Stability of amiodarone hydrochloride in admixtures with other injectable drugs.
The stability of amiodarone hydrochloride in intravenous admixtures was studied. Amiodarone hydrochloride 900 mg was mixed with 500 mL of either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers; identical solutions were also mixed with either potassium chloride 20 meq, lidocaine hydrochloride 2000 mg, quinidine gluconate 500 mg, procainamide hydrochloride 2000 mg, verapamil hydrochloride 25 mg, or furosemide 100 mg. All admixtures were prepared in triplicate and stored for 24 hours at 24 degrees C. Amiodarone concentrations were determined using a stability-indicating high-performance liquid chromatographic assay immediately after admixture and at intervals during storage. Each solution was visually inspected and tested for pH. Amiodarone concentrations decreased less than 10% in all admixtures except those containing quinidine gluconate in polyvinyl chloride containers. The only visual incompatibility observed was in admixtures containing quinidine gluconate and 5% dextrose injection. In most solutions pH either decreased slightly or remained unchanged. Amiodarone hydrochloride is stable when mixed with either 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride or polyolefin containers alone or with potassium chloride, lidocaine, procainamide, verapamil, or furosemide and stored for 24 hours at 24 degrees C. Amiodarone should not be mixed with quinidine gluconate in polyvinyl chloride containers.


A Randomized, Placebo-Controlled Study of Romosozumab for the Treatment of Hip Fractures.
Romosozumab is a bone-forming antibody that increases bone formation and decreases bone resorption. We conducted a double-blinded, randomized, phase-2, dose-finding trial to evaluate the effect of romosozumab on the clinical outcomes of open reduction and internal fixation of intertrochanteric or femoral neck hip fractures. Patients (55 to 94 years old) were randomized 2:3:3:3 to receive 3 subcutaneous injections of romosozumab (70, 140, or 210 mg) or a placebo postoperatively on day 1 and weeks 2, 6, and 12. The primary end point was the difference in the mean timed "Up & Go" (TUG) score over weeks 6 to 20 for romosozumab versus placebo. Additional end points included the time to radiographic evidence of healing and the score on the Radiographic Union Scale for Hip (RUSH). A total of 332 patients were randomized: 243 to receive romosozumab (70 mg, n = 60; 140 mg, n = 93; and 210 mg, n = 90) and 89 to receive a placebo. Although TUG scores improved during the study, they did not differ significantly between the romosozumab and placebo groups over weeks 6 to 20 (p = 0.198). The median time to radiographic evidence of healing was 16.4 to 16.9 weeks across treatment groups. The RUSH scores improved over time across treatment groups but did not differ significantly between the romosozumab and placebo groups. The overall safety and tolerability profile of romosozumab was comparable with that of the placebo. Romosozumab did not improve the fracture-healing-related clinical and radiographic outcomes in the study population. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


Can enhancement be distinguished from prevention in genetic medicine?
In discussions of the ethics of human gene therapy, it has become standard to draw a distinction between the use of human gene transfer techniques to treat health problems and their use to enhance or improve normal human traits. Some dispute the normative force of this distinction by arguing that it is undercut by the legitimate medical use of human gene transfer techniques to prevent disease-such as genetic engineering to bolster immune function, improve the efficiency of DNA repair, or add cellular receptors to capture and process cholesterol. If disease prevention is a proper goal of medicine, these critics argue, and the use of gene transfer techniques to enhance human health maintenance capacities will help achieve that goal, then the "treatment/enhancement" distinction cannot define the limits of legitimate gene therapy. In this paper, I argue that a line can be drawn between prevention and enhancement for gene therapy (and thus between properly medical and nonmedical uses of gene therapy), but only if one is willing to accept two rather old-fashioned claims: 1) Some health problems are best understood as if they were entities in their own right, reifiable as processes or parts in a biological system, with at least as much ontological objectivity and theoretical significance as the functions that they inhibit. 2) Legitimate preventive genetic health care should be limited to efforts to defend people from attack by these more robust pathological entities, rather than changing their bodies to evade social injustices.


Genomics of aggressive B-cell lymphoma.
The growing body of genomic information collected and applied to mature aggressive B-cell lymphoma diagnosis and management has exploded over the last few years due to improved technologies with high-throughput capacity, suitable for use on routine formalin-fixed, paraffin-embedded tissue biopsies, and decreasing costs. These techniques have made evaluation of complete DNA sequences, RNA-expression patterns, translocations, copy-number alterations, loss of heterozygosity, and DNA-methylation patterns possible on a genome-wide level. This chapter will present a case of aggressive B-cell lymphoma and discuss the most important genomic abnormalities that characterize this group of entities in the recent update to the fourth edition of the World Health Organization (WHO) lymphoma classification system. Genomic abnormalities discussed will include those necessary for certain diagnoses such as translocations of MYC, BCL2, or BCL6; gene-expression-profiling categorization; the newly defined Burkitt-like lymphoma with 11q abnormalities; prognostic and predictive mutations, as well as tumor heterogeneity. Finally, our current practices for clinical triage of specimens with a potential diagnosis of aggressive B-cell lymphomas are also described. Options for treatment at relapse, in light of these genomic features, will be discussed in the third presentation from this session.


Less-structured time in children's daily lives predicts self-directed executive functioning.
Executive functions (EFs) in childhood predict important life outcomes. Thus, there is great interest in attempts to improve EFs early in life. Many interventions are led by trained adults, including structured training activities in the lab, and less-structured activities implemented in schools. Such programs have yielded gains in children's externally-driven executive functioning, where they are instructed on what goal-directed actions to carry out and when. However, it is less clear how children's experiences relate to their development of self-directed executive functioning, where they must determine on their own what goal-directed actions to carry out and when. We hypothesized that time spent in less-structured activities would give children opportunities to practice self-directed executive functioning, and lead to benefits. To investigate this possibility, we collected information from parents about their 6-7 year-old children's daily, annual, and typical schedules. We categorized children's activities as "structured" or "less-structured" based on categorization schemes from prior studies on child leisure time use. We assessed children's self-directed executive functioning using a well-established verbal fluency task, in which children generate members of a category and can decide on their own when to switch from one subcategory to another. The more time that children spent in less-structured activities, the better their self-directed executive functioning. The opposite was true of structured activities, which predicted poorer self-directed executive functioning. These relationships were robust (holding across increasingly strict classifications of structured and less-structured time) and specific (time use did not predict externally-driven executive functioning). We discuss implications, caveats, and ways in which potential interpretations can be distinguished in future work, to advance an understanding of this fundamental aspect of growing up.


Leveraging Social Computing for Personalized Crisis Communication using Social Media.
The extensive use of social media in modern life redefines social interaction and communication. Communication plays an important role in mitigating, or exacerbating, the psychological and behavioral responses to critical incidents and disasters. As recent disasters demonstrated, people tend to converge to social media during and following emergencies. Authorities can then use this media and other computational methods to gain insights from the public, mainly to enhance situational awareness, but also to improve their communication with the public and public adherence to instructions. The current review presents a conceptual framework for studying psychological aspects of crisis and risk communication using the social media through social computing. Advanced analytical tools can be integrated in the processes and objectives of crisis communication. The availability of the computational techniques can improve communication with the public by a process of Hyper-Targeted Crisis Communication. The review suggests that using advanced computational tools for target-audience profiling and linguistic matching in social media, can facilitate more sensitive and personalized emergency communication.


Neisseria genomics: current status and future perspectives.
High-throughput whole genome sequencing has unlocked a multitude of possibilities enabling members of the Neisseria genus to be examined with unprecedented detail, including the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae. To maximise the potential benefit of this for public health, it is becoming increasingly important to ensure that this plethora of data are adequately stored, disseminated and made readily accessible. Investigations facilitating cross-species comparisons as well as the analysis of global datasets will allow differences among and within species and across geographic locations and different times to be identified, improving our understanding of the distinct phenotypes observed. Recent advances in high-throughput platforms that measure the transcriptome, proteome and/or epigenome are also becoming increasingly employed to explore the complexities of Neisseria biology. An integrated approach to the analysis of these is essential to fully understand the impact these may have in the Neisseria genus. This article reviews the current status of some of the tools available for next generation sequence analysis at the dawn of the 'post-genomic' era.


New mechanisms for chemistry at surfaces.
It is becoming increasingly apparent that chemistry at surfaces, whether it be heterogeneous catalysis, semiconductors etching, or chemical vapor deposition, is controlled by much more than the nature and structure of the surface. Recent experiments that principally make use of molecular beam techniques have revealed that the energy at which an incident molecule collides with a surface can be the key factor in determining its reactivity with or on the surface. In addition, the collision energy of an incident particle has proven essential to the finding of new mechanisms for reaction or desorption of molecules at surfaces, collision-induced activation and collision-induced desorption. These phenomena are often responsible for the different surface chemistry observed under conditions of high reactant pressure, such as those present during a heterogeneous catalytic reaction, and of low pressure of reactants (< 10(-4) torr), such as those present in an ultrahigh vacuum surface science experiment. This knowledge of the microscopic origins of the effect of pressure on the chemistry at surfaces has allowed the development of a scheme to bypass the high-pressure requirement. Reactions that are normally observed only at high reactant pressures, and which are the ones most often of practical importance, can now be carried out in low-pressure, ultrahigh vacuum environments.


Flow lithography in ultraviolet-curable polydimethylsiloxane microfluidic chips.
Flow Lithography (FL) is the technique used for the synthesis of hydrogel microparticles with various complex shapes and distinct chemical compositions by combining microfluidics with photolithography. Although polydimethylsiloxane (PDMS) has been used most widely as almost the sole material for FL, PDMS microfluidic chips have limitations: (1) undesired shrinkage due to the thermal expansion of masters used for replica molding and (2) interfacial delamination between two thermally cured PDMS layers. Here, we propose the utilization of ultraviolet (UV)-curable PDMS (X-34-4184) for FL as an excellent alternative material of the conventional PDMS. Our proposed utilization of the UV-curable PDMS offers three key advantages, observed in our study: (1) UV-curable PDMS exhibited almost the same oxygen permeability as the conventional PDMS. (2) The almost complete absence of shrinkage facilitated the fabrication of more precise reverse duplication of microstructures. (3) UV-cured PDMS microfluidic chips were capable of much stronger interfacial bonding so that the burst pressure increased to ∼0.9 MPa. Owing to these benefits, we demonstrated a substantial improvement of productivity in synthesizing polyethylene glycol diacrylate microparticles via stop flow lithography, by applying a flow time (40 ms) an order of magnitude shorter. Our results suggest that UV-cured PDMS chips can be used as a general platform for various types of flow lithography and also be employed readily in other applications where very precise replication of structures on micro- or sub-micrometer scales and/or strong interfacial bonding are desirable.


Hepatic ischemia and reperfusion injury and trauma: current concepts.
Ischemia-reperfusion injury is a fascinating topic which has drawn a lot of interest in the last several years. Hepatic ischemia reperfusion injury may occur in a variety of clinical situations. These include transplantation, liver resection, trauma, and vascular surgery. The purpose of this review was to outline the molecular mechanisms underlying hepatic I/R injury and present the latest approaches, both surgical and pharmacological, regarding the prevention of it. A comprehensive electronic literature search in MEDLINE/PubMed was performed to identify relative articles published within the last 2 years. The basic mechanism of hepatic ischemia - reperfusion injury is one of blood deprivation during ischemia, followed by the return of flow during reperfusion. It involves a complex series of events, such as mitochondrial deenergization, adenosine-5'-triphosphate depletion, alterations of electrolyte homeostasis, as well as Kupffer cell activation, oxidative stress changes and upregulation of proinflammatory cytokine signaling. The great number of variable pathways, with several mediators interacting with each other, leads to a high number of candidates for potential therapeutic intervention. As far as surgical approaches are concerned, the modification of existing clamping techniques and the ischemic preconditioning are the most promising techniques till recently. In the search for novel techniques of protecting against hepatic ischemia reperfusion injury, many different strategies have been used in experimental models. The biggest part of this research lies around antioxidant therapy, but other potential solutions have been explored as well. The management of hepatic trauma, in spite of the fact that it has become increasingly nonoperative, there still remains the possibility of hepatic resection in the hepatic trauma setting, especially in severe injuries. Hence, clinicians should be familiar with the concept of hepatic ischemia-reperfusion injury and respond appropriately and timely.


DNA Barcoding as a Diagnostic Tool of a Rare Human Parasitosis: The First Case of Lagochilascaris minor in Quintana Roo, Mexico.
Recently, DNA barcoding based on the mitochondrial gene cytochrome c oxidase subunit 1 (COI) has become a widespread tool to identify animals. Its use with parasites of humans has been limited with some groups of nematodes where the amplification of this gene has been difficult. In this study, we present the first COI barcode sequence of a rare parasite from tropical regions, Lagochilascaris minor, which parasitized a human host from Quintana Roo, southern Yucatán Peninsula, Mexico. Destruction of the mastoid apophysis in the lateral sinus and cerebellar involvement were observed at the site of infection. After a radical mastoidectomy and a treatment with 200 mg oral albendazole for 63 days, the patient completely recovered. Lagochilascaris minor was identified based on the ratio between length of spicules and ejaculatory duct, shape of eggs, and host, as well as comparison with its congeners. The mode of infection is unknown, although it could be after direct exposure to eggs or consumption of uncooked wild meat. Morphology of adults is demonstrated using scanning electron microscopy, and high-quality sequences of COI barcode are presented from amplifications using semi-degenerate primers designed for micro-crustaceans. DNA barcoding proved to be a reliable identification method for L. minor. A comparison of the sequences for this species with 81 ascaridoids obtained from the Barcode of Life Database places it in a unique clade most closely related to Baylisascaris procyonis. Future diagnosis of larval and adult stages of L. minor using DNA barcoding will allow the recognition of its infection parameters, transmission, and precise epidemiology. Reports of lagochilascarosis in the Yucatán Peninsula have been occurred over the last decade, suggesting it is an emerging zoonotic disease in the region.


Neuroprotective effects of the antiparkinson drug Mucuna pruriens.
Mucuna pruriens possesses significantly higher antiparkinson activity compared with levodopa in the 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. The present study evaluated the neurorestorative effect of Mucuna pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned rats. Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but did not affect the total monoamine oxidase activity (in vitro). Unlike synthetic levodopa treatment, Mucuna pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine and serotonin content in the substantia nigra. Nicotine adenine dinucleotide (NADH) and coenzyme Q-10, that are shown to have a therapeutic benefit in Parkinson's disease, were present in the Mucuna pruriens cotyledon powder. Earlier studies showed that Mucuna pruriens treatment controls the symptoms of Parkinson's disease. This additional finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra may be due to increased complex-I activity and the presence of NADH and coenzyme Q-10.


Toward cities without slums: Topology and the spatial evolution of neighborhoods.
The world is urbanizing quickly with nearly 4 billion people presently living in urban areas, about 1 billion of them in slums. Achieving sustainable development from rapid urbanization relies critically on creating cities without slums. We show that it is possible to diagnose systematically the central physical problem of slums-the lack of spatial accesses and related services-using a topological analysis of neighborhood maps and resolved by finding solutions to a sequence of constrained optimization problems. We set up the problem by showing that the built environment of any city can be decomposed into two types of networked spaces-accesses and places-and prove that these spaces display universal topological characteristics. We then show that while the neighborhoods of developed cities express the same common topology, urban slums fall into a different topological class. We demonstrate that it is always possible to find solutions that grow a street network in existing slums, providing universal accesses at minimal disruption and cost. We then show how elaborations of this procedure that include local preferences and reduce travel distances between places result from additional access construction. These methods are presently taking effect in neighborhoods in Cape Town (South Africa) and Mumbai (India), demonstrating their practical feasibility and emphasizing their role as a platform to enable communities and local governments to combine technical knowledge with local aspirations into contextually appropriate urban sustainable development solutions.


Incidences of selected lesions in control female Harlan Sprague-Dawley rats from two-year studies performed by the National Toxicology Program.
The NTP has a long history of using Fischer rats and has compiled a large database of incidences of lesions seen in control animals. Such a database is lacking for Harlan Sprague-Dawley (SD) rats. The intention of this paper is to report spontaneous lesions observed in female vehicle control Harlan SD rats, and to compare the incidence in 2 strains of rats (Fischer and Harlan SD) used in NTP studies. Female Harlan SD rats served as the test animals for a special series of 2-year studies. Male rats were not used in these studies. Complete histopathology was performed on all animals, and the pathology results underwent comprehensive NTP pathology peer review. The most commonly observed neoplasms in these female control Harlan SD rats were mammary gland fibroadenoma (71%), tumors of the pars distalis of the pituitary (41%) and thyroid gland C-cell tumors (30%). Female Fischer rats had incidences of 44% for mammary gland fibroadenomas, 34% for tumors of the pars distalis, and 16% for thyroid gland C-cell tumors. Fischer rats had a 15% incidence of clitoral gland tumors, while the Harlan SD rats had an incidence of < 1%. In contrast to Fischer F344 rats, the Harlan SD rats had a high incidence of squamous metaplasia of the uterus (44.2%). Squamous metaplasia is not a lesion commonly observed in NTP control Fischer rats. The Harlan SD rats had a very low incidence of mononuclear cell leukemia (0.5%), compared with an incidence of 24% in female Fischer rats.


Hormonal treatment of pancreatic carcinoma: a phase II study of LHRH agonist goserelin plus hydrocortisone.
Eighteen consecutive patients with measurable locally advanced or metastatic pancreatic adenocarcinoma were treated with goserelin (Zoladex) 3.6 mg subcutaneously every 4 weeks. Hydrocortisone 20 milligrams twice daily was commenced with the second injection of goserelin. Objective tumour response was monitored by computerised tomography of the abdomen. There was no objective remission in disease sites. Serial measurements of serum tumour markers showed no reduction in serum CA 19-9 and CA 195 concentrations. The median duration of survival of all cases was 5 months. Administration of goserelin resulted in significant reductions in oestradiol, testosterone, androstenedione in males and reductions in FSH and LH in both males and females. The addition of hydrocortisone resulted in further reductions of androstenedione and testosterone levels in males. Thus goserelin showed no anti-tumour effect, but concentrations required for direct inhibitory effects may be higher than those required to produce effects on hormone suppression.


Vitamin D and diabetes.
Vitamin D deficiency predisposes individuals to type 1 and type 2 diabetes, and receptors for its activated form-1alpha,25-dihydroxyvitamin D3-have been identified in both beta cells and immune cells. Vitamin D deficiency has been shown to impair insulin synthesis and secretion in humans and in animal models of diabetes, suggesting a role in the development of type 2 diabetes. Furthermore, epidemiological studies suggest a link between vitamin D deficiency in early life and the later onset of type 1 diabetes. In some populations, type 1 diabetes is associated with certain polymorphisms within the vitamin D receptor gene. In studies in nonobese diabetic mice, pharmacological doses of 1alpha,25-dihydroxyvitamin D3, or its structural analogues, have been shown to delay the onset of diabetes, mainly through immune modulation. Vitamin D deficiency may, therefore, be involved in the pathogenesis of both forms of diabetes, and a better understanding of the mechanisms involved could lead to the development of preventive strategies.


Phylogeny of the filamentous bacterium 'Nostocoida limicola' III from activated sludge.
Five strains of the filamentous bacterium 'Nostocoida limicola' III were successfully isolated into pure culture from samples of activated sludge biomass from five plants in Australia. 16S rRNA gene sequence analyses showed that all isolates were members of the Planctomycetales, most closely related to Isosphaera pallida, but they differed phenotypically from this species in that they did not glide and were not thermotolerant. The ultrastructure of these 'N. limicola' III isolates was also consistent with them being Planctomycetales, in that they possessed complex intracellular membrane systems compartmentalizing the cells. However, the arrangements of these intracellular membranes differed between isolates. These data confirm that 'N. limicola' III is phylogenetically unrelated to both 'N. limicola' I and 'N. limicola' II, activated sludge filamentous bacteria which share morphological features in common with 'N. limicola' III and which have been presumed historically to be the same or very similar bacteria.


HIV-1 nef protein visits B-cells via macrophage nanotubes: a mechanism for AIDS-related lymphoma pathogenesis?
This letter refers to the recent demonstration that HIV-1 infected macrophages form specialized conduits that connect to B-cells (1). The conduit selectively transports the HIV-1 nef protein, providing nef with numerous means to interfere with cellular processes. Currently, no consideration of the connection between the conduit and the development of AIDS-related lymphoma (ARL) has been offered. ARL is one of the primary causes of death in the HIV-infected population and is related to B-cell proliferation and activation. In this letter we discuss several studies that link HIV-infected macrophages and specific forms of the nef protein to the development of ARL. The conduits discovered by Xu et al. may lead to a better understanding of how HIV infection results in lymphomagenesis.


Benzodiazepine Prescribing in Older Adults in U.S. Ambulatory Clinics and Emergency Departments (2001-10).
To assess trends in benzodiazepine use from 2001 to 2010 in older adults in U.S. ambulatory clinics and emergency departments (EDs). Retrospective analysis. 2001 to 2010 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS). Individuals aged 65 and older for whom the reason for visit might prompt a physician to use a benzodiazepine (e.g., anxiety, detoxification, back sprain). The NAMCS and NHAMCS were used to evaluate U.S. ambulatory clinic and ED visits. Encounters involving individuals aged 65 and older for whom a benzodiazepine might be prescribed were analyzed. Trends in benzodiazepine use in these visits were explored, and predictors of use were assessed using survey-weighted chi-square tests and logistic regression. From 2001 to 2010, benzodiazepines were used in 16.6 million of 133.3 million ambulatory clinic visits and 1.9 million of 18.1 million ED visits with the selected reasons for the visits. There was no change in benzodiazepine use in either setting over the study period, although benzodiazepine use for those aged 85 and older increased from 8.9% to 19.3% in ambulatory clinics and 10.1% to 17.2% in EDs. Individuals visiting clinics with anxiety were five times as likely to receive benzodiazepines (odds ratio (OR) = 4.8), and those in EDs were twice as likely (OR = 2.3). Despite safety concerns, benzodiazepine use in older adults in U.S. ambulatory clinics and EDs did not change from 2001 to 2010. In the oldest individuals, who are at higher risk of adverse events, a greater increase was seen than in those aged 65 to 84. Additional measures may be needed to promote alternatives to benzodiazepines.


Origin of non-Nernstian anion response slopes of metalloporphyrin-based liquid/polymer membrane electrodes.
The origin of the non-Nernstian potentiometric anion response behavior exhibited by several metalloporphyrin-based liquid/polymeric membrane electrodes is examined. UV-visible spectrophotometry of organic-phase solutions and thin plasticized PVC films containing In(III) and Ga(III) octaethylporphyrins suggests that, in the absence of preferred axial coordination anions, the metalloporphyrins form hydroxide ion bridged dimers within the organic phases, as indicated by a significant blue shift of the Soret band in the visible spectrum. As increasing levels of the preferred anions are added, the degree of dimerization decreases and the intensity of the Soret band corresponding to the monomer species increases. Observation of Nernstian responses with membranes doped with picket fence-type In(III) and Ga(III) porphyrins not capable of forming hydroxide bridged structures (as determined by UV-visible spectroscopy) confirms that dimerization is likely responsible for the super-Nernstian slopes of membrane electrodes formulated with the non-picket fence species. A phase boundary model based on simultaneous binding equilibria of hydroxide ions with two metalloporphyrins to form the dimeric species, while the target anions bind with metalloporphyrins to form neutral 1:1 complexes, is shown to fully predict the observed non-Nernstian behavior. The prospect of utilizing this anion-dependent dimer-monomer metalloporphyrin equilibrium to fabricate anion-selective optical sensors using thin films of metalloporphyrin-doped polymers is also discussed.


The impact of chronic untreated hyperglycaemia on the long-term stability of paraoxonase 1 (PON1) and antioxidant status in human sera.
Paraoxonase 1 (PON1) is increasingly measured on samples that have been stored for extended durations. The impact of storage and baseline conditions on the stability of the enzyme is however not well documented. We investigated the influence of hyperglycaemia on the stability of PON1 activity and antioxidant status in human sera stored for 12 months. Blood was collected from 60 individuals aged 35-80 years with chronic hyperglycaemia (HbA1c≥6.5%) or normoglycaemia (HbA1c<6.5%) in Cape Town. At baseline and after 12 months at -80°C, levels of PON1 activity (paraoxoase and arylesterase), antioxidant activity (ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC)) and lipid peroxidation (malondialdehyde and oxidised low density lipoprotein (ox-LDL)) were measured and compared. In normoglycaemic samples, 12-month storage led to minor alterations of <10% for the six target variables. In hyperglycaemic samples, alterations ranged from 13% for AREase activity to about 23% for ox-LDLs indicating a twofold to fourfold difference between the two groups in the variables assessed. Changes in levels of FRAP, TEAC and ox-LDL were both statistically and clinically significant. Furthermore, there was evidence of significant statistical interaction by baseline glycaemic status on the alteration of FRAP, TEAC, thiobarbituric acid reactive substances and ox-LDL, but not for PON1 activity. The results indicate that baseline glycaemic status may contribute to a decline in the stability of antioxidant activity and extent of lipid peroxidation but not PON activity.


The extracellular signal-regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis.
Hyperplasia of adipose tissue is critical for the development of obesity, but molecular mechanisms governing normal or pathological recruitment of new adipocytes remain unclear. The extracellular signal-regulated kinase (ERK) pathway plays a pivotal role in many essential cellular functions, such as proliferation and differentiation. Using ERK1(-/-) mice, we investigated the role of this isoform in adipose tissue development. Mice lacking ERK1 have decreased adiposity and fewer adipocytes than wild-type animals. Furthermore, ERK1(-/-) mice challenged with high-fat diet are resistant to obesity, are protected from insulin resistance, and have a higher postprandial metabolic rate. To get insights into cellular mechanisms implicated in reduced adiposity in ERK1(-/-) animals, we analyzed adipocyte differentiation in ERK1(-/-) cells. Compared with wild-type control cells, mouse embryo fibroblasts and cultures of adult preadipocytes isolated from ERK1(-/-) adult animals exhibit impaired adipogenesis. An inhibitor of the ERK pathway does not affect the residual adipogenesis of the ERK1(-/-) cells, suggesting that ERK2 is not implicated in adipocyte differentiation. Our results clearly link ERK1 to the regulation of adipocyte differentiation, adiposity, and high-fat diet-induced obesity. This suggests that a therapeutic approach of obesity targeting specifically the ERK1 isoform and not ERK2 would be of particular interest.


Variability in fecal water genotoxicity, determined using the Comet assay, is independent of endogenous N-nitroso compound formation attributed to red meat consumption.
Red meat consumption causes a dose-dependent increase in fecal apparent total N-nitroso compounds (ATNC). The genotoxic effects of these ATNCs were investigated using two different Comet assay protocols to determine the genotoxicity of fecal water samples. Fecal water samples were obtained from two studies of a total of 21 individuals fed diets containing different amounts of red meat, protein, heme, and iron. The first protocol incubated the samples with HT-29 cells for 5 min at 4 degrees C, whereas the second protocol used a longer exposure time of 30 min and a higher incubation temperature of 37 degrees C. DNA strand breaks were quantified by the tail moment (DNA in the comet tail multiplied by the comet tail length). The results of the two Comet assay protocols were significantly correlated (r = 0.35, P = 0.003), however, only the second protocol resulted in detectable levels of DNA damage. Inter-individual effects were variable and there was no effect on fecal water genotoxicity by diet (P > 0.20), mean transit time (P = 0.588), or weight (P = 0.705). However, there was a highly significant effect of age (P = 0.019). There was no significant correlation between concentrations of ATNCs in fecal homogenates and fecal water genotoxicity (r = 0.04, P = 0.74). ATNC levels were lower in fecal water samples (272 microg/kg) compared to that of fecal homogenate samples (895 microg/kg) (P < 0.0001). Failure to find dietary effects on fecal water genotoxicity may therefore be attributed to individual variability and low levels of ATNCs in fecal water samples.


Comparison of macular thickness measurement and segmentation error rate between stratus and fourier-domain optical coherence tomography.
To compare macular thickness measurements and segmentation error rates between Stratus optical coherence tomography (OCT) (Carl Zeiss Meditec, Inc., Dublin, CA), and Fourier-domain OCT (RTVue, Optovue, Inc., Fremont, CA). A retrospective study was performed of 93 normal and pathologic eyes from 79 subjects imaged with both OCT instruments on the same day. Both the macular thickness measurement for each Early Treatment Diabetic Retinopathy Study (ETDRS) zone and the incidence of segmentation error in the central macula between the two instruments were compared. Macular thickness measurements for all nine ETDRS zones were higher with RTVue compared with Stratus OCT (P < .01). Linear regression analysis showed the highest correlation in the central macula (R(2) = 0.88), with progressively lower correlation peripherally. The overall segmentation error rate was 29% with Stratus OCT versus 32% with RTVue (P > .05). Macular thickness measurement was greater with RTVue than with Stratus OCT in all ETDRS areas, with the best correlation seen in the central macula. No difference in segmentation error rate was noted between the two instruments.


A Doppler echocardiographic method for calculating volume flow across the tricuspid valve: correlative laboratory and clinical studies.
In this study we tested a two-dimensional Doppler echocardiographic method for measuring volume flow across the tricuspid valve. Five anesthetized, open-chest dogs had a calibrated electromagnetic flow probe placed on the ascending aorta. Volume flow across the tricuspid valve was controlled by creating a variable femoral-to-pulmonary arterial shunt. Since no standard plane provided a direct view of the tricuspid valve orifice, tricuspid flow area was estimated by calculating a fixed circular flow orifice from the maximal late diastolic diameter of the tricuspid anulus in a four-chamber view. Doppler-determined velocities across the tricuspid valve and tricuspid anulus images in the four-chamber view were obtained in inspiration and expiration. For 24 cardiac outputs (0.6 to 4.0 liters/min), inspiratory tricuspid flow determined by the Doppler method correlated minimally better (r = .90, SEE = 0.30 liter/min) than did expiratory measurements (r = .89, SEE = 0.35 liter/min) with the time-averaged systemic flow determined electromagnetically. Doppler-determined tricuspid volume flows in four-chamber and short-axis two-dimensional echocardiographic views from 10 children were then compared with values determined simultaneously by thermodilution during cardiac catheterization. In the children, Doppler-determined flows in short-axis and four-chamber views, both in inspiration and expiration, were similar; when results for the two views were averaged in inspiration and expiration, the tricuspid flows predicted by the Doppler method were highly correlated (r = .98, SEE = 0.48 liter/min) with the results of thermodilution. The two-dimensional Doppler echocardiographic method provides a means of estimating volume flow across the tricuspid valve noninvasively.


An Outbreak Investigation Report and Lessons Learned by Multinational Coalition Forces: October 2016, Baghdad, Iraq.
Public health personnel from the 28th Combat Support Hospital in Baghdad, Iraq, conducted an outbreak investigation in response to many local cases of gastrointestinal (GI) illness presenting to U.S. medical facilities. The investigation was conducted to identify the source of the illness, assess the extent of cases, and make recommendations to prevent similar outbreaks. For this retrospective cohort study, medical records and patient outbreak questionnaires were reviewed. A patient case, relative to the outbreak, was defined as any person who had developed a GI illness and presented for medical evaluation to either sick call or an emergency service at a diplomatic or military medical facility in Baghdad from 30 September to 12 October 2016. A total of 123 people met the case definition. The most common presenting symptom was diarrhea (91% to 96% of cases). Other symptoms included abdominal cramps, fatigue, and headache. Most cases were military personnel (n =100). Salad was significantly associated with GI illness (70% of respondents). Five salad ingredients had significantly elevated levels of Escherichia coli. Mitigation strategies to reduce the probability of similar outbreaks include purchasing food solely from approved vendors or thoroughly cooking all foods, including fruits and vegetables.


The emergence of commercial genomics: analysis of the rise of a biotechnology subsector during the Human Genome Project, 1990 to 2004.
Development of the commercial genomics sector within the biotechnology industry relied heavily on the scientific commons, public funding, and technology transfer between academic and industrial research. This study tracks financial and intellectual property data on genomics firms from 1990 through 2004, thus following these firms as they emerged in the era of the Human Genome Project and through the 2000 to 2001 market bubble. A database was created based on an early survey of genomics firms, which was expanded using three web-based biotechnology services, scientific journals, and biotechnology trade and technical publications. Financial data for publicly traded firms was collected through the use of four databases specializing in firm financials. Patent searches were conducted using firm names in the US Patent and Trademark Office website search engine and the DNA Patent Database. A biotechnology subsector of genomics firms emerged in parallel to the publicly funded Human Genome Project. Trends among top firms show that hiring, capital improvement, and research and development expenditures continued to grow after a 2000 to 2001 bubble. The majority of firms are small businesses with great diversity in type of research and development, products, and services provided. Over half the public firms holding patents have the majority of their intellectual property portfolio in DNA-based patents. These data allow estimates of investment, research and development expenditures, and jobs that paralleled the rise of genomics as a sector within biotechnology between 1990 and 2004.


United States Army physical readiness training: rationale and evaluation of the physical training doctrine.
This paper reviews the rationale and evaluations of Physical Readiness Training (PRT), the new U.S. Army physical training doctrine designed to improve soldiers' physical capability for military operations. The purposes of PRT are to improve physical fitness, prevent injuries, progressively train soldiers, and develop soldiers' self-confidence and discipline. The PRT follows the principles of progressive overload, regularity, specificity, precision, variety, and balance. Specificity was achieved by examining the standard list of military (warrior) tasks and determining 1) the physical requirements, 2) the fitness components involved, and 3) the training activities that most likely could improve the military tasks. Injury-prevention features include reduced running mileage, exercise variety (cross-training), and gradual, progressive training. In 3 military field studies, the overall adjusted risk of injury was 1.5-1.8 times higher in groups of soldiers performing traditional military physical training programs when compared with groups using a PRT program. Scores on the Army Physical Fitness Test were similar or higher in groups using PRT programs. In an 8-week laboratory study comparing PRT with a weightlifting/running program, both programs resulted in major improvements in militarily relevant tasks (e.g., 3.2-km walk/run with 32-kg load, 400-m run with 18-kg load, 5- to 30-second rushes to and from prone position, 80-kg casualty drag, obstacle course). When compared with traditional military physical training programs, PRT consistently resulted in fewer injuries and in equal or greater improvements in fitness and military task performance.


Games researchers play--extreme-groups analysis and mediation analysis in longitudinal occupational health research.
The study of causal processes using a longitudinal design is often hampered by two methodological problems. First, the lagged effects of a predictor variable on an outcome variable tend to be weak after control for a previous measure of this outcome. One approach that is advocated when effects are weak is to increase the extremeness of the study groups; this step often increases the significance and sizes of effects. Second, causal links are often mediated through third variables, and thus relatively complex mediational analyses are needed to understand the causal processes underlying particular associations. The present paper shows whether and when these two approaches are useful in longitudinal research. The two approaches were evaluated using data from a three-wave study among 1251 newcomers from various Western countries (mean age 20.6 years, 59% female). Although the significances and effect sizes indeed increased with increasing extremeness of the study groups, extreme-groups analysis in the context of a longitudinal design may grossly bias findings. Cross-sectional applications of mediation analysis cannot provide evidence for any mediational model. Longitudinal models are better suited for examining mediation. Rather than using extreme-groups analysis to obtain significant effects across time, researchers should maximize the amount of change in their data by focusing on groups for which change can be expected. Especially multiphase longitudinal data sets offer good opportunities for analyzing mediation models.


"MATH+" Multi-Modal Hospital Treatment Protocol for COVID-19 Infection: Clinical and Scientific Rationale.
In December 2019, coronavirus disease 2019 (COVID-19), a severe respiratory illness caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working", the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and non-antiviral co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically.


Superior immunomodulatory effects of intravenous immunoglobulins on human T-cells and dendritic cells: comparison to calcineurin inhibitors.
Prophylactic administration of anti-HBs intravenous immunoglobulins (IVIg) in hepatitis B infected-liver transplant patients protects against acute rejection. To explore the suitability of intravenous immunoglobulins (IVIg) as prophylaxis of acute rejection and graft-versus-host disease (GVHD) after allograft transplantation, the effects of IVIg and calcineurin inhibitors (CNI) on human blood-derived T-cells and DC were compared. T-cells were stimulated with phytohemagglutinin (PHA) or allogeneic spleen antigen-presenting cells (APC) and T-cell proliferation and cytokine production were determined in presence or absence of IVIg or CNI. Immature blood dendritic cells (DC) were stimulated in presence or absence of IVIg or CNI, and allogeneic T-cell stimulatory capacity, cell death, and phenotypic maturation were established. IVIg and CNI equally inhibited T-cell proliferation and IFN-gamma production after PHA stimulation or allogeneic stimulation. CD8+ T-cells were preferentially affected by both IVIg and CNI after allogeneic stimulation. Like CNI, addition of IVIg at later time points after T-cell activation suppressed mitotic progression of responding T-cells. IVIg-treated DC were suppressed in their capacity to stimulate allogeneic T-cell proliferation by 73+/-12%, whereas DC-function was not affected by CNI. The decreased allogeneic T-cell stimulatory capacity of IVIg-treated DC correlated to induction of cell death in DC and decreased up-regulation of CD40 and CD80. In vitro IVIg functionally inhibit the two principal immune cell-types involved in rejection and GVHD, i.e. T-cells and DC, whereas CNI only suppress T-cells. By targeting both T-cells and DC, IVIg may be a promising candidate for immunosuppressive treatment after allograft transplantation.


Clinical and molecular classification of cardiomyopathies.
The term "cardiomyopathies" was used for the first time 55 years ago, in 1957. Since then awareness and knowledge of this important and complex group of heart muscle diseases have improved substantially. Over these past five decades a large number of definitions, nomenclature and schemes, have been advanced by experts and consensus panel, which reflect the fast and continued advance of the scientific understanding in the field. Cardiomyopathies are a heterogeneous group of inherited myocardial diseases, which represent an important cause of disability and adverse outcome. Although considered rare diseases, the overall estimated prevalence of all cardiomyopathies is at least 3% in the general population worldwide. Furthermore, their recognition is increasing due to advances in imaging techniques and greater awareness in both the public and medical community. Cardiomyopathies represent an ideal translational model of integration between basic and clinical sciences. A multidisciplinary approach is therefore essential in order to ensure their correct diagnosis and management. In the present work, we aim to provide a concise overview of the historical background, genetic and phenotypic spectrum and evolving concepts leading to the various attempts of cardiomyopathy classifications produced over the decades.


Sensory and motor recovery after repairing transected cervical roots.
Adult mammal sensory axons avulsed through spinal dorsal root traction injuries, especially of the brachial plexus or cauda equina, cannot normally regenerate through axonal outgrowth from the DRG into the spinal cord, thus causing clinical conditions that require neuronal regeneration for sensory recovery and for which no successful treatment has yet been reported. To evaluate the sensory recovery of the forelimb after transection of their left cervical dorsal and ventral roots (C6-C8) at their spinal cord junctions, 22 SD rats were randomly assigned to 3 groups: transection only (control 1); transection followed by repair using intercostal nerve grafts and fibrin glue (control 2); transection, repair, and application of aFGF and fibrin glue (experimental group). The following tests were reperformed after retransecting the repaired nerve roots to discount collateral innervation from adjacent nerve roots: motor function (grasping power), mechanical sensitivity to pain and touch (foot-withdrawal response to mechanical stimuli), temperature sensitivity (foot-withdrawal response to cold stimulus), and electrophysiologic sensory responses (measurement of cortical SEP). After transection and repair, the experimental group rats showed recovery in both motor (grasping power) and sensory (touch, pain, and temperature sensation) nerve functions. Neuronal regeneration was confirmed by the reappearance of cortical SEP and by its disappearance after retransection of the repaired cervical nerve roots. Using our strategy for repairing transected cervical nerve roots, motor and sensory recovery was achieved in adult rats. The success of our study highlights possible treatment options for humans with avulsion injuries of the dorsal roots from the spinal cord.


Early Sex Work Initiation and Violence against Female Sex Workers in Mombasa, Kenya.
Between 20 and 40 % of female sex workers (FSWs) began sex work before age 18. Little is known concerning whether early initiation of sex work impacts later experiences in adulthood, including violence victimization. This paper examines the relationship between early initiation of sex work and violence victimization during adulthood. The sample included 816 FSWs in Mombasa, Kenya, recruited from HIV prevention drop-in centers who were 18 years or older and moderate-risk drinkers. Early initiation was defined as beginning sex work at 17 or younger. Logistic regression modeled recent violence as a function of early initiation, adjusting for drop-in center, age, education, HIV status, supporting others, and childhood abuse. Twenty percent of the sample reported early initiation of sex work. Although both early initiators and other FSWs reported commonly experiencing recent violence, early initiators were significantly more likely to experience recent physical and sexual violence and verbal abuse from paying partners. Early initiation was not associated with physical or sexual violence from non-paying partners. Many FSWs begin sex work before age 18. Effective interventions focused on preventing this are needed. In addition, interventions are needed to prevent violence against all FSWs, in particular, those who initiated sex work during childhood or adolescence.


Analysis of factors influencing levee safety using the DEMATEL method.
River embankments are the basic and the oldest measures of protecting areas potentially subjected to flooding, and at the same time pose a serious threat to their environment in the event of damage or failure. The technical condition of the levees and its regular evaluation is a key element of their safety. A general assessment of the technical condition of a levee is the result of many interacting factors and parameters that depend on each other to a varying degree. Therefore, it is necessary to consider the cause-and-effect links between the interrelationships of numerous parameters and sensors of significant impact. In this article the decision-making trial and evaluation laboratory (DEMATEL) method was applied to develop a cause-and-effect model for factors impacting the condition and safety of levees. Effective factors impacting the technical condition of a levee were identified; relationships between these factors were determined; a cause-and-effect model was developed based on identified factors; factors were categorized based on the dependence scale and influential indicators of each factors used in the DEMATEL method. The obtained results demonstrate that three following factors: hydrological factor, type and condition of soils in levee body and condition of levee areas (inter-levee and landside) play the most important role for levee safety. The results of this study can support traditional assessments of hydrotechnical structure or assist entities managing levees.


Multimodal character of shear viscosity response in hydrogen bonded liquids.
The impact of supramolecular aggregate formation on the shear viscosity response of hydrogen bonded liquids was investigated. In particular, we study the shear mechanical response of several monoalcohols showing exponential and non-exponential shape dielectric Debye-like relaxation. In addition to the structural relaxation, distinctive of the glass transition, and the terminal crossover to pure viscous flow, characteristic of simple liquid flow, systematic analysis of complex viscosity curves evidences the presence of an additional intermediate process between those two. While the recovery of pure viscous flow would reflect the complete relaxation of the hydrogen bonded aggregates the intermediate process correlates with the rotational dynamics of hydroxyl groups, potentially caused by the breaking of individual hydrogen bonds.


Brain activation during mental transformation of size.
Visual comparison between different-sized objects with respect to shape can be done by encoding one of the objects as a mental image, transforming the image to the size format of the other object, and then testing for a match (Bundesen, C., & Larsen, A. [1975]. Visual transformation of size. Journal of Experimental Psychology: Human Perception and Performance, 1, 214-220). To identify the brain structures implicated in mental transformation of size, we measured the distribution of regional cerebral blood flow (rCBF) by positron emission tomography (PET) in 12 normal subjects who compared random stimulus patterns with respect to shape regardless of variations in size in a one-back match-to-sample paradigm. Each subject was PET-scanned 12 times during repetitive injections of H(2)(15)O. In one condition (three scans), all stimulus patterns were small. In a second condition (three scans), all stimuli were large. In the third condition (six scans), the stimuli alternated between small and large. Mental transformation of size should occur in the alternating-size condition but not in the fixed-size conditions. As expected, behavioral measures (reaction time [RT], d', beta) were nearly the same for the two fixed-size conditions but mean RT was longer and d' smaller in the alternating-size condition. Changes in rCBF specific to mental transformation of size were estimated by contrasting the alternating-size with the fixed-size conditions by use of statistical parametric mapping (SPM96) at a threshold of p <. 05 corrected for multiple comparisons. The detected brain structures implicated in mental transformation of size were primarily located in the dorsal pathways, comprising structures in the occipital, parietal, and temporal transition zone (predominantly in the left hemisphere), posterior parietal cortex (bilaterally), area MT/V5 (left), and vermis (bilaterally). Contrasts between the two fixed-size conditions showed significant effects in only the occipital cortex.


AOA membership and board certification of residency graduates: comparison of three programs accepting osteopathic physicians--implications for graduate medical education.
The purpose of this study was to determine membership status in the American Osteopathic Association (AOA) and osteopathic board certification status for osteopathic physicians completing osteopathic, allopathic, and dually accredited residency programs. Rates of AOA membership and osteopathic board certification of osteopathic graduates from a dually accredited residency were compared to rates of osteopathic graduates of an allopathic residency in the same training facility. These same two parameters were compared between the dually accredited residency and an osteopathic residency. Osteopathic graduates from the dually accredited residency had significantly higher rates of AOA membership and osteopathic board certification when compared with the osteopathic graduates of an allopathic residency. Moreover, no significant difference existed between the rates of these two measures for osteopathic resident graduates from the dually accredited residency when compared with graduates of an osteopathic residency. Implications of the results are discussed.


Learning view invariant recognition with partially occluded objects.
This paper investigates how a neural network model of the ventral visual pathway, VisNet, can form separate view invariant representations of a number of objects seen rotating together. In particular, in the current work one of the rotating objects is always partially occluded by the other objects present during training. A key challenge for the model is to link together the separate partial views of the occluded object into a single view invariant representation of that object. We show how this can be achieved by Continuous Transformation (CT) learning, which relies on spatial similarity between successive views of each object. After training, the network had developed cells in the output layer which had learned to respond invariantly to particular objects over most or all views, with each cell responding to only one object. All objects, including the partially occluded object, were individually represented by a unique subset of output cells.


Reduction of molybdate to molybdenum blue by Enterobacter sp. strain Dr.Y13.
Extensive use of metals in various industrial applications has caused substantial environmental pollution. Molybdenum-reducing bacteria isolated from soils can be used to remove molybdenum from contaminated environments. In this work we have isolated a local bacterium with the capability to reduce soluble molybdate to the insoluble molybdenum blue. We studied several factors that would optimize molybdate reduction. Electron donor sources such as glucose, sucrose, lactose, maltose and fructose (in decreasing efficiency) supported molybdate reduction after 24 h of incubation with optimum glucose concentration for molybdate reduction at 1.5% (w/v). The optimum pH, phosphate and molybdate concentrations, and temperature for molybdate reduction were pH 6.5, 5.0, 25 to 50 mM and 37 degrees C, respectively. The Mo-blue produced by cellular reduction exhibited a unique absorption spectrum with a maximum peak at 865 nm and a shoulder at 700 nm. Metal ions such as chromium, cadmium, copper, silver and mercury caused approximately 73, 71, 81, 77 and 78% inhibition of the molybdenum-reducing activity, respectively. All of the respiratory inhibitors tested namely rotenone, azide, cyanide and antimycin A did not show any inhibition to the molybdenum-reducing activity suggesting components of the electron transport system are not responsible for the reducing activity. The isolate was tentatively identified as Enterobacter sp. strain Dr.Y13 based on carbon utilization profiles using Biolog GN plates and partial 16S rDNA molecular phylogeny.


WHAT IS PAIN? A HISTORY THE PROTHERO LECTURE.
What is pain? This article argues that it is useful to think of pain as a 'kind of event' or a way of being-in-the-world. Pain-events are unstable; they are historically constituted and reconstituted in relation to language systems, social and environmental interactions and bodily comportment. The historical question becomes: how has pain been done and what ideological work do acts of being-in-pain seek to achieve? By what mechanisms do these types of events change? Who decides the content of any particular, historically specific and geographically situated ontology?


Effect of carvedilol on reactive oxygen species and enzymes linking innate and adaptive immunity.
Neutrophils and macrophages are critical components of our innate host defenses. They are a potential source of nitric oxide (NO) and superoxide, known to play an important role in many physiological processes including defense, immune and inflammatory responses. Myeloperoxidase (MPO), a major NO scavenger and a marker of oxidative stress, as well as increased inducible nitric oxide synthase (iNOS) expression, may affect the NO-superoxide balance, critical for cellular redox balance in the cardiovascular system at physiologic conditions. The effect of carvedilol was studied on stimulated superoxide generation, MPO release and iNOS expression in phagocytes by using receptor operating stimuli [N-formyl-Met-Leu-Phe (FMLP), lipopolysaccharide (LPS) and specific inhibitors (wortmannin, propranolol). Superoxide generation was measured as superoxide dismutase inhibitable reduction of cytochrome c (550 nm), MPO activity as the oxidation of o-dianisidine in the presence of hydrogen peroxide in a spectrophotometer Hewlet Packard 8452 A (463 nm). Expression of iNOS (Western-blot analysis) in RAW 264.7 cell line (murine macrophages) was stimulated by lipopolysaccharide (LPS). Carvedilol dose-dependently decreased superoxide generation and MPO release from intact neutrophils stimulated by FMLP. In the highest concentration tested, carvedilol pronounced the effect of wortmannin [inhibitor of phospholipase D (PLD) regulatory pathway] and significantly decreased LPS stimulated iNOS expression in RAW 264.7 cell line. The conceivable cumulative non-specific membrane effect of carvedilol and its effect on PLD signalling pathway contribute to the decrease of both superoxide generation and MPO release, thus supporting the restoration of NO-superoxide balance.


Hydrophobicity, Freezing Delay, and Morphology of Laser-Treated Aluminum Surfaces.
Until recently, superhydrophobicity was considered as a hint to predict surface icephobicity, an association of concepts that is by no means universal and that has been proven to depend on different experimental factors and material properties, including the actual morphology and chemical state of surfaces. This work presents a systematic study of the wetting and freezing properties of aluminum Al6061, a common material widely used in aviation, after being subjected to nanosecond pulsed IR laser treatments to modify its surface roughness and morphology. All treated samples, independent of their surface finishing state, presented initially an unstable hydrophilic wetting behavior that naturally evolved with time to reach hydrophobicity or even superhydrophobicity. To stabilize the surface state and to bestow the samples with a permanent and stable hydrophobic character, laser-treated surfaces were covered with a thin layer of CF x prepared by plasma-enhanced chemical vapor deposition. A systematic comparison between freezing delay (FD) and wetting properties of water droplets onto these plasma-/polymer-modified laser-treated surfaces that, under conditions where a heterogeneous nucleation mechanism prevails, surface morphology rather than the actual value of the surface roughness parameter the key feature for long FD times. In particular, it is found that surface morphologies rendering a Cassie-Baxter wetting regime longer FDs than those characterized by a Wenzel-like wetting state. It is that laser treatment, with or without additional coverage with thin CF x coatings, affects wetting and ice formation behaviors and might be an efficient procedure to mitigate icing problems on metal surfaces.


Postnatal development of a large auditory nerve terminal: the endbulb of Held in cats.
The endbulbs of Held are formed by the ascending branches of myelinated auditory nerve fibers and represent one of the largest synaptic endings in the brain. Most of the developmental changes in structure occur during the first 30 postnatal days of age. The neonatal endbulb begins as a flattened expansion with many filopodia, resembling a growth cone and characterized by numerous puncta adherentia and synapses associated with small postsynaptic densities; the most impressive feature of the ending at this age is its highly irregular plasma membrane that interdigitates with that of the postsynaptic spherical bushy cell. During these first 30 days, the number of puncta adherentia diminishes, postsynaptic densities nearly double in size, intermembraneous cisternae emerge, and plasma membranes flatten. These features endow the endbulb with an adult-like appearance. On the other hand, synaptic vesicle density increases progressively from approximately 50/microm2 at birth to 100/microm2 at adulthood. Mitochondria size remains constant over this developmental period but mitochondrial volume fraction increases until 60 days postnatal. Although many features of endbulb morphology stabilize by 30 days, other features suggest that endbulb development continues into the third month of age. Many of these observations correlate with the maturation of physiological response properties and suggest issues for further study.


Effective CRISPR/Cas9-based nucleotide editing in zebrafish to model human genetic cardiovascular disorders.
The zebrafish (Danio rerio) has become a popular vertebrate model organism to study organ formation and function due to its optical clarity and rapid embryonic development. The use of genetically modified zebrafish has also allowed identification of new putative therapeutic drugs. So far, most studies have relied on broad overexpression of transgenes harboring patient-derived mutations or loss-of-function mutants, which incompletely model the human disease allele in terms of expression levels or cell-type specificity of the endogenous gene of interest. Most human genetically inherited conditions are caused by alleles carrying single nucleotide changes resulting in altered gene function. Introduction of such point mutations in the zebrafish genome would be a prerequisite to recapitulate human disease but remains challenging to this day. We present an effective approach to introduce small nucleotide changes in the zebrafish genome. We generated four different knock-in lines carrying distinct human cardiovascular-disorder-causing missense mutations in their zebrafish orthologous genes by combining CRISPR/Cas9 with a short template oligonucleotide. Three of these lines carry gain-of-function mutations in genes encoding the pore-forming (Kir6.1, KCNJ8) and regulatory (SUR2, ABCC9) subunits of an ATP-sensitive potassium channel (KATP) linked to Cantú syndrome (CS). Our heterozygous zebrafish knock-in lines display significantly enlarged ventricles with enhanced cardiac output and contractile function, and distinct cerebral vasodilation, demonstrating the causality of the introduced mutations for CS. These results demonstrate that introducing patient alleles in their zebrafish orthologs promises a broad application for modeling human genetic diseases, paving the way for new therapeutic strategies using this model organism.


Structural basis of histone H2A-H2B recognition by the essential chaperone FACT.
Facilitates chromatin transcription (FACT) is a conserved histone chaperone that reorganizes nucleosomes and ensures chromatin integrity during DNA transcription, replication and repair. Key to the broad functions of FACT is its recognition of histones H2A-H2B (ref. 2). However, the structural basis for how histones H2A-H2B are recognized and how this integrates with the other functions of FACT, including the recognition of histones H3-H4 and other nuclear factors, is unknown. Here we reveal the crystal structure of the evolutionarily conserved FACT chaperone domain Spt16M from Chaetomium thermophilum, in complex with the H2A-H2B heterodimer. A novel 'U-turn' motif scaffolded onto a Rtt106-like module embraces the α1 helix of H2B. Biochemical and in vivo assays validate the structure and dissect the contribution of histone tails and H3-H4 towards Spt16M binding. Furthermore, we report the structure of the FACT heterodimerization domain that connects FACT to replicative polymerases. Our results show that Spt16M makes several interactions with histones, which we suggest allow the module to invade the nucleosome gradually and block the strongest interaction of H2B with DNA. FACT would thus enhance 'nucleosome breathing' by re-organizing the first 30 base pairs of nucleosomal histone-DNA contacts. Our snapshot of the engagement of the chaperone with H2A-H2B and the structures of all globular FACT domains enable the high-resolution analysis of the vital chaperoning functions of FACT, shedding light on how the complex promotes the activity of enzymes that require nucleosome reorganization.


Adolescent gender norms and adult health outcomes in the USA: a prospective cohort study.
Previous research has documented differences in health behaviours between men and women, with differential risks and health outcomes between the sexes. Although some sex-specific differences in health outcomes are caused by biological factors, many others are socially driven through gender norms. We therefore aimed to assess whether gender expression as an adolescent, determined by the degree to which an individual's behvaiours were typical of their gender, were associated with health behaviours and outcomes in adulthood. In this prospective cohort study, we used data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative sample of US adolescents from whom data were collected during adolescence (ages 11-18 years) and adulthood (ages 24-32 years). We created a measure of gender expression that was based on the degree to which male and female adolescents and adults behave in stereotypically masculine (for men) or feminine (for women) ways relative to their same-gender peers. Adolescents were assessed for baseline sociodemographic characteristics and gender expression, and these participants were later assessed, during adulthood, for their gender expression and health behaviours and outcomes, which included depression, self-rated health, drug and alcohol use, cardiovascular risk factors, experience of sexual violence, diet, and obesity. These data were collected via surveys, except for body-mass index, cholesterol, and blood pressure, which were collected as biomarkers. Between April and December, 1995, self-reported data were collected from 10 480 female and 10 263 male adolescents; similar data were subsequently collected in several waves in this cohort, with a final collection between January, 2008, and February, 2009, when participants were aged 24-32 years. We used data from this final wave and from baseline, and our study represents a secondary analysis of these data. Of these participants, complete follow-up data from 6721 (80%) adult women and 5885 (80%) adult men were available. Gender expression was stable for men and women from adolescence to adulthood. High masculinity (vs low masculinity) in adolescent and adult men was positively associated with smoking in the past month, use of marijuana and recreational drugs, prescription drug misuse (adult gender expression only), and consumption of fast food and soda (adolescent gender expression only) in the past week. However, higher masculine gender expression in adult men was negatively associated with diagnosed depression and high cholesterol in adulthood, and masculine gender expression in adolescent and adult men was negatively associated with high blood pressure in adults. High femininity (vs low femininity) in adolescent or adult women was positively associated with high cholesterol and blood pressure (both adult gender expression only), depression, migraines (adult gender expression only), and physical limitations (ie, health problems that limited their daily activities). However, higher femininity in adolescence was negatively associated with self-rated good health in adulthood. Although feminine gender expression in adolescents was predictive of adult recreational and prescription drug and marijuana use and experience of sexual violence, feminine gender expression in adulthood was negatively associated with adult substance use and experience of sexual violence, suggesting that expressions of femininity typical of adolescents impart risks that expression of femininity as an adult does not. Individuals who are highly masculine or feminine seem to be at greatest risk of adverse health outcomes and behaviours. We found compelling evidence that adolescent gender expression is correlated with health in adulthood independently of gender expression as an adult. Although more research is needed to identify causal mechanisms, our results suggest that those designing health behaviour interventions should carefully consider integrating gender transformative components into interventions. Eunice Kennedy Shriver National Institute of Child Health and Human Development, Gender Equality, Integrated Delivery, HIV, Nutrition, Family Planning, and Water Sanitation and Hygiene Program Strategy Teams (Bill and Melinda Gates Foundation).


Pharmaceutical Residues Affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike Wetlands: Sources and Sinks.
This study is the first to investigate the pharmaceutical burden from point sources affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike, Sweden. The investigated Biosphere Reserve is a >1000 km(2) wetland system with inflows from lakes, rivers, leachate from landfill, and wastewater-treatment plants (WWTPs). We analysed influent and treated wastewater, leachate water, lake, river, and wetland water alongside sediment for six model pharmaceuticals. The two WWTPs investigated released pharmaceutical residues at levels close to those previously observed in Swedish monitoring exercises. Compound-dependent WWTP removal efficiencies ranging from 12 to 100 % for bendroflumethiazide, oxazepam, atenolol, carbamazepine, and diclofenac were observed. Surface-water concentrations in the most affected lake were ≥100 ng/L for the various pharmaceuticals with atenolol showing the highest levels (>300 ng/L). A small risk assessment showed that adverse single-substance toxicity on aquatic organisms within the UNESCO Biosphere Reserve is unlikely. However, the effects of combinations of a large number of known and unknown pharmaceuticals, metals, and nutrients are still unknown.


Electrophysiological characterization of cultured hepatic stellate cells in rats.
This study aimed to examine electrophysiological properties of cultured rat hepatic stellate cells (HSCs) using the whole cell configuration of patch-clamp technique. At least three different current components were identified. First, when the membrane was depolarized to voltages more positive than -40 mV, a transient outward K+ current was evoked. Second, membrane hyperpolarization below -60 mV evoked a sustained and inward-rectifying K+ current. The third component was a current flowing outward, which was activated when the cell was depolarized more positively than 0 mV. The channel for this current allowed Na+, K+, and Cl- to pass nonspecifically, suggesting the presence of hemi gap-junctional channel. Furthermore, a laser photobleaching technique revealed the presence of gap junctions between adjacent HSCs. A voltage-gated Ca2+ current, which is known to occur in smooth muscle cells, was searched for but was not detectable. These results suggest that membrane potential of HSCs is determined specifically by the two distinct K+ channels and by an intercellular mechanism involving gap-junctional communication.


Fibulin-4 E57K Knock-in Mice Recapitulate Cutaneous, Vascular and Skeletal Defects of Recessive Cutis Laxa 1B with both Elastic Fiber and Collagen Fibril Abnormalities.
Fibulin-4 is an extracellular matrix protein essential for elastic fiber formation. Frameshift and missense mutations in the fibulin-4 gene (EFEMP2/FBLN4) cause autosomal recessive cutis laxa (ARCL) 1B, characterized by loose skin, aortic aneurysm, arterial tortuosity, lung emphysema, and skeletal abnormalities. Homozygous missense mutations in FBLN4 are a prevalent cause of ARCL 1B. Here we generated a knock-in mouse strain bearing a recurrent fibulin-4 E57K homozygous missense mutation. The mutant mice survived into adulthood and displayed abnormalities in multiple organ systems, including loose skin, bent forelimb, aortic aneurysm, tortuous artery, and pulmonary emphysema. Biochemical studies of dermal fibroblasts showed that fibulin-4 E57K mutant protein was produced but was prone to dimer formation and inefficiently secreted, thereby triggering an endoplasmic reticulum stress response. Immunohistochemistry detected a low level of fibulin-4 E57K protein in the knock-in skin along with altered expression of selected elastic fiber components. Processing of a precursor to mature lysyl oxidase, an enzyme involved in cross-linking of elastin and collagen, was compromised. The knock-in skin had a reduced level of desmosine, an elastin-specific cross-link compound, and ultrastructurally abnormal elastic fibers. Surprisingly, structurally aberrant collagen fibrils and altered organization into fibers were characteristics of the knock-in dermis and forelimb tendons. Type I collagen extracted from the knock-in skin had decreased amounts of covalent intermolecular cross-links, which could contribute to the collagen fibril abnormalities. Our studies provide the first evidence that fibulin-4 plays a role in regulating collagen fibril assembly and offer a preclinical platform for developing treatments for ARCL 1B.


Species status of Neisseria gonorrhoeae: evolutionary and epidemiological inferences from multilocus sequence typing.
Various typing methods have been developed for Neisseria gonorrhoeae, but none provide the combination of discrimination, reproducibility, portability, and genetic inference that allows the analysis of all aspects of the epidemiology of this pathogen from a single data set. Multilocus sequence typing (MLST) has been used successfully to characterize the related organisms Neisseria meningitidis and Neisseria lactamica. Here, the same seven locus Neisseria scheme was used to characterize a diverse collection of N. gonorrhoeae isolates to investigate whether this method would allow differentiation among isolates, and to distinguish these three species. A total of 149 gonococcal isolates were typed and submitted to the Neisseria MLST database. Although relatively few (27) polymorphisms were detected among the seven MLST loci, a total of 66 unique allele combinations (sequence types, STs), were observed, a number comparable to that seen among isolate collections of the more diverse meningococcus. Patterns of genetic variation were consistent with high levels of recombination generating this diversity. There was no evidence for geographical structuring among the isolates examined, with isolates collected in Liverpool, UK, showing levels of diversity similar to a global collection of isolates. There was, however, evidence that populations of N. meningitidis, N. gonorrhoeae and N. lactamica were distinct, with little support for frequent genetic recombination among these species, with the sequences from the gdh locus alone grouping the species into distinct clusters. The seven loci Neisseria MLST scheme was readily adapted to N. gonorrhoeae isolates, providing a highly discriminatory typing method. In addition, these data permitted phylogenetic and population genetic inferences to be made, including direct comparisons with N. meningitidis and N. lactamica. Examination of these data demonstrated that alleles were rarely shared among the three species. Analysis of variation at a single locus, gdh, provided a rapid means of identifying misclassified isolates and determining whether mixed cultures were present.


Multi-institutional analysis of pancreatic adenocarcinoma demonstrating the effect of diabetes status on survival after resection.
The effect of diabetes on survival after resection pancreatic ductal carcinoma (PDAC) is unclear. The present study was undertaken to determine whether pre-operative diabetes has any predictive value for survival. A retrospective review from seven centres was performed. Metabolic factors, tumour characteristics and outcomes of patients undergoing resection for PDAC were collected. Univariate and multivariable analyses were performed to determine factors associated with disease-free (DFS) and overall survival (OS). Of the 509 patients in the present study, 31.2% had diabetes. Scoring systems were devised to predict OS and DFS based on a training set (n= 245) and were subsequently tested on an independent set (n= 264). Pre-operative diabetes (P < 0.001), tumour size >2 cm (P= 0.001), metastatic nodal ratio >0.1 (P < 0.001) and R1 margin (P < 0.001) all correlated with DFS and OS on univariate analysis. Scoring systems were devised based on multivariable analysis of the above factors. Diabetes and the metastatic nodal ratio were the most important factors in each system, earning two points for OS and four points for DFS. These scoring systems significantly correlated with both DFS (P < 0.001) and OS (P < 0.001). Pre-operative diabetes status provides useful information that can help to stratify patients in terms of predicted post-operative OS and DFS.


Short communication: Characterization of Shiga toxin 2-carrying bacteriophages induced from Shiga-toxigenic Escherichia coli isolated from Italian dairy products.
Forty samples of raw milk cheese and 25 samples of raw milk itself were subjected to enrichment culture for Shiga-toxigenic Escherichia coli (STEC), and a single Shiga toxin 2- (Stx(2)) positive strain was obtained from one of the cheese samples. Thus, aged cheeses in which the curd is subsequently heat treated (48°C) cannot be presumed to be STEC free. Infective Stx(2) bacteriophages were induced from 3 STEC strains isolated elsewhere from raw milk and 1 STEC strain from aged cheese sourced in Italy. Data on E. coli host range, morphology, genome size, and genetic variation determined by restriction fragment length polymorphism and multi-locus genotyping are presented. Although all 4 bacteriophages were found to be short-tailed Podoviridae, they exhibited considerable variation in both genome size and content. This extended to the Stx(2) genes themselves, whose sequences contained several point mutations, but these did not translate to amino acid substitutions.


Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population.
Abnormal blood lipid levels are influenced by genetic and lifestyle/dietary factors. Although many genetic variants associated with blood lipid traits have been identified in Europeans, similar data in Middle Eastern populations are limited. We performed a genome-wide association study with Arab individuals (discovery cohort: 1,353; replication cohort: 1,176) from Kuwait to identify possible associations of genetic variants with high lipid levels. We used Illumina HumanOmniExpress BeadChip and candidate SNP genotyping in the discovery and replication phases, respectively. For association tests, we used genetic models that were based on additive and recessive modes of inheritance. High triglycerides (TGs) were recessively associated with six risk variants (rs1002487/RPS6KA1, rs11805972/LAD1) rs7761746/Or5v1, rs39745/CTTNBP2-LSM8, rs2934952/PGAP3, and rs9626773/RP11-191L9.4-CERK) at genome-wide significance (P  6.12E-09), and another six variants (rs10873925/ST6GALNAC5, rs4663379/SPP2-ARL4C, rs10033119/NPY1R, rs17709449/LINC00911-FLRT2, rs11654954/CDK12-NEUROD2, and rs9972882/STARD3) were associated at borderline significance (P  5.0E-08). High TG was also additively associated with rs11654954. All of the 12 identified markers are novel and are harbored in runs of homozygosity. Literature evidence supports the involvement of these gene loci in lipid-related processes. This study in an Arab population augments international efforts to identify genetic regulation of lipid traits.


The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer.
ER-targeted therapeutics provide valuable treatment options for patients with ER+ breast cancer, however, current relapse and mortality rates emphasize the need for improved therapeutic strategies. The recent discovery of prevalent ESR1 mutations in relapsed tumors underscores a sustained reliance of advanced tumors on ERα signaling, and provides a strong rationale for continued targeting of ERα. Here we describe GDC-0810, a novel, non-steroidal, orally bioavailable selective ER downregulator (SERD), which was identified by prospectively optimizing ERα degradation, antagonism and pharmacokinetic properties. GDC-0810 induces a distinct ERα conformation, relative to that induced by currently approved therapeutics, suggesting a unique mechanism of action. GDC-0810 has robust in vitro and in vivo activity against a variety of human breast cancer cell lines and patient derived xenografts, including a tamoxifen-resistant model and those that harbor ERα mutations. GDC-0810 is currently being evaluated in Phase II clinical studies in women with ER+ breast cancer.


Swimming exercise demonstrates advantages over running exercise in reducing proteinuria and glomerulosclerosis in spontaneously hypertensive rats.
Experimental studies in animal models have described the benefits of physical exercise (PE) to kidney diseases associated with hypertension. Land- and water-based exercises induce different responses in renal function. Our aim was to evaluate the renal alterations induced by different environments of PE in spontaneously hypertensive rats (SHRs). The SHRs were divided into sedentary (S), swimming exercise (SE), and running exercise (RE) groups, and were trained for 8 weeks under similar intensities (60 min/day). Arterial pressure (AP) and heart rate (HR) were recorded. The renal function was evaluated through urinary volume at each week of training; sodium and potassium excretions, plasma and urinary osmolarities, glomerular filtration rate (GFR), levels of proteinuria, and renal damage were determined. SE and RE rats presented reduced mean AP, systolic blood pressure, and HR in comparison with S group. SE and RE rats showed higher urine osmolarity compared with S. SE rats showed higher free water clearance (P < 0.01), lower urinary density (P < 0.0001), and increased weekly urine volume (P < 0.05) in comparison with RE and S groups. GFR was increased in both SE and RE rats. The proteinuria of SE (7.0 ± 0.8 mg/24 h) rats was decreased at the 8th week of the PE in comparison with RE (9.6 ± 0.8 mg/24 h) and S (9.8 ± 0.5 mg/24 h) groups. The glomerulosclerosis was reduced in SE rats (P < 0.02). SE produced different response in renal function in comparison with RE, in which only swimming-trained rats had better profile for proteinuria and glomerulosclerosis.


Clinical analysis of voice change as a parameter of premenstrual syndrome.
We have evaluated the relationship between voice change and premenstrual syndrome (PMS) by comparing acoustic measurements made during the follicular phase and the premenstrual phase. Twenty-eight women were followed for 2 months for this study. Each participant was asked to produce an /a/ sound for 5 seconds at the midfollicular phase of the menstrual cycle and then 2-3 days before menstruation. Each voice sample was stored and analyzed by the Dr. Speech Science program. The voice data collected from all subjects during the two phases were compared. After that, the subjects were divided into a PMS-positive and PMS-negative group according to the criteria cited in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV); the voice data from each group were compared separately between the two phases. There was no significant difference in the acoustic parameters between the two phases in all subjects (N = 28). In the PMS-positive group (N = 16), jitter was significantly increased during the premenstrual phase compared to the follicular phase (p = 0.048). The patient's PMS score was not correlated with the severity of voice change. We conclude that the change of voice parameter was objectively identified in the PMS-positive group, therefore more careful voice habituation is required during the premenstrual phase in that group.


"Women's bodies are shops": beliefs about transactional sex and implications for understanding gender power and HIV prevention in Tanzania.
Although transactional sex has been linked to undesirable sexual health outcomes, there is a lack of clarity as to the meaning of the practice, which appears to extend beyond behaviors related to women's economic circumstances. This article explored the perspectives of parents and unmarried young people on motivations for, and beliefs about, transactional sex in rural Tanzania using an ethnographic research design. Data collection involved 17 focus groups and 46 in-depth interviews with young people aged 14-24 years and parents/caregivers. Transactional sex was widely accepted by both parents and young people. Male parents equated sexual exchange to buying meat from a butcher and interpreted women's demand for exchange before sex with personal power. Young men referred to transactional sex as the easiest way to get a woman to satisfy their sexual desires while also proving their masculinity. Young women perceived themselves as lucky to be created women as they could exploit their sexuality for pleasure and material gain. They felt men were stupid for paying for "goods" (vagina) they could not take away. Mothers were in agreement with their daughters. Although young women saw exploitation of the female body in positive terms, they were also aware of the health risks but ascribed these to bad luck. Interventions aimed at tackling transactional sex in the interests of women's empowerment and as a strategy for HIV prevention need to understand the cultural beliefs associated with the practice that may make it thrive despite the known risks.


Intraperitoneal chemotherapy for ovarian cancer: where are we now?
Patients with advanced epithelial ovarian cancer are conventionally treated with intravenous (IV) platinum- and taxane-based chemotherapy to try to eradicate residual disease after optimal cytoreductive surgery, resulting in a median overall survival of 49 months. The Gynecologic Oncology Group (GOG) conducted 3 large randomized, phase III clinical trials of intraperitoneal (IP) chemotherapy (GOG 104, 114, and 172) that clearly showed superior progression-free and overall survival with IP chemotherapy compared with IV chemotherapy. All 3 clinical trials investigated IP cisplatin, with the last one adding IP paclitaxel. The most recent study (GOG 172) resulted in a median survival of 66 months for patients in the IP arm versus 50 months for those in the IV arm. Fewer patients in the IP arm than in the IV arm completed all 6 treatment cycles (42% vs. 83%, respectively) because of the toxic effects of chemotherapy and IP catheter-related complications. Initially, patients in the IP arm reported significantly worse quality of life than those in the IV arm. However, at 12-month follow-up, the groups experienced no difference in quality of life, except that paresthesias were more likely to persist at moderate levels among patients in the IP arm. Based on these clinical trials, the National Cancer Institute issued a clinical announcement recommending that women with stage III ovarian cancer who undergo optimal surgical cytoreduction be considered for IP chemotherapy.


Internet-Based Vestibular Rehabilitation for Older Adults With Chronic Dizziness: A Randomized Controlled Trial in Primary Care.
Vestibular rehabilitation is an effective intervention for dizziness due to vestibular dysfunction, but is seldom provided. We aimed to determine the effectiveness of an Internet-based vestibular rehabilitation program for older adults experiencing dizziness in primary care. We undertook a single-center, single-blind randomized controlled trial comparing an Internet-based vestibular rehabilitation intervention (Balance Retraining, freely available from https://balance.lifeguidehealth.org) with usual primary care in patients from 54 primary care practices in southern England. Patients aged 50 years and older with current dizziness exacerbated by head movements were enrolled. Those in the intervention group accessed an automated Internet-based program that taught vestibular rehabilitation exercises and suggested cognitive behavioral management strategies. Dizziness was measured by the Vertigo Symptom Scale-Short Form (VSS-SF) at baseline, 3 months, and 6 months. The primary outcome was VSS-SF score at 6 months. A total of 296 patients were randomized in the trial; 66% were female, and the median age was 67 years. The VSS-SF was completed by 250 patients (84%) at 3 months and 230 patients (78%) at 6 months. Compared with the usual care group, the Internet-based vestibular rehabilitation group had less dizziness on the VSS-SF at 3 months (difference, 2.75 points; 95% CI, 1.39-4.12; P <.001) and at 6 months (difference, 2.26 points; 95% CI, 0.39-4.12; P = .02, respectively). Dizziness-related disability was also lower in the Internet-based vestibular rehabilitation group at 3 months (difference, 6.15 points; 95% CI, 2.81-9.49; P <.001) and 6 months (difference, 5.58 points; 95% CI, 1.19-10.0; P = .01). Internet-based vestibular rehabilitation reduces dizziness and dizziness-related disability in older primary care patients without requiring clinical support. This intervention has potential for wide application in community settings.


Male smoking reduction behaviour in response to China's 2015 cigarette tax increase.
This study aims to evaluate Chinese male smokers' responses to China's 2015 6% ad valorem and RMB0.1 specific excise tax increase per cigarettes pack. A male population-based cross-sectional survey with multistaged stratified sampling was employed to collect data in six cities in China. Descriptive methods and logistic models were used to assess responses and associated factors following the cigarette tax increase among male Chinese smokers. Among a potential sample of 6500 Chinese males, 6010 individuals were contacted and 5782 participants completed the questionnaires. Of the 2852 current smokers, 60.7% (95% CI: 58.9 to 62.5) did not think cigarettes were expensive, 77.9% (95% CI: 76.4 to 79.5) reported no reduction in smoking in response to the 2015 tax increase and 21.3% (95% CI: 19.8 to 22.8) were not aware of the cigarette tax increase. Smokers who were occasional smokers, intended to quit and thought cigarettes expensive were more likely to report reducing cigarette smoking following the tax increase, while those who had higher household income per capita, smoked more cigarettes, and purchased more expensive cigarettes were less likely to report reducing cigarette consumption. About one in five male Chinese smokers reported reduction in smoking following China's 2015 cigarette tax increase. This is a relatively large impact given the very modest tax increase. Even with the 2015 increase, the excise tax represents only 36.3% of the cigarette price in China. Tax increases are needed to achieve the WHO's recommended level of 70%.