Indications for performing flexible bronchoscopy: Trends over 34 years at a tertiary care hospital.
Due to its easy maneuverability, patient comfort and documented safety as an outpatient procedure, flexible bronchoscopy (FB) has replaced rigid bronchoscopy for routine diagnostic use. Herein, we report our 34-year experience with outpatient performance of FB. This was a retrospective analysis of all FB procedures performed between September 1979 and November 2013 (period I: 1979-1990; period II: 1991-2000; period III: 2001-2013) in a tertiary care hospital. Demographic profile of patients, indications for performing FB, and annual and seasonal trends were noted from the records. A total of 24,814 bronchoscopies were performed during the study period. The mean (SD) age of patients (71.6% males) was 48.4 (15.5) years. The number of procedures performed per decade showed an absolute increase by 322%. The most common indication for FB was suspected bronchogenic carcinoma (32.2%) followed by pulmonary infections (18.6%) and interstitial lung diseases (13%). The proportion of annual cases due to interstitial lung diseases (3.9% in period I to 16.2% in period III) increased over the years, whereas disorders such as hemoptysis and pleural effusion showed a declining trend as an indication for FB. A seasonal trend was observed for diseases such as sarcoidosis, bronchogenic carcinoma and pulmonary infections. Six deaths were encountered during the study period in patients undergoing FB. FB is increasingly being performed in the diagnosis of respiratory disorders and is a safe outpatient procedure. Although bronchogenic carcinoma remains a common indication for performing FB, benign conditions such as pulmonary infections and sarcoidosis constitute important indications in the Indian scenario.


Chorioretinal folds and a macular hole secondary to craniofacial surgery.
Chorioretinal folds have been reported as a result of many intraocular and extraocular inflammatory processes or tumors. Visual loss is usually secondary to a combination of the underlying process and chorioretinal folds involving the macula. We report a patient who developed decreased vision, metamorphopsia, chorioretinal folds, and a lamellar macular hole secondary to global compression by a bone fragment. The chorioretinal folds regressed and his vision stabilized following surgical decompression. Chorioretinal folds and lamellar macular hold formation are previously unrecognized complications of reconstructive craniofacial surgery.


Influence of viral hepatitis status on operative morbidity and mortality in patients with primary hepatocellular carcinoma.
The influence of associated viral hepatitis status on 119 patients with primary hepatocellular carcinoma (HCC) undergoing hepatic resection was investigated. Operative morbidity and mortality were examined in three patient groups: 31 patients (group B) positive for hepatitis B surface antigen (HBsAg), 14 (group Be) positive for both HBsAg and hepatitis B e antigen, and 74 (group C) positive for hepatitis C virus antibody (HCVAb). Preoperative liver function in groups Be and C was similar and more impaired than that of patients in group B; combined active hepatitis was seen most frequently in group C (68 per cent). The tumour size in group B was significantly greater than that in groups Be and C. Postoperative complications occurred more frequently in group C (39 per cent) and early postoperative deaths, other than those from cancer, were seen in nine patients positive for HCVAb, of whom three developed postoperative liver failure. Patients with HCC and hepatitis B without seroconversion as well as hepatitis C frequently have active hepatitis, which may impair liver function and play an important role in operative morbidity and mortality.


Tracheoesophageal fistula--a complication of prolonged tracheal intubation.
Tracheoesophageal fistula most commonly occurs as a complication of prolonged tracheal intubation. The incidence decreased after the use of low pressure and high volume endotracheal cuffs, but the intensive care units continue to provide such cases. The abnormal tracheoesophageal communication causes pulmonary contamination (with severe suppuration) and impossibility to feed the patient. The prognosis is reserved, because most patients are debilitated and ventilator dependent, with severe neurological and cardiovascular diseases. The therapeutic options are elected based on respiratory, neurological and nutritional status. The aim of conservative treatment is to stop the contamination (drainage gastrostomy, feeding jejunostomy) and to treat the pulmonary infection and biological deficits. Endoscopic therapies can be tried in cases with surgical contraindication. Operation is addressed to selected cases and consists in the dissolution of the fistula, esophageal suture with or without segmental tracheal resection associated. Esophageal diversion is rarely required. The correct indication and timing of surgery, proper surgical technique and postoperative care are prerequisites for adequate results.


Alcohol and substance dependence in the United Arab Emirates: a scoping review protocol.
Despite cultural, religious and legal constraints, alcohol and drug abuse is rising in the United Arab Emirates (UAE). Therefore, we aim to produce a scoping review to summarise available scientific literature on alcohol and substance dependence (ASD) in all ethnic and religious groups in the UAE to inform future scientific inquiries. Social work faculty from the UAE University will conduct the scoping review between March 2023 and February 2024. Drawing on the participants, concept, context (PCC) framework, the following review question was developed: What can be learnt from a review of scientific literature on alcohol and substance abuse in all ethnic and religious groups in the UAE? The scientific literature on ASD in the UAE published between 1971 and January 2023, in either English or Arabic, will be considered, including all ethnic, religious and age groups. Grey literature, such as postgraduate dissertations and conference proceedings, will also be considered. Eight English and two Arabic databases and print copies of literature sources in university libraries will be included. EndNote and Covidence software will be used for deduplication, screening and data extraction. Screening and reviewing search results will involve two English-speaking and two Arabic-speaking team members who will work independently. A third reviewer will resolve conflicts. The inter-rater reliability data from the title and abstract screening stage will be exported, and Cohen's kappa coefficient will be calculated. Data charting informed by the Covidence data extraction tool 2.0 will occur after pilot testing, followed by qualitative content analysis. Reporting of the findings will align with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews tool. Ethical approval is not required for this study because this is a scoping review of published studies and grey literature. Findings will be disseminated via peer-reviewed journal publications, scientific conferences and a policy brief.


Hepatitis B among pregnant women attending health care facilities in rural Bangladesh.
This study assessed hepatitis B prevalence among pregnant women attending health care facilities in rural Bangladesh. Blood samples were collected from 480 participants. HBsAg was positive in 0.4% of subjects, anti-HBc was positive in 21.5% and anti-HBs was positive in 8.5% of subjects. HBsAg was more prevalent among the older age group. Hepatitis B has a low prevalence among pregnant women in rural Bangladesh. Existing hepatitis B vaccination schedule in the Expanded Program on Immunization (EPI) to vaccinate the children in rural Bangladesh is appropriate.


Copper halide-incorporated tellurium-iron carbonyl complexes: transformation, electrochemical properties, and theoretical calculations.
When the tellurium-capped tri-iron carbonyl cluster [Et(4)N](2)[TeFe(3)(CO)(9)] was treated with 1 equiv of CuX in THF at 0 degrees C, CuX-incorporated clusters [Et(4)N](2)[TeFe(3)(CO)(9)CuX] (X = Cl, [Et(4)N](2)[1a]; Br, [Et(4)N](2)[1b]; I, [Et(4)N](2)[1c]) were formed, respectively. X-ray analysis showed that 1a-1c each exhibited a TeFe(3) core with one Fe-Fe bond bridged by one CuX fragment. When the reactions were carried out at a molar ratio of 1:2 (X = Cl, Br) or 1:3 (X = I) in tetrahydrofuran (THF) or MeCN at 0 degrees C, Cu(2)X(2)-incorporated clusters [Et(4)N](2)[TeFe(3)(CO)(9)Cu(2)X(2)] (X = Cl, [Et(4)N](2)[2a]; Br, [Et(4)N](2)[2b]; I, [Et(4)N](2)[2c]) were obtained, respectively. Cluster 2a was structurally characterized by X-ray analysis to display a TeFe(3) core, in which one TeFe(2) plane was asymmetrically bridged and capped by one mu(3)-CuCl and another mu(4)-CuCl with two Cu atoms bonded. Complexes 1a-1c underwent skeleton expansion to form Cu(3)X-incorporated di-TeFe(3) clusters [{TeFe(3)(CO)(9)}(2)Cu(3)X](2-) (X = Cl, 3a; Br, 3b; I, 3c), respectively, upon treatment with 1 equiv of [Cu(MeCN)(4)][BF(4)] at 0 degrees C. X-ray analysis showed that 3b and 3c each consisted of two TeFe(3) clusters that were linked by a Cu(3)X moiety. However, a similar reaction for 1a and 1b with 1 equiv of [Cu(MeCN)(4)][BF(4)] at room temperature produced Cu(4)X(2)-linked di-TeFe(3) clusters [{TeFe(3)(CO)(9)}(2)Cu(4)X(2)](2-) (X = Cl, 4a; Br, 4b). Cluster 4a was shown by X-ray analysis to have two TeFe(3) cores linked by a Cu(4)Cl(2) moiety. Clusters 4a and 4b were also produced directly from the reaction of [Et(4)N](2)[TeFe(3)(CO)(9)] with 4 equiv of CuX (X = Cl, Br) in THF. Furthermore, the nature, the formation, the cluster transformation, and the electrochemistry of the CuX-incorporated mono- or di-TeFe(3) clusters are explained in terms of the effects of tellurium, copper halide, and the size of the metal skeleton, all of which are elucidated by molecular calculations at the B3LYP level of density functional theory.


Anonymous-authentication scheme based on fog computing for VANET.
Privacy protection in vehicular ad hoc networks (VANETs) has always been a research hotspot, especially the issue of vehicle authentication, which is critical to ensure the safe communication of vehicles. However, using the real identity in the process of authentication can easily result in a leak of the privacy information of the vehicles. Therefore, most existing privacy-protection schemes use anonymous authentication and require one-to-one communication between vehicles and the trusted authority (TA). However, when the number of vehicles is too large, network congestion can take place. In addition, the process of updating the anonymous by the TA or the vehicle itself, can result in both poor real-time performance and leakage of the system master key. To solve these problems, this study proposes a fog-computing-based anonymous-authentication scheme for VANETs; the scheme reduces the communication burden of the TA by enabling self-authentication between vehicles and road-side units (RSUs), thus improving the vehicle-authentication efficiency. For updating the anonymous, we design a fog-computing-based pseudonym-updating and -tracking strategy, which guarantees real-time communication and reduces the instances of re-authentication interactions for legitimate vehicles. The experimental results show that the scheme not only meets the privacy-protection requirements of VANETs but also offers better performance than that of the existing anonymous-authentication schemes.


Occipital condyle fractures.
There is insufficient evidence to support diagnostic standards. Computed tomographic imaging is recommended for establishing the diagnosis of occipital condyle fractures. Clinical suspicion should be raised by the presence of one or more of the following criteria: blunt trauma patients sustaining high-energy craniocervical injuries, altered consciousness, occipital pain or tenderness, impaired cervical motion, lower cranial nerve paresis, or retropharyngeal soft tissue swelling. Magnetic resonance imaging is recommended to assess the integrity of the craniocervical ligaments. There is insufficient evidence to support treatment standards. There is insufficient evidence to support treatment guidelines. Treatment with external cervical immobilization is recommended.


The aging population and Natural Occurring Retirement Communities (NORCs); local government, healthy aging, and healthy-NORCs.
The term Naturally Occurring Retirement Communities (NORCs) has been used since the 1980s. NORCs are defined as communities where people remain or move to when they retire. NORCs develop 'naturally', meaning that seniors tend to remain or move there when they retire, although the residences and physical environment were not constructed for a senior population. The term, Healthy-NORC, has been introduced and is associated with healthy aging. We describe how demographic trends will facilitate a dramatic growth in NORCs. Acknowledging the 'Determinants of Health' model, we suggest that some determinants impact people differently at different ages. We also suggest that more attention be focused on the impact of physical/social environments on health, and that some determinants of health are particularly relevant for seniors. We argue that NORCs exist on a spectrum, from NORC to H-NORC, and that health benefits for seniors increase as NORCs adopt additional characteristics associated with improved senior health. We also illustrate H-NORC research methods and policy options for local governments. Compared to the provision of additional medical and social services, H-NORCs represent a low-cost approach to facilitating healthy aging. Municipal governments can promote healthy aging and should pursue policies that will stimulate H-NORC development.


Dietary sulfur amino acid requirement of juvenile yellow perch fed the maximum cystine replacement value for methionine.
We conducted three separate experiments designed to determine the dietary methionine requirement, ability of cyst(e)ine to spare methionine, and the total sulfur amino acid requirement (TSAA) of juvenile yellow perch when fed the maximal amount of cyst(e)ine. The purified basal diet used in each experiment contained 33.6 g of crude protein/100 g diet and 12.0 g of lipid/100 g diet. In the first experiment,;>L-methionine was added to eight diets providing methionine concentrations ranging from 0.37 to 1.77 g/100 g diet in gradations of 0.2 g/100 g diet. Diets were fed for 12 wk to juvenile yellow perch initially weighing 4.7 g/fish. Broken-line analyses of weight gain and feed efficiency data indicated that the dietary methionine requirement was 1.0 g/100 g diet (3.1 g TSAA/100 g dietary protein) and 1.1 g/100 g diet (3.4 g TSAA/100 g dietary protein), respectively. In the second experiment, various ratios of L-cyst(e)ine and L-methionine were added to the basal diet and fed for 12 wk to determine the cyst(e)ine replacement value of yellow perch initially weighing 19.3 g/fish. Weight gain and feed efficiency (FE) data indicated that cyst(e)ine spared up to 51% of the methionine requirement. In the final experiment, graded levels of cyst(e)ine plus methionine in a ratio of 51:49 were added to the basal diet in gradations of 0.1 g/100 g diet (0.5 to 1.2 g TSAA/100 g diet) to determine the dietary total sulfur amino acid requirement. Diets were fed to satiation for 10 wk to fish initially weighing 8. 1 g. Broken-line analyses of weight gain, feed intake and FE data indicated that the dietary TSAA requirement was 0.85, 0.87 and 1.0 g of TSAA/100 g diet (2.5 to 3.0 g of TSAA/100 g of dietary protein), respectively. The majority of dietary TSAA requirements of fish are in the range of 2 to 4 g/100 g of dietary protein and are generally similar to those of both birds and swine, but lower than estimates for rodents.


The prevalence and pattern of pneumatization of Onodi cell in Thai patients.
The Onodi cell (sphenoethmoidal cell) is an anatomical variation of the most posterior ethmoid air cell the pneumatizes laterally and/or superiorly to the sphenoid sinus and is intimately in contact with the optic nerve. If it is infected or goes unrecognized during surgery it may result in serious damage to the optic nerve. Nowadays, computed tomographic scans of paranasal sinuses (CT PNS) have been used to detect variations in paranasal sinus anatomy However there is a lack of data about the variations of Onodi cell. To determine the prevalence and various patterns of Onodi cell. Axial, coronal, sagittal and sagittal oblique (parallel to the optic canal) CT scans of the paranasal sinuses, nasopharynx, neck and orbit performed at Srinagarind Hospital between January 1, 2004 and November 30, 2006 were reviewed A pilot study was carried out to investigate the inter-rater reliability of the identification of Onodi cell between the radiologist and rhinologist until the kappa value was 0.74. During the main study, the radiologist and rhinologist interpreted the CT scans independently. If there was a discordant opinion concerning the presence of Onodi cell, a consensus was reached by discussion between the rhinologist and the radiologist. 187 CT scans (374 sides) were included Sagittal oblique view detected Onodi cell in 185 sides 49.5% (95% CI: 44.4-54.5). The patterns of Onodi cell were classified into three patterns. In the first pattern, the Onodi cell extended only superiorly to sphenoid sinus (46%; 95% CI: 38.9-53.1). In the second pattern, it extended only laterally to sphenoid sinus (1%; 95% CI: 0.3-3.9). The last pattern was a combined type, lateral and superior to sphenoid sinus (53%; 95% CI: 45.8-60.0). The prevalence of Onodi cell diagnosed by CT scans was 49.5% (95% CI 44.4-54.5) and the most common pattern was the combined type. This information may be useful for those who perform endoscopic sinus surgery.


[Patient with Gerstmann-Striussler-Scheinker syndrome (GSS P102L) presenting high intensity lesions in the cerebral cortex on diffusion weighted MRI].
A 59-year-old woman with Gerstmann-Sträussler-Scheinker syndrome (GSS P102L) was reported. She slowly developed progressive gait disturbance and limb ataxia by the age of 58, subsequently followed by dementia and myoclonus. EEG showed periodic synchronous discharges, and MRI by diffusion weighted imaging revealed abnormal high signal intensity lesions in the bilateral cerebral cortex and basal ganglia. A prorin-for-leution substitution at codon 102 of the prion protein gene was demonstrated; and thus, she was diagnosed as GSS (P102L). This is a case of GSS presenting high intensity lesions in the cerebral cortex on diffusion weighted MRI; it suggests that MRI findings disease stages in GSS.


[The biological importance of C-reactive proteins in non-specific defense mechanisms].
The C-reactive serum protein (CRP) is a classical acute-phase reactant of increasing diagnostical value in clinical practice. It is drastically elevated during reactions of inflammation and tissue destruction, and it binds selectively to necrotic cells of inflamed tissue. The phylogenetically rather ancient protein displays a cyclic pentameric symmetry (pentraxin). CRP undergoes specific binding to phosphocholine esters, polycations and galactans (lectin character). Aggregated CRP activates complement, has opsonin properties and interacts with lymphocytes and thrombocytes. Probably CRP is part of an early unspecific protective mechanism, whereby potentially toxic materials can be detected and eliminated.


Design and Evaluation of the Veterinary Epidemiology Teaching Skills (VETS) Workshop: Building Capacity in the Asia-Pacific Region.
Building workforce capacity in epidemiology skills for veterinarians in the Asia-Pacific region is crucial to health security. However, successful implementation of these programs requires a supply of trained veterinary epidemiology teachers and mentors. We sought to design and evaluate delivery of a 4-day Veterinary Epidemiology Teaching Skills (VETS) workshop as part of a larger project to strengthen field veterinary epidemiology capacity. Thirty-five veterinarians were selected to participate in the 4-day VETS workshop, consisting of nine modules delivered synchronously online. Participants were formatively assessed and given feedback from peers and facilitators on all activities. Data were collected with pre- and post-course questionnaires. Numeric values were categorized to convert into an ordinal scale with four categories. Qualitative data were analyzed using thematic analysis. Thirty-four veterinary epidemiologists from eight countries of the Asia-Pacific completed the workshop. Participants felt able to achieve most key learning outcomes through provision of succinct literature, teaching frameworks, and active participation in small groups, with multiple opportunities to give and receive feedback. Although the online workshop provided flexibility, participants felt the addition of face-to-face sessions would enrich their experience. Additionally, protected time from work duties would have improved their ability to fully engage in the workshop. The VETS workshop granted an effective online framework for veterinary epidemiologists to develop and practice skills in teaching, facilitation, assessment, feedback, case-based learning, program evaluation, and mentorship. A challenge will be ensuring provision of local teaching and mentoring opportunities to reinforce learning outcomes and build workforce capacity.


A review on the vascular features of the hyperimmunoglobulin E syndrome.
Autosomal recessive, autosomal dominant and the sporadic forms of hyperimmunoglobulin E syndrome (HIES) are multi-system disorders. Although HIES patients may present with cold abscesses, the vascular features of HIES are not well recognized. The objective of this review is to characterize the nature and spectrum of vascular abnormalities in HIES patients. Vascular abnormalities in HIES patients were reviewed with Medline and Google Scholar-based searches. In brief, the searches combined terms related to HIES with the terms related to vasculature. Furthermore, reference lists from the original studies and review papers identified were screened. There were vascular abnormalities in 25 patients with HIES. These abnormalities were identified as aneurysms (coronary, aortic, carotid and cerebral), pseudoaneurysms, congenital patent ductus venosus, superior vena cava syndrome, vasculitides, vascular ectasia, thrombosis and others. They may be congenital or acquired, in the veins and arteries, affecting both sexes. These abnormalities can be seen in all subtypes of HIES. They could be also fatal in children and adults. Limited pathological investigations revealed the presence of vasculitis. Three of the patients were found to have overlap diseases. In this review, the spectrum of vascular abnormalities in HIES are documented and discussed in detail for the first time. They highlight a previously under-recognized and potentially devastating complication of these disorders. These vascular abnormalities constitute one of the major clinical characteristics in HIES. The presence of hypereosinophilia, vasculitis and defective angiogenesis in HIES may contribute to the formation of vascular abnormalities in HIES.


A photoregulated split aptaswitch for small molecules with improved sensitivity.
Here we show the design of a photoregulated split aptaswitch (PSA) for the challenging small-molecule biorecognition and its sensing application. The PSA specifically binds with the target in a binary reaction, and can easily rule out false positive signals by azobenzene photoisomerization, exhibiting an approximately 50-fold improved sensitivity over a control assay.


[Leiomyomatosis peritonealis disseminata].
Leiomyomatosis peritonealis disseminata is an uncommon condition characterized by subperitoneal proliferation of benign nodules mainly composed of benign smooth muscle cells. This entity generally appears in premenopausal women and hormonal influences may play a role in its pathogenesis. The macroscopic appearance mimics peritoneal carcinomatosis. The characteristic clinical course is asymptomatic and diagnosis is only feasible after microscopic examination. To date, less than 100 cases have been reported in the literature. We report the case of a 40-year-old woman who underwent surgery in our department.


Purification of heterologous sarcoplasmic reticulum Ca2+-ATPase Serca1a allowing phosphoenzyme and Ca2+-affinity measurements.
We describe here a protocol to prepare milligrams of active and stable heterologous sarcoplasmic reticulum Ca(2+)-ATPase (Serca1a). Serca1a was tagged with 6 histidines at its C-terminal end and overexpressed using the baculovirus-Sf9 system. In a first trial, Serca1a accounted for 24% of membrane proteins, 95% of which were inactive. Glucose in the culture medium reduced the production of Serca1a to 3 to 5% of membrane proteins and all Serca1a was active. Seventy-five percent of active Serca1a was solubilized by C(12)E(8) in the presence of phosphatidylcholine under conditions avoiding denaturation. Purification by Ni(2+)-nitrilo-triacetic acid affinity chromatography was tried, but only 3% of active Serca1a remained bound to the column, as if the His-tag were not accessible. Yields of 43% were reached by purification on reactive red 120 columns when eluting with 2 M NaCl. The purity was about 25% and Serca1a was stable for at least 1 week at 0 degrees C. Typically, 500 ml of culture medium produced 3 mg of active Serca1a and 1 mg of purified active Serca1a allowing measurements of phosphoenzyme (2 nmol/mg) or Ca(2+) affinity (2 microM at pH 7).


In Vitro Antioxidant and Anti-Colon Cancer Activities of Sesamum indicum L. Leaf Extract and Its Major Component, Pedaliin.
Sesame (Sesamum indicum L.) leaves (SLs) are used as vegetables and traditional medicines in Asian and African countries. We investigated in vitro antioxidant and anti-colon cancer efficacy of ethanol extract of SL (SLE) and its major bioactive component. SLE contained appreciable amount of major classes of antioxidant phytochemicals, such as total polyphenols, total flavonoids, and carotenoids, and correspondingly exhibited antioxidant activities, such as radical scavenging activity and ferric reducing antioxidant power (FRAP). A cell viability assay showed that SLE time- and dose-dependently attenuated the growth of human colon cancer cells, HT29 and HCT116. Flow cytometry analysis showed that SLE increased sub-G1 (in HT29 and HCT116) and G2/M (in HCT116) cell populations, suggesting that the growth inhibition by SLE was due to induction of apoptosis and G2/M cell cycle arrest. Trans-well and wound-healing assays showed that SLE alleviated invasion and migration of HT29 and HCT116 cells in non-cytotoxic conditions. High-performance liquid chromatography analysis revealed that pedaliin (6-hydroxylueolin 7-methyl ether 6-glucoside; pedalitin-6-O-glucoside) was a major constituent of SLE. Moreover, FRAP, growth-inhibitory, anti-invasive, and anti-migratory activities of pedaliin were found. These results demonstrated that SLE possesses in vitro antioxidant and anti-colon cancer activities and that pedaliin is a major component contributing to such activities.


Treatment of chronic hepatitis E in a patient with HIV infection.
Hepatitis E virus (HEV) infections in immunosuppressed patients can result in chronic hepatitis that rapidly progresses to cirrhosis (1, 2). When immunosuppressed transplant recipients are treated with pegylated -interferon and ribavirin, HEV clears and liver histology improves (2). However, we are not aware of reports about how this therapy works in patients with HIV infection. To describe the clinical and laboratory response to antiviral therapy for chronic HEV infection in a patient also infected with HIV. We studied a 48-year-old bisexual male with HIV- 1 infection who was chronically infected with HEV genotype 3a and had several years of painful sensory neuropathy of uncertain cause in the lower limbs (3). He had malaise, persistently abnormal liver function tests, and active inflammation and cirrhosis on liver biopsy (Figure).Before beginning anti-HEV therapy, the patient had an undetectable HIV viral load and a CD4 cell count between 30 and 150 cells/mL for the previous 2 years while receiving combination antiretroviral therapy (abacavir–lamivudine once daily and lopinavir–ritonavir twice daily).


Nrf2 activation in myeloid cells and endothelial cells differentially mitigates sickle cell disease pathology in mice.
Sickle cell disease (SCD) is caused by a monogenic mutation of the β-globin gene and affects millions of people worldwide. SCD is associated with sustained hemolytic anemia, vasoocclusion, ischemia-reperfusion injury, oxidative tissue damage, inflammatory cell activation, and systemic endothelial dysfunction. The transcription factor Nrf2 coordinates the expression of a wide variety of genes encoding antioxidant, detoxification, and metabolic enzymes. Nrf2 participates in suppressing proinflammatory cytokines and organ protection in SCD. However, little is known regarding the mechanisms by which Nrf2 ameliorates SCD pathology or how some cells respond to Nrf2 stimuli to alleviate SCD pathology. Here, we asked whether monocytes/granulocytes and/or endothelial cells are particularly critical in alleviating the pathology of SCD. By targeting these cells with a Cre recombinase system, we generated SCD::Keap1F/F::LysM-Cre and Tie1-Cre mice with constitutive Nrf2 activation in monocytes/granulocytes and endothelial cells, respectively. Analyses of SCD::Keap1F/F::LysM-Cre and SCD::Keap1F/F::Tie1-Cre mice revealed significantly reduced inflammation, along with decreased white blood cell counts and lower Tnfα and Il1β expression in the lungs. Notably, SCD::Keap1F/F::LysM-Cre mice exhibited reduced heme distribution in the liver, consistent with a decrease in the damaged areas. Vascular function in SCD::Keap1F/F::Tie1-Cre mice was significantly improved, with a 50% decrease in vascular leakage and low expression of the adhesion molecules Vcam1 and P-selectin. Thus, Nrf2 activation in monocytes/granulocytes and endothelial cells contributes differentially and cooperatively to the improvement of SCD pathology.


Effect of Auricularia auricula fermentation broth on the liver and stomach of mice with acute alcoholism.
In this paper, the protective effect of Auricularia auricula (A. auricula) fermentation broth on the liver and stomach of mice with acute alcoholism was studied. The A. auricula fermentation broth was prepared by adding Bacillus subtilis, lactic acid bacteria, and Saccharomyces cerevisiae to A. auricula solution. The changes of physical and chemical indexes during the fermentation of A. auricula were monitored, and the results showed the content of polysaccharides and protein in the two kinds of fermentation broth after the fermentation was completed. Furthermore, the characteristic structures of active substances such as proteins, polysaccharides and phenolics were found in the A. auricula fermentation by structural analysis. Antioxidant activity test results showed that the A. auricula fermentation broth had a strong ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals. Cell experiments showed that the fermentation broth of A. auricula could significantly enhance the activity of NRK cells and protect NRK cells from H2O2 damage. Animal experiments showed that the A. auricula fermentation broth had protective effects on the liver and stomach of mice with acute alcoholism, and significantly reduced the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and triglycerides (TG) in serum. These results indicated that the A. auricula fermentation broth had protective effects on the liver and stomach of mice with acute alcoholism, and could be used as a potential functional food to prevent liver and stomach damage caused by acute alcoholism.


A Platform for Designing Genome-Based Personalized Immunotherapy or Vaccine against Cancer.
Due to advancement in sequencing technology, genomes of thousands of cancer tissues or cell-lines have been sequenced. Identification of cancer-specific epitopes or neoepitopes from cancer genomes is one of the major challenges in the field of immunotherapy or vaccine development. This paper describes a platform Cancertope, developed for designing genome-based immunotherapy or vaccine against a cancer cell. Broadly, the integrated resources on this platform are apportioned into three precise sections. First section explains a cancer-specific database of neoepitopes generated from genome of 905 cancer cell lines. This database harbors wide range of epitopes (e.g., B-cell, CD8+ T-cell, HLA class I, HLA class II) against 60 cancer-specific vaccine antigens. Second section describes a partially personalized module developed for predicting potential neoepitopes against a user-specific cancer genome. Finally, we describe a fully personalized module developed for identification of neoepitopes from genomes of cancerous and healthy cells of a cancer-patient. In order to assist the scientific community, wide range of tools are incorporated in this platform that includes screening of epitopes against human reference proteome (http://www.imtech.res.in/raghava/cancertope/).


Time trends in the HERS secondary prevention trial: much ado about nothing?
The Heart and Estrogen/progestin Replacement Study was the first randomized, double-blind, placebo-controlled study evaluating whether hormone replacement therapy (HRT) reduces the incidence of nonfatal myocardial infarction (MI) and coronary heart disease (CHD) death. The main conclusion was that HRT provided no benefit for secondary prevention. This paper examines the statistical evidence for a subsidiary analysis suggesting that the effects of HRT varied over time; that the HRT group had more cardiac events in year 1, but fewer by the last years of the study. An accurate reading of the HERS results indicates an increased incidence of MI and CHD death in the HRT group in year 1, but no evidence that the HRT group had fewer CHD events by the end of the study.


The Tamang: a case of hybridization.
The Tamang, a Mongoloid and hybrid population of the eastern part of the cis-Himalayan region of West Bengal, have been studied for an estimation of the Tibetan and Nepalese components. The degree of admixture of the two parental stocks is found to be about 59 and 41%, respectively. The deviation between the observed and expected gene frequencies of the hybrid is insignificant.


Sexual Harassment by Patients, Clients, and Residents: Investigating Its Prevalence, Frequency and Associations with Impaired Well-Being among Social and Healthcare Workers in Germany.
Social and healthcare workers are at high risk of experiencing sexual harassment in the workplace. Although sexual harassment is detrimental to people's well-being, only a few studies have systematically investigated social and healthcare workers' experiences of different forms of sexually harassing behaviors by patients, clients, and residents in Germany. This study aimed to address this gap by determining the prevalence rates and frequency of nonverbal, verbal, and physical sexual harassment by patients, clients, and residents against social and healthcare workers. In addition, we examined the associations of sexual harassment with workers' well-being and described employees' awareness of offers of organizational support for sexual harassment prevention and aftercare. Data were collected from n = 901 employees working in a total of 61 facilities, including inpatient and outpatient care, psychiatric facilities, hospitals, and facilities for persons with disabilities. While the prevalence, frequency, and predominant forms of sexual harassment differed across sectors, the results indicated that nonverbal, verbal and physical sexual harassment were highly prevalent in social and healthcare work, with both men and women being affected. Furthermore, we found that sexual harassment was positively related to impaired well-being (e.g., depressiveness and psychosomatic complaints). In terms of support offers for sexual harassment prevention and aftercare, we found that approximately one-third of social and healthcare workers were not aware of any offers at their facilities. In addition to highlighting the problem of sexual harassment by patients, clients, and residents in social and healthcare settings, this study provides recommendations for the development of interventions and suggests several avenues for future research.


Development and evaluation of pharmacosomes of aceclofenac.
Pharmacosomes are amphiphilic lipid vesicular systems containing phospholipid complexes with a potential to improve bioavailability of poorly water soluble as well as poorly lipophilic drugs. To improve the water solubility, bioavailability and minimize the gastrointestinal toxicity of aceclofenac, its pharmacosomes were prepared. Aceclofenac was complexed with phosphatidylcholine (80%) in two different ratios (1:1 and 2:1) using conventional solvent evaporation technique. Pharmacosomes thus prepared were subjected to solubility and drug content evaluation, scanning electron microscopy, differential scanning calorimetry, X ray powder diffraction and in vitro dissolution study. Pharmacosomes of aceclofenac were found to be disc shaped with rough surface in scanning electron microscopy. Drug content was found to be 91.88% (w/w) for aceclofenac phospholipid complex (1:1) and 89.03% (w/w) aceclofenac-phospholipid complex (2:1). Differential scanning calorimetric thermograms and X ray powder diffraction datas confirmed the formation of phospholipid complex. Solubility and dissolution profile of the prepared complex was found to be much better than aceclofenac.


Bilaminate synthetic dressing for partial thickness burns. Lack of cost reduction for inpatient care.
Forty-nine cases of second degree burns initially treated as inpatients from April 1984 through December 1987 are reviewed. Thirty-four patients were treated with bilaminate synthetic dressing (Biobrane) application, while 15 were treated with a topical antimicrobial, usually silver sulfadiazine. The burns ranged from 1 to 25 per cent total body surface area and were comparable in both groups. The mean age in each group was 30 years. Thirty patients were successfully treated with Biobrane, and their average hospital stay was 9.1 +/- 5.4 days compared with 9.2 +/- 8.6 days for the topically treated group. The mean hospital cost for dressings and supplies for the Biobrane group was $360 +/- $90 compared with $310 +/- $190 for the topical group. Four patients (12%) required Biobrane removal during their hospitalization, one due to increasing burn depth and three due to purulent fluid collections beneath the Biobrane. These burns were subsequently treated with topical antimicrobial agents and healed primarily. The mean total hospital stay for this group was 18.0 +/- 11.9 days with the costs being much higher secondary to the initial cost of the Biobrane, the costs associated with topical antibiotic therapy, and extended hospital stay. Although there was a decrease in nursing time and a subjective decrease in patient discomfort associated with using synthetic dressing, no benefit was found in either decreasing hospital stay or total cost of hospitalization and supplies used for inpatients treated at this institution.


TRITIUM, HYDROGEN AND OXYGEN ISOTOPE COMPOSITIONS IN MONTHLY PRECIPITATION SAMPLES COLLECTED AT TOKI, JAPAN.
Monthly precipitation samples have been collected at Toki, Japan, from November 2013 to March 2017. In this report, selected data were analysed to identify the regional hydrogen and oxygen isotope compositions. Tritium (3H) concentration in the precipitation ranged from 0.10 to 0.61 Bq L-1 and higher 3H concentrations were observed in spring rather than in other seasons. This range was similar to values reported in Chiba City, Japan. 3H concentration and the ratio d-excess, and δD values were roughly clustered according to each separate season. These regional hydrogen and oxygen isotope compositions will be used for environmental assessments of effects of the deuterium plasma experiments of the large fusion test device.


Effect of a titanium cage as a stand-alone device on biomechanical stability in the lumbosacral spine of canine cadavers.
Degenerative lumbosacral stenosis is a common disease in dogs characterised by intervertebral disc herniation, loss of disc height and stenosis. Decompressive dorsal laminectomy and partial discectomy can cause spinal instability and worsen foraminal stenosis. Pedicle screw and rod fixation (PSRF) with an intervertebral body cage allows for distraction and restoration of disc height and restores foraminal apertures. The aim of this study was to evaluate the ex vivo biomechanical properties of a titanium intervertebral cage alone and in combination with PSRF in the lumbosacral spine of dogs. The range of motion, neutral zone, neutral zone stiffness and elastic zone stiffness of the lumbosacral joint (L7-S1) of nine canine cadavers were determined in flexion/extension, lateral bending and axial rotation for four conditions: (1) native (unmodified) spine; (2) dorsal laminectomy and discectomy; (3) stand-alone cage; and (4) cage in combination with PSRF. The intervertebral disc height decreased after dorsal laminectomy, but increased after insertion of the cage. Insertion of the stand-alone cage decreased the range of motion and neutral zone compared to the laminectomy-discectomy and increased neutral zone stiffness in all directions. The range of motion further decreased after PSRF. From a biomechanical point of view, the use of a stand-alone intervertebral cage is a potential alternative to dorsal fixation of the lumbosacral junction, since it increases spinal stability and restores disc height.


Is there an advantage over SF-36 with a quality of life measure that is specific to systemic lupus erythematosus?
To assess whether the Lupus Quality of Life (LupusQoL) questionnaire contributed additional information not obtained using the Medical Outcomes Study Short-Form 36 questionnaire (SF-36) in a cohort of patients with systemic lupus erythematosus (SLE). Forty-one patients seen at a single center were followed at monthly intervals for 12 months. The LupusQoL and the SF-36 questionnaires were coadministered monthly. Disease activity was determined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) every 30 days. We determined the correlation of the 4 comparable domains of both questionnaires. For the 4 noncomparable domains of the LupusQoL we determined the correlation between each domain with the Physical Component Summary scores (PCS) and the Mental Component Summary scores (MCS) of the SF-36. The effect size (ES) and the standardized response mean (SRM) were used to compare the responsiveness of both questionnaires when a clinically significant change in disease activity occurred as determined by SLEDAI-2K. Three hundred seventy-six patient visits were recorded. There was a strong correlation between comparable domains in both questionnaires. For the 4 noncomparable domains of the LupusQoL, there was a correlation with the MCS and PCS of SF-36. The mean scores for comparable domains in both questionnaires were similar. Both questionnaires displayed responsiveness, as determined by ES and SRM among patients who flared and improved, but not among patients in remission, when compared to the previous visit. LupusQoL and SF-36 were equivalent in assessing quality of life over time in this group of patients. Both questionnaires are responsive measures of quality of life in patients with SLE flares and improvement.


[Anemia of chronic diseases: current state of the problem and perspectives].
Anemia of chronic diseases is a condition, that accompanies several chronic conditions, that have inflammation as an underlying cause. The article covers current concepts of pathogenesis, evaluation and treatment of this type of anemia. The new perspectives in the development of investigational methods and treatment are discussed. The new methods of iron deficiency assessment in patients with systemic inflammation are discussed separately.


[Arthroscopic findings of cartilage changes in knees with rheumatoid arthritis].
We evaluated 28 cases (45 knee joints) with rheumatoid arthritis as our subjects using simple X-rays of the knee joints according to their Larsen grade and also measured the femoro-tibial angle (FTA). Moreover, using an arthroscope we observed 6 regions, namely, the medial femoral condyle, medial tibial plateau, medial meniscus, lateral femoral condyle, lateral tibial plateau, and lateral meniscus, and evaluated the degree of cartilage degeneration according to a 5-point grade classification of our own devising. We studied the relationship between the simple X-ray findings and the arthroscopic findings of cartilage degeneration and reached the following conclusions. Even when simple X-ray findings are slight as in Larsen grade I, various degrees of cartilage degeneration are observed and moreover, as the stage of the disease progresses, cartilage degeneration becomes more severe. The progression of cartilage degeneration up to Larsen grade III is not uniform but degenerative changes in the lateral meniscus progress. Also, a correlation was observed between the nature of the cartilage destruction and the FTA.


The S68G polymorphism is a compensatory mutation associated with the drug resistance mutation K65R in CRF01_AE strains.
The rate of S68G mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase has increased and is closely related to the K65R mutation among CRF01_AE-infected patients who failed treatment. We aimed to explore the temporal association of S68G and K65R mutations and disclose the role of the former on susceptibility to nucleotide/nucleoside reverse transcriptase inhibitor (NRTI) and viral replication with the K65R double mutations among CRF01_AE-infected patients who failed treatment. The occurrence of S68G and K65R mutations was evaluated among HIV-1 of various subtypes in the global HIV Drug Resistance Database. The temporal association of S68G and K65R mutations was analyzed through next-generation sequencing in four CRF01_AE-infected patients who failed treatment with tenofovir/lamivudine/efavirenz. The impact of the S68G mutation on susceptibility to NRTI and replication fitness was analyzed using pseudovirus phenotypic resistance assays and growth competition assays, respectively. The frequency of the S68G mutation increased by 1.4-9.7% in almost all HIV subtypes and circulating recombinant forms in treatment-experienced patients, except subtype F. The S68G mutation often occurred in conjunction with the K65R mutation among RTI-treated patients, with frequencies ranging 21.1-61.7% in various subtypes. Next-generation sequencing revealed that the S68G mutation occurred following the K65R mutation in three of the four CRF01_AE-infected patients. In these three patients, there was no significant change detected in the half maximal inhibitory concentration for zidovudine, tenofovir, or lamivudine between the K65R and K65R/S68G mutations, as demonstrated by the phenotypic resistance assays. Virus stocks of the K65R and K65R/S68G mutations were mixed with 4:6, 1:1, and 9:1 and cultured for 13 days, the K65R/S68G mutants outgrew those of the K65R mutants irrespective of the input ratio. S68G may be a natural polymorphism and compensatory mutation of K65R selected by NRTIs in the CRF01_AE strain of HIV-1. This mutation does not affect susceptibility to NRTI; however, it improves the replication fitness of K65R mutants. This study deciphers the role of the S68G mutation in the HIV reverse transcriptase of the CRF01_AE strain and provides new evidence for the interpretation of drug-resistant mutations in non-B subtypes of HIV-1.


Transfusional malaria in the neonatal period in Lagos, South-West Nigeria.
Sick neonates in malaria endemic areas are frequently transfused with donor blood unscreened for malaria parasite. Consequently, they are at risk of transfusional malaria which can lead to increased neonatal mortality. The study aimed to determine the burden of transfusional malaria in neonates to help in policy formulation on prevention of transfusional malaria. One hundred and sixty four neonates admitted into the neonatal unit of a tertiary hospital over a 10 month period who were scheduled for blood transfusion were screened for malaria parasites pre-transfusion, at three and 14 days post transfusion using Giemsa stained thick and thin films. Donor blood was screened for malaria parasites at the point of transfusion. Neonates who developed malaria parasitaemia post transfusion were followed up for signs of malaria. All recruited neonates tested negative to malaria parasite pre- transfusion. One hundred and twenty (73.2%) were term neonates with 94(57.3%) aged 1-7days. Four (2.4%) neonates developed malaria parasitaemia three days post transfusion and all four developed fever that resolved on treatment for malaria. Three (1.8%) of 164 donor blood samples had malaria parasitaemia and all three (100%) neonates who were transfused with the infected donor blood developed malaria parasitaemia post transfusion. However, one neonate who developed malaria parasitaemia post transfusion was transfused with non-infected donor blood. The prevalence of transfusional malaria in this study is low (2.4%). However, 100% of neonates who received malaria infected donor blood developed transfusional malaria. We therefore recommend routine screening of donor pre-transfusion, testing of neonates who develop fever post transfusion and treatment of those who test positive to malaria.


Dermatologic surgery in the demented patient.
Dementia is an organic mental disorder that is characterized by a general loss of intellectual abilities involving impairment of memory, judgment, and abstract thinking as well as changes in personality. Demented patients are a growing subgroup within the practice of dermatologic surgery and especially in Mohs surgery. These patients often have other medical and social concerns in addition to their dementia. Demented patients require specific knowledge of their problems to care for them properly, especially in cases in which prolonged procedures are required such as Mohs surgery. A review the literature is given regarding this subgroup of patients and how to best prepare and care for them before, during, and after dermatologic surgery. Demented patients often have other medical concerns and therefore have associated medications, medical ailments, postsurgical care, and social and mental challenges. The dermatologic surgeon needs to be aware of the special concerns of demented patients, especially in prolonged and potentially complicated surgeries. Not only do they have mental challenges, but they often have other medical and social challenges that need to be specifically accounted for before, during, and after dermatologic surgery.


[Recognition of fatigue status of pilots based on deep contractive auto-encoding network].
We proposed a new deep learning model by analyzing electroencephalogram signals to reduce the complexity of feature extraction and improve the accuracy of recognition of fatigue status of pilots. For one thing, we applied wavelet packet transform to decompose electroencephalogram signals of pilots to extract the δ wave (0.4-3 Hz), θ wave (4-7 Hz), α wave (8-13 Hz) and β wave (14-30 Hz), and the combination of them was used as de-nosing electroencephalogram signals. For another, we proposed a deep contractive auto-encoding network-Softmax model for identifying pilots' fatigue status. Its recognition results were also compared with other models. The experimental results showed that the proposed deep learning model had a nice recognition, and the accuracy of recognition was up to 91.67%. Therefore, recognition of fatigue status of pilots based on deep contractive auto-encoding network is of great significance.


Management of chronic hepatitis B and C in HIV-coinfected patients.
One-third of HIV-infected individuals worldwide suffer from chronic hepatitis C virus (HCV) infection, but chronic hepatitis C affects more than 75% of HIV-positive subjects infected parenterally, such as haemophiliacs and intravenous drug users. Chronic hepatitis B virus (HBV) infection, on the other hand, occurs in 10% of HIV-infected persons, coinfection being more prevalent in Southeast Asia. There are two main reasons for considering HCV and HBV therapy as a priority in HIV-coinfected patients: first, the more rapid liver disease progression seen in this population, leading to end-stage liver disease complications, including hepatocellular carcinoma, at younger ages; and second, the higher risk of developing hepatotoxicity following the initiation of antiretroviral therapy in subjects with underlying chronic hepatitis than in HIV-monoinfected individuals. As highly active antiretroviral therapy (HAART) has dramatically improved the prognosis of those with HIV disease, the consequences of associated illnesses such as hepatitis B and C, which are currently among the leading causes of hospital admission and death in the HIV-infected population, have become more relevant. Therefore, the adequate management of viral hepatitis should now be considered a priority in HIV-coinfected patients. Several guidelines have recently been released in response to this demand. In this article, we discuss the most critical issues highlighted in these documents.


[De- and remineralization processes of the surface layer of the enamel in intact and pulp-extirpated teeth].
Clinico-laboratory investigation of 61 intact teeth and 61 teeth after pulp extraction was performed, including in vivo acid enamel biopsy and intravital staining with 2% methylene blue solution. The regularities were established governing Ca and P efflux from superficial enamel layer of intact and pulp-extracted teeth into the acid solution with respect to age, group of the tooth and pulp extraction terms. The pulp extraction factor was investigated with special reference to the tooth acid resistance and its remineralization rate.


Monosaccharide-linked inhibitors of O(6)-methylguanine-DNA methyltransferase (MGMT): synthesis, molecular modeling, and structure-activity relationships.
A series of potential inhibitors of the human DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) were synthesized, characterized in detail by NMR, and tested for their ability to deplete MGMT activity in vitro. The new compounds, omega-[O(6)-R-guan-9-yl]-(CH(2))(n)-beta-d-glucosides with R = benzyl or 4-bromothenyl and omega = n = 2, 4,. 12, were compared with the established inhibitors O(6)-benzylguanine (O(6)-BG), 8-aza-O(6)-benzylguanine (8-aza-BG), and O(6)-(4-bromothenyl)guanine (4-BTG), which exhibit in an in vitro assay IC(50) values of 0.62, 0.038, and 0.009 microM, respectively. Potential advantages of the glucosides are improved water solubility and selective uptake in tumor cells. The 4-BTG glucosides with n = 2, 4, 6 show moderate inhibition with an IC(50) of ca. 0.5 microM, while glucosides derived from BG and 8-aza-BG showed significantly poorer inhibition compared to the parent compounds. The 4-BTG glucosides with n = 8, 10, 12 were effective inhibitors with IC(50) values of ca. 0.03 microM. To understand this behavior, extensive molecular modeling studies were performed using the published crystal structure of MGMT (PDB entry: ). The inhibitor molecules were docked into the BG binding pocket, and molecular dynamics simulations with explicit water molecules were carried out. Stabilization energies for the interactions of specific regions of the inhibitor and individual amino acid residues were calculated. The alkyl spacer is located in a cleft along helix 6 of MGMT. With increasing spacer length there is increasing interaction with several amino acid residues which play an important role in the proposed nucleotide flipping mechanism required for DNA repair.


Sequence-specific binding behavior of coralyne toward triplex DNA: An ultrafast time-resolved fluorescence spectroscopy study.
Triplex DNA structure has potential therapeutic application in inhibiting the expression of genes involved in cancer and other diseases. As a DNA-targeting antitumor and antibiotic drug, coralyne shows a remarkable binding propensity to triplex over canonical duplex and thus can modulate the stability of triplex structure, providing a prospective gene targeting strategy. Much less is known, however, about coralyne-binding interactions with triplex. By combining multiple steady-state spectroscopy with ultrafast fluorescence spectroscopy, we have investigated the binding behaviors of coralyne with typical triplexes. Upon binding with a G-containing triplex, the fluorescence of coralyne is markedly quenched owing to the photoinduced electron transfer (PET) of coralyne with the G base. Systematic studies show that the PET rates are sensitive to the binding configuration and local microenvironment, from which the coexisting binding modes of monomeric (full and partial) intercalation and aggregate stacking along the sugar-phosphate backbone are distinguished and their respective contributions are determined. It shows that coralyne has preferences for monomeric intercalation within CGG triplex and pure TAT triplex, whereas CGC+ triplex adopts mainly backbone binding of coralyne aggregates due to charge repulsion, revealing the sequence-specific binding selectivity. The triplex-DNA-induced aggregation of coralyne could be used as a probe for recognizing the water content in local DNA structures. The strong π-π stacking of intercalated coralyne monomer with base-triplets plays an important role in stabilizing the triplex structure. These results provide mechanistic insights for understanding the remarkable propensity of coralyne in selective binding to triplex DNA and shed light on the prospective applications of coralyne-triplex targeted anti-gene therapeutics.


Purification and characterization of a natural agglutinin in the hemolymph of the prawn Penaeus indicus H. Milne Edwards.
A natural agglutinin in the hemolymph of the marine prawn Penaeus indicus was isolated by gel filtration chromatography, purified using polyacrylamide gel electrophoresis, and characterized. Prawn agglutinin has a native molecular mass of 181 kDa and consists of two monomeric units (97 and 84 kDa), maintains some agglutinating activity over a wide pH range (7-9), and is inactivated at 85 degrees C. The agglutinin was denatured upon mixing with trichloroacetic acid, phenol, chloroform, and 45% ammonium sulfate. It was also sensitive to trypsin digestion. The results indicate that prawn agglutinin is proteinaceous in nature, with agglutinating, hemolytic, and antibacterial properties against marine bacteria and erythrocytes with carbohydrate binding sites.


Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells.
The melanocortin peptides have marked anti-inflammatory potential, primarily through inhibition of proinflammatory cytokine production and action on phagocytic cell functions. Gout is an acute form of arthritis caused by the deposition of urate crystals, in which phagocytic cells and cytokines play a major pathogenic role. We examined whether alpha-melanocyte-stimulating hormone (alpha-MSH) and its synthetic derivative (CKPV)2 influence urate crystal-induced monocyte (Mo) activation and neutrophil responses in vitro. Purified Mos were stimulated with monosodium urate (MSU) crystals in the presence or absence of melanocortin peptides. The supernatants were tested for their ability to induce neutrophil activation in terms of chemotaxis, production of reactive oxygen intermediates (ROIs), and membrane expression of CD11b, Toll-like receptor-2 (TLR2) and TLR4. The proinflammatory cytokines interleukin (IL)-1beta, IL-8, and tumor necrosis factor-alpha (TNF-alpha) and caspase-1 were determined in the cell-free supernatants. In parallel experiments, purified neutrophils were preincubated overnight with or without melanocortin peptides before the functional assays. The supernatants from MSU crystal-stimulated Mos exerted chemoattractant and priming activity on neutrophils, estimated as ROI production and CD11b membrane expression. The supernatants of Mos stimulated with MSU in the presence of melanocortin peptides had less chemoattractant activity for neutrophils and less ability to prime neutrophils for CD11b membrane expression and oxidative burst. MSU crystal-stimulated Mos produced significant levels of IL-1beta, IL-8, TNF-alpha, and caspase-1. The concentrations of proinflammatory cytokines, but not of caspase-1, were reduced in the supernatants from Mos stimulated by MSU crystals in the presence of melanocortin peptides. Overnight incubation of neutrophils with the peptides significantly inhibited their ability to migrate toward chemotactic supernatants and their capacity to be primed in terms of ROI production. Alpha-MSH and (CKPV)2 have a dual effect on MSU crystal-induced inflammation, inhibiting the Mos' ability to produce neutrophil chemoattractants and activating compounds and preventing the neutrophil responses to these proinflammatory substances. These findings reinforce previous observations on the potential role of alpha-MSH and related peptides as a new class of drugs for treatment of inflammatory arthritis.


Immunogenic potentials of copolymer I in normal human lymphocytes.
Copolymer I (COP I), a nonencephalitogenic polypeptide analogous to myelin basic protein, is currently being tested for possible effectiveness in treating MS. Peripheral blood mononuclear cells from normal human donors respond blastogenically to the L-form of COP I. This response was greater than that obtained with either bovine or guinea pig myelin basic protein (GPMBP), with no specificity for a particular T-cell subset. Analyses of culture supernatants demonstrated the presence of interleukin-2 and gamma interferon. Mononuclear cells from human fetal cord blood also responded blastogenically to COP I, but the magnitude of the response did not differ from that induced by GPMBP.


Hallucinations in schizophrenia.
The prevalence of different types of hallucinations and their clinical correlates were examined in 117 DSM-III-R schizophrenic or schizoaffective disorder patients. Auditory hallucinations were by far the most common, followed by visual hallucinations, and then by tactile and olfactory or gustatory hallucinations. Auditory hallucinations were associated with an earlier age of first hospitalization among the schizophrenics. Global severity of the illness for schizophrenics was related to the presence of visual hallucinations, but not other types of hallucinations. Tactile and olfactory or gustatory hallucinations were strongly correlated with each other and with the severity of delusions for both schizophrenic and schizoaffective patients. The results suggest that important clinical differences exist between patients with different types of hallucinations, and that these clinical variables need to be controlled for in cross-cultural studies of hallucinations.


Investigation of the level of safety and appropriateness of playgrounds in Elazig city in Turkey.
This study was conducted to identify and evaluate the degree of appropriateness of children's playground standards and the level of compliance with the current safety specifications of the playgrounds in Elazig city in Turkey. This was accomplished by on-site observation and measurement in the total of 24 playgrounds present in this city centre. It was determined that 83.3% of the playgrounds were next to a street and in 60% of these playgrounds there were no fences or any barrier to keep children from running into the street. In 87.5% of playgrounds the surfacing was not in proper depth and good order. Separate playgrounds for different ages were provided in only 12.5% of the playgrounds. In 62.5% of the playgrounds children were supervised to make sure they were safe. There was unsafe equipment in 95.8% of the playgrounds. In 83.3% of the playgrounds there were sharp edges, pinch points, or playground debris that might injure a child. The findings of the present study indicate that nearly all of the playgrounds in Elaziğ city center do not meet the criteria for playground standards and are not in compliance with the current safety specifications and need improvement.


Affinity chromatography of rat alpha-fetoprotein on estradiol-agarose columns.
The use of 17 beta-estradiol-17-hemisuccinate coupled to agarose beads is shown to be a rapid and simple procedure for the isolation of alpha-fetoprotein (AFP) from amniotic fluid. The elution profile of the affinity column shows that AFP is sufficiently retarded by the gel to perform the purification of the protein without specific elution with high-affinity AFP ligands. Rat AFP appeared as a single symmetric peak, a profile that is in good agreement with the existence of a single population of AFP molecules having estrogen-binding properties.


Immunohistochemical study of nuclear changes associated with male germ cell death and spermiogenesis.
In a previous study on the effects of gestational and lactational exposure of para-nonylphenol on male rats, we noted in both induced and uninduced rats, that variations in cleaved caspase-3 immunostaining patterns were associated with distinct nuclear alterations in mainly basally located germ cells (spermatogonia and preleptotene spermatocytes). These were re-analysed and compared with cleaved caspase-3-labeled germ cells in the aging human and the spermatogenically active catfish testis. In the rat testes, cytoplasmic immunostaining was progressively associated with lateral compression of the nucleus, its break up into large pieces which can contain immunostained marginated chromatin masses. The pale remnants of the nucleus continued to shrink in size concomitant with the appearance of blue-purplish stained regions in the cytoplasm similar in color to the condensed chromatin in spermatids, a condition which was TUNEL-negative. These large clumps of chromatin also eventually disappeared, giving rise to cells resembling cytoplasmic ghosts, a condition which was TUNEL-positive. By contrast, the immunolabeled nuclei of human and catfish germ cells condensed into a single mass, after which they lost immunoreactivity. To exclude the possibility that these observations could reflect alterations in Sertoli nuclei, rat testicular sections were probed with a mouse anti-human GATA-4 monoclonal (MHM) antibody. The MHM was, however, the second of two GATA-4 antibodies tested, with a goat anti-mouse polyclonal (GMP) initially used to label the rat Sertoli nuclei. GMP unexpectedly, but distinctly labeled the complete development of the acrosome in the rat testis, a fortuitous finding with utility for staging of the seminiferous epithelium.


Synthesis and antiproliferative activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives.
A series of 2,5,6-substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives have been prepared and were tested for antiproliferative activity on cancer cells at the National Cancer Institute. Results showed that molecules with a benzyl group at position 2, exhibited an increase in activity for the introduction of a formyl group at the 5 position. The compound 2-benzyl-5-formyl-6-(4-bromophenyl)imidazo[2,1-b][1,3,4]thiadiazole 22 has been chosen for understanding the mechanism of action by various molecular and cellular biology studies. Results obtained from cell cycle evaluation analysis, analysis of mitochondrial membrane potential and Annexin V-FITC by flow cytometric analysis, ROS production and expression of apoptotic and DNA-repair proteins suggested that compound 22 induced cytotoxicity by activating extrinsic pathway of apoptosis, however, without affecting cell cycle progression.


Capillary gas chromatographic analysis of pyrrolidinedithiocarbamate metal chelates.
Pyrrolidinedithiocarbamate (PDTC) chelates of Zn(II), Cu(II), Ni(II), Co(III), Fe(III), Mn(II), Cr(III), and VO(II) were analysed by capillary GC on a DB-1701 column (30 m x 0.25 mm id) with flame ionisation detection (FID). Linear calibrations were attained within "1-30 microg/mL" for Ni(II), Fe(III), Mn(II), Cr(III), Cu(II), and VO(II), and within "2-50 microg/mL" for Co(III) and Zn(II). The limits of detection were in the "150-500 ng/mL" range, corresponding to 15-50 pg amounts reaching the FID system. The optimised method was applied to the determination of Cu(II) and Ni(II) in coins, and that of Zn(II), Cu(II), Ni(II), Fe(III), Mn(II), Cr(III), and VO(II) in pharmaceutical preparations with relative standard deviations within 1.1-5.2%. The results obtained are in good agreement with sewage water samples and the declared values for the pharmaceutical formulations, or with the results of AAS of metal contents in coins, pharmaceutical preparations, and sewage water samples.


Validation of a High-Performance Liquid Chromatography with Photodiode Array Detection Method for the Separation and Quantification of Antioxidant and Skin Anti-Aging Flavonoids from Nelumbo nucifera Gaertn. Stamen Extract.
Nelumbo nucifera Gaertn., or the so-called sacred lotus, is a useful aquatic plant in the Nelumbonaceae family that has long been used to prepare teas, traditional medicines as well as foods. Many studies reported on the phytochemicals and biological activities of its leaves and seeds. However, to date, only few studies were conducted on its stamen, which is the most important ingredient for herbal medicines, teas and other phytopharmaceutical products. Thus, this present study focuses on the following: (1) the application of high-performance liquid chromatography with photodiode array detection for a validated separation and quantification of flavonoids from stamen; (2) the Nelumbo nucifera stamen's in vitro and in cellulo antioxidant activities; as well as (3) its potential regarding the inhibition of skin aging enzymes for cosmetic applications. The optimal separation of the main flavonoids from the stamen ethanolic extract was effectively achieved using a core-shell column. The results indicated that stamen ethanolic extract has higher concentration of in vitro and in cellulo antioxidant flavonoids than other floral components. Stamen ethanolic extract showed the highest protective effect against reactive oxygen/nitrogen species formation, as confirmed by cellular antioxidant assay using a yeast model. The evaluation of potential skin anti-aging action showed that the stamen extract has higher potential to inhibit tyrosinase and collagenase compared with its whole flower. These current findings are the first report to suggest the possibility to employ N. nucifera stamen ethanolic extract as a tyrosinase and collagenase inhibitor in cosmetic applications, as well as the utility of the current separation method.


Do honeybees detect colour targets using serial or parallel visual search?
In humans, visual search tasks are commonly used to address the question of how visual attention is allocated in a specific task and how individuals search for a specific object (;target') among other objects (;distractors') that vary in number and complexity. Here, we apply the methodology of visual search experiments to honeybees, which we trained to choose a coloured disc (target) among a varying number of differently coloured discs (distractors). We measured accuracy and decision time as a function of distractor number and colour. We found that for all colour combinations, decision time increased and accuracy decreased with increasing distractor number, whereas performance increased when more targets were present. These findings are characteristic of a serial search in primates, when stimuli are examined sequentially. We found no evidence for parallel search in bees, which would be characterized by a ;pop out' effect, in which the slope of decision time (and accuracy) over distractor number would be near zero. Additionally, we found that decision time and number of errors were significantly higher when bees had to choose a blue target among yellow distractors compared with the inverse colour combination, a phenomenon known as search asymmetry in humans.


Application of palaeogenetic techniques to historic mollusc shells reveals phylogeographic structure in a New Zealand abalone.
Natural history collections worldwide contain a plethora of mollusc shells. Recent studies have detailed the sequencing of DNA extracted from shells up to thousands of years old and from various taphonomic and preservational contexts. However, previous approaches have largely addressed methodological rather than evolutionary research questions. Here, we report the generation of DNA sequence data from mollusc shells using such techniques, applied to Haliotis virginea Gmelin, 1791, a New Zealand abalone, in which morphological variation has led to the recognition of several forms and subspecies. We successfully recovered near-complete mitogenomes from 22 specimens including 12 dry-preserved shells up to 60 years old. We used a combination of palaeogenetic techniques that have not previously been applied to shell, including DNA extraction optimized for ultra-short fragments and hybridization-capture of single-stranded DNA libraries. Phylogenetic analyses revealed three major, well-supported clades comprising samples from: (1) The Three Kings Islands; (2) the Auckland, Chatham and Antipodes Islands; and (3) mainland New Zealand and Campbell Island. This phylogeographic structure does not correspond to the currently recognized forms. Critically, our nonreliance on freshly collected or ethanol-preserved samples enabled inclusion of topotypes of all recognized subspecies as well as additional difficult-to-sample populations. Broader application of these comparatively cost-effective and reliable methods to modern, historical, archaeological and palaeontological shell samples has the potential to revolutionize invertebrate genetic research.


Minimax spectrum shaping with a bandwidth constraint.
A new approach to spectrum shaping, in which the maximum of the spectrum is minimized subject to a constraint on the bandwidth, is considered. The results can be applied to a variety of methods of digital holography. A lower bound for the maximum and a figure of merit are obtained. Practical methods for minimax shaping of the spectrum are described and compared via computer simulations. The results of these simulations indicate that the lower bound is relatively tight, and the figure of merit is a good one.


Reactive optical information processing. I: theory of information recovery and resonator mode structure.
A method of processing optical information is described in which the use of absorptive spatial filters is replaced by suitable mirrors with spatially varying reflectances. When these mirrors are made the terminal planes of a laser resonator, the light which is lost in conventional spatial filtering systems, is stored in the laser cavity. It is shown that shallowly modulated phase objects may be imaged outside the resonator without any appreciable effect on the modes of the resonator.


Multicompartment model for mechanics and energetics of fibrillating ventricle.
We propose a new mechanical model of a fibrillating ventricle to interrelate ventricular mechanics and energetics during fibrillation. The model consists of multiple asynchronously contracting compartments with identical time-varying elastances but with different contraction phase lags. Pressures in all compartments are common, and volumes of all compartments change, keeping their sum constant in the model. We evaluated the mechanical behavior of each compartment by simulating this model on a personal computer. Results showed that each compartment contracts quasi-isobarically. We calculated the pressure-volume area (PVAc) of each compartment as a measure of the total mechanical energy generated by a contraction of the compartment. We found that the sum of PVAcs of all compartments agreed with the area (equivalent PVA; ePVA) surrounded by the end-systolic and end-diastolic pressure-volume relations and the isobaric line at the mean pressure of the fibrillating ventricle. We conclude that ePVA represents the total mechanical energy of the fibrillating ventricle model. The multicompartment model is useful for insight into the interrelation between ventricular mechanics and energetics during ventricular fibrillation.


Differentially regulated genes as putative targets of amplifications at 20q in ovarian cancers.
Frequent amplification of DNA at 20q or part of 20q has been demonstrated by comparative genomic hybridization in ovarian cancer (OC), but the genetic target(s) of these amplification events remain unknown. We examined copy-number changes with respect to six candidate genes, E2F1 (20q11.2), TGIF2 (20q11.2), AIB1 (20q12), PTPN1 (20q13.1), ZNF217 (20q13.2), and BTAK (20q13), and then measured transcription levels of each candidate in 18 OC cell lines. Three distinct cores of amplification were identified: 20q11.2, harboring E2F1 and TGIF2 (region I; 1 of 18 cell lines, 5.6%); 20q13.1, harboring PTPN1 (region II; 5 lines, 27.8%); and 20q13.2, harboring ZNF217 and BTAK (region III; 6 lines, 33.3%). Among the six genes examined, expression levels of PTPN1 and ZNF217 were significantly correlated with absolute copy-number, and those of PTPN1 and TGIF2 were significantly correlated with copy-number relative to the centromere of chromosome 20 (20cen). Among 19 primary OCs examined, moreover, we observed amplification of TGIF2, PTPN1 and ZNF217 in five (26.3%), ten (52.6%), and twelve (63.2%) tumors, respectively. Expression levels of PTPN1 and ZNF217 were significantly correlated with their copy-numbers in those primary OCs. Our results suggest that 20q amplifications in OCs can be extensive and complex, probably due to synergistic or non-synergistic amplification of separate regions of 20q, involving multiple, independently amplified targets.


Plasmin: its role in the extracellular processing of progalanin in tumor tissue.
Galanin is a neuropeptide that is widely distributed in the central and peripheral nervous systems. In a previous study, we showed that a small cell lung carcinoma (SCLC) cell line, SBC-3A, released progalanin but not galanin, and that progalanin was then converted to galanin(1-20), the active form. Because the galanin(1-20) had undergone hydrolysis at Arg and Lys residues, the protease concerned was surmised to have a trypsin-like activity. The present study was performed to identify the trypsin-like protease which had previously been found to activate progalanin in this tumor tissue. The protease was isolated using chromatography and electrophoresis, and identified in tumor extracts from SBC-3A tumor-bearing mice; the major protease was found to be plasmin. We next confirmed that extracellular processing of progalanin occurs in SCLC tumor tissue (tumors produced by the implantation of SBC-3A cells into mice), and in two types of breast tumor tissue (obtained by implantation into mice of BT-549 and MDA-MB-436 cells). In cell culture, processed forms of progalanin were undetectable in SBC-3A, BT-549 or MDA-MB-436 cells. Conversely, gel filtration chromatography analysis of tumor extracts from SBC-3A, BT-549 and MDA-MB-436-bearing mice, revealed that galanin-like immunoreactivity (galanin-LI) in these tumor extracts was due to the presence of progalanin (14 kDa) and galanin(1-20) (2 kDa). Moreover, trypsin-like protease activity was elevated, and plasmin was expressed abundantly in SBC-3A, BT-549 and MDA-MB-436 tumors in mice. In addition, tranexamic acid, a plasmin inhibitor, inhibited progalanin conversion to galanin(1-20). The present study revealed that plasmin was present in tumor tissue, and that it was responsible for processing progalanin to galanin(1-20) in the extracellular environment.


Interaction between Gemcitabine and Warfarin Causing Gastrointestinal Bleeding in a Patient with Pancreatic Cancer.
Gemcitabine (Gemzar) is the only chemotherapeutic agent approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced pancreatic cancer. Thromboembolism requiring anticoagulation is a common paraneoplastic complication in these patients. We report a case of patient with pancreatic cancer, complicated by gastrointestinal bleeding following therapy with concomitant gemcitabine-warfarin (Coumadin).The patient was a 65-year-old male with medical history notable for atrial fibrillation for which he was taking warfarin 57.5 mg/week (international normalized ratio [INR] 1.94). He received capecitabine-radiotherapy for locally advanced pancreatic cancer. Later, he developed multiple liver metastases. The patient was started on gemcitabine. At the end of first cycle, he experienced bright red blood per rectum. His platelet count was normal, but his INR was noted to be significantly elevated at 8.00. Esophagogastroduodenoscopy (EGD) revealed 2 antral ulcers and a duodenal ulcer. The patient was stabilized and recovered without further incident.Patients with pancreatic cancer who receive warfarin and gemcitabine should be monitored for any potential drug interactions. Weekly prothrombin time (PT)/INRs for anticoagulated patients receiving gemcitabine is suggested.


Individualised unsupervised exercise training in adults with cystic fibrosis: a 1 year randomised controlled trial.
Short term studies of exercise training have shown benefits in cystic fibrosis. Transferring exercise programmes to the community and sustaining them long term is a challenge for the patient. The effectiveness of an individualised unsupervised home based exercise programme was examined in adults with cystic fibrosis over a 1 year period. Subjects were randomised to undertake three sessions per week of upper and lower body exercise based on individualised preferences (n = 30) or to a control group (n = 18). They were evaluated at baseline and at 12 months. The primary outcome measure was improved fitness as assessed by change in blood lactate concentration at the end of an identical constant work rate for both arm and leg ergometric testing. Secondary outcome measurements were heart rate and pulmonary function. For leg exercise, significant differences were seen at 12 months between the active and control groups in the mean (SE) change in blood lactate levels (-0.38 (0.23) mmol/l v 0.45 (0.25) mmol/l, p<0.05) and heart rate (-4.8 (2.5) bpm v 3.4 (2.5) bpm, p<0.05), confirming a training effect. For arm ergometry there was no change in lactate levels at 12 months but there was a significant difference in forced vital capacity (46 (72) ml v -167 (68) ml, p<0.05). A training effect, as measured by a reduction in lactate levels and heart rate, can be achieved with unsupervised individualised home exercise in adults with cystic fibrosis. A benefit to pulmonary function was observed and together these findings suggest that exercise programmes should be encouraged as an important component of care in cystic fibrosis.


Skin-derived precursor cells promote wound healing in diabetic mice.
Impaired wound healing as one of the complications arising from diabetes mellitus is a serious clinical issue. Recently, various cell therapies have been reported for promotion of wound healing. Skin-derived precursor cells (SKPs) are multipotent adult stem cells with the tendency to differentiate into neurons. We investigated the potency of promoting diabetic wound healing by the application of SKPs. Skin-derived precursor cells isolated from diabetic murine skin were cultured in sphere formation medium. At passage 2, they were suspended in phosphate-buffered saline (PBS), and applied topically to full-thickness excisional cutaneous wounds in diabetic mice. Application of PBS served as controls (n = 21 for each group; n = 42 total). Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 10 and 28 days and then processed, sectioned, and stained (CD31, α-smooth muscle actin, and neurofilament heavy chain) to quantify vascularity and neurofilaments. Wounds treated with SKPs demonstrated a significantly decreased time to closure (18.63 days) compared with PBS-control wounds (21.72 days, P < 0.01), and a significant improvement in percentage closure at 7, 10, 14, and 18 days compared with PBS-control wounds (P < 0.01). Histological analysis showed that the Capillary Score (the number of vessels/mm2) was significantly higher in SKP-treated wounds at day 10 but not at day 28. Nerve Density (the number of neurofilaments/mm2) had increased significantly in SKP-treated wounds at day 28 compared with control group. Some applied SKPs were stained by neurofilament heavy chain, which demonstrates that SKPs directly differentiated into neurons. Skin-derived precursor cells promoted diabetic wound healings through vasculogenesis at the early stage of wound healing. Skin-derived precursor cells are a possible therapeutic tool for diabetic impaired wound healing.


[Diagnostic and treatment approaches to alcohol-related disorders].
Due to their high prevalence alcohol related disorders (dependent, harmful and at risk drinking) are of major importance for the general practitioner (GP). The aim of this study was to examine the diagnostic and treatment strategies employed by the general practitioners. A standardized 10-page questionnaire was mailed to a representative sample (n = 1232) of the general practitioners in south-west Germany. They were asked about diagnostic and therapeutic procedures they had employed in the last patient seen. Further questions regarded patient-related and structural problems. The response rate was 24.3 %. The reported patients had a mean age of 49 +/- 10.3 years. 70.6 % were of male sex. The mean duration of the last patient contact was 18.7 minutes. The diagnosis originated more in clinical impression than in use of screening instruments (0.7 % of patients) or formal diagnostic criteria. 76.7 % fulfilled ICD-10 criteria for dependent drinking, 65.0 % were judged dependent drinkers by the GP's. In most cases the patient had been referred to inpatient services. The main intervention (97.3 % of cases) was disease related counseling. 69.4 % were judged to be quite ill and severely ill. In most cases an inpatient referral had taken place. Pharmacotherapeutic measures were relatively rarely employed (11.3 %). As the major impediments of treatment patient related factors were stated (lack of acceptance of diagnosis, resistance to treatment). The majority of patients described by the GP's were dependent drinkers. This indicates that many at risk drinkers might perhaps not be correctly identified. Concerning therapeutic competency patient-related factors are considered as the major impediments for the delivery of effective care. This reflects a view of GP's that patients with alcohol problems are being difficult and time consuming. This should be carefully addressed by future GP-education programs.


Personality Factors and Sick Leave Days. Evidence from a Nationally Representative Longitudinal Study in Germany.
The question of whether employees' sickness absence from the workplace depends on personality has been researched. Existing evidence mostly stems from cross-sectional studies, mainly showing that personality factors were not associated with the number of sick leave days, except for neuroticism, which was positively associated with sick leave days. Based on the above, it remains an under researched question whether intraindividual changes in personality factors are associated with changes in sick leave days. Thus, based on a nationally representative sample, the current study aimed to investigate the relationship between personality factors and sick leave days longitudinally based on a nationally representative sample of individuals in Germany. The present study used data from the German Socio-Economic Panel (GSOEP), a longitudinal survey of private households in Germany. Information from the years 2005, 2009, 2013 were used. The Big Five Inventory-GSOEP (BFI-S) was used to measure personality. Sick leave days in the preceding year were recorded. Poisson fixed effects regressions were used. Adjusting for potential confounders, regressions showed that increases in neuroticism were associated with increased sick leave days. The longitudinal association between extraversion and sick leave days was marginally significant (p < 0.10). Other personality factors were not significantly associated with sick leave days. In addition, sick leave days increased with worsening self-rated health, presence of severe disability and increasing age. The findings of the current study highlight the association between neuroticism and sick leave days longitudinally. Further research is required to elucidate the underlying mechanisms.


An evaluation of a school-based comprehensive public oral health care programme.
This study evaluates a comprehensive oral health care programme seven years after it started in 1986 at a public dental health clinic in Cape Town. Five primary schools served by the clinic were selected for a community trial. Three schools were randomly allocated to receive the programme and two to a non-participating control group. An evaluation to assess the effectiveness of the programme was carried out by comparing the mean DMFS scores of the experimental (programme) schools with control (non-programme) schools. One hundred and ten children who entered the programme in 1986 and 102 non-programme children of similar age were examined and compared in 1992. In the experimental group the mean DMFS score was 1.94 compared to a mean DMFS of 6.12 in the control group. The percentage of caries-free children in the experimental group was 62.5 per cent and in the control group 37.5 per cent. The frequency distribution of the DMFS scores showed that one subject from the programme group had a score of > or = 15 and thirteen non-programme subjects had scores > or = 15. All the comparisons between the two groups reported above were highly significant (P < 0.005). The study shows that the programme has been very effective in reducing the prevalence of dental caries in the schools that received the programme.


Patients' dreams in ICU: recall at two years post discharge and comparison to delirium status during ICU admission. A multicentre cohort study.
Discharged intensive care unit (ICU) patients often recall experience vivid dreams, hallucinations or delusions. These may be persecutory in nature and are sometimes very frightening. It is possible that these memories stem from times when the patient was experiencing delirium, a common syndrome in the critically ill. Routine screening for delirium in ICU is becoming more prevalent, however, little has been published comparing the objective development of delirium (patient observations using screening tools) and patients' subjective recollection of dreams and unreal experiences in the ICU. This study describes the relationship between observed behaviour during ICU admission and the subjective memories of ICU experiences amongst 41 participants in three ICUs up to 24 months post discharge. Overall, 44% of patients (n=18) recalled dreams during their ICU admission. There was a trend to increased prevalence of dreaming (50% versus 39%) amongst the 18 patients who were delirious during their ICU admission than in the 23 non-delirious patients. Dreaming was significantly associated on logistic regression with increased length of stay (OR 1.39, 95% CI 1.08-1.79, p=0.01), but not delirium status (OR 1.56, 95% CI 0.45-5.41, p=0.49). A longer ICU stay was significantly associated with the experience of ICU dreaming. As many dreams are disturbing, we suggest providing information and counselling about delirium to patients who remain in ICU for longer periods.


Cardiovascular and Pre-Frailty Risk Assessment during Shelter-In-Place Measures Based on Multimodal Biomarkers Collected from Smart Telemedical Wearables.
Wearable devices play a growing role in healthcare applications and disease prevention. We conducted a retrospective study to assess cardiovascular and pre-frailty risk during the Covid-19 shelter-in-place measures on human activity patterns based on multimodal biomarkers collected from smartwatch sensors. For methodology validation we enrolled five adult participants (age range: 32 to 84 years; mean 57 ± 22.38; BMI: 27.80 ± 2.95 kg/m2) categorized by age who were smartwatch users and self-isolating at home during the Covid-19 pandemic. Resting heart rate, daily steps, and minutes asleep were recorded using smartwatch sensors. Overall, we created a dataset of 464 days of continuous measurement that included 50 days of self-isolation at home during the Covid-19 pandemic. Student's t-test was used to determine significant differences between the pre-Covid-19 and Covid-19 periods. Our findings suggest that there was a significant decrease in the number of daily steps (-57.21%; -4321; 95% CI, 3722 to 4920) and resting heart rate (-4.81%; -3.04; 95% CI, 2.59 to 3.51) during the period of self-isolation compared to the time before lockdown. We found that there was a significant decrease in the number of minutes asleep (-13.48%; -57.91; 95% CI, 16.33 to 99.49) among older adults. Finally, cardiovascular and pre-frailty risk scores were calculated based on biomarkers and evaluated from the clinical perspective.


Simultaneous genotyping of rs12979860 and rs8099917 variants near the IL28B locus associated with HCV clearance and treatment response.
Recent genome-wide association studies have identified two host single-nucleotide polymorphisms (SNPs) near the IL28B gene (rs12979860 C/T and rs8099917 T/G) that are associated with sustained virological response in patients infected with the hepatitis C virus. Herein, we describe a rapid multiplexed dual-color fluorescence resonance energy transfer (FRET) probe assay that accurately genotypes for both SNPs simultaneously. A single-nucleotide extension assay was also developed for verification of genotypes. Agreement (100%) was observed in genotype calls between the FRET and single-nucleotide extension methods for both SNPs, yielding 100% analytical sensitivity and specificity. By using the FRET assay, 443 samples of varying ethnic backgrounds were genotyped and six different compound genotypes (rs12979860/rs8099917) were detected in whites, Asians, Middle Easterners, Hispanics, and African Americans, at the following frequencies: CC/TT (39.2%, 78.9%, 40.0%, 33.9%, and 16.8%), CT/TT (20.8%, 0%, 40%, 9.3%, and 37.0%), TT/TT (2.4%, 0%, 0%, 3.4%, and 35.3%), CT/TG (24.0%, 19.7%, 20%, 39.8%, and 3.4%), TT/TG (8.0%, 1.4%, 0%, 3.4%, and 5.9%), and TT/GG (5.6%, 0%, 0%, 10.2%, and 1.7%), respectively. The multiplexed FRET assay can be used to effectively genotype for both SNPs in a single tube, with high analytical sensitivity and specificity.


Effect of Red and Blue Light on Anthocyanin Accumulation and Differential Gene Expression in Strawberry (Fragaria × ananassa).
Light conditions can cause quantitative and qualitative changes in anthocyanin. However, little is known about the underlying mechanism of light quality-regulated anthocyanin accumulation in fruits. In this study, light-emitting diodes (LEDs) were applied to explore the effect of red and blue light on strawberry coloration. The results showed contents of total anthocyanins (TA), pelargonidin 3-glucoside (Pg3G) and pelargonidin 3-malonylglucoside (Pg3MG) significantly increased after blue and red light treatment. Pg3G was the major anthocyanin component in strawberry fruits, accounting for more than 80% of TA, whereas Pg3MG accounted for a smaller proportion. Comparative transcriptome analysis was conducted using libraries from the treated strawberries. A total of 1402, 5034, and 3764 differentially-expressed genes (DEGs) were identified in three pairwise comparisons (red light versus white light, RL-VS-WL; blue light versus white light, BL-VS-WL; blue light versus red light, BL-VS-RL), respectively. Photoreceptors and light transduction components remained dynamic to up-regulate the expression of regulatory factors and structural genes related to anthocyanin biosynthesis under red and white light, whereas most genes had low expression levels that were not consistent with the highest total anthocyanin content under blue light. Therefore, the results indicated that light was an essential environmental factor for anthocyanin biosynthesis before the anthocyanin concentration reached saturation in strawberry fruits, and blue light could quickly stimulate the accumulation of anthocyanin in the fruit. In addition, red light might contribute to the synthesis of proanthocyanidins by inducing LAR and ANR.


[Treating scars with lipofilling].
Hypertrophic, keloidal and contracted scars can be cosmetically and functionally debilitating, and by patients this is often perceived as traumatising. Psychological and social impairments are common in these types of scars. Currently, autologous lipofilling, with or without enrichment with stem cells, is performed to improve scar quality. In this review, we evaluate the evidence on lipofilling as a treatment of scars. The literature mainly consists of studies of low-level evidence, i.e. they lack controls and randomisation. Nevertheless, all studies indicate, that lipofilling may improve the quality of scars.


The sexual relationship of male alcoholics and their female partners during periods of drinking and abstinence.
The quality of the sexual relationship between alcoholic male veterans admitted to an alcohol treatment program and their stable nonalcoholic female partners was assessed in relation to time intervals of abstinence and drinking. Repeated measures analyses performed on the LoPiccolo Sexual History Form provided information on sexual problems associated with the desire, arousal and orgasm phases of the sexual response cycle and other kinds of information relevant to sexual functioning. Results indicate that the sexual relationship varies in relation to drinking or abstinence. Sexual intimacy appears quite normal and satisfactory during abstinent periods; however, female partners present an internally consistent picture of neither desiring nor enjoying sex during drinking periods, though accepting sex reluctantly. For male alcoholics, satisfaction with sex while drinking continues to be reported despite awareness of their partner's negative emotional reactions during sex. Clinicians and researchers are cautioned to differentiate drinking and abstinent periods when assessing the sexual relationship of alcoholic couples.