Overweight (BMI of 25-30) Is Independently Associated With Significantly Higher Prevalence of Systolic and Diastolic Hypertension in Adults.
Hypertension (HTN) is a major risk factor for cardiovascular disease. Obesity has been found to be associated with HTN. However, there are not many studies available to evaluate any association between overweight alone and HTN. A database from the Anthony Bates Foundation that performs preventive cardiovascular examinations including measurement of body mass index (BMI) and blood pressure across the United States was used for our study. Using recorded measurements, we evaluated any association between being overweight defined as a BMI of 25 to 30 and the occurrence of systolic and diastolic HTN in adults over the age of 18 years. A total of 1558 participants with documented BMI and blood pressure over the age of 18 years were studied. Among them, 758 participants had a normal BMI, and 800 had a BMI in overweight category. The prevalence of systolic and diastolic HTN was significantly higher in participants in the overweight versus normal weight cohort. Systolic HTN was present in 36% of participants in the overweight versus 14% of the normal weight group ( P < 0.00.1). Diastolic HTN was present in 43% of participants with overweight versus 21% of normal weight cohort ( P < 0.001). After adjusting for age and gender, high systolic blood pressure (SBP) and diastolic blood pressure (DBP) remained independently associated with overweight (SBP prevalence OR, 2.8; CI, 2.1-3.6; P < 0.001; DBP prevalence OR, 2.1; CI, 1.7-2.7; P < 0.001). Our study found that increased BMI in the overweight category alone is independently associated with SBP and DBP in adults undergoing screening warranting further investigation.


Nerve conduction velocity, microscopic, and electron microscopy studies comparing repaired adult and baby monkey median nerves.
Three to three and a half years after repair of monkey nerves, comparison of total myelinated nerves, electron microscopic sections, and nerve conduction velocities delineated no significant difference between nerves sutured in adult life and those sutured in infancy. Extrapolating these results to the human clinical situation, central nervous system adaption in young patients could explain the better clinical results.


Simultaneous enhancement of methane production and methane content in biogas from waste activated sludge and perennial ryegrass anaerobic co-digestion: The effects of pH and C/N ratio.
It is necessary to find an appropriate strategy to simultaneously enhance the methane production and methane content in biogas from waste activated sludge (WAS) and grass co-digestion. In this study an efficient strategy, i.e., adjusting the initial pH 12 and C/N ratio 17/1, for simultaneous enhancement of methane production and methane content in biogas from WAS and perennial ryegrass co-digestion was reported. Experimental results indicated that the maximal methane production was 310mL/gVSadd at the optimum conditions after 30-d anaerobic digestion, which was, respectively, about 1.5- and 3.8-fold of the sole WAS and sole perennial ryegrass anaerobic digestion. Meanwhile, the methane content in biogas was about 74%, which was much higher than that of sole WAS (64%) or sole perennial ryegrass (54%) anaerobic digestion.


[Effect of a safe-sex campaign on women attending a clinic of venereology. Sex behavior and prevalence of sexually transmitted diseases in women examined at the Venereaklinik in Copenhagen in 1984 and 1988].
Consecutive female patients attending the Copenhagen Venereal Disease Clinic were interviewed about sexual behaviour in 1984 (981 women) and in 1988 (684 women). Details of symptoms, age at coitarche, number of sexual partners, contraceptive methods, and obstetric history were recorded together with the results of the venereological examination. A substantially higher proportion of women used condoms in 1988 (51%) than in 1984 (11%), but otherwise the safe sex campaigns had had a limited effect on the sexual behaviour in this group of women until 1988. The prevalence of gonorrhea decreased significantly (from 22% to 6%, p < 0.01), whereas an increase in the prevalence of genital warts was observed (from 4% to 10%, p < 0.01).


Questions and answers on the use of aspirin for primary prevention of cardiovascular disease in diabetes.
Patients with diabetes have a prothrombotic state and a 2 to 4 times higher risk of cardiovascular events than those without diabetes. Aspirin is the cornerstone of treatment in patients withcardiovascular disease, irrespective of diabetes status, being able to confer a 19% relative risk reduction per year in serious vascular events compared with placebo at long-term follow-up (6.7% vs 8.2% per year, p < 0.0001). Data regarding the benefit-risk ratio of aspirin prescribed to patients with diabetes without established cardiovascular disease are less convincing, especially when compared to other preventive strategies. Of note, in primary prevention trials, aspirin allocation yielded a significant 12% proportional reduction in serious vascular events, irrespective of diabetes status, corresponding to a small annual absolute risk reduction (0.06% per year). However, in everyday clinical practice aspirin is still largely prescribed by both diabetologists and cardiologists. In this article, we provide eight questions and answers corroborated by available evidence on the use of aspirin for primary prevention of cardiovascular disease in diabetes.


Phosphagen kinase in Schistosoma japonicum: characterization of its enzymatic properties and determination of its gene structure.
Phosphagen kinases (PKs) play a major role in the regulation of energy metabolism in animals. Creatine kinase (CK) is the sole PK in vertebrates, whereas several PKs are present in invertebrates. Here, we report the enzymatic properties and gene structure of PK in the trematode Schistosoma japonicum (Sj). SjPK has a unique contiguous dimeric structure comprising domain 1 (D1) and domain 2 (D2). The three states of the recombinant SjPK (D1, D2, and D1D2) show a specific activity for the substrate taurocyamine. The comparison of the two domains of SjPK revealed that D1 had a high turnover rate (kcat=52.91) and D2 exhibited a high affinity for taurocyamine (Km(Tauro) =0.53±0.06). The full-length protein exhibited higher affinity for taurocyamine (Km(Tauro) =0.47±0.03) than the truncated domains (D1=1.30±0.10, D2=0.53±0.06). D1D2 also exhibited higher catalytic efficiency (kcat/Km(Tauro) =82.98) than D1 (40.70) and D2 (29.04). These results demonstrated that both domains of SjTKD1D2 interacted efficiently and remained functional. The three-dimensional structure of SjPKD1 was constructed by the homology modeling based on the transition state analog complex state of Limulus AK. This protein model of SjPKD1 suggests that the overall structure is almost conserve between SjPKD1 and Limulus AK except for the flexible loops, that is, particularly guanidino-specificity (GS) region, which is associated with the recognition of the corresponding guanidino substrate. The constructed NJ tree and the comparison of exon/intron organization suggest that SjTK has evolved from an arginine kinase (AK) gene. SjTK has potential as a novel antihelminthic drug target as it is absent in mammals and its strong activity may imply a significant role for this protein in the energy metabolism of the parasite.


Modeling pi-pi interactions with the effective fragment potential method: the benzene dimer and substituents.
This study compares the results of the general effective fragment potential (EFP2) method to the results of a previous combined coupled cluster with single, double, and perturbative triple excitations [CCSD(T)] and symmetry-adapted perturbation theory (SAPT) study [Sinnokrot and Sherrill, J. Am. Chem. Soc., 2004, 126, 7690] on substituent effects in pi-pi interactions. EFP2 is found to accurately model the binding energies of the benzene-benzene, benzene-phenol, benzene-toluene, benzene-fluorobenzene, and benzene-benzonitrile dimers, as compared with high-level methods [Sinnokrot and Sherrill, J. Am. Chem. Soc., 2004, 126, 7690], but at a fraction of the computational cost of CCSD(T). In addition, an EFP-based Monte Carlo/simulated annealing study was undertaken to examine the potential energy surface of the substituted dimers.


Efficacy of continuous local anesthetic infusion for postoperative pain after radical retropubic prostatectomy.
To determine whether a subfascial continuous infusion of local anesthetic in patients undergoing radical retropubic prostatectomy would result in a reduction in postoperative opioid requirements and an improvement in pain scores. This was a prospective, double-blind, placebo-controlled, randomized trial in patients undergoing elective radical retropubic prostatectomy. A small catheter was placed subfascially at the end of surgery and attached to an elastomeric pump that administered either 0.5% bupivacaine or normal saline into the wound at a rate of 2 mL/hr until discharge on postoperative day 3. The outcomes assessed included the dosage of hydromorphone used by a patient-controlled analgesic system, a visual analog scale (VAS) for pain at rest and with activity, a VAS of nausea, and length of hospital stay. A total of 100 patients were successfully randomized, with all patients completing the protocol. No differences were found between the groups with regard to VAS pain at rest, VAS pain with activity, intravenous or oral analgesic consumption, or VAS nausea scores. Continuous subfascial infusion of local anesthetic did not result in a postoperative reduction in opioid requirements or an improvement in pain scores in patients undergoing radical retropubic prostatectomy.


A prominent microtubule cytoskeleton in Acanthamoeba.
A method for preparing by detergent extraction the cytoskeletons of substrate-attached, motile Acanthamoeba castellanii is described. A monoclonal antibody to yeast alpha tubulin has been used to demonstrate the presence of abundant microtubules in the cytoskeleton of this amoeba by fluorescence and whole-mount electron microscopy. Individual microtubules, often more than 10 micron long, interweave to form a well-developed 3-D network pervading the cytoplasm and embracing the nucleus. In some cases immunofluorescent staining reveals distinct nodes in the perinuclear region of this microtubular network.


Ethics of life-sustaining treatment in locked-in syndrome: A Chinese survey.
Locked-in syndrome (LIS) characterizes individuals who have experienced pontine lesions, who have limited motor output but with preserved cognitive abilities. Despite their severe physical impairment, individuals with LIS self-profess a higher quality of life than generally expected. Such third-person expectations about LIS are shaped by personal and cultural factors in western countries. We sought to investigate whether such opinions are further influenced by the cultural background in East Asia. We surveyed attitudes about the ethics of life-sustaining treatment in LIS in a cohort of medical and non-medical Chinese participants. The final study sample included 1545 respondents: medical professionals (n=597, 39%), neurologists (n=303, 20%), legal professionals (n=276, 18%) and other professionals (n=369, 24%), including 180 family members of individuals with LIS. Most of the participants (70%), especially neurologists, thought that life-sustaining treatment could not be stopped in individuals with LIS. It might be unnecessary to withdraw life-sustaining treatment, because the condition involved is not terminal and irreversible, and physical treatment can be beneficial for the patient. A significant proportion (59%) of respondents would like to be kept alive if they were in that condition; however, older people thought the opposite. Families experience the stress of caring for individuals with LIS. The mean (SD) quality of life score for relatives was 0.73 (2.889) (on a -5, +5 scale), which was significantly lower than that of non-relatives, 1.75 (1.969) (P<0.001). Differences in opinions about end of life in LIS are affected by personal characteristics. The current survey did not identify a dissociation between personal preferences and general opinions, potentially because of a social uniformity in China where individualism is less pronounced. Future open-ended surveys could identify specific needs of caregivers so that strategic interventions to reduce ethical debasement are designed.


Two-year online measurements of volatile organic compounds (VOCs) at four sites in a Chinese city: Significant impact of petrochemical industry.
Volatile organic compounds (VOCs) management has been recently given a high priority in China to mitigate ozone (O3) air pollution. However, there is a relatively poor understanding of VOCs due to their complexity and fewer observations. To better understand the pollution characteristics of VOCs and their impact on O3 pollution, two-year continuous measurements were conducted at four representative sites in Ji'nan, eastern China. These four sites cover urban, background, and industrial areas (within a petroleum refinery). Ambient VOCs showed higher concentrations at industrial site than at urban and background sites, owing to intensive emissions from petrochemical industry. The VOCs compositions present spatial heterogeneity with alkenes dominated in total reactivity at urban and background sites, while alkenes and aromatics together dominated at industrial site. The VOCs emission profile from petrochemical industry was calculated based on observational data, which revealed a huge impact on light alkanes (C2-C5), light alkenes (ethene), and aromatics (toluene and m/p-xylene). The positive matrix factorization (PMF) model analysis further refined the impact of different petrochemical industrial processes. Alkanes and alkenes dominated the emissions during refining process, while aromatics dominated during solvent usage process. Analysis by an observation-based model indicated stronger in-situ O3 production and higher sensitivity to nitrogen oxides at industrial site compared to urban and background sites. The reduction of VOCs emissions from petrochemical industry would significantly reduce the O3 concentrations. The analyses underline the significant impact of petrochemical industry on VOCs and O3 pollution, and provide important reference for the formulation of refined and effective control strategies.


Clinical writing and the documentary construction of schizophrenia.
Psychiatric practice involves writing as much as it involves talking. This study examines the interpretive processes of reading, writing and interviewing which are central to the clinical interaction. It is part of a broader ethnographic study of an Australian psychiatric hospital (which specializes in the treatment of patients with a diagnosis of schizophrenia). The paper examines two major types of written assessment of patients--the admission assessment and the 'complete work-up.' Writing is analyzed as performance, thereby focusing on the transformations that are effected in patients, their perceptions of their schizophrenia, and their total identity. One crucial transformation is from 'person suffering from schizophrenia' to 'schizophrenic.' The paper aims to show that as much as psychiatry is a 'talking cure' it is also a 'writing cure.'


Suppression of HDAC2 by sodium butyrate alleviates apoptosis of kidney cells in db/db mice and HG‑induced NRK‑52E cells.
Butyrate is short‑chain fatty acid, which is produced by intestinal microbiota metabolizing dietary fibers. Butyrate participates in various physiological processes predominantly by activating G‑coupled‑receptors, inhibiting histone deacetylases (HDACs) and serving as an energy substrate. Previous studies have shown that butyrate plays a protective role in diabetic nephropathy (DN); however, the exact mechanism remains unclear. The present study identified that providing sodium butyrate (NaBu) by gavage relieved renal damage and apoptosis in db/db mice, which is a widely used type 2 DN model. In vitro, NaBu suppressed high glucose (HG)‑induced apoptosis in normal rat kidney tubular epithelial (NRK‑52E) cells. Of the eleven HDACs (HDAC1‑11) studied, only the mRNA expression of HDAC2 was attenuated by NaBu in NRK‑52E cells under the HG condition. Overexpression of HDAC2 offset the anti‑apoptotic effect of NaBu. NaBu also suppressed HG‑induced oxidative stress. Additionally, H2O2 induced an upregulation of HDAC2 in NRK‑52E cells, while NaBu inhibited this process. Mechanistically, NaBu acted as an antioxidant in HG‑induced NRK‑52E cells and suppressed HG‑induced apoptosis of NRK‑52E cells through inhibiting HDAC2 by virtue of its anti‑oxidative property.


pH and lipase-responsive nanocarrier-mediated dual drug delivery system to treat periodontitis in diabetic rats.
Precise and controlled drug delivery to treat periodontitis in patients with diabetes remains a significant clinical challenge. Nanoparticle-based drug delivery systems offer a potential therapeutic strategy; however, the low loading efficiency, non-responsiveness, and single effect of conventional nanoparticles hinder their clinical application. In this study, we designed a novel self-assembled, dual responsive, and dual drug-loading nanocarrier system, which comprised two parts: the hydrophobic lipid core formed by 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly (ethylene glycol) (DSPE-PEG) loaded with alpha-lipoic acid (ALA); and a hydrophilic shell comprising a poly (amidoamine) dendrimer (PAMAM) that electrostatically adsorbed minocycline hydrochloride (Mino). This unique design allows the controlled release of antioxidant/ALA under lipase stimulation from periodontal pathogens and antimicrobial/Mino under the low pH of the inflammatory microenvironment. In vivo and in vitro studies confirmed that this dual nanocarrier could inhibit the formation of subgingival microbial colonies while promoting osteogenic differentiation of cells under diabetic pathological conditions, and ameliorated periodontal bone resorption. This effective and versatile drug-delivery strategy has good potential applications to inhibit diabetes-associated periodontal bone loss.


Study on dissolution mechanism of cortisol and cortisone from hair matrix with liquid chromatography-tandem mass spectrometry.
Hair cortisol has been used as a biomarker of chronic stress. The detected contents of hair cortisol might depend on the incubation duration in solvents for no-milled hair samples with 3-layer structure. However, there was no research on the dissolution mechanism of hair analytes. After uniform mixture, no-milled hair samples were incubated in methanol and water for the 12 different durations and milled hair was done as comparison. Hair cortisol and cortisone were determined with high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The measured concentrations of hair cortisol and cortisone showed ≥2 maxima during the entire incubation in methanol and water from 5 min to 72 h for no-milled hair. Hair cortisol concentration measured by LC-MS/MS was increased with the incubation duration. Conversely, it was not held when hair was powdered prior to the incubation in methanol. Hair cortisol and cortisone were dissolved from hair matrix through the 2-stage or multistage mechanism, which might depend on the hair 3-layer structure and its degree of damage.


DNA sequence and analysis of a 90.1-kb plasmid in Shiga toxin-producing Escherichia coli (STEC) O145:NM 83-75.
Shiga toxin-producing Escherichia coli (STEC) strains belonging to serogroup O145 are important emerging food-borne pathogens responsible for sporadic cases and outbreaks of hemorrhagic colitis and hemolytic uremic syndrome. A large plasmid carried by STEC O145:NM strain 83-75 and named pO145-NM was sequenced, and the genes were annotated. pO145-NM is 90,103bp in size and carries 89 open reading frames. Four genes/regions in pO145-NM encode for STEC virulence factors, including toxB (protein involved in adherence), espP (a serine protease), katP (catalase peroxidase), and the hly (hemolysin) gene cluster. These genes have also been identified in large virulence plasmids found in other STEC serogroups, including O26, O157, O111, and O103. pO145-NM carries the espPα subtype that is associated with STEC strains that cause more severe disease. Phylogenetic analyses of HlyB, EspP, and ToxB in various STEC strains showed a high degree of similarity of these proteins in E. coli serotypes O145:NM, O26:H11/H-, O111:NM/H-, and O157:H7 potentially placing these STEC into a related group.


Treatment of out-of-hospital cardiac arrest with LUCAS, a new device for automatic mechanical compression and active decompression resuscitation.
Lund University Cardiopulmonary Assist System (LUCAS) is a new gas-driven CPR device providing automatic chest compression and active decompression. This is a report of the first 100 consecutive cases treated with LUCAS due to out-of-hospital cardiac arrest (58% asystole, 42% ventricular fibrillation (VF)). Safety aspects were also investigated and it was found that LUCAS can be used safely regarding noise levels and oxygen concentrations within the ambulance. A crash test (10G) showed no displacement of the device from the manikin. Of the 71 patients with witnessed cardiac arrest, 39% received bystander CPR. In those 28 patients where LUCAS-CPR was initiated more than 15 min after the ambulance alarm and in the 29 unwitnessed cases, none survived for 30 days. Of the 43 witnessed cases treated with LUCAS within 15 min, 24 had VF and 15 (63%) of these cases achieved a stable return of spontaneous circulation (ROSC) and 6 (25%) of them survived with a good neurological recovery after 30 days; 5 (26%) of the 19 patients with asystole achieved ROSC and 1 (5%) survived for over 30 days. One patient where ROSC could not be achieved was transported with on-going LUCAS-CPR to the catheter laboratory and after PCI for an occluded LAD a stable ROSC occurred, but the patient never regained consciousness and died 15 days later. To conclude, establishment of an adequate cerebral circulation as quickly as possible after cardiac arrest is mandatory for a good outcome. In this report patients with a witnessed cardiac arrest receiving LUCAS-CPR within 15 min from the ambulance call had a 30-day survival of 25% in VF and 5% in asystole, but if the interval was more than 15 min, there were no 30-day survivors.


Waptia revisited: Intimations of behaviors.
The middle Cambrian taxon Waptia fieldensis offers insights into early evolution of sensory arrangements that may have supported a range of actions such as exploratory behavior, burrowing, scavenging, swimming, and escape, amongst others. Less elaborate than many modern pancrustaceans, specific features of Waptia that suggest a possible association with the pancrustacean evolutionary trajectory, include mandibulate mouthparts, a single pair of antennae, reflective triplets on the head comparable to ocelli, and traces of brain and optic lobes that conform to the pancrustacean ground pattern. This account revisits an earlier description of Waptia to further interpret the distribution of its overall morphology and receptor arrangements in the context of plausible behavioral repertoires.


Does a Delay in Anterior Cruciate Ligament Reconstruction Increase the Incidence of Secondary Pathology in the Knee? A Systematic Review and Meta-Analysis.
Previous systematic reviews looking at timing of anterior cruciate ligament reconstruction (ACLR) examined the functional outcomes and range of motion; however, few have quantified the effect of timing of surgery on secondary pathology. The goal of this study was to analyze the effects of early ACLRs versus delayed ACLR on the incidence of meniscal and chondral lesions. We searched MEDLINE, EMBASE, and CINAHL on March 20, 2018, for randomized control trials (RCTs) that compared early and delayed ACLR in a skeletally mature population. Two reviewers independently identified trials, extracted trial-level data, performed risk-of-bias assessments using the Cochrane Risk of Bias tool, and evaluated the study methodology using the Detsky scale. A meta-analysis was performed using a random-effects model with the primary outcome being the total number of meniscal and chondral lesions per group. Of 1887 citations identified from electronic and hand searches, we included 4 unique RCTs (303 patients). We considered early reconstruction as <3 weeks and delayed reconstruction as >4 weeks after injury. There was no evidence of a difference between early and late ACLR regarding the incidence of meniscal [relative risk (RR), 0.98; 95% confidence interval (CI), 0.74-1.29] or chondral lesions (RR, 0.88; 95% CI, 0.59-1.29), postoperative infection, graft rupture, functional outcomes, or range of motion. We found no evidence of benefit of early ACLR. Further studies may consider delaying surgery even further (eg, >3 months) to determine whether there are any real benefits to earlier reconstruction.


Self-regulated immobilization behavior of multiple heavy metals via zeolitization towards a novel hydrothermal technology for soil remediation.
More efficient soil remediation technologies are highly anticipated to treat large quantities of heavy metal-polluted urban sites nowadays. Herein, a novel hydrothermal technology of converting heavy metal-polluted soils into zeolites for in-situ immobilizing heavy metals was proposed. The zeolites (analcime and cancrinite) could be synthesized hydrothermally with certain Na/Si and Al/Si ratios. The formed zeolites could manage to change their species and structure during zeolitization to accommodate different heavy metals in soil according to their size and charge. Since smaller-size Cu2+ was introduced, analcime and some cancrinite possessing small cages could be formed adaptively to immobilize the Cu2+ by replacing Na+ and forming Cu2+-OH and Cu2+-O. Whereas, cancrinite with large channels managed to form to immobilize the larger-size Cd2+ by forming Cd2+-O. Interplanar spacing variation of zeolites also corresponded to their structural change for accommodating different heavy metals. Leaching results showed the amounts of Cu and Cd leached from the synthesized zeolites were reduced to 0.005% and 0.05% respectively, reflecting a more stable immobilization of smaller heavy metals by small cages, in agreement with the results of distribution coefficient (Kd). Negligible effect of pH environment on the leaching rates further confirmed the stable structural immobilization of heavy metals by zeolites.


Mediterranean diet and olive oil, microbiota, and obesity-related cancers. From mechanisms to prevention.
Olive oil (OO) is the main source of added fat in the Mediterranean diet (MD). It is a mix of bioactive compounds, including monounsaturated fatty acids, phytosterols, simple phenols, secoiridoids, flavonoids, and terpenoids. There is a growing body of evidence that MD and OO improve obesity-related factors. In addition, obesity has been associated with an increased risk for several cancers: endometrial, oesophageal adenocarcinoma, renal, pancreatic, hepatocellular, gastric cardia, meningioma, multiple myeloma, colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancer. However, the epidemiological evidence linking MD and OO with these obesity-related cancers, and their potential mechanisms of action, especially those involving the gut microbiota, are not clearly described or understood. The goals of this review are 1) to update the current epidemiological knowledge on the associations between MD and OO consumption and obesity-related cancers, 2) to identify the gut microbiota mechanisms involved in obesity-related cancers, and 3) to report the effects of MD and OO on these mechanisms.


Liver transplantation for Hepatitis-B-associated liver disease - Three decades of experience.
Hepatitis B (HBV)-associated end-stage liver disease used to be a relevant indication for liver transplantation (LT). After transplantation, HBV-reinfection remains a serious issue. Different strategies to prevent HBV-reinfection range from the single application of immunoglobulins (HBIG), to the use of modern nucleoside/nucleotide analogues (NUC) in combination with HBIG, followed by HBIG-discontinuation. The aim of this analysis was to compare different strategies and to sum up the results of 30 years at a high-volume transplant center and deliver additional information on the histopathological level. Data of 372 liver transplantations performed for the HBV-induced liver disease in 352 patients were extracted from a prospectively organized database. HBV-reinfection was determined in the entire cohort, according to the mode of HBV-prophylaxis. Differences in survival rates were analyzed in patients with successful prophylaxis, untreated and controlled HBV-reinfection. Histopathological results were obtained from protocol biopsies in 151 patients. HBV-reinfection was significantly associated with the type of prophylaxis, presence of HBs-Antigen at the moment of LT, transplant year and influencing the overall survival before 2005. After the introduction of modern NUCs, HBV-reinfection stopped to impact HBV-associated transplant loss and survival. Controlled HBV-infection prevents from HBV-associated transplant hepatitis and fibrosis development. The role of HBIG declines in favor of NUCs. Uncontrolled HBV-reinfection does not occur any more. Even in the presence of Hbs-antigen, transplant fibrosis does not develop. The most reliable mode to prevent HBV-recurrence remains the combination of NUCs with a high genetic barrier and HBIG. However, HBIG can safely be discontinued after LT.


[Microbial growth on bitumen and chlorcaoutchouc under laboratory conditions (author's transl)].
Formerly published examinations of coating materials for drinking water reservoirs under working conditions were extended to those under laboratory standard. The tests of bitumen, chlorcaoutchouc, asbestos cement and polyacryl delivered results comparable to those achieved under working conditions.


The effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial.
In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study. This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated. The H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice. The study was retrospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).


Resistin increases with obesity and atherosclerotic risk factors in patients with myocardial infarction.
The objective of the study was to assess the relation of resistin to the anthropometric parameters, metabolic risk factors, and C-reactive protein (CRP) in men with myocardial infarction. Subjects were 40 obese (age, 53.6 +/- 7.39 years; body mass index, > or =30 kg/m2) and 40 lean (age, 54.4 +/- 6.62 years; body mass index, <25 kg/m2) men with first acute myocardial infarction. Waist and hip circumferences, CRP, uric acid, fasting glucose, lipid profile, and blood resistin concentration were measured. In obese patients, triglycerides, fasting glucose, and CRP were significantly higher whereas high-density lipoprotein cholesterol was lower than in lean patients. The range of blood resistin concentration was 6.0 to 70.5 ng/mL: 27.84 +/- 12.15 ng/mL in obese subjects and 17.35 +/- 11.08 ng/mL in lean subjects (P < .0001). Significant positive correlation was revealed between blood resistin concentration and each of the analyzed anthropometric parameter and with fasting glucose, low-density lipoprotein cholesterol, and CRP, whereas negative relation was observed between resistin and high-density lipoprotein cholesterol. As revealed by univariate logistic regression analysis, risk of blood resistin concentration being greater than the median value (19.75 ng/mL) was increased by obesity, high-density lipoprotein cholesterol <40 mg/dL, hypertension, and CRP. In multivariate model, independent variables associated with higher median of resistin were obesity and CRP. Obesity increased 5.5-fold the probability of blood resistin concentration being greater than 19.75 ng/mL, whereas each 1-mg/dL increase in CRP increased this probability by 13%. In patients with acute myocardial infarction, obesity is positively related to blood resistin concentration. Resistin is likely to play a major role in the atherogenesis and its complications, and this action seems to be mostly related to the inflammatory reaction.


Prenatal and presymptomatic diagnosis of the Marfan syndrome using fluorescence PCR and an automated sequencer.
The Marfan syndrome (MFS) is a heritable connective tissue disorder characterized by skeletal, ocular, and cardiovascular abnormalities. Defects in fibrillin, an elastin-associated microfibrillar protein, are now known to cause MFS. Since the discovery of fibrillin as the gene responsible for MFS, requests for prenatal and presymptomatic diagnosis have become common-place. Here we report the use of the polymerase chain reaction (PCR), using fluorescence labelled primers and an automated sequencer, to establish linkage data for 'molecular diagnosis'. The mistaken clinical diagnosis of MFS based on the appearance of a common cardiovascular manifestation, mitral valve prolapse, and a positive family history is also discussed.


The de novo and salvage pathways of GDP-mannose biosynthesis are both sufficient for the growth of bloodstream-form Trypanosoma brucei.
The sugar nucleotide GDP-mannose is essential for Trypanosoma brucei. Phosphomannose isomerase occupies a key position on the de novo pathway to GDP-mannose from glucose, just before intersection with the salvage pathway from free mannose. We identified the parasite phosphomannose isomerase gene, confirmed that it encodes phosphomannose isomerase activity and localized the endogenous enzyme to the glycosome. We also created a bloodstream-form conditional null mutant of phosphomannose isomerase to assess the relative roles of the de novo and salvage pathways of GDP-mannose biosynthesis. Phosphomannose isomerase was found to be essential for parasite growth. However, supplementation of the medium with low concentrations of mannose, including that found in human plasma, relieved this dependence. Therefore, we do not consider phosphomannose isomerase to be a viable drug target. We further established culture conditions where we can control glucose and mannose concentrations and perform steady-state [U-(13) C]-D-glucose labelling. Analysis of the isotopic sugar composition of the parasites variant surface glycoprotein synthesized in cells incubated in 5 mM [U-(13) C]-D-glucose in the presence and absence of unlabelled mannose showed that, under physiological conditions, about 80% of GDP-mannose synthesis comes from the de novo pathway and 20% from the salvage pathway.


Fungal Infections of the External Auditory Canal and Emerging Pathogens.
Fungal infections of the external auditory canal can range from common (otomycosis) to life threatening (necrotizing otitis externa). Proper identification of fungal pathogens is necessary to guide appropriate therapy, and a high index of suspicion for fungal causes of ear canal disease is critical. Fungal pathogens may be an especially important cause of ear canal disease in certain populations, including patients with diabetes, patients recently treated with antibiotics, and immunosuppressed patients. Opportunistic fungal infections of the ear canal are an emerging concern.


Return of epidemic dengue in the United States: implications for the public health practitioner.
Conditions that facilitate sustained dengue transmission exist in the United States, and outbreaks have occurred during the past decade in Texas, Hawaii, and Florida. More outbreaks can also be expected in years to come. To combat dengue, medical and public health practitioners in areas with mosquito vectors that are competent to transmit the virus must be aware of the threat of reemergent dengue, and the need for early reporting and control to reduce the impact of dengue outbreaks. Comprehensive dengue control includes human and vector surveillance, vector management programs, and community engagement efforts. Public health, medical, and vector-control communities must collaborate to prevent and control disease spread. Policy makers should understand the role of mosquito abatement and community engagement in the prevention and control of the disease.


Pharmacokinetics of gabapentin during delivery, in the neonatal period, and lactation: does a fetal accumulation occur during pregnancy?
To study the pharmacokinetics of gabapentin (GBP) during delivery, lactation, and in the neonatal period. GBP concentrations in plasma and breast milk were determined with high-performance liquid chromatography in samples from six women treated with GBP and in their offspring. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions during 2 days after delivery. GBP concentration also was determined in breast milk and in blood collected from five of the mothers and suckling infants 2 weeks to 3 months after birth. The umbilical cord/maternal plasma concentration ratios ranged from 1.3 to 2.1 (mean, 1.7). GBP plasma concentrations in the neonates declined with an estimated half-life of 14 h. Mean GBP plasma concentrations in the infants were 27% of the cord plasma levels (range, 12-36%) 24 h postpartum. The mean milk/maternal plasma concentration ratio was 1.0 (range, 0.7-1.3) from 2 weeks to 3 months. The infant dose of GBP was estimated to 0.2-1.3 mg/kg/day, equivalent to 1.3-3.8% of the weight-normalized dose received by the mother. The plasma concentrations in the breast-fed infants were approximately 12% of the mother's plasma levels, but no adverse effects were observed. Our limited observations suggest an active transplacental transport of GBP, with accumulation in the fetus as a consequence. We suggest that this could be by the specific L-type amino acid transporter 1 (LAT-1), which is expressed in the placenta. Newborns seem to have a slightly lower capacity to eliminate GBP than do adults. Transfer of GBP to breast milk is extensive, but plasma concentrations appear to be low in suckling infants. No adverse effects were observed in the newborn. Although more data are needed, our observations suggest that breastfeeding in conjunction with GBP treatment is safe.


The yeast ski complex: crystal structure and RNA channeling to the exosome complex.
The Ski complex is a conserved multiprotein assembly required for the cytoplasmic functions of the exosome, including RNA turnover, surveillance, and interference. Ski2, Ski3, and Ski8 assemble in a tetramer with 1:1:2 stoichiometry. The crystal structure of an S. cerevisiae 370 kDa core complex shows that Ski3 forms an array of 33 TPR motifs organized in N-terminal and C-terminal arms. The C-terminal arm of Ski3 and the two Ski8 subunits position the helicase core of Ski2 centrally within the complex, enhancing RNA binding. The Ski3 N-terminal arm and the Ski2 insertion domain allosterically modulate the ATPase and helicase activities of the complex. Biochemical data suggest that the Ski complex can thread RNAs directly to the exosome, coupling the helicase and the exoribonuclease through a continuous RNA channel. Finally, we identify a Ski8-binding motif common to Ski3 and Spo11, rationalizing the moonlighting properties of Ski8 in mRNA decay and meiosis.


Pustulosis palmaris et plantaris: its association with chronic recurrent multifocal osteomyelitis.
Palmoplantar pustules may rarely be associated with chronic recurrent multifocal osteomyelitis in children and young adults. Additional features of this disorder are recurrent low-grade fevers and bone pain. Skeletal radiographs and bone films suggest osteomyelitis, but bone cultures yield no growth of organisms. The cause of this disorder is unknown, and treatment remains unsatisfactory.


[Ebrictus study. Functional results, survival, and potential years of life lost after the first stroke].
To determine the mortality, degree of dependence, survival, and years of life lost (YLL) after first episode of stroke. Cohort study. Community based register. A total of 553 subjects between 15-90 years with a first episode of definitive or transitory stroke were recruited between 01/04/2006 and 31/03/2008. The analyses were performed with the use of time-to-event methods, according to the intention-to-treat principle. The level of dependency was assessed according to the Barthel Scale one year after stroke; YLL (1-70 years) from the mean life expectancies at birth; survival analysis by Kaplan-Meier's curves, bivariate analysis comparing the variables between patients who had survived and those who died, and Cox's multivariate. The mean age was 73.3 (±11.6 years. The mean time of follow-up was 29.7 ± 13,4 months, during which 26.6% of the patients died. The mean Barthel score fell by >20%, particularly among women. There was moderate or greater dependence in 41.5% (95%CI 30.6-52.8%) of the subjects. The overall accumulative probability of survival was 0.96 (95% CI 0.94-0.97) in the first month and 0.69 (95% CI 0.65-0.72) in the fourth year. The thrombolytic treatment showed a protective effect on mortality, particularly among the women. The main predictive variables were, history of recurrent cardiovascular event (RR 6.7, 95% CI 2.2-21.7) and aging (RR 1.08, 95% CI 1.01-1.2). The average YLL was 11.5/10000/year SD7.2, and higher among men. There are differences in functional outcome, mortality, and potential years of life lost by gender. A new cardiovascular event is an independent prognostic factor of survival.


Physical condition and activity of daily living among aging inpatients with mental disorders in Guangzhou, China: a cross-sectional study.
The number of elderly with mental disorders is increasing, but few studies have been concerned with the physical condition and activities of daily living (ADL) of these patients. This study aims to describe the physical condition and ADL of patients with mental illnesses (PMI) from different age groups, which provides evidence to improve mental health services for PMI. In this prospective cross-sectional study, the samples were divided into three groups of less than 60 years old (group 1), 60-74 years old (group 2), and over 75 years old (group 3) for comparison. Participants' ADL and physical condition were measure by Barthel Index (BI), Functional Activities Questionnaire (FAQ), Standardised swallowing assessment (SSA) and Short Form of Mini Nutrition Assessment (MNA-SF). The Brief Psychiatric Rating Scale (BPRS) and the Mini-Mental State Examination (MMSE) were used to measure psychological condition. Totally, 392 participants had been recruited, meanwhile 86% of them were diagnosed with at least one physical disease. There were statistically significant differences in the three groups of participants in BI (F = 50.603, P < 0.001), FAQ (F = 40.332, P < 0.001), SSA (F = 28.574, P < 0.001), and MNA-SF (F = 18.366, P < 0.001). Group 2 and group 3 had significantly lower scores in BI and FAQ than group 1, and the SSA scores were significantly higher than the participants in group 1. In the negative symptoms subscale of BPRS, the mean score of group 3 was significantly higher than groups 1 and 2. Negative symptom subscale has different degrees of correlation with BI (r = -0.537), FAQ (r = 0.643), SSA (r = 0.480), MNA (r = -0.325) and MMSE (r = 0.607). In addition, the participants with comorbidities were related to BI (r = -0.364). Somatic comorbidities play a pivotal role in the clinical characteristics of elderly patients with mental illness, thus greater effort should be paid to elderly patients suffering from mental illness with dysphagia, malnutrition, and cognitive decline. Further, the negative symptoms of elderly patients with mental disorders also deserve attention.


Influence of Catastrophizing and Personality Traits on Recalled Ratings of Acute Pain Experience in Healthy Young Adults.
To investigate whether pain catastrophizing and personality traits bias recalled ratings of acute pain in an experimental tonic pain model. Fifty-six undergraduates (14 males) recruited from the University of Peradeniya (mean age 21.7 ± 0.8 SD years). Participants completed the Pain Catastrophizing Scale and the Eysenck Personality Questionnaire. They were subjected to two cold pressor tests (dominant and non-dominant hands) and pain threshold, maximum pain intensity, and pain tolerance were recorded. One-week later, the maximum pain intensities of both hands were recalled and percentage distortions in recalling were calculated. Based on a 180 s cutoff, two participants were considered pain-insensitive during the test and were excluded from the analysis. The maximum pain intensity was recalled with a moderate accuracy (Intraclass Correlation Coefficients = 0.68 for dominant and 0.59 for non-dominant hands). Hierarchical multiple regression analyses revealed that maximum pain intensity ( P < 0.001) and pain catastrophizing ( P < 0.001) contributed significantly to recalled pain intensity, and only pain catastrophizing contributed significantly ( P < 0.001) to percentage distortion in recalling with positive β-coefficients. Participants who consistently overrated pain for both hands in recalling scored significantly higher on catastrophizing ( P < 0.001). This study demonstrated that memory for painful events in healthy subjects was reasonably accurate over a period of 1 week. Pain catastrophizing biased pain recall, whereas among personality traits only neuroticism exhibited a weak positive association with the recalled ratings.


Water content of latent fingerprints - Dispelling the myth.
Changing procedures in the handling of rare and precious documents in museums and elsewhere, based on assumptions about constituents of latent fingerprints, have led the author to an examination of available data. These changes appear to have been triggered by one paper using general biological data regarding eccrine sweat production to infer that deposited fingerprints are mostly water. Searching the fingerprint literature has revealed a number of reference works similarly quoting figures for average water content of deposited fingerprints of 98% or more. Whilst accurate estimation is difficult there is no evidence that the residue on fingers could be anything like 98% water, even if there were no contamination from sebaceous glands. Consideration of published analytical data of real fingerprints, and several theoretical considerations regarding evaporation and replenishment rates, indicates a probable initial average water content of a fingerprint, soon after deposition, of 20% or less.


Protection by indomethacin and aspirin against genotoxicity of ochratoxin A, particularly in the urinary bladder and kidney.
Ochratoxin A (OTA) is a ubiquitous nephrotoxic mycotoxin which was shown to be carcinogenic to laboratory animals and may be responsible for kidney pelvis, ureter and urinary bladder tumors associated with Balkan endemic nephropathy in man. Previous evidence from this laboratory demonstrated that OTA exposure results in adduct formation on kidney, testicles, liver and spleen DNA. We show in this study that after a single oral administration of OTA to mice (2 mg/kg body weight) a high level of DNA adducts (150 per 10(9) nucleotides) is also detected in the urinary bladder. The metabolic pathway of OTA leading to genotoxic compounds is not yet known. We demonstrate here that two inhibitors of the prostaglandin H synthase, indomethacin and aspirin, administered to mice before OTA treatment, dramatically reduce the amounts of DNA adducts, particularly in the urinary bladder and kidney. This suggests a role of protaglandin H synthase in the metabolism of OTA leading to active metabolites which react with DNA.


Effect of disulfiram (DS) on mitochondria from rat hippocampus: metabolic compartmentation of DS neurotoxicity.
This experiment was designed to study the acute effects of disulfiram on mitochondrial enzymes in nonsynaptic and synaptic mitochondria from rat hippocampus. Cytochrome c oxidase, monoamine oxidase-B, glycerolphosphate acyltransferase and beta-hydroxybutyrate dehydrogenase were studied. Differences in enzyme activity were seen in controls. Cytochrome c oxidase activity was higher in synaptic mitochondria whereas glycerolphosphate acyltransferase activity was higher in nonsynaptic mitochondria. Mitochondria from disulfiram treated rats, particularly synaptic mitochondria, exhibited lower specific activities of cytochrome c oxidase and monoamine oxidase-B. These alterations were not limited to either the inner or outer mitochondrial membrane. Transmission electron microscopy revealed that mitochondria from disulfiram treated rats were severely altered in isolated preparations as well as in those from whole tissue. This study shows that disulfiram exerts a differential effect on mitochondrial subpopulations.


Di-tert-butylsilylene-directed alpha-selective synthesis of 4-methylumbelliferyl T-antigen.
[reaction: see text] We have succeeded in the facile synthesis of 4-methylumbelliferyl T-antigen as a substrate for endo-alpha-N-acetylgalactosaminidase by exploiting the combination of the di-tert-butylsilylene effect and the Mitsunobu reaction.


Cartilage oligomeric matrix protein and hyaluronic acid are sensitive serum biomarkers for early cartilage lesions in the knee joint.
The purpose of this study was to evaluate the relationship between five previously established serum osteoarthritis biomarkers and the severity of cartilage lesions in the knee. Cartilage damage (classified according to the Outerbridge scoring system) and serum concentrations of cartilage oligomeric matrix protein (COMP), collagen type II C-telopeptide (CTX-II), matrix metalloproteinase-3 (MMP-3), collagen type III N-propeptide, (PIIINP), and hyaluronic acid (HA) were determined in 79 patients who underwent knee arthroscopy or total knee replacement. HA and COMP concentrations were significantly higher in the Outerbridge score 1 and 2 groups, respectively. These results suggest that serum COMP and HA concentrations can be used to predict early cartilage lesions in the knee.


[The "retention complex" and its relationship to abutments: what is today's thought?].
Based up on a review of the literature, the authors have tried to define the possible responsibility of each component of a retention complex (occlusal support--cross-piece--locking arm--retention arm) in the mechanical mobilisation of abutment teeth supporting partial removable prostheses (Kennedy, Class I and II). Taken separately, all these components are intrinsically able to mobilise the teeth. However, no "modern" retention complex (Nally & Martinet--R.P.I.--R.P.A.--"equipoise"...) should jeopardize the abutments, as long as they have been correctly prepared as well as the entire prosthesis.


Acceptance and commitment therapy and contextual behavioral science: examining the progress of a distinctive model of behavioral and cognitive therapy.
A number of recent authors have compared acceptance and commitment therapy (ACT) and traditional cognitive behavior therapy (CBT). The present article describes ACT as a distinct and unified model of behavior change, linked to a specific strategy of scientific development, which we term "contextual behavioral science." We outline the empirical progress of ACT and describe its distinctive development strategy. A contextual behavioral science approach is an inductive attempt to build more adequate psychological systems based on philosophical clarity; the development of basic principles and theories; the development of applied theories linked to basic ones; techniques and components linked to these processes and principles; measurement of theoretically key processes; an emphasis on mediation and moderation in the analysis of applied impact; an interest in effectiveness, dissemination, and training; empirical testing of the research program across a broad range of areas and levels of analysis; and the creation of a more effective scientific and clinical community. We argue that this is a reasonable approach, focused on long-term progress, and that in broad terms it seems to be working. ACT is not hostile to traditional CBT, and is not directly buoyed by whatever weaknesses traditional CBT may have. ACT should be measured at least in part against its own goals as specified by its own developmental strategy.


Long-term mebendazole therapy may be parasitocidal in alveolar echinococcosis.
Long-term chemotherapy of human alveolar echinococcosis with benzimidazole compounds (mebendazole, albendazole) has been shown to be primarily parasitostatic, but its curative (parasitocidal) efficacy is debated. This article reports on a 67-year-old male patient with non-resectable alveolar echinococcosis of the liver who had been continuously treated for 13 years with mebendazole (approximately 45-48 mg/kg body weight per day) and who was closely monitored according to a specific protocol. At the age of 80 years the patient died of oesophageal variceal bleeding. During treatment the hepatic lesion had decreased markedly in size in association with progression of perifocal calcification. At autopsy, a well-demarcated, necrotic, partially calcified, parasite-induced lesion of the right liver lobe and secondary biliary cirrhosis were found. Remnants of parasite tissue obtained from the periphery of the lesion showed a small-cystic structure, but it was not viable, as evidenced by transplantation of tissue blocks to rodents. The case is suggestive for a parasitocidal efficacy of mebendazole treatment carried out for 13 years, and is discussed in context with conflicting literature data.


ACR Appropriateness Criteria® Gestational Trophoblastic Disease.
Gestational trophoblastic disease (GTD), a rare complication of pregnancy, includes both benign and malignant forms, the latter collectively referred to as gestational trophoblastic neoplasia (GTN). When metastatic, the lungs are the most common site of initial spread. Beta-human chorionic gonadotropin, elaborated to some extent by all forms of GTD, is useful in facilitating disease detection, diagnosis, monitoring treatment response, and follow-up. Imaging evaluation depends on whether GTD manifests in one of its benign forms or whether it has progressed to GTN. Transabdominal and transvaginal ultrasound with duplex Doppler evaluation of the pelvis are usually appropriate diagnostic procedures in either of these circumstances, and in posttreatment surveillance. The appropriateness of more extensive imaging remains dependent on a diagnosis of GTN and on other factors. The use of imaging to assess complications, typically hemorrhagic, should be guided by the location of clinical signs and symptoms. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Serum apolipoprotein profile of patients with chronic renal failure.
Serum concentrations of apolipoproteins A-I, A-II, B, C-I, C-II, C-III and E were determined by electroimmunoassay in 56 patients with chronic renal failure (CRF) in the predialytic phase. The results were compared with those obtained in asymptomatic normolipidemic subjects, patients with type IV hyperlipoproteinemia, and patients with type II diabetes mellitus. CRF patients had reduced concentrations of ApoA-I and ApoA-II, normal levels of ApoB and ApoC-I, and increased concentrations of ApoC-II and, in particular, of ApoC-III. There was a significant reduction in the levels of ApoE, especially in male patients. In comparison with type IV, hyperlipoproteinemic patients, CRF patients had lower concentrations of ApoA-I, ApoA-II, ApoB, ApoC-I and, particularly, ApoE; there was no difference in ApoC-III levels reflecting the hypertriglyceridemia common to both disorders. Similar but less marked differences were also found in comparison with type II diabetics. The findings suggest that in CRF, the accumulation of ApoC-III-enriched lipoprotein particles accompanied by a moderate hypertriglyceridemia may be caused more probably by an impaired catabolism than overproduction of triglyceride-rich lipoproteins. CRF patients with vascular disease tended to have higher serum concentrations of triglycerides, cholesterol and ApoB and lower ApoA-I/ApoC-III and ApoA-I/ApoB ratios than patients without vascular disease.


Whole-cell recording of light-evoked photoreceptor responses in a slice preparation of the cuttlefish retina.
A new tissue slice preparation of the cuttlefish eye is described that permits patch-clamp recordings to be acquired from intact photoreceptors during stimulation of the retina with controlled light flashes. Whole-cell recordings using this preparation, from the retinas of very young Sepia officinalis demonstrated that the magnitude, latency, and kinetics of the flash-induced photocurrent are closely dependent on the magnitude of the flash intensity. Depolarizing steps to voltages more positive than -40 mV, from a membrane holding potential of -60 mV, induced a transient inward current followed by a larger, more sustained outward current in these early-stage photoreceptors. The latter current resembled the delayed rectifier (I(K)) already identified in many other nerve cells, including photoreceptors. This current was activated at -30 mV from a holding potential of -60 mV, had a sustained time course, and was blocked in a dose-dependent manner by tetraethylammonium chloride (TEA). The smaller, transient, inward current appeared at potentials more positive than -50 mV, reached peak amplitude at -30 mV and decreased with further depolarization. This current was characterized as the sodium current (I(Na)) on the basis that it was inactivated at holding potentials above -40 mV, was blocked by tetrodotoxin (TTX) and was insensitive to cobalt. Intracellular perfusion of the photoreceptors, via the patch pipette, demonstrated that U-73122 and heparin blocked the evoked photocurrent in a dose-dependent manner, suggesting the involvement of the phospholipase C (PLC) and inositol 1,4,5-triphosphate (InsP(3)), respectively, in the phototransduction cascade. Perfusion with cyclic GMP increased significantly the evoked photocurrent, while the inclusion of phorbol-12,13-dibutyrate reduced significantly the evoked photocurrent, supporting the involvement of cGMP and the diacylglycerol (DAG) pathways, respectively, in the cuttlefish transduction process.


The capacity of interleukin-4 to induce in vitro IgE synthesis by B cells of patients with common variable immunodeficiency.
Interleukin-4 (IL-4) has been shown to induce IgE synthesis by peripheral blood mononuclear cells (PBMC) of normal donors in vitro. However, induction of PBMC of patients with common variable immunodeficiency (CVI) with IL-4 resulted in IgE production in only two out of eight cases tested. PBMC of the first patient that produced IgE in response to IL-4 also secreted normal levels of IL-4 upon activation. PBMC of the second patient secreted very low levels of IL-4 in vitro which may account for the very low serum IgE levels in this patient. Of the other six patients who had very low serum IgE levels and whose PBMC failed to produce IgE in response to IL-4 in vitro, five did not secrete IL-4 upon in vitro activation. The capacity of the T cells to produce IL-4 was intact in the sixth patient. Collectively our data indicate that PBMC of the majority of patients with CVI are defective since they failed to respond appropriately to IL-4 and they failed to produce IL-4, contributing to the view that CVI is a heterogeneous disorder in which a variety of T and B cell defects occur.


A tubular segmented-flow bioreactor for the infection of insect cells with recombinant baculovirus.
A continuous process of insect cell (S f9) growth and baculovirus infection is tested with the sequential combination of a CSTR and a tubular reactor. A tubular infection reactor enables continuous introduction of baculovirus and therefore avoids the 'passage effect' observed in two-stage CSTR systems. Moreover, a tubular reactor can be used to test cell infection kinetics and the subsequent metabolism of infected insect cells. Unlike batch and CSTR culture, cells in a horizontally positioned tubular reactor settle due to poor mixing. We have overcome this problem by alternately introducing air bubbles and media and by maintaining a linear velocity sufficient to keep cells suspended. This article addresses the development of the tubular reactor and demonstrates its use as an infection system that complements the two-stage CSTR.


Feedback loop process to control acoustic cavitation.
Applications involving acoustic cavitation mechanisms, such as sonoporation, are often poorly reproducible because of the unstationary behavior of cavitation. For this purpose, this study proposes to work at a fixed cavitation level instead of a fixed acoustic intensity. A regulated cavitation generator has been developed in an in vitro configuration of standing wave field. This system implements the regulation of the cavitation level during sonication by modulating the applied acoustic intensity with a feedback loop based on acoustic measurements. The experimental setup consists of a plane piezoelectric transducer for sonication (continuous wave, frequency 445 kHz) and a hydrophone pointing to the sonicated medium. The cavitation level is quantified every 5 ms from a spectral analysis of the acoustic signal. The results show that the regulation device generates reproducible mean cavitation levels with a standard deviation lower than 1.6% in the applied intensity range (from 0.12 to 3.44 W/cm(2)), while this standard deviation can reach 76% without regulation. The feedback loop process imposes precise cavitation level even in low applied acoustic intensity.


Adenovirus-mediated delivery of bFGF small interfering RNA reduces STAT3 phosphorylation and induces the depolarization of mitochondria and apoptosis in glioma cells U251.
Glioblastoma multiforme (GBM) carries a dismal prognosis primarily due to its aggressive proliferation in the brain regulated by complex molecular mechanisms. One promising molecular target in GBM is over-expressed basic fibroblast growth factor (bFGF), which has been correlated with growth, progression, and vascularity of human malignant gliomas. Previously, we reported significant antitumor effects of an adenovirus-vector carrying bFGF small interfering RNA (Ad-bFGF-siRNA) in glioma in vivo and in vitro. However, its mechanisms are unknown. Signal transducer and activator of transcription 3 (STAT3) is constitutively active in GBM and correlates positively with the glioma grades. In addition, as a specific transcription factor, STAT3 serves as the convergent point of various signaling pathways activated by multiple growth factors and/or cytokines. Therefore, we hypothesized that the proliferation inhibition and apoptosis induction by Ad-bFGF-siRNA may result from the interruption of STAT3 phosphorylation. In the current study, we found that in glioma cells U251, Ad-bFGF-siRNA impedes the activation of ERK1/2 and JAK2, but not Src, decreases IL-6 secretion, reduces STAT3 phosphorylation, decreases the levels of downstream molecules CyclinD1 and Bcl-xl, and ultimately results in the collapse of mitochondrial membrane potentials as well as the induction of mitochondrial-related apoptosis. Our results offer a potential mechanism for using Ad-bFGF-siRNA as a gene therapy for glioma. To our knowledge, it is the first time that the bFGF knockdown using adenovirus-mediated delivery of bFGF siRNA and its potential underlying mechanisms are reported. Therefore, this finding may open new avenues for developing novel treatments against GBM.


Males and females--some vital differences.
More boys are born than girls, yet at older ages women far outnumber men. This article quantifies, for England and Wales, how and why this disparity in the sex ratio varies with age, and looks at changes over the course of this century. The differences between male and female mortality and migration--which lead to these imbalances in numbers--are also set out.


The Role of MCA-STA Bypass Surgery After COSS and JET: The European Point of View.
The results of the previously published Carotid Occlusion Surgery Study (COSS) and the Japanese EC-IC Bypass Trial (JET) seem to influence the position towards surgical treatment for ischemic cerebrovascular disease (Ogasawara and Ogawa, Nihon Rinsho 64(Suppl 7):524-527, 2006; Powers et al., JAMA 306:1983-1992, 2011).The goal of this article is to give the European point of view after COSS and JET on behalf of the Cerebrovascular Section of the European Association of Neurological Surgeons (EANS).


MiR-1224-5p Activates Autophagy, Cell Invasion and Inhibits Epithelial-to-Mesenchymal Transition in Osteosarcoma Cells by Directly Targeting PLK1 Through PI3K/AKT/mTOR Signaling Pathway.
Osteosarcoma (OS) is one of the most common malignant bone tumors with a poor overall prognosis. MiR-1224-5p plays an important role in cancer, but its function and mechanism in OS have not been studied. The expression of miR-1224-5p and PLK1 was detected by qRT-PCR in OS cells, adjacent tissues, and cell lines. Dual-luciferase reporter gene assay was used to verify the interaction between miR-1224-5p and PLK1. The expression of miR-1224-5p and PLK1 was intervened by transfection with miR-1224-5p mimic, NC mimic, pc-NC and PLK1, respectively. MTT, colony formation assay, Transwell and flow cytometry were used to observe the cell proliferation, invasion and apoptosis. Western blot was used to detect the expression levels of PLK1, PI3K/AKT/mTOR signaling pathway-related proteins, autophagy-related proteins, and epithelial-mesenchymal transition (EMT)-related proteins in the cells. We found that miR-1224-5p was down-regulated and PLK1 expression was up-regulated in OS tissues and cells. On the other hand, it is further confirmed that PLK1 was a target gene of miR-1224-5p. Overexpression of miR-1224-5p inhibited the proliferation, invasion while promoted the apoptosis of OS cells, whereas overexpression of PLK1 promoted the proliferation, invasion and inhibited the apoptosis of OS cells. In the miR-1224-5p group (overexpression of miR-1224-5p), PI3K, AKT, and mTOR protein phosphorylation levels were significantly reduced, while autophagic activity was significantly activated, and the degree of EMT was significantly reduced. But the results in the PLK1 group (overexpression of PLK1) were the opposite. In addition, overexpression of miR-1224-5p reversed the effect of PLK1 upregulation on OS cells. MiR-1224-5p targets PLK1 to inhibit PI3K/AKT/mTOR signaling pathway, thus mediating the proliferation, invasion, apoptosis, autophagy and EMT in OS cells.


Fetal teratomas - A retrospective observational single-center study.
Evaluation of course and outcome of pregnancies with prenatally diagnosed fetal teratomas of various locations in a single center between 2002 and 2019. Retrospective observational single-center study including prenatally suspected or diagnosed fetal teratomas. Focus was put on ultrasound findings during pregnancy. Complications, need for intervention and outcomes were compared according to tumor location. 79 cases of fetal teratomas were seen at our center between 2002 and 2019. Most frequent tumor locations were the sacrococcygeal region (59.5%), neck (20.2%) and oropharynx (7.6%). Complications mainly included polyhydramnios and cardiac compromise. Need for intervention during pregnancy was significantly higher in pericardial teratomas. Preterm birth before 37 and early preterm birth before 32 weeks occurred in 72.7% and 29.1%, respectively. Major causes of perinatal death were tumor bleeding in sacrococcygeal teratomas (SCTs) and respiratory failure in cervical and oropharyngeal teratomas. There is a high need for intervention in pregnancies complicated by fetal teratomas. Pericardiocentesis in pericardial teratomas is often inevitable to reduce the risk of intrauterine demise. Amniotic fluid drainage in associated severe polyhydramnios helps to reduce the risk of preterm birth, a major cause of additional morbidity and mortality. MRI in supplement to prenatal ultrasound is useful in fetal teratomas of the neck and oropharynx in order to plan delivery.


Advances on the Bioactivities, Total Synthesis, Structural Modification, and Structure-Activity Relationships of Cytisine Derivatives.
Cytisine is a quinolizidine alkaloid isolated from various Leguminosae plants. Cytisine and its derivatives exhibit a broad range of biological properties, such as smoking cessation aid, antidepressant, neuroprotective, nootropic, anticancer, antiviral, antiparasitic, antidiabetic, insecticidal, and nematicidal activities. In this review, the progress of cytisine and its derivatives in regard to bioactivities, total synthesis, structural modifications focusing on their N-12 position and lactam ring is reported. Additionally, the structure-activity relationships of cytisine and its derivatives are also discussed.


PAR1-mediated NFkappaB activation promotes survival of prostate cancer cells through a Bcl-xL-dependent mechanism.
We have previously reported that protease-activated receptor 1 (PAR1 or thrombin receptor) is over-expressed in metastatic prostate cancer cell lines compared to prostate epithelial cells. In this study, we examined 1,074 prostate biopsies by tissue microarray analysis and demonstrated that PAR1 expression is significantly increased in prostate cancer compared to normal prostate epithelial cells and benign prostatic hyperplasia. We hypothesized that PAR1 activation contributed to prostate cancer cell progression. We demonstrated that stimulation of PAR1 by thrombin or thrombin receptor activating peptide (TRAP6), in androgen-independent DU145 and PC-3 cells resulted in increased DNA binding activity of the NFkappaB p65 subunit. IL-6 and IL-8 levels were also elevated in conditioned media by at least two-fold within 4-6 h of PAR1 activation. This induction of cytokine production was abrogated by pretreatment of cells with the NFkappaB inhibitor caffeic acid phorbol ester. The p38 and ERK1/2 MAPK signaling cascades were also activated by PAR1 stimulation, whereas the SAPK/JNK pathway was unaffected. Inhibition of p38 and ERK1/2 by SB-203589 and PD-098059, respectively, did not abrogate NFkappaB activity, suggesting an independent induction of NFkappaB by PAR1 stimulation. Furthermore, TUNEL assay showed that activation of PAR1 attenuated docetaxel induced apoptosis through the upregulation of the Bcl-2 family protein Bcl-xL. Akt activation was not observed, suggesting that drug resistance induced by PAR1 was independent of PI3K signaling pathway. Because thrombin and PAR1 are over-expressed in prostate cancer patients, targeting the inhibition of their interaction may attenuate NFkappaB signaling transduction resulting in decreased drug resistance and subsequent survival of prostate cancer cells.


Gelled oil particles: a new approach to encapsulate a hydrophobic metallophthalocyanine.
Chloroaluminum phthalocyanine (ClAlPc) is a promising sensitizer molecule for photodynamic therapy, but its hydrophobicity makes it difficult to formulate. In this study, we have efficiently encapsulated ClAlPc into gelled soybean oil particles dispersed in water. 12-Hydroxystearic acid (HSA) and polyethyleneimine (PEI) were the gelling and stabilizing agents, respectively. The preparation process involved hot emulsification above the gelation temperature (Tgel), followed by cooling to room temperature, which gave a colloidal dispersion of gelled particles of oil in aqueous medium. The gelled particles containing ClAlPc had a medium diameter of 280 nm, homogeneous size distribution (polydispersity index ≈0.3) and large positive zeta potential (about +50 mV) and showed a spherical morphology. The gelled oil particle formulations exhibited good physical stability over a 6-month period. ClAlPc interfered with the HSA self-assembly only slightly, and decreased the gelation temperature to a small extent; however it did not affect gelation process of the oil droplets. The amounts of PEI and HSA employed during the preparation allowed us to control particle size and the dispersion stability, a phenomenon that results from complex electrostatic interactions between the positively charged PEI and the negatively charged HSA fibers present on the gelled particles surface. In summary, by using the right ClAlPc, HSA, and PEI proportions, we prepared very stable dispersions of gelled soybean oil particles with excellent ClAlPc encapsulation efficiency. The obtained colloidal formulation of gelled oil particles loaded with ClAlPc shall be very useful for photodynamic therapy protocols.


Postextubation hypoxemia treated with a continuous positive airway pressure mask.
Twenty-seven surgical patients who developed post-extubation hypoxemia unresponsive to routine respiration therapy (incentive spirometry and chest physical therapy) received continuous positive airway pressure (CPAP) delivered through a mask at an inspired oxygen fraction (FIO2) of 0.45. All patients responded with an increased PaO2 and achieved a PaO2/FIO2 ratio of at least 300 with a mean CPAP of 8.3 +/- 2.8 cm H2O. Mean duration of treatment was 23 +/- 14 h. Two (7%) patients required reintubation, one for control of excessive secretions and the other for persistent Pseudomonas pneumonia. Mask CPAP was an effective treatment for postextubation hypoxemia in this group of surgical patients.


Continuous-wave Doppler of vertebral arteries in noninvasive diagnosis and management of vertebro-basilar TIAs.
Continuous-wave Doppler and angiography of the vertebro-basilar system were used in 38 patients with vertebro-basilar transient ischemic attacks. 63 vertebral arteries were studied. Among 47 normal Doppler parameters, 46 were confirmed by angiography. The sonographic diagnostic procedure showed a very high negative predictive value (97.87%), while the positive predictive value was relatively low (56.25%). Data from literature were reviewed. The authors suggest that when Doppler of vertebral arteries is negative, there is a very low probability that a follow-up angiography will reveal pathologic conditions calling for a surgical approach.


Criteria-based audit of quality of care to women with severe pre-eclampsia and eclampsia in a referral hospital in Accra, Ghana.
Severe pre-eclampsia and eclampsia are one of the major causes of maternal mortality globally. Reducing maternal morbidity and mortality demands optimizing quality of care. Criteria-based audits are a tool to define, assess and improve quality of care. The aim of this study was to determine applicability of a criteria-based audit to assess quality of care delivered to women with severe hypertensive disorders in pregnancy, and to assess adherence to protocols and quality of care provided at a regional hospital in Accra, Ghana. Checklists for management of severe preeclampsia, hypertensive emergency and eclampsia were developed in an audit cycle based on nine existing key clinical care protocols. Fifty cases were audited to assess quality of care, defined as adherence to protocols. Analysis was stratified for complicated cases, defined as (imminent) eclampsia, perinatal mortality and/or one or more WHO maternal near miss C-criteria. Mean adherence to the nine protocols ranged from 15-85%. Protocols for 'plan for delivery' and 'magnesium sulphate administration' were best adhered to (85%), followed by adherence to protocols for 'eclampsia' (64%), 'severe pre-eclampsia at admission' (60%), 'severe pre-eclampsia ward follow-up' (53%) and 'hypertensive emergency' (53%). Protocols for monitoring were least adhered to (15%). No difference was observed for severe disease. Increased awareness, protocol-based training of staff, and clear task assignment were identified as contributors to better adherence. A criteria-based audit is an effective tool to determine quality of care, identify gaps in standard of care, and allow for monitoring and evaluation in a health facility, ultimately resulting in improved quality of care provided and reduced maternal morbidity and mortality. In our audit, good adherence was observed for plan for delivery and treatment with magnesium sulphate. Substandard adherence to a number of protocols was identified, and points towards opportunities for targeted improvement strategies.


Association of Helicobacter pylori infection with survival outcomes in advanced gastric cancer patients treated with immune checkpoint inhibitors.
Accumulating evidence has revealed that the gut microbiota influences the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. As a part of the human microbiome, Helicobacter pylori (H. pylori) was reported to be associated with reduced effectiveness of anti-PD1 immunotherapy in patients with non-small-cell lung cancer (NSCLC). Gastric cancer is more closely related to H. pylori, so we conducted a retrospective analysis to verify whether the association of H. pylori and effectiveness is applicable to advanced gastric cancer (AGC) patients. AGC patients who had evidence of H. pylori and received anti-PD-1 antibodies were enrolled in the study. The differences in the disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) between the H. pylori-positive group and the negative group were compared. A total of 77 patients were included in this study; 34 patients were H. pylori positive, and the prevalence of H. pylori infection was 44.2%. Compared with the H. pylori-negative group, patients in the H. pylori-positive group had a higher risk of nonclinical response to anti-PD-1 antibody, with an OR of 2.91 (95% CI: 1.13-7.50). Patients in the H. pylori-negative group had a longer OS and PFS than those in the positive group, with an estimated median OS of 17.5 months vs. 6.2 months (HR = 2.85, 95% CI: 1.70-4.78; P = 0.021) and a median PFS of 8.4 months vs. 2.7 months (HR = 3.11, 95% CI: 1.96-5.07, P = 0.008). Multivariate analysis indicated that H. pylori infection was independently associated with PFS (HR = 1.90, 95% CI: 1.10-3.30; P = 0.022). Our study unveils for the first time that H. pylori infection is associated with the outcome of immunotherapy for AGC patients. Multicenter, large sample and prospective clinical studies are needed to verify the association.


Role of calcium ions in defining the bioactivity of surface modified Ti metal.
Nano-structured hydrogen titanate and sodium hydrogen titanate layers were formed when Ti metal was treated with H2O2 and NaOH solutions, respectively. The chemically treated Ti metals upon subsequent treatment with Ca(NO3)2 and CaCl2 solutions, resulted in incorporation of Ca2+ ions into the nano-structured titanate layer. Thus formed nano-structured titanate layers containing Ca2+ ions when subjected to heat treatment, forms anatase and calcium titanate-rutile phases, respectively. In vitro apatite-forming ability in simulated body fluid (SBF) was positive for H2O2-Ca and heat-treated Ti metal in contrast to NaOH-Ca and heat treatment. Formation of anatase phase together with Ca2+ ion release into SBF was found to be the key driving force for such a high bioactivity of Ca2+ containing H2O2 treated Ti metal on contrary to NaOH and heat treatment. This study provides a new insight into the factors accelerating the bioactivity of Ti metals during various chemical and thermal treatments, which further aid and abet to design dental and orthopaedic implants with high bone-bonding ability.


Resistance to apoptosis of harringtonine-resistant HL60 cells induced by tetrandrine.
To study the mechanism of resistance to apoptosis in the harringtonine (Har)-resistant HL60 cells with tetrandrine (Tet). Growth inhibition, flow cytometry, DNA agarose gel electrophoresis, protein phosphorylation, and RNA dot hybridization. The resistant cells had no cross resistance to Tet. Tet induced the sensitive but not the Har-resistant HL60 cells to apoptosis. The high phosphorylation of protein < 30 kDa occurred when the resistant cells were treated with Tet. Tet and Har increased the expression of c-myc mRNA in the sensitive HL60 cells. The expression of c-myc mRNA in the resistant cells was obviously decreased and almost not changed in treatment with Tet and Har. Tet induced the sensitive but not the Har-resistant HL60 cells to apoptosis, and the resistance to apoptosis induced by Tet was associated with the high protein phosphorylation and reduction of the expression of c-myc mRNA.


Mat-O-Covid: Validation of a SARS-CoV-2 Job Exposure Matrix (JEM) Using Data from a National Compensation System for Occupational COVID-19.
Background. We aimed to assess the validity of the Mat-O-Covid Job Exposure Matrix (JEM) on SARS-CoV-2 using compensation data from the French National Health Insurance compensation system for occupational-related COVID-19. Methods. Deidentified compensation data for occupational COVID-19 in France were obtained between August 2020 and August 2021. The case acceptance was considered as the reference. Mat-O-Covid is an expert-based French JEM on workplace exposure to SARS-CoV-2. Bi- and multivariable models were used to study the association between the exposure assessed by Mat-O-Covid and the reference, as well as the area under the curve (AUC), sensitivity, specificity, predictive values, and likelihood ratios. Results. In the 1140 cases included, there was a close association between the Mat-O-Covid index and the reference (p < 0.0001). The overall predictivity was good, with an AUC of 0.78 and an optimal threshold at 13 per thousand. Using Youden's J statistic resulted in 0.67 sensitivity and 0.87 specificity. Both positive and negative likelihood ratios were significant: 4.9 [2.4−6.4] and 0.4 [0.3−0.4], respectively. Discussion. It was possible to assess Mat-O-Covid's validity using data from the national compensation system for occupational COVID-19. Though further studies are needed, Mat-O-Covid exposure assessment appears to be accurate enough to be used in research.


Human Disease Insight: An integrated knowledge-based platform for disease-gene-drug information.
The scope of the Human Disease Insight (HDI) database is not limited to researchers or physicians as it also provides basic information to non-professionals and creates disease awareness, thereby reducing the chances of patient suffering due to ignorance. HDI is a knowledge-based resource providing information on human diseases to both scientists and the general public. Here, our mission is to provide a comprehensive human disease database containing most of the available useful information, with extensive cross-referencing. HDI is a knowledge management system that acts as a central hub to access information about human diseases and associated drugs and genes. In addition, HDI contains well-classified bioinformatics tools with helpful descriptions. These integrated bioinformatics tools enable researchers to annotate disease-specific genes and perform protein analysis, search for biomarkers and identify potential vaccine candidates. Eventually, these tools will facilitate the analysis of disease-associated data. The HDI provides two types of search capabilities and includes provisions for downloading, uploading and searching disease/gene/drug-related information. The logistical design of the HDI allows for regular updating. The database is designed to work best with Mozilla Firefox and Google Chrome and is freely accessible at http://humandiseaseinsight.com.


Oro-anal sexual practice among female sex workers in Melbourne: implication for extragenital gonorrhoea and chlamydia transmission.
Background The prevalence of sexually transmissible infections has been low among female sex workers (FSWs) in Melbourne, Australia. However, the prevalence of gonorrhoea and chlamydia, especially at extragenital sites, has increased since the mid-2010s. Oro-anal sex (i.e. rimming) has been identified as a risk factor for extragenital gonorrhoea and chlamydia. However, rimming has rarely been studied among the FSW population. The aim of this study was to examine the proportion of FSWs who had had rimming with their male clients. A cross-sectional survey among FSWs attending the Melbourne Sexual Health Centre in Australia in March 2018 was conducted. All females aged ≥18 years and self-reported as a sex worker were eligible. The survey included questions related to the number of insertive and receptive rimming partners with their male clients in an average working week. Forty-five FSWs completed the survey; five (11.1%; 95% CI: 3.7-24.1%) FSWs had had insertive rimming and 19 (42.2%; 95% CI: 27.7-57.8%) had had receptive rimming with their male clients in an average working week. The median number of insertive rimming partners was two (interquartile range (IQR) 1-5) and the median number of receptive rimming partners was one (IQR 1-3). Insertive rimming is more commonly practiced than receptive rimming among FSWs with their male clients in an average working week.


A state-of-the-art review on miRNA in prevention and treatment of Alzheimer's disease.
Alzheimer's disease (AD) is a multifactorial and heterogenic disorder. MiRNA is a class of non-coding RNAs with 19-22 nucleotides in length that can regulate the expression of target genes in the post-transcriptional level. It has been found that the miRNAome in AD patients is significantly altered in brain tissues, cerebrospinal fluid and blood circulation, as compared to healthy subjects. Experimental studies have suggested that expression changes in miRNA could drive AD onset and development via different mechanisms. Therefore, targeting miRNA expression to regulate the key genes involved in AD progression is anticipated to be a promising approach for AD prevention and treatment. Rodent AD models have demonstrated that targeting miRNAs could block biogenesis and toxicity of amyloid β, inhibit the production and hyper-phosphorylation of τ protein, prevent neuronal apoptosis and promote neurogenesis, maintain neural synaptic and calcium homeostasis, as well as mitigate neuroinflammation mediated by microglia. In addition, animal and human studies support the view that miRNAs are critical players contributing to the beneficial effects of cell therapy and lifestyle intervention to AD. This article reviews the most recent advances in the roles, mechanisms and applications of targeting miRNA in AD prevention and treatment based on rodent AD models and human intervention studies. The potential opportunities and challenges in clinical application of targeting miRNA for AD patients are also discussed.


Exposing culprit organic pollutants: a review.
There is a continuing need for monitoring the health of the environment due to the presence of pollutants. Here, we review the development and attributes of biosensors by which bacteria have been genetically modified to express the luminescence genes, i.e. to glow, in a quantified manner, in response to pollutants. We have concentrated on the detection of organic hydrocarbon pollutants and discussed the molecular mechanisms by which some of these chemicals act as effector molecules on the respective regulatory systems. The future of environmental biosensors is predictably bright. As more knowledge is gathered on the sensing regulatory component, the possibility of developing targeted or pollutant-specific biosensors is promising. Moreover, the repertoire of biosensors for culprit organic pollutants is expected to be enlarged through advances in genomics technology and identification of new sensory or receptor molecules. The need for pollutant detection at concentrations in the parts per trillion range or biosensors configured in a nanoscale is anticipated.


SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks.
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) has a dNTPase-independent function in promoting DNA end resection to facilitate DNA double-strand break (DSB) repair by homologous recombination (HR); however, it is not known if upstream signaling events govern this activity. Here, we show that SAMHD1 is deacetylated by the SIRT1 sirtuin deacetylase, facilitating its binding with ssDNA at DSBs, to promote DNA end resection and HR. SIRT1 complexes with and deacetylates SAMHD1 at conserved lysine 354 (K354) specifically in response to DSBs. K354 deacetylation by SIRT1 promotes DNA end resection and HR but not SAMHD1 tetramerization or dNTPase activity. Mechanistically, K354 deacetylation by SIRT1 promotes SAMHD1 recruitment to DSBs and binding to ssDNA at DSBs, which in turn facilitates CtIP ssDNA binding, leading to promotion of genome integrity. These findings define a mechanism governing the dNTPase-independent resection function of SAMHD1 by SIRT1 deacetylation in promoting HR and genome stability.


A simple broth-disk elution test for screening methicillin-resistant (heteroresistant) staphylococci.
Forty-six strains of Staphylococcus aureus and 47 strains of unspeciated coagulase-negative staphylococci were inoculated in tubes containing a cation-supplemented Mueller-Hinton broth with 4% (wt/vol) NaCl. A critical concentration of methicillin (10 micrograms/ml) or oxacillin (6 micrograms/ml) was achieved in each tube by adding the appropriate number of antibiotic disks. Growth was interpreted as resistance. Results obtained with fully resistant or fully sensitive strains showed complete agreement with the reference method. Four strains with intermediate sensitivity (two S. aureus and two coagulase-negative staphylococci) were classified as resistant by the broth-disk elution test.


From victims to citizens: Emerging activist identities in the anti-fracking movement in Bulgaria.
The anti-fracking movement in Bulgaria, 2011-2013, was a successful grassroots effort to influence national environmental policy. The study draws on social movements and community psychology scholarship to investigate the emergence, development, and implications of activist identities as an important force for the movement's success. Within a qualitative design, data were collected from interviews with activists, observations of organizing events, movement documents, and media publications. Structured and open coding followed by qualitative analyses produced descriptions and explanations of the construction and use of identities in the movement. Four major identities emerged in social and discursive interactions among activists and between activists and contextual forces: Victims, Bulgarians, Nature-protectors, and Citizens. The four identities were used interchangeably and afforded differential empowerment and opportunities for participation in policy-making. The emerging activist identities were processes and products of the complex relationships between agency and context. The study contributes in illuminating the links between policy context, empowerment, participation, and political action.


Reduction of nitrobenzene with alkaline ascorbic acid: Kinetics and pathways.
Alkaline ascorbic acid (AA) exhibits the potential to reductively degrade nitrobenzene (NB), which is the simplest of the nitroaromatic compounds. The nitro group (NO2(-)) of NB has a +III oxidation state of the N atom and tends to gain electrons. The effect of alkaline pH ranging from 9 to 13 was initially assessed and the results demonstrated that the solution pH, when approaching or above the pKa2 of AA (11.79), would increase reductive electron transfer to NB. The rate equation for the reactions between NB and AA at pH 12 can be described as r=((0.89±0.11)×10(-4) mM(1-(a+b))h(-1))×[NB](a=1.35±0.10)[AA](b=0.89±0.01). The GC/MS analytical method identified nitrosobenzene, azoxybenzene, and azobenzene as NB reduction intermediates, and aniline (AN) as a final product. These experimental results indicate that the alkaline AA reduction of NB to AN mainly proceeds via the direct route, consisting of a series of two-electron or four-electron transfers, and the condensation reaction plays a minor route. Preliminary evaluation of the remediation of spiked NB contaminated soils revealed that maintenance of alkaline pH and a higher water to soil ratio are essential for a successful alkaline AA application.


Pediatric eye injuries presenting to United States emergency departments: 2001-2007.
The epidemiology of pediatric eye injuries is not well-documented. This study describes the characteristics of non-fatal eye injuries in pediatric patients (<18 years of age) presenting to United States (US) emergency departments (EDs). Retrospective cohort study utilizing the National Electronic Injury Surveillance System All Injury Program (NEISS-AIP) from 2001 to 2007 to perform a descriptive analysis of eye injury case information for patients <18 years of age, including demographic variables, locales, diagnoses, causes, and hospital disposition. In 2001-2007, an estimated 1,048,500 (95% confidence interval [CI] 878,198-1,218,801) ED visits for eye injury occurred among children less than 18 years of age, representing a rate of 14.31 per 1,000 children. Males accounted for 61.75% (CI 541,971-752,839) of visits. The rate of eye injury was highest in the 15-17 year old age group (18.74 per 1,000 children; CI 199,224-267,132). The most common diagnosis was contusion/abrasion (53.68%; CI 468,035-657,638). The most frequent cause of eye injury was being struck by or against an object (56.63%; CI 491,760-695,758). The majority of injuries occurred at home (65.84%; CI 382,443-588,416) and took place during the spring and summer (39.26%; CI 343,535-479,888). This study suggests that the risk for pediatric eye injuries is highest for adolescents 15-17 years of age and at home. Further research is needed to determine risk and protective factors associated with injuries in this age group and location to design appropriate prevention strategies.


Inulin as a novel biocompatible coating: evaluation of surface affinities toward CaHPO4, α-Fe2O3, ZnO, CaHPO4@ZnO and α-Fe2O3@ZnO nanoparticles.
The introduction of biocompatible coatings onto nanoparticle surfaces can be synthetically challenging. In this work, calcium phosphate (brushite, CaHPO4⋅2H2O), iron oxide (hematite, α-Fe2O3), zinc oxide (ZnO), and CaHPO4@ZnO and α-Fe2O3@ZnO nanoparticles were synthesized and treated with the biocompatible, biodegradable, polysaccharide inulin {(2R,3S,4S,5R)-2-[[(2R,3S,4S,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxymethyl]-5-(hydroxymethyl)oxolane-2,3,4-triol} under mild conditions. The products were fully characterized by Fourier transforms infrared (FTIR) spectroscopy, energy dispersive spectroscopy (EDS), dynamic light scattering (DLS), differential thermogravimetric/differential thermal analysis (TGA/DTA), transmission electron microscopy (TEM) and powder X-ray diffraction (XRD). Surface interactions among hematite and brushite with inulin are weak, but coating the nanoparticle surface with ZnO increased the affinity toward the polysaccharide. Inulin adsorption on the nanoparticle surface was confirmed by thermal and spectroscopic analyses. The nanoparticles had diameters ranging from 50 to 80nm, with nearly spherical morphology. The nanoparticles sizes, stability and solubility in water could make them useful as components for enriched foods.


[Stress Management Interventions at the Workplace Improve Perceived Stress Reactivity of Men at Higher Risk].
A randomised controlled trial was conducted in a metal working plant. The primary endpoint was perceived stress reactivity (Stress Reactivity Scale, SRS). 174 participants were randomly assigned to a stress-management intervention (SMI) (IG) or a waiting control group (CG). N=174 participants (171 male) were recruited at t0, 154 (89%) were still taking part after one year (t1), 131 (76%) after 2 years. The SRS score decreased in both groups. The conducted SMI proved to be effective over both a 1- and a 2-year period.