of calcium solution relative to water intake than any other group. This increase in relative calcium solution intake occurred early in lactation and appeared not to correlate with increases in milk production.


An ultrastructural study of the intimal hyperplasia in healing microarterial anastomoses.
The purpose of the study was to investigate the ultrastructure of intimal hyperplastic cells. End-to-end microarterial anastomoses were studied in a rabbit free-tissue-transfer model. There were five experimental groups, with 1, 3, 7, 14, or 28 days follow-up. At sacrifice the anastomoses were tested for patency and then examined by light and electron microscopy. At days 1 and 3 the repaired intima was covered with macrophages and extravasated erythrocytes. At day 7 spindle-shaped fibroblasts with copious rough endoplasmic reticulum were seen. Some of these cells also contained pinocytotic vesicles, filaments with focal densities, and subplasmalemmal attachment sites, the features of smooth muscle cells. At day 14, more cells contained smooth muscle features and these features were also more pronounced. These young myofibroblasts were plumper than adjacent fibroblasts. At day 28 mature myofibroblasts with a full complement of organelles were present. The results, therefore, supported the hypothesis that myofibroblasts are present in the intimal hyperplasia of healing microarterial anastomoses.


Quality of life in patients with benign anorectal disorders.
Benign proctological conditions are very common in Western civilization. However, to date quality of life in these patients has not been evaluated comprehensively. The aim of this study was to investigate whether the Gastrointestinal Quality of Life Index (GIQLI) is a useful instrument for measuring quality of life in these patients, and subsequently to establish baseline values for different anorectal disorders. The questionnaire was completed by 325 consecutive patients (182 men; mean age 49 years) seen at the proctology outpatient clinic. For further analysis patients were classified into nine subgroups according to the primary diagnosis: group 1, haemorrhoids (n=96); group 2, anal fissure (n=38); group 3, fistula in ano (n=22); group 4, severe constipation (n=14); group 5, faecal incontinence (n=35); group 6, symptomatic anterior rectocele (n=12); group 7, perianal abscess (n=7); group 8, perianal thrombosis (n=7); and group 9, miscellaneous conditions (e.g. skin tags, anal papillomas, mild constipation, rectal polyps) (n=94). The GIQLI scores were compared between the subgroups. In addition the GIQLI scores of age-matched healthy controls, derived from data in the literature, were compared with the patients' scores. The mean GIQLI score for all patients was 113 (78.5 per cent of the maximum score of 144). Mean scores for the nine diagnostic subgroups were: group 1, 120; group 2, 104; group 3, 119; group 4, 94; group 5, 93; group 6, 112; group 7, 115; group 8, 129; and group 9, 117. Age-matched controls from a series published previously had a significantly higher GIQLI score compared with all patients (P < 0.0001). However, only the subgroups of patients with miscellaneous conditions, fissures, severe constipation and faecal incontinence had a significantly poorer quality of life than age-matched healthy individuals. The GIQLI is a valuable instrument for measuring quality of life in patients with benign anorectal disorders. Although certain diseases do not seem to affect quality of life profoundly, certain subgroups of patients, most notably those with incontinence and severe constipation, are extremely compromised. Severely constipated individuals exhibit the same poor quality of life as patients with faecal incontinence.


Use of Artificial Intelligence for the Interpretable Prediction of the Pathologic Diagnosis and Molecular Abnormalities of Flat Urothelial Lesions.
Flat urothelial lesions are important because of their potential for carcinogenesis and development into invasive urothelial carcinomas. However, it is difficult for pathologists to detect early flat urothelial changes and accurately diagnose flat urothelial lesions. To predict the pathologic diagnosis and molecular abnormalities of flat urothelial lesions from pathologic images, artificial intelligence with an interpretable method was used. Next-generation sequencing on 110 hematoxylin and eosin-stained slides of normal urothelium and flat urothelial lesions, including atypical urothelium, dysplasia, and carcinoma in situ, detected 17 types of molecular abnormalities. To generate an interpretable prediction, a new method for segmenting urothelium and a new pathologic criteria-based artificial intelligence (PCB-AI) model was developed. κ Statistics and accuracy measurements were used to evaluate the ability of the model to predict the pathologic diagnosis. The likelihood ratio test was performed to evaluate the logistic regression models for predicting molecular abnormalities. The diagnostic prediction of the PCB-AI model was almost in perfect agreement with the pathologists' diagnoses (weighted κ = 0.98). PCB-AI significantly predicted some molecular abnormalities in an interpretable manner, including abnormalities of TP53 (P = 0.02), RB1 (P = 0.04), and ERCC2 (P = 0.04). Thus, this study developed a new method of obtaining accurate urothelial segmentation, interpretable prediction of pathologic diagnosis, and interpretable prediction of molecular abnormalities.


Neutrophil depletion fails to improve neurologic outcome after cardiac arrest in dogs.
We tested the hypothesis that polymorphonuclear leukocytes (neutrophils) contribute to morbidity and mortality in a canine model of cardiac arrest-induced central nervous system ischemia. Circulating neutrophils were depleted by administration of a neutrophil-specific sheep immune serum before a ten-minute cardiac arrest in ten experimental animals. Ischemic damage measured by a neurologic deficit score in these animals was compared with that in 12 animals that received either vehicle control or nonimmune sheep serum. Animals receiving immune serum averaged 89% depletion of neutrophils immediately after resuscitation (neutrophils +/- SEM: 703 +/- 123/mm3 after antiserum versus 6,384 +/- 1,171/mm3 before immune serum) and 70% depletion over the first three hours after resuscitation. Neurologic deficit scores assessed at one, two, six, 12, and 24 hours after arrest did not vary between depleted dogs and controls. Overall survival time in neutrophil-depleted dogs was less than in controls (15.5 +/- 1.3 versus 19.5 +/- 1.3 hours; P = .04). These results suggest that neutrophils may not contribute to clinically important central nervous system dysfunction after resuscitation from a ten-minute cardiac arrest.


[Results of application of endolymphatic polychemotherapy and local supra-high frequency hyperthermia in comprehensive treatment of rectal cancer].
The treatment efficacy of a widespread cancer of recti using neoadjuvant endolymphatic polychemotherapy and local suprahigh frequency hyperthermy in a radically operated patients was studied up. In patients without regional metastases the five-year survival index have increased from 63 to 81%, and the recurrencies occurrence frequency have lowered from 20 to 10%. The method proposedhas small efficacy in patients with metastases in regional lymph nodes.


miR-524-5p of the primate-specific C19MC miRNA cluster targets TP53IPN1- and EMT-associated genes to regulate cellular reprogramming.
Introduction of the transcription factors Oct4, Sox2, Klf4, and c-Myc (OSKM) is able to 'reprogram' somatic cells to become induced pluripotent stem cells (iPSCs). Several microRNAs (miRNAs) are known to enhance reprogramming efficiency when co-expressed with the OSKM factors. The primate-specific chromosome 19 miRNA cluster (C19MC) is essential in primate reproduction, development, and differentiation. miR-524-5p, a C19MC member, is highly homologous to the reprogramming miR-520d-5p; we also reported that miR-524-5p was expressed in iPSCs but not mesenchymal stem cells (MSCs). This study aimed to elucidate possible contributions of miR-524-5p to the reprogramming process. A miR-524-5p precursor was introduced into human fibroblast HFF-1 in the presence of OSKM, and the relative number of embryonic stem cell (ESC)-like colonies that stained positively with alkaline phosphatase (AP) and Nanog were quantified to determine reprogramming efficiency. A miR-524-5p mimic was transfected to MSCs to investigate the effects of miR-524-5p on TP53INP1, ZEB2, and SMAD4 expression by real-time polymerase chain reaction (PCR) and Western blot. Direct gene targeting was confirmed by luciferase activity. A phylogenetic tree of TP53INP1 was constructed by the Clustal method. Contribution of miR-524-5p to cell proliferation and apoptosis was examined by cell counts, BrdU, MTT, and cell death assays, and pluripotency gene expression by real-time PCR. Co-expressing the miR-524 precursor with OSKM resulted in a two-fold significant increase in the number of AP- and Nanog-positive ESC-like colonies, indicating a role for miR-524-5p in reprogramming. The putative target, TP53INP1, showed an inverse expression relationship with miR-524-5p; direct TP53INP1 targeting was confirmed in luciferase assays. miR-524-5p-induced TP53INP1 downregulation enhanced cell proliferation, suppressed apoptosis, and upregulated the expression of pluripotency genes, all of which are critical early events of the reprogramming process. Interestingly, the TP53INP1 gene may have co-evolved late with the primate-specific miR-524-5p. miR-524-5p also promoted mesenchymal-to-epithelial transition (MET), a required initial event of reprogramming, by directly targeting the epithelial-to-mesenchymal transition (EMT)-related genes, ZEB2 and SMAD4. Via targeting TP53INP1, ZEB2, and SMAD4, miR-524-5p contributes to the early stage of inducing pluripotency by promoting cell proliferation, inhibiting apoptosis, upregulating expression of pluripotency genes, and enhancing MET. Other C19MC miRNAs may have similar reprogramming functions.


The potential of the use of deep eutectic solvents and amino acid-based ionic liquids to enhance the chiral discrimination ability of different chiral selectors in capillary electrophoresis.
The effect of the combined use of amino acid-based ionic liquids (AAILs) and deep eutectic solvents (DESs) with either cyclodextrin- (CD) or cyclofructan- (CF) based chiral selectors for the chiral separation of amphetamine derivatives was investigated in the present study. A non-significant improvement in enantiomeric separation of target analytes was observed when AAILs were combined with either CF or CD. On the other side, a markedly improved chiral separation of enantiomers was obtained using the dual carboxymethyl-β-cyclodextrin/DES system, highlighting the existence of a synergistic effect. After the addition of 0.5% v/v of choline chloride-ethylene glycol, the resolution of the enantiomers of amphetamine, methamphetamine and 3-fluorethamphetamine, increased from 1.4, 1.1, 1.0 to 1.8, 1.8, and 1.5 min, and the analysis times increased from 19.54, 20.48, 18.71 to 35.71, 35.78 and 32.90 min, respectively. This was not the case for the CF/DES dual system, in which the separation of amphetamines worsened, indicating an antagonistic effect. In conclusion, DESs are a very promising additive in capillary electrophoresis that can improve the separation of chiral molecules in combination with CDs but not CFs.


Prostate cancer research in China.
Prostate cancer (PCa) research in China has been on a rocketing trend in recent years. The first genome-wide association study (GWAS) in China identified two new PCa risk associated single nucleotide polymorphisms (SNPs). Next generation sequencing is beginning to be used, yielding novel findings: gene fusions, long non-coding RNAs and other variations. Mechanisms of PCa progression have been illustrated while various diagnosis biomarkers have been investigated extensively. Personalized therapy based on genetic factors, nano-medicine and traditional Chinese medicine has been the focus of experimental therapeutic research for PCa. This review intends to shed light upon the recent progress in PCa research in China and points out the possible breakthroughs in the future.


Advances in metabolic modeling of oleaginous microalgae.
Production of biofuels and bioenergy precursors by phototrophic microorganisms, such as microalgae and cyanobacteria, is a promising alternative to conventional fuels obtained from non-renewable resources. Several species of microalgae have been investigated as potential candidates for the production of biofuels, for the most part due to their exceptional metabolic capability to accumulate large quantities of lipids. Constraint-based modeling, a systems biology approach that accurately predicts the metabolic phenotype of phototrophs, has been deployed to identify suitable culture conditions as well as to explore genetic enhancement strategies for bioproduction. Core metabolic models were employed to gain insight into the central carbon metabolism in photosynthetic microorganisms. More recently, comprehensive genome-scale models, including organelle-specific information at high resolution, have been developed to gain new insight into the metabolism of phototrophic cell factories. Here, we review the current state of the art of constraint-based modeling and computational method development and discuss how advanced models led to increased prediction accuracy and thus improved lipid production in microalgae.


Hormone-replacement therapy and the risk of breast cancer.
At least 30 epidemiologic studies designed to identify an association between hormone-replacement therapy and breast cancer risk have been published since 1974. In general, the design, quality, and analytic strategies used in these studies have improved over the years, and the number of subjects in each study has increased. The results from studies published prior to 1985 can be summarized as showing a small increase in the risk of breast cancer after many years of estrogen use. Even this tentative conclusion is debatable, however, since many rigorous studies showed no association between estrogen use and breast cancer. This review will summarize the earlier findings and emphasize several large, recent studies that add at least two new dimensions to this body of research; they provide data from Europe and on the addition of progestins to the therapeutic regimen. This review indicates the following: 1. Analyses of ever versus never use of estrogen-replacement therapy show no association with breast cancer risk. 2. Duration of estrogen-replacement therapy affects risk. Based on studies in the United States, a relative risk of about 1.5 may be reached after 15 or more years of use. 3. The increase in risk after long-duration hormone use is present for women with either a natural or a surgical menopause. 4. European studies exhibit higher risks after shorter durations of hormone use than do US studies. 5. The type of estrogen used and the addition of progestins to hormone-replacement therapy may alter the risk of breast cancer. Data that substantiate these points are reviewed and placed in context with hormonal theories of carcinogenesis.


Prevention of urethral fibrosis induced by transforming growth factor beta 1 using selective Wnt/β-catenin signaling inhibitors in a rat model.
To determine the anti-fibrotic effects of Wnt/β-catenin signaling inhibitors on urethral stricture. Human fibroblasts were exposed to transforming growth factor beta 1 combined with various concentrations of Wnt/β-catenin inhibitors (ICG-001, IWR-1, and PRI-724), and cell proliferation and migration were evaluated. Urethral fibrosis was induced in male Sprague-Dawley rats by urethral injection of transforming growth factor beta 1 and co-treatement with inhibitors. Urethral tissues were harvested 2 weeks after the injection. The messenger ribonucleic acid and protein expression was examined for fibrosis markers Axin-1, collagen type 1, alpha smooth muscle actin, and β-catenin. Histological analysis of fibrosis and collagen deposition was also performed. Cell migration was ameliorated by ICG-001 and PRI-724. Protein and messenger ribonucleic acid expression of collagen type 1 and alpha smooth muscle actin in transforming growth factor beta 1-treated fibroblasts decreased in a concentration-dependent manner with the ICG-001 and PRI-724 treatments (P < 0.05). However, there were no significant changes with the IWR-1 treatment. Collagen type I and alpha smooth muscle actin messenger ribonucleic acid and protein expression were both significantly increased in the urethral tissues of rats with transforming growth factor beta 1-induced urethral fibrosis. Rats co-treated with ICG-001 or PRI-724 showed relatively mild fibrosis and significantly reduced collagen type I and alpha smooth muscle actin messenger ribonucleic acid and protein expression (P < 0.05). ICG-001 and PRI-724 significantly ameliorated urethral fibrosis induced by transforming growth factor beta 1 in rats. These results suggest that ICG-001 and PRI-724 can be developed as therapeutics for treating urethral stricture.


Coronary spastic angina is associated with insulin resistance - possible involvement of endothelial dysfunction.
In this study, we examined whether coronary spastic angina (CSA) is associated with insulin resistance. There is increasing evidence that insulin resistance is associated with endothelial dysfunction. Patients with CSA show endothelial dysfunction. The study participants include 111 CSA patients (81 men and 30 women, mean age 62±12 years) and 53 participants without CSA (24 men and 29 women, mean age 63±10 years), serving as the controls. The oral glucose tolerance test was performed, and anthropometric parameters, plasma glucose and insulin levels, lipid profiles, and other laboratory parameters were evaluated. Homeostasis model assessment of insulin resistance (HOMA-IR), Log HOMA-IR, the quantitative insulin sensitivity check index, the insulin sensitivity index, and insulin resistance 60-120 min after glucose load (log post-glucose-IR) were calculated as surrogate markers of insulin resistance. The number of men, the number of smokers, log post-glucose-IR, the insulin sensitivity index, and fasting plasma glucose levels were higher in CSA patients compared with controls (P=0.001, 0.001, 0.004, 0.012, and 0.013, respectively), whereas plasma high-density lipoprotein cholesterol levels were lower (P<0.001). Insulin resistance on glucose load (log post-glucose-IR), plasma high-density lipoprotein cholesterol levels, and smoking were significantly associated with CSA (r=0.225, P=0.004; r=-0.313, P<0.001; and r=0.258, P=0.001, respectively).


Purification of a phospholipase B inhibitor from Saccharomyces cerevisiae.
The phospholipase B activity of plasma membrane vesicles from Saccharomyces cerevisiae is inhibited by the 100 000 X g supernatant of mechanically disrupted yeast cells. A 1850-fold purification of the inhibitor activity was achieved by gel filtration, ion exchange chromatography with DEAE-cellulose and hydrophobic interaction chromatography with Octyl-Sepharose. SDS-polyacrylamide gel electrophoresis of the purified inhibitor revealed two main bands with an apparent Mr of 60 000 and 26 500. The phospholipase B activity was strongly reduced but not completely blocked by this preparation, while the lysophospholipase and transacylase reactions, which are catalyzed by the same membrane-bound enzymes (Witt, W. et al. (1984) Biochim. Biophys. Acta 795, 108-116), were not affected.


Vigorous physical activity and self-rated health during adolescence: A cross-sectional survey.
Despite the positive relationship between self-rated health and general physical activity, very little research has touched upon the relationship between self-rated health and vigorous physical activity. Such research will help to promote self-rated health among adolescents by addressing the close relationship between self-rated health and the components of physical activity. In this study, the relationship between self-rated health and vigorous physical activity among Chinese adolescents were analyzed. The current study was based on a collaborative survey conducted by the WHO in several nations, and the data generated by Health Behavior in School-aged Children every 4 years on health behavior were adopted. The school class was taken as a basic unit for sampling. Cluster sampling was performed systematically, and the possibility was proportional to the population. The sampling was conducted to collect typical cases. The class teachers were informed of the sampling activities, and they were to collect data on the students by distributing the questionnaires. The research included 116,828 respondents from 36 countries. Among them, 51.82% were girls and 48.18% were boys. A total of 98.54% of the respondents considered their health status as fair or above when completing the questionnaire, while 1.46% believed that their health status was poor. Moreover, more than 86% of the respondents participated in vigorous exercise more than weekly, and better self-health ratings were found among respondents who exercised more than weekly (once a week: OR = 1.95, CI: 1.86-2.04; two or three times a week: OR = 1.69, CIL: 1.63-1.76; four or six times a week: OR = 1.30, CI: 1.25-1.35). Certain respondents reported better results for self-rated health (4-6 h every week: OR = 1.36, CI: 1.30-1.43; 2 or 3 h every week: OR = 1.48, CI: 1.42-1.55; 1 h every week: OR = 1.64, CI: 1.57-1.72). In this study, empirical evidence is provided for the relationship between self-rated health and vigorous physical activity among adolescents. From the results, it can be observed that there is a positive relationship between self-rated health and vigorous physical activity among adolescents.


Association of body mass index with cognitive function in elderly hypertensive Japanese.
As hypertension, obesity, and leanness are reported to be associated with poor cognitive function, it is possible that obesity or leanness in hypertensive patients may also be associated strongly with poor cognitive function. We recruited 184 elderly hypertensive patients comprising 93 very elderly (aged >or=80 years) and 91 younger elderly (aged 61-79 years) subjects. A mini-mental state examination (MMSE) and 24-h ambulatory blood pressure monitoring (ABPM) were performed in all participants. Patients were classified as either lean, normal physique, or obese according to the body mass index (BMI) quartile. The prevalence of poor cognitive function, total MMSE score, and MMSE subscores were compared between the groups. The prevalence of poor cognitive function, total MMSE score, and MMSE subscore attention/calculation were significantly different between the groups both in the total study population and in the very elderly patients. The multiple logistic regression model showed that leanness was a significant determinant of poor cognitive function in both the total study population (odds ratio (OR) 2.54, 95% confidence interval (CI) 1.13-5.73, P = 0.02) and the very elderly patients (OR 3.94, 95% CI 1.31-11.82, P = 0.01). Obesity was not a significant determinant in either the total study population, very elderly, or younger elderly groups. While obesity in hypertensive elderly patients was not associated with poor cognitive function, leanness in hypertensive elderly patients was, especially in the very elderly.


Maintenance of a male-killing Wolbachia in Drosophila innubila by male-killing dependent and male-killing independent mechanisms.
Many maternally inherited endosymbionts manipulate their host's reproduction in various ways to enhance their own fitness. One such mechanism is male killing (MK), in which sons of infected mothers are killed by the endosymbiont during development. Several hypotheses have been proposed to explain the advantages of MK, including resource reallocation from sons to daughters of infected females, avoidance of inbreeding by infected females, and, if transmission is not purely maternal, the facilitation of horizontal transmission to uninfected females. We tested these hypotheses in Drosophila innubila, a mycophagous species infected with MK Wolbachia. There was no evidence of horizontal transmission in the wild and no evidence Wolbachia reduced levels of inbreeding. Resource reallocation does appear to be operative, as Wolbachia-infected females are slightly larger, on average, than uninfected females, although the selective advantage of larger size is insufficient to account for the frequency of infection in natural populations. Wolbachia-infected females from the wild-although not those from the laboratory-were more fecund than uninfected females. Experimental studies revealed that Wolbachia can boost the fecundity of nutrient-deprived flies and reduce the adverse effect of RNA virus infection. Thus, this MK endosymbiont can provide direct, MK-independent fitness benefits to infected female hosts in addition to possible benefits mediated via MK.


Pancreatic spasmolytic polypeptide (PSP): I. Preparation and initial chemical characterization of a new polypeptide from porcine pancreas.
A novel polypeptide, named Pancreatic Spasmolytic Polypeptide (PSP), was discovered in a side-fraction from the purification of porcine insulin. PSP was prepared by two different purification methods based on combinations of precipitations, anion-exchange and cation-exchange chromatography. The highest yield obtained, 52 mg PSP/kg pancreas, indicates that the content of PSP in porcine pancreas is about half the content of insulin. Both preparations appeared to be very pure as judged by basic disc electrophoresis, isoelectric focusing, analytical gel filtration and radioimmunoassays for various polypeptides known to be present in pancreas. The PSP molecule contains 106 amino acids (MW about 11 700). PSP is an acidic (pI 4.4), non-glycosylated protein without free N-terminal amino groups, and with high contents of proline and cystine. The high content of S-S bridges (7 per molecule), an unexpected low apparent MW determined by gel filtration, and a remarkable resistance towards treatment with trypsin and chymotrypsin, point to a compact structure of the PSP molecule.


Comparison of five-view and three-view cervical spine series in the evaluation of patients with cervical trauma.
The three-view trauma series has been the standard screening examination for patients with cervical spine trauma. We conducted a prospective study to determine if the addition of supine oblique views to the three-view series would improve detection of fractures, subluxations, dislocations, or locked facets. All patients over a two-year period with suspected cervical spine injury had a five-view series obtained (three-view series and supine oblique views), and selected high-risk patients underwent thin-section conventional tomography of the cervical spine. Films were interpreted separately by two radiologists and an emergency physician, and the tomography results were used as the gold standard for comparison. Thirty-three of 58 high-risk patients had one or more fractures, subluxation, or dislocation demonstrated on tomography. There were no fractures or dislocations detected on the five-view series that were not detected or suspected on the three-view series. In areas of the cervical spine reported to be better visualized by supine oblique views than three-view series, our results indicate that supine oblique views did not improve detection but did, in certain cases, allow more specific diagnosis of injuries. Our data do not support the routine use of supine oblique views in the initial radiographic evaluation of patients with cervical spine trauma.


Fat depot-specific gene signature and ECM remodeling of Sca1(high) adipose-derived stem cells.
Stem cell antigen-1 (Sca1 or Ly6A/E) is a cell surface marker that is widely expressed in mesenchymal stem cells, including adipose-derived stem cells (ASCs). We hypothesized that the fat depot-specific gene signature of Sca1(high) ASCs may play the major role in defining adipose tissue function and extracellular matrix (ECM) remodeling in a depot-specific manner. Herein we aimed to characterize the unique gene signature and ECM remodeling of Sca1(high) ASCs isolated from subcutaneous (inguinal) and visceral (epididymal) adipose tissues. Sca1(high) ASCs are found in the adventitia and perivascular areas of adipose tissues. Sca1(high) ASCs purified with magnetic-activated cell sorting (MACS) demonstrate dendrite or round shape with the higher expression of cytokines and chemokines (e.g., Il6, Cxcl1) and the lower expression of a glucose transporter (Glut1). Subcutaneous and visceral fat-derived Sca1(high) ASCs particularly differ in the gene expressions of adhesion and ECM molecules. While the expression of the major membrane-type collagenase (MMP14) is comparable between the groups, the expressions of secreted collagenases (MMP8 and MMP13) are higher in visceral Sca1(high) ASCs than in subcutaneous ASCs. Consistently, slow but focal MMP-dependent collagenolysis was observed with subcutaneous adipose tissue-derived vascular stromal cells, whereas rapid and bulk collagenolysis was observed with visceral adipose tissue-derived cells in MMP-dependent and -independent manners. These results suggest that the fat depot-specific gene signatures of ASCs may contribute to the distinct patterns of ECM remodeling and adipose function in different fat depots.


Association Between Unstable Work and Occupational Wellbeing Among Artists in Finland: Results of a Psychosocial Survey.
Although artistic work is in transition, the occupational wellbeing of artists has been less studied than wellbeing among other workers. This study aimed to explore the relationship between work characteristics and occupational (psychosocial) wellbeing of artists. A national questionnaire was sent to all artists (theatre artists, writers, and visual artists) reached by four major labor unions in Finland. Type of employment (permanent full-time work vs other), working field (own field of art vs other), regularity of working hours (regular vs irregular), and control of workload were assessed. The wellbeing outcomes were work engagement, recovery from work, and experience of stress and low mood. Full-time permanent employment, regular working hours, and working in one's own field of art were positively associated with work engagement. Furthermore, regular working hours were positively associated with recovery and negatively associated with subjective report of low mood. Ability to control workload was positively associated with recovery and negatively associated with stress and low mood. Higher age was associated with lower stress and better recovery. Artists with regular working hours, secure employment, ability to control workload, working in one's own field of art, and higher age reported better wellbeing in this study. The late stages of career appear to guarantee more stability and wellbeing than the more insecure beginning of a career.


Modified graphites: application to the development of enzyme-based amperometric biosensors.
For a series of graphite electrodes, modified with microquantities of Pd+Pt mixture in varied proportions, surface morphology of the catalytically active phase was studied with scanning electron microscopy (SEM), while the catalytic activity was examined at electrochemical reduction of hydrogen peroxide by means of steady-state polarization curves and constant potential amperometry. It was proven that the graphite, exhibiting the highest electrocatalytic activity (modified with Pd+Pt mixed in the ratio 70%:30% at t(deposit)=10 s) is distinguished with the smallest average size of the microformations. The operational characteristics of the same electrode and graphite modified with microquantities of Pd+Au mixed in the same ratio (70%:30%; t(deposit)=10 s) were compared. The application of these electrodes as basic transducers in highly selective biosensors for glucose and xanthine was demonstrated.