A Mutant of Synechococcus PCC7942 Incapable of Adapting to Low CO(2) Concentration.
Some properties of a mutant (RK1) of Synechococcus PCC7942, which requires high CO(2) for growth, are described. The photosynthetic affinity for inorganic carbon (C(i)) in RK1 was about 40 times lower than that in the wild type (WT) when grown at 3% CO(2) (H-cells) and did not change during 10 hours of exposure to low CO(2) (air containing 0.04% CO(2)). The gas exchange of WT and RK1 cells was measured using an open gas-analysis system. All the measurements were performed at a CO(2) concentration of 400 microliters per liter under the conditions where photosynthetic CO(2) fixation is inhibited. When the suspension of H-cells of WT or RK1 was illuminated, the rate of CO(2) influx from the gas phase into the suspension was low and addition of carbonic anhydrase during illumination released only a small amount of CO(2) from the medium into the gas phase. The rate of CO(2) influx and the amount of CO(2) released by carbonic anhydrase were increased in WT during low CO(2) adaptation. These changes did not occur in RK1 during exposure to low CO(2). Cytoplasmic membrane from H-cells of WT or RK1 contained small amount of 42-kilodalton polypeptide. Exposure of RK1 to low CO(2) did not have significant effect on the amount of 42-kilodalton polypeptide, while the same treatment on WT resulted in a large increase of this polypeptide. The RK1 mutant appears to be defective in its ability to utilize the intracellular C(i) pool for photosynthesis and also to transmit a low CO(2) signal for inducing the functional and compositional changes observed in WT during low CO(2) adaptation.


Introduction to the Special Issue on Clinical Neuropsychology of Movement Disorders.
The special issue on the clinical neuropsychology of movement disorders provides an overview for the non-subspecialist clinical neuropsychologist and other clinical neuroscientists of the neuropsychological features, assessment and treatment of Parkinson's disease and Lewy body dementias, atypical parkinsonian disorders (corticobasal syndrome, progressive supranuclear palsy, and multiple system atrophy), Huntington's disease, dystonia, and amyotrophic lateral sclerosis. Additionally, articles provide overviews of neuropsychological and ethical issues related to deep brain stimulation and a discussion of non-pharamcologic and non-invasive treatment of cognitive dysfunction in Parkinson's disease. A search of PubMed using neuropsycholog* and parkinson* as search terms indicates that the number of articles dealing with neuropsychology of parkinsonian disorders has more than doubled in each of the past three decades (1990-99:269 entries, 2000-09:575 entries, 2010-17:967 entries). This rapid growth of research makes a special issue on the topic very timely.


Preliminary Study on the Application of Ultrahigh Field Magnetic Resonance in Moyamoya Disease.
Magnetic resonance imaging (MRI) is widely used for the evaluation of moyamoya disease (MMD). In this paper, we describe the features of time-of-flight magnetic resonance angiography (TOF-MRA) and susceptibility-weighted imaging (SWI) at 7 T in a series of MMD patients. In this prospective pilot study, 7 patients (median age: 45.6 years; range: 30-52 years) with MMD and no contraindications for MRI underwent T2-weighted, SWI, and TOF-MRA sequences using a research 7 T head-only scanner. We show that such sequences at ultrahigh field (UHF) represent new and valuable approaches to unravel and characterize MMD. While SWI reveals more remarkable imaging signs related to an improved magnitude and phase contrast imaging, the collateral network pathways in MMD could be excellently delineated using 7 T TOF-MRA. In particular, using SWI and MRA fusion images in UHF MRI helps to improve the detection of bleeding points in hemorrhagic MMD. Our findings indicate that ultrahigh field MRI is very promising to access the severity of the disease and may facilitate revascularization surgery of MMD patients.


Metabolic and Bariatric Surgery in Adolescents: For Whom, When, and How?
Severe obesity in adolescence profoundly impacts health and social well-being. Lifestyle modifications are seldom successful in maintaining sufficient weight loss to mitigate the risk of complications. Metabolic and bariatric surgery (MBS) is a standard treatment for adult patients and has emerged as an option for adolescent patients. Several high-quality studies of adolescent MBS show substantial and sustained improvements both in weight and cardiometabolic parameters, as well as a safety profile similar to that seen in adult patients. Patients report improvements in health- and weight-related quality of life. Concerns around adolescent MBS can be attributed to a fear of side effects on growth and puberty, risk of nutritional deficiencies and osteoporosis, alcohol abuse, psychosocial vulnerability, and the ability to consent in the decision process. Guidelines give somewhat different recommendations, but the most comprehensive guidelines from the American Society for Metabolic and Bariatric Surgery recommend MBS for class III obesity or class II obesity with comorbidity. This mini-review aimed to pre-sent published data on MBS in adolescents. We discuss indications for MBS and the optimal timing in the young person's life, the choice of surgical method, and MBS in relation to the new anti-obesity medications. Based on data primarily from the USA and Sweden, we conclude that MBS is a valuable treatment option for adolescents with severe obesity that appears underutilized against the backdrop of the poor prognosis of severe obesity. We argue for continued research, development of guidelines, multi-professional teamwork, long-term follow-up, and centralization of adolescent MBS.


Pharmacology and pharmacokinetics of esmolol.
Esmolol is an ultra-short-acting beta-adrenergic blocking agent that possesses minimal partial agonist activity or direct membrane depressant activity. The short duration of action of esmolol is attributable to rapid enzymatic hydrolysis by red blood cell esterases, forming ASL-8123 and methanol. Experiments in the constant-flow-perfused isolated canine hindlimb indicate that therapeutic (beta blocking) doses of esmolol lack direct vascular effects and alpha-adrenergic blocking activity and that therapeutic doses do not interfere with vascoconstrictor effects of peripheral sympathetic nerve stimulation. Esmolol produces cardiac electrophysiologic and hemodynamic effects consistent with those of beta blockade. Specifically, esmolol decreases heart rate, depresses atrioventricular nodal conduction, and decreases determinants of myocardial oxygen demand. The beneficial antiarrhythmic and infarct-size limiting effects of esmolol have been demonstrated in several experimental models. Whereas beta blockers in general are effective in settings of supraventricular arrhythmias, sinus tachycardia, and myocardial ischemia, esmolol provides the added dimension of "titratability." Thus, the short duration of action of esmolol allows for very rapid titration to a preferred steady-state level of beta blockade; rapid adjustment to different steady-state levels of beta blockade, as may be required by changing status of the patient, and rapid disappearance of beta blockade following discontinuation of esmolol infusion, should this be necessary in the event of deleterious cardiac hemodynamic effects. Thus, esmolol is ideally suited for use in the treatment of patients in whom beta blockade is desirable, but in whom level of beta blockade must be very carefully modulated.


Hypertension in pediatric patients admitted to inpatient ward at King Abdulaziz Universty Hospital in Saudi Arabia: Prevalence, causes, and outcomes.
The secondary hypertension (HTN) is the predominant form of HTN in pediatrics. Renal diseases and renovascular anomalies are the most commonly reported causes. In this study, we aimed to identify the prevalence, causes, and outcomes of secondary HTN in Saudi Arabia. A retrospective study was conducted among 3,640 pediatric patients aged between 0 and 18 years, admitted to the pediatric nephrology ward at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. The study has been approved by the ethics review committee of King Abdulaziz University. Prevalence of secondary HTN due to renal disease was (77.0%). Most of the cases were diagnosed with stage 5 renal disease (78.3%). Small kidney size was frequently diagnosed (n = 29, 11.9%), followed by large kidney size (n = 26, 10.7%). One third of the cases (n = 79, 32.4%) were under control, 49 (20.1%) lost follow-up, and 24 (10.1%) deceased. A total of 61 (33.1%) patients progressed to end-stage renal disease and patientswere managed by different types of treatments. The prevalence of secondary HTN due to renal disease is considered to be high in pediatric patients admitted to King Abdulaziz University. Several renal diseases in the renal system are associated with secondary HTN mostly attriubuted to renal malformation. In addition, renal affection, cerebral infarction, bleeding, left ventricular hypertrophy, and valvular lesion are the highest reported complications in our population. Follow-up with ECHO and brain CT is highly recommended in pediatric HTN. Future studies on a larger sample and vigorous follow-up are recommended.


Effects of Tetracycline and Rifampicin Treatments on the Fecundity of the Wolbachia -Infected Host, Tribolium confusum (Coleoptera: Tenebrionidae).
We examined the effects of Wolbachia bacteria on the reproduction of the flour beetle Tribolium confusum (Coleoptera: Tenebrionidae) using different antibiotics and across generations. We first removed infections by rearing insects on a diet with tetracycline (T; 1.0, 2.0, 3.0, 5.0, 10.0 mg/g) or rifampicin (R; 0.1, 0.2, 0.3, 0.5, 1.0 mg/g). We then performed experimental crosses using adults two generations (G2) and four generations (G4) removed from antibiotic treatments. Results showed that use of rifampicin more readily cured infections. Egg hatch from crosses of uninfected females and infected males was 0, but averaged 84 to 91% for eggs from all other crosses. Elevated fecundity was observed for T-G2 females, but not for T-G4, R-G2, or R-G4 females. Cross type had little or no effect on the sex of F 1 offspring, which averaged 52% female. These collective results support previous findings that show that Wolbachia in T. confusum causes 100% cytoplasmic incompatibility and emphasize that the antibiotic treatment used to remove infections may have additional consequences (e.g., elevated fecundity) that may not be apparent in subsequent generations.


Increased myofiber size and reduced satellite cell numbers in medial rectus muscle of patients with intermittent exotropia.
To elucidate the differences in muscle bundle and satellite cells in medial rectus muscle through histological and Immunofluorescence studies of intermittent exotropia patients and normal controls. Materials and Methods: From January 2015 to December 2017, 15 patients who underwent medial rectus resection surgery at Kosin University Gospel Hospital were enrolled. Four medial recti muscles collected from two brain-dead men without strabismus were used as controls and compared with the intermittent exotropia group. Hematoxylin and eosin (HE) staining were performed, and all muscle bundle diameters were measured with the Image J program and compared to the mean value. Immunological staining for MyoHC (Myosin Heavy Chain), PAX7 (Transcription Factor), and PCNA (Proliferating Cell Nuclear Antigen) were performed to analyze the distribution of myocytes and PAX7-positive and PCNA-positive cells. Results: The mean ages of the strabismus and control groups were 17.33 ± 13.05 and 22.0 ± 5.85 years, respectively, and the male to female ratio was 7:2 and 2:0. The average angle of deviation in the exotropia patients was 36.0 ± 16.83 prism diopters. The mean muscle bundle diameter under light microscopy was 60.21 ± 1.48 in the exotropia group and 52.27 ± 0.74 in the control group. The exotropia group showed significantly greater mean muscle bundle diameter (p < .001) and diameter regularity than the control group. The PAX7(+)/muscle bundle number ratio was 0.016 ± 0.014 and 0.056 ± 0.015 in the exotropia group and control group, respectively (p < .001), and the PCNA(+)/muscular bundle number ratio was 0.015 ± 0.017 and 0.182 ± 0.102 (p < .001). Both were significantly higher in the control group compared to that in the exotropia patients. Conclusion: In the exotropia group, mean diameter of medial rectus muscle bundle was significantly larger than that of control group. The ratios of PAX7 and PCNA to muscle bundle number were significantly higher in the control group than intermittent extropia group. We found the negative relationship between activation of satellite cells and muscle bundle diameter, and it might take one step forward to elucidate the pathogenesis of intermittent extropia.


A novel gene delivery system targeting cells expressing VEGF receptors.
Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-beta-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) and human malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with the relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.


Interferon alpha-induced hashimoto thyroiditis followed by transient graves disease in a patient with chronic HCV infection.
The case of a 37-year-old man with chronic hepatitis C virus (HCV) infection is presented. The patient had received a 6-month course of antiviral therapy with peg interferon alpha-2a and ribavirin, with concomitant clearance of hepatitis C virus ribonucleic acid (HCV-RNA) from serum at the end of treatment. Three months after the treatment course he developed clinical and laboratory features of hypothyroidism along with high titers of thyroid peroxidase antibodies. Later on, while on treatment with levothyroxine, he developed all the clinical features of Graves disease along with increased levels of thyroid stimulating hormone (TSH)-receptor antibodies.This patient exhibited a rare sequence of immune-mediated thyroid disorders as a result of interferon alpha treatment. At the end of treatment, the patient developed Hashimoto thyroiditis, a typically Th1-response-mediated disease, followed sequentially after 6 months by Graves disease, a typically Th2-response-mediated disorder. Although both clinical entities have been described in patients receiving interferon-based regimens, to our knowledge, the changing pattern of immune-mediated thyroid disease in the same individual has not been reported in the literature.


["Difficult" venous ulcers of the legs].
The aim of the study was to analyze the diagnostic and surgical criteria in cases of "critical" venous leg ulcers. This report describes the management of 200 patients with trophic lesions of the lower limbs. Patients with venous leg ulcers were identified with the aid of ultrasonography and echocolor Doppler. Among these patients, according to the chronic evolution of the lesions, we identified all those with critical venous leg ulcers. The management of the lesions involved both medical and fairly aggressive surgical treatment with the use of general anaesthesia and deep surgical toilette of the ulcer. In the cases with poor epithelialisation we adopted oxygen therapy and skin grafts using the "mesh graft" technique. Critical venous leg ulcers were identified in 23 patients (19%). After surgical treatment, we observed complete epithelialisation of the lesion only in 5 cases (21.7%). In 13 patients (56.6%) the use of oxygen therapy was necessary and epithelialisation occurred on postoperative day 12. Skin grafts were used in 5 cases (21.7%). Only one recurrence was observed one year after operation in an area adjacent to the site of the graft. The "golden goal" of critical venous leg ulcer management is to establish a correct aetiological diagnosis, distinguishing between venous leg ulcers and other trophic lesions of the lower limbs. The medical and surgical treatment described in this report reduce healing time and the social costs of the disease, without any significant complications for the patient.


XanFur, a novel Fur protein induced by H2O2, positively regulated by the global transcriptional regulator Clp and required for the full virulence of Xanthomonas oryzae pv. oryzae in rice.
Although Xanthomonas oryzae pv. oryzae (Xoo) has been found to be a bacterial pathogen causing bacterial leaf blight in rice for many years, the molecular mechanisms of the rice-Xoo interaction has not been fully understood. In this study, we found that XanFur of Xoo is a novel ferric uptake regulator (Fur) protein conserved among major pathogenic Xanthomonas species. XanFur is required for the virulence of Xoo in rice, and likely involved in regulating the virulence determinants of Xoo. The expression of xanfur is induced by H2O2, and positively regulated by the global transcriptional regulator Clp. Our results reveal the function and regulation of the novel virulence-related Fur protein XanFur in Xoo, providing new insights into the interaction mechanisms of rice-Xoo.


Murine glomerular leukotriene B4 synthesis. Manipulation by (n-6) fatty acid deprivation and cellular origin.
Leukotriene (LT) B4 is an important pro-inflammatory autocoid. In order to investigate the potential role of this eicosanoid in renal inflammation, in this study we determined the capability of glomeruli to synthesize this mediator. Glomeruli were able to synthesize LTB4 when provided with exogenous substrate in a dose-dependent fashion in the presence of ionophore A23187. Ionophore, although by itself a weak agonist for LTB4 formation, was required for LTB4 production from exogenous arachidonate. The identity of LTB4 was confirmed by specific radioimmunoassay, high pressure liquid chromatography, and gas chromatography/mass spectrometry. The synthesis of LTB4 was inhibited by BW755C (a lipoxygenase/cyclooxygenase inhibitor) but not indomethacin. Essential fatty acid (EFA) deficiency, obtained by the deprivation of (n-6) fatty acids, is known to exert a protective effect in renal inflammatory states. This dietary manipulation markedly attenuated the ability of glomeruli to synthesize LTB4. In contrast, the synthesis of cyclooxygenase products from exogenous arachidonate was increased by EFA deficiency. Because EFA deficiency has been shown to deplete glomeruli of resident mesangial macrophages, it was hypothesized that this effect accounted for the diminished LTB4 synthesis. To test this hypothesis, glomeruli were depleted of macrophages using x-irradiation. Glomeruli from these animals exhibited a marked decrease in LTB4 synthesis. Glomerular synthesis of cyclooxygenase products was unaffected by irradiation. In sum, glomeruli have the capability to synthesize LTB4, and this capacity is correlated with the presence of glomerular macrophages. EFA deficiency attenuates the ability of glomeruli to synthesize LTB4 by depleting them of macrophages.


Dietary Habits of a Group of Children with Crohn's Disease Compared to Healthy Subjects: Assessment of Risk of Nutritional Deficiencies through a Bromatological Analysis.
Diet is a matter of interest in the pathogenesis and management of Crohn's Disease (CD). Little is known about CD children's dietary habits. Our aim was assessing the quality and the amount of nutrient intake in a group of CD pediatric patients. Data were compared with those of healthy subjects (HS). In total, 20 patients (13 males) and 48 HS (24 males) aged 4-18 years were provided with a food diary to fill out for one week. Winfood software performed the bromatological analysis, providing data about intakes of proteins and amino acids, fatty acids, carbohydrates, cholesterol, fibers, minerals, vitamins, and polyphenols. Estimates of the antioxidant activity of foods and of the dietetic protein load were also calculated. The diet of CD patients was poorer in fibers, polyphenols, vitamin A, beta-carotene, and fatty acids, and richer in animal proteins, vitamin B12, and niacin. PRAL was higher in CD patients' diets, while ORAC was higher in HS. No significant differences were observed in carbohydrate and other macro- and micronutrient consumptions. CD dietary habits seem to reflect the so-called Western diet, possibly involved in CD pathogenesis. Furthermore, analysis of dietary habits allows for prevention of nutritional deficiencies and timely correction through education and supplementation.


Treatment responses in collagenous colitis.
In the nearly 20 yr since collagenous colitis was first recognized, the results of therapies have not been systematically described in substantial numbers of patients. We have therefore conducted a retrospective analysis of 26 patients treated in this institution during the years 1991-1994. Twenty-nine cases of collagenous colitis were obtained by review of biopsy specimens collected between 1991 and 1994 at The Mount Sinai Hospital. Each chart was reviewed for patient demographics, symptoms, coexisting conditions, specific therapies, and therapeutic outcomes. Additional data were obtained from telephone calls to patients when deemed necessary. Three patients were exeluded from the study because of lack of follow-up. Therapeutic outcomes were defined as follows: Complete Remission (CR): normalization of bowel function; Partial Remission (PR): 50% reduction in frequency of bowel movements; Failure: <50% reduction in frequency of bowel movements; or Relapse: return of symptoms after cessation of treatment. Median follow-up was 58 wk from time of diagnosis, with a range of 22-376 wk. The 26 patients (25 women, one man) had a mean age of 62 yr (range, 22-85 yr) at diagnosis. Of 26 patients, 22 responded to some form of therapy and one had spontaneous remission. Six of the responders ultimately remained in CR with no therapy. Twelve are maintained on 5-aminosalicylic acid (5-ASA) and or antidiarrheals to control symptoms. An additional six required prednisone throughout the follow-up period to remain in CR or PR. Two patients failed all therapy. Collagenous colitis is a treatable condition in most patients. We recommend initial therapy with antidiarrheals, followed by a trial of 5-ASA agent. A trial of 5-ASA in combination with prednisone should be attempted in patients refractory to 5-ASA alone, with subsequent attempts in the responders to taper prednisone and maintain remission with no therapy, if possible, or with 5-ASA and/or antidiarrheal agents if necessary.


Graph-Based Semantic Web Service Composition for Healthcare Data Integration.
Within the numerous and heterogeneous web services offered through different sources, automatic web services composition is the most convenient method for building complex business processes that permit invocation of multiple existing atomic services. The current solutions in functional web services composition lack autonomous queries of semantic matches within the parameters of web services, which are necessary in the composition of large-scale related services. In this paper, we propose a graph-based Semantic Web Services composition system consisting of two subsystems: management time and run time. The management-time subsystem is responsible for dependency graph preparation in which a dependency graph of related services is generated automatically according to the proposed semantic matchmaking rules. The run-time subsystem is responsible for discovering the potential web services and nonredundant web services composition of a user's query using a graph-based searching algorithm. The proposed approach was applied to healthcare data integration in different health organizations and was evaluated according to two aspects: execution time measurement and correctness measurement.


Tracking Neutrophil Migration in Zebrafish Model Using Multi-Channel Feature Learning.
Tracking cells over time is crucial in the fields of computer vision and biomedical science. Studying neutrophils and their migratory profile is the highly topical fields in inflammation research due to determining role of these cells during immune responses. As neutrophils generally are of various shapes and motion, it remains challenging to track and describe their behaviours from multi-dimensional microscopy datasets. In this study, we propose a robust novel multi-channel feature learning (MCFL) model inspired by deep learning to extract the complex behaviour of neutrophils moved in time lapse images. In this model, the convolutional neural networks along with cell relocation distance and orientation channels learn the robust significant spatial and temporal features of an individual neutrophil. Additionally, we also proposed a new cell tracking framework to detect and track neutrophils in the original time-laps microscopy images, entails sampling, observation, and visualisation functions. Our proposed cell tracking-based-multi channel feature learning method has remarkable performance in rectifying common cell tracking problem compared with state-of the-art methods.


Risedronate's Role in Reducing Hip Fracture in Postmenopausal Women with Established Osteoporosis.
Osteoporosis is a significant concern for postmenopausal women and is a critical factor in hip fracture. Examining evidence for osteoporosis medications in hip fracture is important for optimizing treatment. Review risedronate's role for hip fracture in postmenopausal women. A literature search was conducted using Medline and Web of Science. The search was limited using the terms "risedronate" and "hip fracture," and to studies that included women. Similar articles linked to the search and pertinent articles in bibliographies were also examined. Risedronate has demonstrated efficacy and cost effectiveness for hip fracture, but may not be beneficial for patients with low fracture risk. Risedronate is generally well tolerated, but may cause side effects in some patient populations. Risedronate has benefit for hip fracture, but patients should be carefully screened to determine the appropriateness of risedronate before starting treatment.


Fragment-based screening using surface plasmon resonance technology.
Surface plasmon resonance (SPR) technology has emerged as a new and powerful technique to investigate the interaction between low-molecular-weight molecules and target proteins. In the present work, the authors assemble from a large compound collection a library of 2226 molecules (fragments having low molecular weights between 100 and 300 Da) to screen them for binding to chymase, a serine protease. Both the active chymase and a zymogen-like form of the protein were used in parallel to distinguish between specific and unspecific binding. The relative ligand-binding activity of the immobilized protein was periodically measured with a reference compound. The screening experiments were performed at 25 degrees C at a fragment concentration of 200 microM in the presence of 2% DMSO. Applying the filter cascade, affinity-selectivity-competition (competition with reference compounds and cross-competition with fragments), 80 compounds show up as positive screening hits. Competition experiments between fragments show that they bind to different parts of the active site. Of 36 fragments co-crystallized for X-ray studies, 12 could be located in the active site of the protein. These results validate the authors' library and demonstrate that the application of SPR technology as a filter in fragment screening can be achieved successfully.


Novel Technique with Double Free Flap Design for Advanced Mandibular Osteoradionecrosis: A Case Series.
Advanced mandibular osteoradionecrosis is arguably among the most challenging cases for reconstructive head and neck surgeons. Several reconstructive methods for complex mandibular defects have been reported; however, for advanced mandibular osteoradionecrosis, a safe option that minimizes the risk of renewed fistulation and infections is needed. For this purpose, we present a new technique using a fascia-sparing vertical rectus abdominis musculocutaneous flap as protection for a vascularized free fibula graft (FFG). This technique also optimizes recipient site healing and functionality while minimizing donor site morbidity. Our initial experiences from a 4 patient case series are included. Mean operative time was 551 minutes (SD: 81 minutes). All donor sites were closed primarily. Mean time to discharge was 13 days (SD: 7 days), and mean time to full mobilization was 2 days (SD: 1 days). This double free flap technique completely envelops the FFG and plate with nonirradiated muscle. It allows for the transfer of an FFG without a skin island, thus avoiding the need for split skin graft closure. This results in faster healing and minimizes the risk of fibula donor site morbidity. The skin island of the vertical rectus abdominis musculocutaneous flap has the added benefit of providing intraoral lining, which minimizes contractures and trismus. Although prospective long-term studies comparing this approach to other double flap procedures are needed, we argue that this technique is an optimal approach to safeguard the mandibular FFG reconstruction against the inherent risks of renewed complications in irradiated unhealthy tissue.


Clinical otorhinolaryngological presentation of COVID-19 patients in Saudi Arabia: A multicenter study.
To assess the otorhinolaryngological (ORL) symptoms, including their prevalence, severity, and early presentations among coronavirus disease-19 (COVID-19) patients in the Saudi population. This was a multicentric, cross-sectional study carried out on severe acute respiratory syndrome coronavirus-2 positive patients at 3 COVID-19 centres; Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, ALKhobar, Qatif Central Hospital, AlQatif, and Ohud Hospital, Al Madinah Al Munawarah, Saudi Arabia. The validated survey consisted of sociodemographic data, general symptoms of COVID-19, and ORL manifestations. A total of 1734 COVID-19 positive patients were included in the study (mean age: 37.7±11.6 years). Most of the cases were mild (51.8%), followed by moderate (45.6%), and severe (2.6%) cases. Approximately 33.7% were asymptomatic. Severity of symptoms was significantly associated with male gender (p=0.017), higher age-group (p=0.04), and smoking (p<0.001). The most common initial ORL presentations were sore throat (20.9%), anosmia (15.5%), hyposmia (10%), and loss of taste (11.4%). Overall, 79.5% showed ORL symptoms as the initial presenting symptoms for COVID-19, with anosmia and sore throat being the most common symptoms. This study confirmed the prevalence of ORL symptoms among COVID-19 patients in Saudi Arabia. Moreover, these symptoms could also be considered for early detection of COVID-19 as they might appear prior to other symptoms.


Promising results from cyclophosphamide based immunosuppression therapy of thrombotic thrombocytopenic purpura.
Thrombotic thrombocytopenic purpura is a rare disease. Therefore, the small numbers of patients in trials results in statistically weak evidence supporting treatment guidelines. The aetiology of this disease is based on a deficiency of metalloproteinase 13 (ADAMTS-13), which leads to the creation of von Willebrand factor polymers and platelet microthrombosis in small vessels. Treatment relies on plasma exchange. Immunosuppression based on cyclophosphamide is not recommended in current guidelines. The aim of this study was to assess the early and long-term effects of treatment, and to evaluate therapy prognostic factors. This was a retrospective study of 10 patients hospitalized 14 times due to new or recurrent onset of TTP. Currently recommended treatment was used in all cases, including total plasma exchange (range 0.5-2 plasma volume). The volume of exchange plasma was 24.6 L (mean) over 20 days (median). All patients received glucocorticosteroids. Immuno-uppression (based on cyclophosphamide in 7 cases) was utilized in 70% of patients (9 patients). Of all 11 patients 9 (70%) survived and achieved remission. Fifty percent of patients stayed in long-lasting remission. Average follow-up time was 36 months (median 14.5 months, range 10 days to 108 months). Factors improving the chance of remission were: age below 55 years (p < 0.05), no tachycardia on admission to hospital (p < 0.001), and immunosuppression based on cyclophosphamide (p = 0.032). Presence of tachycardia on TTP onset and age above 55 years reduce the survival and remission rate. Remission from TTP is suggested to be caused by immunosuppression based on cyclophosphamide.


HIV serophobia in the mortuary: an algorithm system for handling high-risk forensic cases.
A serophobia of the human immunodeficiency virus type 1 (HIV-1) is very noticeable in mortuaries handling high-risk cases. The morbid anxiety about occupationally acquired HIV infection in the forensic practice has made mortuary workers unduly overcautious. Despite the availability of codes of practice and informed principles of health and safety, there is considerable anxiety that an HIV carrier with no identifiable risk factors may be overlooked or a seronegative body may be inadvertently assumed to be uninfected. In contrast, a false sense of safety can pose a health hazard and has public health implications. An algorithm system is outlined for selective handling of unsuspected or unrecognized high-risk cases. It is necessary that guidelines are reasonably simple and incorporate statutory health and safety regulations and local safe working practice in the mortuary. Although it is not a legal obligation, approval by the coroners should facilitate consistent implementation of a protocol. A common experience in public and NHS hospital mortuaries in the London coroners' jurisdictions is characterized.


Specification and survival of post-metamorphic branchiomeric neurons in the hindbrain of a non-vertebrate chordate.
Tunicates are the sister group to the vertebrates, yet most species have a life cycle split between swimming larva and sedentary adult phases. During metamorphosis, larval neurons are largely replaced by adult-specific ones. Yet the regulatory mechanisms underlying this neural replacement remain largely unknown. Using tissue-specific CRISPR/Cas9-mediated mutagenesis in the tunicate Ciona, we show that orthologs of conserved hindbrain and branchiomeric neuron regulatory factors Pax2/5/8 and Phox2 are required to specify the "Neck", a compartment of cells set aside in the larva to give rise to cranial motor neuron-like neurons in the adult. Using bulk and single-cell RNAseq analyses, we also characterize the transcriptome of the Neck downstream of Pax2/5/8. Surprisingly, we find that Neck-derived adult ciliomotor neurons begin to differentiate in the larva, contrary to the long-held assumption that the adult nervous system is formed only after settlement and the death of larval neurons during metamorphosis. Finally, we show that manipulating FGF signaling during the larval phase alters the patterning of the Neck and its derivatives. Suppression of FGF converts Neck cells into larval neurons that fail to survive metamorphosis, while prolonged FGF signaling promotes an adult neural stem cell-like fate instead.


The Promoter Targeting Sequence mediates epigenetically heritable transcription memory.
Large gene complexes frequently use "specialized" DNA elements to ensure proper regulation of gene activities. The Promoter Targeting Sequence (PTS) from the Abdominal-B locus of the Drosophila Bithorax complex overcomes an insulator, and facilitates, yet restricts, distant enhancers to a single promoter. We found that this promoter-targeting activity is independent of an enhancer's tissue or temporal specificity, and can be remembered in all somatic cells in the absence of promoter activation. It requires an insulator for its establishment, but can be maintained by the PTS in the absence of an insulator. More importantly, the promoter-targeting activity can be remembered after the transgene is translocated to new chromosomal locations. These results suggest that promoter targeting is established independent of enhancer activity, and is maintained epigenetically throughout development and subsequent generations.


The effect of air bags on pregnancy outcomes in Washington State: 2002-2005.
To estimate whether air-bag deployment is associated with an increased risk of adverse pregnancy outcomes. We performed a retrospective cohort study to assess the effect of air-bag availability and air-bag deployment on the risk of adverse pregnancy outcomes among pregnant, front-seat occupants in motor vehicle crashes in Washington State. Pregnant women involved in motor vehicle crashes were identified by linking birth and fetal death certificate data with Washington State Patrol crash data, which reported air-bag availability and deployment. We calculated relative risks (RRs) of adverse maternal and perinatal outcomes and 95% confidence intervals (CIs) using Poisson regression, adjusted for maternal age, seatbelt use, and vehicle model year. We found no increased risk of adverse maternal or perinatal pregnancy outcomes among occupants of air-bag-equipped vehicles in all collisions (n=2,207) compared with those in vehicles without air bags (n=1,141). Among crashes in which air-bag deployment would be likely, we found a nonsignificant 70% increased risk of preterm labor (RR 1.7, 95% CI 0.9-3.2) and a nonsignificant threefold increased risk (RR 3.1, 95% CI 0.4-22.1) of fetal death among occupants in vehicles with air-bag deployment compared with occupants in vehicles without air bags, although fetal death results were limited by small numbers (2/198 [1.0%] in pregnant women whose air bags deployed; 2/622 [0.3%] in pregnant women whose air bags did not deploy). Our findings provide clinicians with evidence to advise women that air bags do not seem to elevate risk of most potential adverse outcomes during pregnancy. II.


Phenelzine poisoning.
A 46-year-old female with severe phenelzine poisoning was managed successfully by alpha blockade and fluid loading, with the aid of invasive haemodynamic monitoring. The pathophysiology was documented, showing elevated plasma and urinary catecholamines, cardiovascular abnormalities and a contracted blood volume. Most of these changes were reversed following treatment.


Pattern of disease recurrence and its implications for postoperative surveillance after curative hepatectomy for hepatocellular carcinoma: experience from a single center.
Hepatectomy is a widely accepted curative treatment for hepatocellular carcinoma (HCC). However, the disease frequently recurs after a curative hepatectomy. The objective of this study is to provide a better understanding of the pattern of disease recurrence and the risk factors involved so as to improve the postoperative surveillance. A retrospective study for all patients receiving hepatectomy for HCC between 2003 and 2014 was performed. Emphasis was made on the timing and pattern of recurrent disease, and type of treatment given. There were 506 patients in the study. Median follow-up was 43.7 months. The 1-, 3-, 5-, 10-year overall and disease free survival were 89.5%, 74.1%, 63.9%, 49.0% and 69.5%, 54.3%, 43.4%, 30.9% respectively. Recurrent disease occurred in 267 patients, 47.2% occurred within 9 months of hepatectomy and 80.1% recurred only in liver. Median survival was shorter for recurrence occurring within 9 months compared with those occurring between 10 months and 2 years postoperatively (36.2 vs. 65.7 months, P<0.01) whilst less curative treatment was offered for patients with early (within 9 months) intrahepatic alone recurrence (22.2% vs. 51.7%, P<0.01). Multivariate analysis revealed tumor size >3.5 cm and history of rupture were risk factors for recurrence within 9 months. These findings suggest that recurrent diseases are common after curative hepatectomy for HCC and most recurrences occur in the remnant liver. Since almost half of recurrences occurred within first 9 months after hepatectomy, a more stringent postoperative surveillance with target imaging of liver in this period is needed. Early diagnosis of recurrent disease and curative retreatment hopefully can bring about a longer survival.


[Work demands and alcohol consumption: the job group's role].
The current study aimed to determine whether workgroup identification and alcohol consumption social norms of workgroup moderates the relationship between job demands and alcohol consumption in workers. Regression analysis using the moderated moderation macro in a sample of workers from a telecommunications company in Chile (N = 1,143) supports the hypothesis of moderated moderation: high workgroup identification with with unfavorable social norms of alcohol consumption by the group buffered the relationship between job demands and alcohol consumption of workers (B = -0.080; t = -2.01; p = 0.04; 95%CI: -0.1600; -0.0024), and the high workgroup identification with favorable social norms of alcohol consumption by the group increases the relationship between job demands and alcohol consumption of workers (B = 0.170; t = 2.36; p = 0.01; 95%CI: 0.030; 0.322). The results suggest that strong identification with workgroup and their social norms for alcohol consumption are job resources that can jointly affect or protect workers exposed to heavy work demands. Attention should thus be focused on the potential positive versus harmful effects of these work resources.


Ring-in-a-Triangle Nanoframes: Integrating with Intra- and Interhotspots for Highly Amplified Near-Field Focusing.
The development of a stepwise synthetic strategy for Au ring-in-a-triangle nanoframes with a high degree of structural solidity is essential to the advancement of highly amplified near-field focusing. This strategy leads to the formation of an inscribed nanoring in a triangular metal frame with stability to withstand elevated temperatures and an oxidizing environment, which is critical for successful single-particle surface-enhanced Raman scattering (SERS). The existence of inscribed nanorings plays an important role in enhancing the so-called "lightning rod effect," whereby the electromagnetic near-field enhancement occurs on the highly curved curvature of a metallic interface. We evaluated the corresponding single-particle SERS as a function of the thickness of the rims and then constructed two-dimensional (2D) bulk SERS substrates, wherein an ensemble of hotspots exists. The synergic contribution from both inter- and intrahotspots allowed the outstanding linearity of the calibration curve and the lowest limit of detection, ∼10-18 M for the analyte concentration.


Differential Regulation of Gene Expression in Lung Cancer Cells by Diacyglycerol-Lactones and a Phorbol Ester Via Selective Activation of Protein Kinase C Isozymes.
Despite our extensive knowledge on the biology of protein kinase C (PKC) and its involvement in disease, limited success has been attained in the generation of PKC isozyme-specific modulators acting via the C1 domain, the binding site for the lipid second messenger diacylglycerol (DAG) and the phorbol ester tumor promoters. Synthetic efforts had recently led to the identification of AJH-836, a DAG-lactone with preferential affinity for novel isozymes (nPKCs) relative to classical PKCs (cPKCs). Here, we compared the ability of AJH-836 and a prototypical phorbol ester (phorbol 12-myristate 13-acetate, PMA) to induce changes in gene expression in a lung cancer model. Gene profiling analysis using RNA-Seq revealed that PMA caused major changes in gene expression, whereas AJH-836 only induced a small subset of genes, thus providing a strong indication for a major involvement of cPKCs in their control of gene expression. MMP1, MMP9, and MMP10 were among the genes most prominently induced by PMA, an effect impaired by RNAi silencing of PKCα, but not PKCδ or PKCε. Comprehensive gene signature analysis and bioinformatics efforts, including functional enrichment and transcription factor binding site analyses of dysregulated genes, identified major differences in pathway activation and transcriptional networks between PMA and DAG-lactones. In addition to providing solid evidence for the differential involvement of individual PKC isozymes in the control of gene expression, our studies emphasize the importance of generating targeted C1 domain ligands capable of differentially regulating PKC isozyme-specific function in cellular models.


Tomboy as protective identity.
The tomboy in contemporary U.S. culture is a complex identity, providing meaning to many girls and women. In this article, we argue tomboy as a gendered social identity also provides temporary "protections" to girls and women in three main ways. First, tomboy identity can excuse masculine-typed behavior in girls and women and, in doing so, protect women from presumptions about sexual reputation and sexual orientation. Second, tomboy identities can provide some protection for lesbian girls and women who prefer to not divulge their sexual orientation. And, third, tomboy identity can gain women limited privilege to spaces for which masculinity is an unspoken requirement. The temporary nature of the protections provided to tomboys undermines the ability of tomboys to truly transcend the binary gender system.


Rucaparib in the landscape of PARP inhibition in ovarian cancer.
Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings. Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research. Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.


Spherical hyperlens for two-dimensional sub-diffractional imaging at visible frequencies.
Hyperlenses have generated much interest recently, not only because of their intriguing physics but also for their ability to achieve sub-diffraction imaging in the far field in real time. All previous efforts have been limited to sub-wavelength confinement in one dimension only and at ultraviolet frequencies, hindering the use of hyperlenses in practical applications. Here, we report the first experimental demonstration of far-field imaging at a visible wavelength, with resolution beyond the diffraction limit in two lateral dimensions. The spherical hyperlens is designed with flat hyperbolic dispersion that supports wave propagation with very large spatial frequency and yet same phase speed. This allows us to resolve features down to 160 nm, much smaller than the diffraction limit at visible wavelengths, that is, 410 nm. The hyperlens can be integrated into conventional microscopes, expanding their capabilities beyond the diffraction limit and opening a new realm in real-time nanoscopic optical imaging.


Real-World Multicenter Experience in Tumor Debulking Prior to Blinatumomab Administration in Adult Patients With Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia.
Blinatumomab is an immunotherapeutic agent with dual specificity for CD3 and CD19 that is approved for the treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). A steroid based pre-treatment is recommended before administering blinatumomab to patients with a high tumor burden to minimize the risk of tumor lysis syndrome, but the optimal debulking regimen and whether it can improve responses remain unclear. The present study retrospectively evaluated real-world outcomes following tumor debulking and blinatumomab infusion in R/R B-ALL adult patients treated at 7 Italian centers. Data were collected from 34 patients. The choice of the cytoreductive therapy was made by the treating clinician on an individual patient basis; regimens included chemotherapy (n=23), steroids (n=7) and tyrosine kinase inhibitors alone or in combination (n=4). The rate of complete responses (CR) and complete minimal residual disease (MRD) responses in CR patients were 67.6% and 81% respectively, after 2 cycles of blinatumomab. Moreover, among patients with a high tumor burden 50% obtained a CR, with 89% of them also achieving a complete MRD response. Favorable responses were also obtained in patients over 50 years of age at treatment initiation. Overall, 7 of 23 patients in CR after blinatumomab underwent hematopoietic stem cell transplantation. The results of this retrospective study highlight the heterogeneity in the use of pre-blinatumomab tumor debulking in real-life clinical practice. Nonetheless, debulking pre-treatment enhanced responses to blinatumomab compared to historic studies, indicating that this strategy may help to improve outcomes for R/R B-ALL patients.


Neuroendocrine carcinomas of the larynx. A study of two types, one of which mimics thyroid medullary carcinoma.
We studied 13 neuroendocrine carcinomas of the larynx. They constituted 59% of the 22 nonepidermoid carcinomas of the larynx seen at Memorial Hospital during a 45-year period, and for which adequate material was available for review. Four tumors were histologically identical to small cell carcinomas of the lung and were classified as small cell neuroendocrine carcinomas (SCNC). One case represents one of the original descriptions of the laryngeal SCNC. No SCNC was argyrophil, and of the three studied immunohistochemically, all contained neuron-specific enolase, one carcinoembryonic antigen (CEA) and one serotonin. Nine tumors were large cell carcinomas (LCNC). Eight LCNC were argyrophil, and all nine contained neuron-specific enolase, six calcitonin, four CEA, one HCG, two serotonin, and two somatostatin. The laryngeal neuroendocrine carcinomas commonly presented in chronic cigarette smokers with mean ages of 63 (SCNC) and 60 (LCNC), were not associated with other endocrine tumors, and proved highly fatal in spite of radical surgery and radiation therapy. At last follow-up only one patient was alive (after 13 months). Patients dying with SCNC survived a mean of 11 months, and those with LCNC, 36 months. To determine whether the laryngeal LCNC most closely resembles pulmonary neuroendocrine tumors, head and neck paragangliomas, or thyroid medullary carcinoma (TMC), they were histologically, histochemically, and immunohistochemically compared with control cases of each group. Overall, LCNC most closely resembles TMC, and given the frequency with which each presents as a neck mass, misinterpretation of one for the other is very possible. Evidence is provided suggesting that some LCNC have also been mistaken for the laryngeal paraganglioma.


A localized differentiation-inducing-factor sink in the front of the Dictyostelium slug.
Differentiation-inducing factor 1 [DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)-hexan-1-one] induces stalk cell differentiation during Dictyostelium development. It is present as a gradient in the multicellular slug, its lowest concentration being in the anterior. Here we demonstrate the existence of a localized sink for DIF-1, also in the anterior of the slug, which could be responsible for generating the DIF-1 gradient. DIF-1 is metabolized extensively by developing cells, initially by a mono-dechlorination. We used an enzyme assay for DIF-1 dechlorinase to examine its distribution in the slug. DIF-1 dechlorinase activity is 30-fold higher in prestalk cells (largely anterior) compared with prespore cells (posterior) when these are separated from each other on Percoll density gradients. Dissection experiments showed that DIF-1 dechlorinase is 25-fold enriched in the anterior 13% of the slug compared with the rest. These experiments also showed that DIF-1 dechlorinase is more anterior-enriched than the standard prestalk markers, the ecmA and ecmB mRNAs. When cut from a slug, both prestalk and prespore fragments regulate to restore the missing cell type. Prespore fragments rapidly regain (by 30 min) a DIF-1 sink in their anteriors, and prestalk fragments restore a posterior zone with low DIF-1 dechlorinase by 4 hr after cutting. The reappearance of the DIF-1 sink in the anterior of prespore fragments is accomplished without detectable cell sorting and may, therefore, be in response to positional signals. Finally, a localized sink may provide a general way of producing a gradient of a signal substance in a developing embryo.


Management of oxytocin for labour augmentation in relation to mode of birth in Robson group 1.
To compare mode of birth in Robson group 1 according to administration of oxytocin for labour augmentation. A retrospective review of 724 medical records from women in Robson group 1 was performed. The outcome measurements were: mode of birth in relation to presence of labour dystocia when initiating augmentation with oxytocin, duration of augmentation with oxytocin, increase of the oxytocin infusion according to recommendations and cervical dilation when initiating augmentation with oxytocin. The review was based on medical records from a medium-sized tertiary level obstetric unit in southern Sweden, with approximately 3700 births per year. Data was collected between January 2017 and October 2017. Oxytocin for labour augmentation was used in 64.1% of the births. Oxytocin administered according to the national recommendations was related to a greater likelihood of vaginal birth than when these recommendations were not followed. Only 47.8% of the women who underwent a caesarean section was treated according to recommendations. Receiving augmentation with oxytocin at a later stage of labour was related to a greater likelihood of a vaginal birth. The total time treated with oxytocin was significantly longer in women who had an assisted vaginal birth or a caesarean section than those who had a vaginal birth with augmentation. Oxytocin for labour augmentation was over-used in Robson group 1. Oxytocin early in labour, a long duration of stimulation with oxytocin and a slower increase of the infusion than recommended had a relationship with caesarean section. Due to risks for adverse maternal and neonatal outcomes when using oxytocin for labour augmentation, caregivers should implement strict protocols for its use. According to a high use of oxytocin there is a need to describe women's experiences of labour augmentation in labour dystocia but also when received despite normal labour progress.


Spiral artery of placenta: development and pathology-immunohistochemical, microscopical, and electron-microscopic study.
The spiral artery (=SA) is an important muscular artery, which controls the blood volume to the placenta. Preeclampsia is thought to be induced by the failure of the placenta by dysfunction of SA. To clarify the function of SA, we examined forty-eight placentae and its morphological and biological characteristics: 36 normal placentae and 12 placentae with preeclampsia. Gestational age of normal placentas was between 19 and 40 weeks and placentae with preeclampsia was between 31-36 weeks. The wall of the placental segment of SA by both light and electron microscope, and the wall width of SA and gestation age were compared each other. The wall of SA, with the invasion of trophoblast, was thin, but SA without trophoblasts was thick in width. At normal placenta, the diameter of SA was dilative constantly, but the width of the wall showed a tendency of getting thinning as advances. Ultrastructually, we found the trophoblast of thin wall of SA with dilated lumen. These ultrastructual alternations were consistence with the light microscopical findings. In preeclampsia, the lumen of SA between normal pregnancy and one with preeclampsia was almost same, but the wall width was thick, compared with normal pregnancy (P<0.05). We concluded that trophoblastic invasion control the functions of SA.


Determinants of enhanced thromboxane biosynthesis in patients with systemic lupus erythematosus.
To evaluate the rate of thromboxane biosynthesis in patients with systemic lupus erythematosus (SLE), exploring the interplay between antiphospholipid antibodies (aPL) and 2 markers of endothelial perturbation: thrombin generation and platelet activation. A comparison of 11-dehydrothromboxane B2 (TXB2) excretion, which is a marker of in vivo platelet activation, aPL, von Willebrand factor (vWF) and tissue plasminogen activator (tPA), which are 2 circulating markers of endothelial perturbation, and plasma levels of the prothrombin fragment F1+2, which is a marker of thrombin generation, was performed in 40 SLE patients and 40 healthy subjects. Thromboxane metabolite excretion was also measured in 8 SLE patients before and after treatment with low-dose aspirin. SLE patients had significantly higher 11-dehydro-TXB2 excretion, plasma F1+2, vWF, and tPA levels than controls. A statistically significant correlation was found between plasma levels of vWF and tPA and excretion of thromboxane metabolite. Moreover, significantly higher 11-dehydro-TXB2 was found in patients with aPL positivity and endothelial perturbation. Low-dose aspirin suppressed 11-dehydro-TXB2 by 80%, suggesting a predominant platelet source of enhanced thromboxane biosynthesis. After a median followup of 48 months, all SLE patients who experienced major cardiovascular events had thromboxane metabolite excretion, aPL positivity, and signs of endothelial perturbation. We have characterized a sensitive marker of platelet activation, which is abnormal in SLE patients who were positive for aPL and endothelial perturbation. This analytical approach may help identify those patients at increased risk of thrombosis as potential candidates for antiplatelet therapy.


Current aspects of therapeutic reduction mammaplasty for immediate early breast cancer management: An update.
Breast-conservation surgery (BCS) is established as a safe surgical treatment for most patients with early breast cancer. Recently, advances in oncoplastic techniques are capable of preserving the breast form and quality of life. Although most BCS defects can be managed with primary closure, the aesthetic outcome may be unpredictable. Among technical options, therapeutic reduction mammaplasty (TRM) remains a useful procedure since the BCS defect can be repaired and the preoperative appearance can be improved, resulting in more proportional breasts. As a consequence of rich breast tissue vascularization, the greater part of reduction techniques have based their planning on preserving the pedicle of the nipple-areola complex after tumor removal. Reliable circulation and improvement of a conical shape to the breast are commonly described in TRM reconstructions. With an immediate approach, the surgical process is smooth since both procedures can be carried out in one operative setting. Additionally, it permits wider excision of the tumor, with a superior mean volume of the specimen and potentially reduces the incidence of margin involvement. Regardless of the fact that there is no consensus concerning the best TRM technique, the criteria is determined by the surgeon's experience, the extent/location of glandular tissue resection and the size of the defect in relation to the size of the remaining breast. The main advantages of the technique utilized should include reproducibility, low interference with the oncological treatment and long-term results. The success of the procedure depends on patient selection, coordinated planning and careful intra-operative management.


Do grandmaternal smoking patterns influence the etiology of childhood asthma?
Animal data suggest that tobacco smoke exposure of a mother when she is in utero influences DNA methylation patterns in her offspring and that there is an effect on the respiratory system, particularly airway responsiveness. The only study, to our knowledge, in humans suggests that there is a similar effect on asthma. The present study tests whether an association with respiratory problems can be confirmed in a large population study and aims to determine whether in utero exposure of the father has similar effects on his offspring. Information from the Avon Longitudinal Study of Parents and Children was used to compare the offspring of women and of men who had themselves been exposed to cigarette smoke in utero; separate analyses were performed for children of women smokers and nonsmokers. The outcome measures were trajectories of history of early wheezing, doctor-diagnosed asthma by age 7 years, and results of lung function and methacholine challenge tests at 8 years. A variety of social and environmental factors were taken into account; offspring sexes were examined separately. There was no association with any outcome in relation to maternal prenatal exposure. There was some evidence of an increase in asthma risk with paternal prenatal exposure when the study mother was a nonsmoker (adjusted OR, 1.17; 95% CI, 0.97-1.41). This was particularly strong for girls (adjusted OR, 1.39; 95% CI, 1.04-1.86). We did not find that maternal prenatal exposure to her mother's smoking had any effect on her children's respiratory outcomes. There was suggestive evidence of paternal prenatal exposure being associated with asthma and persistent wheezing in the granddaughters.


Workplace Experiences of Women With Disability in Sport Organizations.
Women with disability often experience barriers to employment and career progression, most notably in hyper-masculinised industry sectors such as sport. Applying an intersectionality lens and insights from critical disability theory, this research explores the lived experiences of eight women with varying types of disability through their stories of working and volunteering in sport organizations in Victoria (Australia). Analyses of the interviews highlighted the importance that these women attached to their identity as a woman with disability and the intrapersonal and organizational factors that impacted on initial sport workplace attraction and retention. The findings discuss the relationship management strategies adopted to manage these factors in workplace interactions. The interactive effect between disability and gender contributes to building a meaningful understanding of the intersectionality for women with disability in sport organizations.


Calcium absorption from three salts and CaSO(4)-fortified bread in premenopausal women.
Two studies were conducted to measure calcium absorption from calcium sulfate fortified bread and three salts (calcium lactate, calcium carbonate, and calcium sulfate) in healthy premenopausal women using a crossover design. In study I, calcium fractional absorption levels from the three salts labeled with a stable isotope, 44Ca, were not significantly different (0.039-0.47) as determined by the fecal recovery method. In a second study, absorption of 45Ca from CaSO(4)-fortified labeled bread or labeled milk was measured in serum exactly 5 h postingestion. Fractional calcium absorption was slightly but significantly greater from fortified bread than from milk (mean within subject difference = 0.0675 +/- 0.016). Calcium sulfate is a bioavailable fortificant for white bread that compares favorably with milk and two other salts.


Use of virtual reality in managing paediatric procedural pain and anxiety: An integrative literature review.
This integrative review aimed to identify, analyse and synthesise studies investigating the clinical efficacy of virtual reality (VR) distraction for children undergoing varying painful and anxiety-inducing medical procedures across different hospital settings and to identify implications for research and clinical practice. Virtual reality has been leveraged as a distraction tool in the healthcare setting to help patients manage procedural pain and anxiety. Initial studies in the burn wound care setting using VR as a non-pharmacological analgesia led to the use of VR during other medical procedures. An integrative review of the literature was conducted following the PRISMA guidelines across four electronic databases. Published studies between 2000 and 2020 investigating the clinical efficacy of VR in managing paediatric procedural pain or anxiety were included for review. Reviewed studies collectively included 2,174 patients aged 6 months-18 years used VR during burn wound care, post-burn physiotherapy, dental, needle-related and other procedures. Additionally, ten studies included samples with adults, for which paediatric data could not be isolated (n = 507). Overall, studies supported the efficacy of VR in managing procedural pain and anxiety in the paediatric setting. Virtual reality is redefining pain management by immersing children in a virtual world, reducing pain and anxiety at the hospital. A notable gap was the neglected use of VR in children with chronic conditions receiving orthopaedic procedures as part of their standard care. Ultimately, VR distraction will reduce the fear associated with medical interventions, preventing increased pain sensitivity, exacerbated anxiety and healthcare avoidance in adulthood. Nurses will play an important role in ensuring the smooth integration of VR in clinical practice by championing the technology and transferring evidence-based methods for VR use.


Transcription factor expression in cell lines derived from natural killer-cell and natural killer-like T-cell leukemia-lymphoma.
Although a number of transcription factors (TFs) have been identified that play a pivotal role in the development of hematopoietic lineages, only little is known about factors that may influence development and lineage commitment of natural killer (NK) or NK-like T (NKT)-cells. Obviously to fully appreciate the NK- and NKT-cell differentiation process, it is important to identify and characterize the TFs effecting the NK- and NKT-cell lineage. Furthermore, these TFs may play a role in NK- or NKT-cell leukemias, in which the normal differentiation program is presumably disturbed. The present study analyzed the expression of the following 13 TFs: AML1, CEBPA, E2A, ETS1, GATA1, GATA2, GATA3, IKAROS, IRF1, PAX5, PU1, TBET and TCF1 in 7 malignant NK-cell lines together with 5 malignant NKT-cell lines, 5 T-cell acute lymphoblastic leukemia (ALL) cell lines including 3 gamma/delta T-cell receptor (TCR) type and 2 alpha/beta TCR type, and 3 B-cell precursor (BCP) leukemia cell lines. AML1, E2A, ETS1, IKAROS and IRF1 were found to be positive for all cell lines tested whereas GATA1 turned out to be universally negative. CEBPA, PAX5 and PU1 were negative for all cell lines tested except in the three positive BCP-cell lines. GATA2 was positive for 3/5 T-cell lines but negative for the other cell lines. GATA3 was positive for 7/7 NK-, 4/5 NKT-, 5/5 T- and 2/3 BCP-cell lines. TBET was positive for all NK- and NKT-cell lines and negative for all T- and BCP-cell lines except one BCP-cell line. In contrast to the expression of TBET, TCF1 was negative for all NK- and NKT-cell lines, being positive for 4/5 T- and 1/3 BCP-cell lines. Expression analysis of TFs revealed that NK- and NKT-cell lines showed identical profiles, clearly distinct from those of the other T-ALL or BCP-ALL leukemia-derived cell lines..


[A case of diabetic glomerulosclerosis without concurrent diabetes mellitus].
Diabetic nephropathy is a complication of diabetes mellitus that is characterized by the appearance of diffuse and nodular glomerulosclerosis A 46-year-old man presented with generalized edema. He had severe nephrotic syndrome, renal insufficiency and hypertension without a family history or clinical evidence of diabetes mellitus. Oral glucose tolerance test showed impaired glucose tolerance, but several fasting plasma glucose determinations and serum hemoglobin A1c levels were normal. Renal biopsy revealed nodular and diffuse glomerulosclerosis characteristic of diabetic nephropathy. The present case demonstrates that nodular glomerulosclerosis may be present without clinically overt diabetes mellitus.


Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine.
Helper T cells are classified into Th1 and Th2 subsets based on their profiles of cytokine production. Th1 cells are involved in cell-mediated immunity, whereas Th2 cells induce humoral responses. Selective recruitment of these two subsets depends on specific adhesion molecules and specific chemoattractants. Here, we demonstrate that the T cell-directed CC chemokine thymus and activation-regulated chemokine (TARC) was abundantly produced by monocytes treated with granulocyte macrophage colony stimulating factor (GM-CSF) or IL-3, especially in the presence of IL-4 and by dendritic cells derived from monocytes cultured with GM-CSF + IL-4. The receptor for TARC and another macrophage/dendritic cell-derived CC chemokine macrophage-derived chemokine (MDC) is CCR4, a G protein-coupled receptor. CCR4 was found to be expressed on approximately 20% of adult peripheral blood effector/memory CD4+ T cells. T cells attracted by TARC and MDC generated cell lines predominantly producing Th2-type cytokines, IL-4 and IL-5. Fractionated CCR4+ cells but not CCR4- cells also selectively gave rise to Th2-type cell lines. When naive CD4+ T cells from adult peripheral blood were polarized in vitro, Th2-type cells selectively expressed CCR4 and vigorously migrated toward TARC and MDC. Taken together, CCR4 is selectively expressed on Th2-type T cells and antigen-presenting cells may recruit Th2 cells expressing CCR4 by producing TARC and MDC in Th2-dominant conditions.


The first 3 years of Medicare prospective payment: an overview.
This article provides a synopsis of the available evidence on the impact of the Medicare prospective payment system (PPS) for hospitals over the first 3 years of its implementation. The impact of PPS on hospitals, Medicare beneficiaries, post-hospital care, other payers for inpatient hospital services, other health care providers, and Medicare program operations and expenditures is examined.


Guidelines in Practice: Preoperative Patient Skin Antisepsis.
Surgical site infections (SSIs) frequently involve resident bacteria (eg, Staphylococcus aureus) on the patient's skin. Strategies to help prevent SSIs include removing soil and transient microorganisms from the skin before surgery. Preoperative decolonization, preoperative bathing, and application of an effective skin antiseptic at the surgical site are components of a multimodal approach to reducing microorganisms to subpathogenic levels. As members of an interdisciplinary team, perioperative RNs are essential in the development and implementation of SSI prevention bundles to promote patient safety. This article discusses recommendations from the AORN "Guideline for preoperative patient skin antisepsis" for decolonization protocols, preoperative bathing, and selection of surgical site antiseptics. A scenario describes the process a facility team uses to determine components of an SSI prevention bundle after recognizing an increase in infections from multidrug-resistant organisms.


[Postmaterialism and fertility].
"Though changes in values have been analysed [for] two decades, their impact on actual behaviour has almost been neglected. This especially is the case with values concerning marriage and the family which [have been] responsible for behavioural changes. Here, the impact of emerging postmaterialistic values on fertility are analysed, deriving from the assumption that the effect of children on the general life-style is large enough to let fertility behaviour be influenced by general value orientations. The main result is that the emergence of postmaterialism has led to postponement of parenthood whereas the number of children is left untouched." (SUMMARY IN ENG)


Cementless fixation in revision total knee arthroplasty.
A surgical approach to revision total knee arthroplasty that includes minimal bone resection, minimal soft-tissue stripping, cementless fixation of the femoral and tibial components, and morselized allografting of defects was used and evaluated in 105 patients (110 knees) with severe bone loss. The patients were followed for 60 to 127 months postoperatively. Fixation included a tightly-fit fluted titanium stem in the femoral and tibial canals and rim contact on the peripheral rim of the tibia. One tibia loosened and one knee failed because of infection. Ligamentous stability and pain relief were consistent through the followup period. At 10 years the mean valgus laxity was 4 degrees +/- 2.5 degrees, and the mean varus laxity was 5.2 degrees +/- 3.3 degrees. Mean Knee Society pain score was 47 +/- 2.1. Pain was mild in 28 knees, moderate in eight knees, and severe in two knees. Evidence of bone healing occurred in the bone defects that could be seen on radiographs. Increase in radiodensity always was found at postoperative intervals greater than one year. An approach to revision total knee arthroplasty that maintains bone and soft tissue about the knee establishes an effective and durable construct. Therapeutic study, level II (prospective study). See Guidelines for Authors for a complete description of levels of evidence.


Correlation Between Caregiver Reports of Physical Function and Performance-based Measures in a Cohort of Older Adults With Alzheimer Disease.
The objectives of this report are to determine the association between performance-based measures of physical function with caregiver reports of physical function in older adults with Alzheimer disease (AD) and to examine whether those associations vary by the level of patients' cognitive functioning. Subjects included 180 patient-caregiver dyads who are enrolled in a clinical trial testing the impact of an occupational therapy intervention plus guideline-level care to delay functional decline among older adults with AD. The primary caregiver-reported measure is the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory (ADCS-ADL). Performance-based measures include the Short Physical Performance Battery and the Short Portable Sarcopenia Measure. Analysis of covariance (ANCOVA) models were used to determine the associations of each physical performance measure with ADCS-ADL, adjusting for cognition function and other covariates. We found significant correlations between caregiver reports and observed performance-based measures across all levels of cognitive function, with patients in the lowest cognitive group showing the highest correlation. These findings support the use of proxy reports to assess physical function among older adults with AD.


Borrelia burgdorferi-associated lymphocytoma cutis simulating a primary cutaneous large B-cell lymphoma.
The distinction between primary cutaneous B-cell lymphoma and B-cell pseudolymphoma on a histologic basis may be difficult, particularly in some cases of Borrelia burgdorferi-associated lymphoid proliferations. We report two cases of B. burgdorferi-associated pseudolymphoma that showed a dense infiltrate with a predominance of large atypical B cells. Because of this misleading histologic feature, a diagnosis of primary cutaneous large B-cell lymphoma was first suspected in both cases. In one case, successive recurrences led to aggressive therapies before the B. burgdorferi infection was recognized. However, a detailed review of histologic and immunohistochemical features was finally suggestive of a B. burgdorferi-associated pseudolymphoma in both cases. The etiologic role of B. burgdorferi was confirmed by serology, polymerase chain reaction analysis of B. burgdorferi DNA within the lesional skin, and response to antibiotic therapy. Because the distinction between B. burgdorferi-associated pseudolymphoma and primary cutaneous B-cell lymphomas may be difficult and true B. burgdorferi-associated B-cell lymphomas have been described, we suggest that antibiotic therapy should be considered as a first-line treatment in suspected or confirmed cases of primary cutaneous B-cell lymphoma in regions with endemic B. burgdorferi infection.


Primary testicular dysfunction is a major contributor to abnormal pubertal development in males with Prader-Willi syndrome.
Recent studies challenge the assumption that hypogonadism in Prader-Willi syndrome (PWS) is due only to hypothalamic dysfunction. The aims of the study were to characterize sexual development and reproductive hormones in PWS males and investigate the etiology of hypogonadism. Physical examination and blood sampling were performed on 37 PWS males, ages 4 months to 32 yr. All had a history of undescended testes; age at orchiopexy ranged from 2 months to 6 yr. Pubertal signs were variable, but none achieved full genital development. Anti-Mullerian hormone (AMH) levels in PWS boys were near the lower limits of normal, decreasing from 44.4 +/- 17.8 ng/ml (mean +/- sd) in young children to 5.9 +/- 4.7 ng/ml in adolescents, similar to normal males. In contrast, inhibin B was consistently low (27.1 +/- 36.1 pg/ml) or undetectable in all age groups. In adult males, FSH levels were high (20.3 +/- 18.3 IU/liter), LH levels were normal (4.2 +/- 4.3 IU/liter), and testosterone levels were low (1.87 +/- 1.17 ng/ml). Only two adults had severe hypogonadotropic hypogonadism with undetectable levels of LH and FSH and high AMH levels (34.9 and 36.7 ng/ml), unlike the other nine adults with AMH levels 2.6 +/- 2.1 ng/ml. Androstenedione (1.06 +/- 0.30 ng/ml) and DHEAS (281.1 +/- 143.6 microg/dl) in adult PWS were normal. Pubertal development in PWS is characterized by normal adrenarche, variable hypothalamic dysfunction, and hypogonadism due to a unique testicular defect. Primary testicular dysfunction is a major component of hypogonadism in PWS.


Influence of different light sources on microtensile bond strength and gap formation of resin cement under porcelain inlay restorations.
Clinical success with ceramic inlays/onlays has been assisted by the ability to develop a reliable bond of composite resin to dental tissues. The purpose of this study was to test the efficiency of two different light sources on microtensile bond strength and the gap formation of resin cement under class II porcelain inlay restorations. Standardized mesio-occlusal cavities were prepared in 30 freshly extracted, intact human premolar teeth. Then impressions were made and ceramic inlays were fabricated. In the cementation process, the resin cement/inlay combinations were exposed to two different photopolymerization units. The polymerizations through 15 specimens were performed with a conventional halogen light source for 60 s, and the other specimens were cured by a plasma arc light for 9 s. After the cementation process, two 1.2 x 1.2 mm wide 'I' shape sections per tooth were produced with a sectioning machine and sections were subjected to microtensile testing after 24 h or 1 week. Gap formation of specimens cured by different photopolymerization units were evaluated with scanning electron microscopy (SEM). Statistically significant differences were found between the microtensile bond strength of inlays exposed to conventional light and plasma arc curing unit (P < 0.001). Plasma arc curing units make it possible to polymerize composite in much shorter times than conventional curing unit. However, the samples polymerized with conventional halogen light produced better microtensile bond strength than the plasma arc unit.


Effects of upper body resistance training on pulmonary functions in sedentary male smokers.
Cigarette smoking is well correlated with lung diseases such as chronic obstructive pulmonary disease. It is common among men than women in India. In addition, sedentary lifestyle is associated with less efficient pulmonary function. Effectiveness of upper body resistance training (UBRT) in improving pulmonary function is unclear. Keeping all these factors in view, this study aims to examine the effect of UBRT on pulmonary function in male sedentary smokers. This study recruited 36 sedentary male smokers, of which 30 were randomized into two groups after fulfilling eligibility criteria-an exercising experimental group (EG) (N=15) or non-exercising control group (CG) (N=15). The EG group were assigned to exercise for 4 weeks, 3 times weekly on non-consecutive days using UBRT program and breathing exercise. In the CG, only breathing exercise was given for 10 min. Both groups were equivalent in baseline characteristics. The improvement in forced expiratory volume in one second (FEV(1)) and FEV(1)/forced vital capacity (FVC) values were seen significant in EG after 4 weeks of UBRT: from 3.62±0.56 to 3.96±0.51 (P=0.000) and 0.88±0.11 to 0.96±0.13 (P<0.001), respectively. But FVC did not show significant change in the EG (P=0.430). There were no significant changes in FEV(1), FVC, and FEV(1)/FVC values in CG after 4 weeks of intervention. On intergroup comparison, significant difference was found between CG and EG for FEV(1) and FEV(1)/FVC values. Four weeks of UBRT program brought about significant changes in the pulmonary function in male sedentary smokers.


[Consequences of oocyte dysmorphy on the fertilization rate and embryo development after intracytoplasmic sperm injection. A prospective multicenter study].
This prospective study aimed to evaluate the impact of oocyte dysmorphy on the fertilization rate and embryonic development rate in an ICSI programme. Three hundred and two couples have been included during 302 ICSI cycles, and 1970 oocytes have been studied in 4 ART centres. After decoronisation, 18 morphological criteria, including the size and shape of the oocyte, the thickness of the zona pellucida, the presence or not of debris in the perivitelline space, as well as the appearance of the cytoplasm and polar body have been noted. In total 61.3% of the oocytes presented a dysmorphy, involving, almost equally, the different oocyte compartments. Among the dysmorphic oocytes, half presented more than one anomaly. On average, 9.2% of the oocytes were lysed the day after the micro-injection. The oocytes presenting an enlarged perivitelline space, or multiple vacuoles had a significantly raised lyse rate, 16.3% and 27.8%, respectively. The day after micro-injection, 61.3% of the intact oocytes were fertilized. The rate of fertilization was correlated to the number of abnormalities per oocyte: 1 anomaly: 64.6%, > or = 3 anomalies: 54.6%. The oocytes presenting a large perivitelline space had a slightly lowered fertilization rate (53.4%). On the other hand, those showing a cytoplasm containing refractile bodies had a slightly raised fertilization rate (68.6%). We did not see any statistically significant difference between the different types of oocytes concerning embryonic development at d2. These results confirm and contribute new elements with respect to previously published data, showing that (i) oocyte morphology little affects fertilization and the first stages of embryonic development; (ii) certain dysmorphies, (enlargement of the perivitelline space) are specifically deleterious at certain stages in the process (lowering the fertilization rate); (iii) certain morphological differences (the presence of refringent bodies) are not anomalies, but can reflect physiological cellular changes.


Surgical and medical management of patients with pulmonary metastasis from parathyroid carcinoma.
The aim of this study was to characterize patients with pulmonary metastasis of parathyroid carcinoma and to evaluate the long-term effect of surgical and medical therapy. Seven patients with pulmonary metastasis of parathyroid carcinoma were treated between 1980 and 1992. Six patients underwent resection of pulmonary metastases, and one patient has had long-term bisphosphonate therapy alone. Bisphosphonate was also given before or after operation to three patients. Two patients underwent a unilateral thoracotomy for a single pulmonary lesion, and four other patients with multiple lesions underwent staged bilateral thoracotomies. The postoperative serum calcium level returned to normal after each thoracotomy in three patients who were alive and well 3, 8, and 12 years after the first thoracotomy. Hypercalcemia persisted in the other three patients. In two of the patients, bisphosphonate therapy was also unable to control hypercalcemia. In one patient the serum calcium level has been maintained in the 13 mg/dl range by bimonthly bisphosphonate therapy alone for 3 years. The aggressive surgical approach to pulmonary metastasis of parathyroid carcinoma was shown to be effective for palliation in selected patients. Bisphosphonate therapy is an alternative to resection but has only a temporary calcium-lowering effect.


Mortality in psittacine birds resembling Pacheco's disease in Spain.
The sudden death of five sulphur-crested cockatoos (Cacatua galerita) with no apparent clinical signs was investigated. The birds had hepatitis with intranuclear inclusion bodies (IIBs), as well as IIBs in mononuclear spleen cells, epithelial cells of the kidney tubules and endothelial cells of the glomerular capillaries. Ultrastructurally, icosahedral herpesvirus-like particles, 110 to 115 nm in diameter were found consistent with Pacheco's disease. This is the first time the disease has been reported in cockatoos in Spain.


Subjective well-being of the elderly in Xi Cheng District, Beijing.
In 2010 the Beijing Municipal Government promulgated a policy aimed at improving the quality of life and subjective well-being of elderly residents that included a component focused on mental health. Identify factors associated with subjective well-being in a representative sample of elderly residents of Xi Cheng District in Beijing. This cross-sectional study administered a self-completion survey to a stratified random sample of 2342 residents of Xi Cheng District who were 60 to 80 years of age. The level of well-being was assessed using a validated Chinese version of the Memorial University of Newfoundland Scale of Happiness (MUNSH). Detailed socioeconomic variables were obtained using a questionnaire developed by the authors. Social support, anxiety, and depression were assessed using validated Chinese versions of the Social Support Rating Scale (SSRS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Among the 2342 respondents, 1616 (69.0%) had a total MUNSH score of 32 or above, indicating a high level of happiness; 423 (18.1%) has a total SSRS score 32 or below, indicating poor social support; 201 (8.6%) had a total SDS score of 53 or above, indicating significant depression; and 126 (5.3%) had a total SAS score of 50 or above, indicating significant anxiety. In the multivariate regression analysis the self-reported level of depression was the most important factor related to well-being. Anxiety, social support, income level, the quality of family relationships, the ability to self-regulate emotions, and regular exercise were also significantly related to well-being; but gender, marital status, age and educational level were not associated with well-being. Among elderly urban residents in Beijing, self-reports of poor subjective well-being are closely associated with self-reports of depressive and anxiety symptoms and also associated with social factors such as social support, income level and family relationships. Prospective studies are needed to identify the causal relationships of these variables and, based on the findings, to develop targeted interventions aimed at improving the quality of life and well-being of elderly community members.


Identification of a novel enhancer of brain expression near the apoE gene cluster by comparative genomics.
Comparative analysis of the human and mouse genomic sequences downstream of the apolipoprotein E gene (APOE) revealed a highly conserved element with previously undefined function. In reporter gene transfection studies, this element which is located approximately 42 kb distal to APOE was found to have silencer activity in a subset of cell lines examined. Analysis of transgenic mice containing a fusion construct linking this distal 631 bp conserved element to a reporter gene comprised of the human APOE gene with its proximal promoter resulted in robust brain expression of the transgenic human apoE mRNA in three independent transgenic lines, supporting the identification of a novel brain controlling region (BCR). Further studies using immunohistochemistry revealed widespread human apoE localization throughout the brains of the BCR-apoE transgenic mice with prominent expression in the cortex and diencephalon. In addition, double-label immunofluorescence performed on brain sections and cultures of primary cortical cells localized human apoE protein to cortical neurons and microglia. These studies demonstrate that comparative sequence analysis is a successful strategy to predict candidate regulatory regions in vivo, although they do not imply that this element controls apoE expression physiologically.


[Analysis of enzyme activity and the level of malondialdehyde in the saliva of children with gingivitis].
By analysing activity of some of the enzymes normally present in the saliva and the level of malondialdehyde in gingivitis, it is possible to estimate the functional condition of parodontium, and the examined parametres can be considered as biochemical markers of its functional condition. The aim of this paper was to examine activity of alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase and the level of malondialdehyde in the saliva of children affected with gingivitis, as well as the values of the mentioned parametres in relation to the level of the inflammation of gingiva. The research included 120 children at the age of 12.2 with permanent dentition. Löe and Silness gingival index was used to estimate the condition of gingiva, based on which the childen were classified into four groups: the children with healthy gingiva (the control groups), the children with mild, moderate and severe inflammation of gingiva (the study group). Enzymes of the saliva were determined by the use of original tests and measured by the autoanalyser (Bio Systems A25, Spain). A modified method with tiobarbituric acid was used to determine malondialdehyde in nonstimulated mixed saliva. The results of the examined enzyme activity and the level of malondialdehyde in the saliva of the study groups showed statistically considerably higher values for the level of malondialdehyde (p < 0.001), for the activity of aspartate aminotransferase and gamma glutamyl transferase (p < 0.01), as well as for alanine aminotransferase (p < 0.05) in comparison with the control group, whereas the activity of lactate dehydrogenase did not show a statistically significant increase. In relation to the level of the inflammation of gingiva, the results of the examination of the enzyme activity in the study groups showed statistically significantly higher values in the group with severe inflammation in comparison with those with mild, as well as the moderate inflamatiory, except for the gamma glutamyl transferase, and in the group with moderate inflammation compared to that with the mild one, except for alanine aminotransferase. The results of the examination of the level of malondialdehyde in the saliva of the study groups did not show a statistically significantly increase in relation to the level of the inflammation of gingiva. There is a higher level of alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and lactate dehydrogenase enzyme activity together with the higher level of malondialdehyde in the saliva of children with gingivitis in comparison with the activity of the same enzymes and the level of malondialdehyde in the saliva of children without gingivitis. The activity of the examined enzymes in the saliva of children with gingivitis increases in relation to the intensity of the pathological process, whereas the level of malondialdehyde shows no significant difference in relation to the level of the inflammation of gingiva.


Methylation of deoxycytidine in replicating cells treated with ultraviolet radiation and chemical carcinogens.
5-Methyl-2'-deoxycytidine (m5dC) levels were measured in DNA from three types of cultured cells following treatment with u.v. radiation and two chemical carcinogens, N-methyl-N-nitrosourea (MNU) and N-acetoxy-2-acetylaminofluorene (NA-AAF). Control values for m5dC in Raji cells (a human lymphoblastoid cell line), S49 cells (a mouse thymic lymphoma cell line) and human diploid fibroblasts are 3.6%, 3.6% and 3.2%, respectively. None of the damaging agents produced a detectable change in methylation levels of newly replicated DNA, even at levels of damage that inhibited replication by 95%. In contrast, treatment with 5-aza-2'-deoxycytidine, a known methyltransferase inhibitor, transiently reduced genomic methylation by 89% and 74% in Raji and S49 cells, respectively. Although other investigators have found a marked reduction in m5dC in DNA replicated after carcinogen treatment, our experiments indicate that extensive demethylation is not a necessary consequence of DNA damage.


The Need of Support and Service Questionnaire (NSSQ): a brief scale to assess needs in clients with long-term mental disabilities.
We present the Need of Support and Service Questionnaire (NSSQ), a new instrument developed to provide professionals in psychiatric care and community social services with a tool to assess needs of support and service in mentally disabled clients. The final version of the instrument was designed after comments from professionals in psychiatric care, community social services, and the clients and their relatives. A reliability study (test-retest, n=77), inter-rater (n=69) and a validity study (n=529) were performed. In the validity study, comparisons were done with the Camberwell Assessment of Need (CAN) scale, the Global Assessment of Functioning (GAF) scale and the Social and Occupational Functioning Assessment Scale (SOFAS). The test-retest and inter-rater reliability were 0.86 and 0.76, respectively. The percentage of agreement on the individual items ranged from 83.1% to 100.0% (test-retest) and 76.8% to 100.0% (inter-rater reliability). The corresponding kappa coefficients ranged from 0.63 to 1.00 (test-retest) and 0.33 to 1.00 (inter-rater reliability). The comparison between NSSQ and CAN items demonstrated high sensitivity and specificity as well as satisfactory likelihood ratios (LRs). The correlations between GAF and SOFAS scores and the number of needs of support, number of needs of service and the total number of needs of support and service were -0.49, -0.32 and -0.47, and -0.48, -0.26 and -0.45, respectively. All correlations were statistically significant (P<0.01). The results demonstrated that the psychometric characteristics of the NSSQ were satisfactory. Moreover, professionals without any formal training easily used it.


Tennis elbow.
Tennis elbow is the most common cause of lateral-sided elbow pain with a major socioeconomic impact. The etiology of tennis elbow is not completely understood, but there are many different treatment options. This review gives an overview of the current concepts of diagnosis and treatment of tennis elbow and the impact on work participation.


Meta-analysis of binary outcomes from two-by-two tables when the length of follow-up varies and hazards are proportional.
Odds ratios (ORs) and relative risks (RRs) are sensitive to the length of follow-up. In meta-analyses, pooling such results from studies with different lengths of follow-up may lead to an artificial heterogeneity and discrepancy caused by the choice of the summary index. In this article, we explore the utility of a meta-analysis method that uses the ratio of logarithms of survival probability as the measure of association, and that avoids the problems mentioned above when hazards are proportional. Meta-analyses of ORs, RRs and ratios of logarithms of survival probability are compared through a simulation study, in which data are simulated from a proportional hazard model and the length of follow-up varies across studies using realistic patterns of variability. Results show that the heterogeneity increases with the variability of length of follow-up for OR and RR, but not for the ratio of the logarithms of survival probability. A published meta-analysis is used to illustrate the method.


The low-density lipoprotein receptor gene family: a cellular Swiss army knife?
The low-density lipoprotein receptor gene family is an evolutionarily conserved group of cell-surface receptors produced by mammals and other organisms. Initially thought to be endocytic receptors that mediate the uptake of lipoproteins, recent findings have shown that these receptors have other roles in a range of cellular processes. Among other activities, members of this family act as signal transducers in neuronal migration processes, regulate synaptic plasticity or control vitamin homeostasis. Such multifunctionality is achieved by interaction with diverse cell-surface proteins including glycolipid-anchored receptors, G-protein-coupled receptors and ion channels. Here, we review the molecular interactions of this protein family with other cell-surface proteins that provide specificity and versatility - a versatility that may be reminiscent of a cellular Swiss army knife.