Multi-step immunofluorescent analysis of vitamin D receptor loci and myosin heavy chain isoforms in human skeletal muscle.
Vitamin D receptors have been shown to be present in human skeletal muscle using different techniques. We developed a multi-staining immunofluorescent method to detect vitamin D receptor expression and co-localize it with myosin heavy chain isoform expression in skeletal muscle biopsies in older female subjects. Serial sections were cut from frozen samples obtained by needle biopsy of the vastus lateralis. Samples were probed with a primary vitamin D receptor monoclonal antibody and then re-probed with a type IIa myosin heavy chain isoform-specific antibody. Independent unfixed sections followed a similar protocol and were probed with type IIx and type I myosin heavy chain isoform-specific antibodies. Immunohistochemistry and fluorescent microscopy co-localized vitamin D receptor loci and myosin heavy chain isoforms in whole skeletal muscle sections. We quantified intranuclear vitamin D receptor staining patterns and number of individual muscle fiber subtypes within a muscle section. Immunohistochemical staining of the vitamin D receptor was confirmed by Western blot using the same monoclonal antibody. This multi-staining immunofluorescent technique allows for measurement of intranuclear vitamin D receptor expression in the context of the specific muscle fiber type profile in a single section. This method can thus be a useful approach to study potential relationships between muscle fiber subtypes and vitamin D receptor expression.


Fracture toughness of posterior resin composites.
The purpose of this study was to evaluate and compare the resistance to crack propagation, as measured by the fracture toughness, of some packable posterior resin composites with other posterior resin composite materials. Fracture toughness determinations were made for the 5 packable and the other posterior resin composites using 3-point flexure of beams with a standardized central single-edge notch. Ten beams of each material were tested on an Instron test machine. The maximum loads were determined, from which the fracture toughness values (KIC) were calculated. The data were analyzed statistically using ANOVA and t tests. The resin composites tested demonstrated a range of KIC values. The materials were separated according to the mean KIC values into 5 groups that were statistically different. While 2 packable resin composites had KIC values that were among the highest, the other packables were substantially lower than nonpackables. The intermediate value group consisted of 3 of the conventional posterior resin composites. There was a very weak correlation between fracture toughness and reported volume concentration of particulate reinforcing elements. The posterior resin composites tested exhibited a spectrum of KIC values. The packable resin composites were distributed along this spectrum, with 2 products exhibiting high potential for resistance to crack propagation.


Who responds best to text-delivered cannabis use disorder treatment? A randomized clinical trial with young adults.
Young adults ages 18 to 25 have the highest percentage (5%) of cannabis use disorder (CUD) among all age groups, and are the least likely to receive treatment compared with other age groups. Because this population is in need of creative approaches for treatment engagement, we tested Peer Network Counseling-txt (PNC-txt), a 4-week, automated text-delivered cannabis treatment that focuses on close peer relations with 96 treatment seeking young adults. Participants meeting CUD criteria were randomized to PNC-txt, or assessment only control condition and followed for 3-months. At 3-months, the PNC-txt group reduced number of heavy cannabis-use days and relationship problems due to cannabis use compared with controls. Subgroup analyses were conducted with cases having more and fewer CUD symptoms than the full sample. For cases with fewer symptoms, but not for those with more, PNC-txt reduced past 30-day use, urges to use, memory problems, and relationship problems due to cannabis use compared with controls. Treatment satisfaction data from the full sample indicated that participants thought the intervention texts helped them reduce or manage their cannabis use and increased their understanding of the negative relational effects associated with ongoing cannabis use. Findings provide evidence of the efficacy of PNC-txt in treating CUD in young adults, support clinically targeting peer relations, and suggest that PNC-txt may be most helpful for those with mild to moderate CUD severity. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Multilayered Tuning of Dosage Compensation and Z-Chromosome Masculinization in the Wood White (Leptidea sinapis) Butterfly.
In species with genetic sex determination, dosage compensation can evolve to equal expression levels of sex-linked and autosomal genes. Current knowledge about dosage compensation has mainly been derived from male-heterogametic (XX/XY) model organisms, whereas less is understood about the process in female-heterogametic systems (ZZ/ZW). In moths and butterflies, downregulation of Z-linked expression in males (ZZ) to match the expression level in females (ZW) is often observed. However, little is known about the underlying regulatory mechanisms, or if dosage compensation patterns vary across ontogenetic stages. In this study, we assessed dynamics of Z-linked and autosomal expression levels across developmental stages in the wood white (Leptidea sinapis). We found that although expression of Z-linked genes in general was reduced compared with autosomal genes, dosage compensation was actually complete for some categories of genes, in particular sex-biased genes, but equalization in females was constrained to a narrower gene set. We also observed a noticeable convergence in Z-linked expression between males and females after correcting for sex-biased genes. Sex-biased expression increased successively across developmental stages, and male-biased genes were enriched on the Z-chromosome. Finally, all five core genes associated with the ribonucleoprotein dosage compensation complex male-specific lethal were detected in adult females, in correspondence with a reduction in the expression difference between autosomes and the single Z-chromosome. We show that tuning of gene dosage is multilayered in Lepidoptera and argue that expression balance across chromosomal classes may predominantly be driven by enrichment of male-biased genes on the Z-chromosome and cooption of available dosage regulators.


Determination of the rough interface parameters using the self-imaging effect.
In this work, a linear grating is used to project a periodic light intensity distribution on a rough interface, and the near field transmitted light scattering is studied. It is shown theoretically that the intensity in the Fresnel regime depends on statistical properties of the rough interface and the light intensity period. The self-image contrast exponentially depends on the interface height-height correlation function. The correlation is obtained in terms of multiplication of the self-image number and the period of the light intensity distribution. Therefore, the roughness and the correlation length of the interface can be obtained by determining the contrast of the self-images when the light intensity period is smaller than the interface correlation length. For periods longer than twice the correlation length, the contrast measurements only provide the interface roughness. In experimental studies, the roughness of interfaces is determined by square gratings with periods much longer than the correlation lengths. The rough interfaces are prepared by roughening sheet glass by powders of different grit numbers. The results for different gratings and light wavelengths are quite consistent.


Optimal dosing of galantamine in patients with mild or moderate Alzheimer's disease: post Hoc analysis of a randomized, double-blind, placebo-controlled trial.
Galantamine (hydrobromide), a reversible acetylcholinesterase inhibitor and allosteric nicotinic receptor modulator, slows cognitive and functional decline in mild to moderate dementia of the Alzheimer's type. Although several drugs are indicated for mild to moderate Alzheimer's disease (AD), no published study has separately analysed mild and moderate AD subgroups to assess the effect of dosage. To compare the efficacy and safety of galantamine 16 and 24 mg/day in patient subgroups with mild or moderate AD. This post hoc analysis (n = 838) of a 5-month, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of galantamine 16 and 24 mg/day in a subgroup of patients with mild AD (Mini-Mental State Examination [MMSE] >18) and a subgroup with moderate AD (MMSE 10-18). Efficacy outcomes included the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) score and treatment response (ADAS-cog maintenance [>or=0-point improvement], improvement >or=4 points and improvement >or=7 points). Mean ADAS-cog scores of patients with mild AD demonstrated significant improvement from baseline with galantamine 16 and 24 mg/day (p < 0.001 for both), whereas cognitive function did not change significantly for placebo recipients (p = 0.559). Patients with moderate AD improved with galantamine 24 mg/day (p = 0.009) but not with 16 mg/day (p = 0.768); a decline occurred with placebo (p < 0.001). A greater proportion of patients treated with galantamine 16 mg/day (76% and 52% for mild and moderate AD, respectively) or 24 mg/day (69% and 61%, respectively) demonstrated a treatment response (i.e. ADAS-cog was maintained or improved) relative to placebo (55% and 28%, respectively; p < 0.05). Patients with moderate AD trended toward greater response with the 24 mg/day dosage than with the 16 mg/day dosage. Galantamine was well tolerated. Adverse events were comparable for all study groups with mild or moderate AD. This post hoc analysis suggests that galantamine 16 mg/day is the optimal dosage for patients with mild AD, as similar efficacy is observed with the 24 mg/day dose. However, patients with moderate AD appear to gain additional benefit from galantamine 24 mg/day.


Self reported outcomes and adverse events after medical abortion through online telemedicine: population based study in the Republic of Ireland and Northern Ireland.
Objectives To assess self reported outcomes and adverse events after self sourced medical abortion through online telemedicine.Design Population based study.Setting Republic of Ireland and Northern Ireland, where abortion is unavailable through the formal healthcare system except in a few restricted circumstances.Population 1000 women who underwent self sourced medical abortion through Women on Web (WoW), an online telemedicine service, between 1 January 2010 and 31 December 2012.Main outcome measures Successful medical abortion: the proportion of women who reported ending their pregnancy without surgical intervention. Rates of adverse events: the proportion who reported treatment for adverse events, including receipt of antibiotics and blood transfusion, and deaths reported by family members, friends, or the authorities. Care seeking for symptoms of potential complications: the frequency with which women reported experiencing symptoms of a potentially serious complication and the proportion who reported seeking medical attention as advised.Results In 2010-12, abortion medications (mifepristone and misoprostol) were sent to 1636 women and follow-up information was obtained for 1158 (71%). Among these, 1023 women confirmed use of the medications, and follow-up information was available for 1000. At the time women requested help from WoW, 781 (78%) were <7 weeks pregnant and 219 (22%) were 7-9 weeks pregnant. Overall, 94.7% (95% confidence interval 93.1% to 96.0%) reported successfully ending their pregnancy without surgical intervention. Seven women (0.7%, 0.3% to 1.5%) reported receiving a blood transfusion, and 26 (2.6%, 1.7% to 3.8%) reported receiving antibiotics (route of administration (IV or oral) could not be determined). No deaths resulting from the intervention were reported by family, friends, the authorities, or the media. Ninety three women (9.3%, 7.6% to 11.3%) reported experiencing any symptom for which they were advised to seek medical advice, and, of these, 87 (95%, 87.8% to 98.2%) sought attention. None of the five women who did not seek medical attention reported experiencing an adverse outcome.Conclusions Self sourced medical abortion using online telemedicine can be highly effective, and outcomes compare favourably with in clinic protocols. Reported rates of adverse events are low. Women are able to self identify the symptoms of potentially serious complications, and most report seeking medical attention when advised. Results have important implications for women worldwide living in areas where access to abortion is restricted.


Tibial Stress Fracture Secondary to Half-Pins in Circular Ring External Fixation for Charcot Foot.
There is an increasing trend for surgical correction of the deformity associated with Charcot neuroarthropathy of the foot and ankle (Charcot foot) in order to allow ambulation with commercially available therapeutic footwear. The significant rate of surgical and medical morbidity associated with extensive conventional operative correction has led many surgeons to use limited surgical dissection and stabilization with circular ring external fixation. A retrospective chart review was performed on 254 patients at 2 academic medical centers who underwent surgical correction for diabetes-associated Charcot foot deformity with limited soft tissue dissection and stabilization accomplished with a statically applied circular external fixator. Tibial stress fractures developed in 10 of the patients. Seven of the fractures developed in the 42 patients in whom tibial block fixation was accomplished with half-pins (16.7%), and 3 fractures developed in the 202 patients in whom tibial block fixation was accomplished with tensioned fine wires (1.5%). Three of the tibial stress fractures were successfully treated with extension of the circular frame above the level of the stress fracture. Four fractures were successfully treated with closed intramedullary nailing and 3 with weight-bearing total contact casts. Two tibial fractures occurred through pin sites (all half-pins) in 120 nonneuropathic patients who underwent application of circular ring external fixators during the same 6-year period. Tibial stress fracture is an unusual complication associated with the use of circular ring external fixation. This investigation highlights the significantly greater risk for the development of this complication in diabetic patients undergoing surgical correction for Charcot foot deformity when half-pins are used for tibial block stabilization, compared with tensioned fine wires. We now recommend the universal use of tensioned fine wires for tibial block fixation when circular ring fixation is performed in patients with Charcot foot arthropathy. Level IV, retrospective case series.


Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome.
In diploid mammalian genomes, parental alleles can exhibit different methylation patterns (allele-specific DNA methylation, ASM), which have been documented in a small number of cases except for the imprinted regions and X chromosomes in females. We carried out a chromosome-wide survey of ASM across 16 human pluripotent and adult cell lines using Illumina bisulfite sequencing. We applied the principle of linkage disequilibrium (LD) analysis to characterize the correlation of methylation between adjacent CpG sites on single DNA molecules, and also investigated the correlation between CpG methylation and single nucleotide polymorphisms (SNPs). We observed ASM on 23% approximately 37% heterozygous SNPs in any given cell line. ASM is often cell-type-specific. Furthermore, we found that a significant fraction (38%-88%) of ASM regions is dependent on the presence of heterozygous SNPs in CpG dinucleotides that disrupt their methylation potential. This study identified distinct types of ASM across many cell types and suggests a potential role for CpG-SNP in connecting genetic variation with the epigenome.


Ocean acidification alters early successional coral reef communities and their rates of community metabolism.
Ocean acidification is expected to alter community composition on coral reefs, but its effects on reef community metabolism are poorly understood. Here we document how early successional benthic coral reef communities change in situ along gradients of carbon dioxide (CO2), and the consequences of these changes on rates of community photosynthesis, respiration, and light and dark calcification. Ninety standardised benthic communities were grown on PVC tiles deployed at two shallow-water volcanic CO2 seeps and two adjacent control sites in Papua New Guinea. Along the CO2 gradient, both the upward facing phototrophic and the downward facing cryptic communities changed in their composition. Under ambient CO2, both communities were dominated by calcifying algae, but with increasing CO2 they were gradually replaced by non-calcifying algae (predominantly green filamentous algae, cyanobacteria and macroalgae, which increased from ~30% to ~80% cover). Responses were weaker in the invertebrate communities, however ascidians and tube-forming polychaetes declined with increasing CO2. Differences in the carbonate chemistry explained a far greater amount of change in communities than differences between the two reefs and successional changes from five to 13 months, suggesting community successions are established early and are under strong chemical control. As pH declined from 8.0 to 7.8, rates of gross photosynthesis and dark respiration of the 13-month old reef communities (upper and cryptic surfaces combined) significantly increased by 10% and 20%, respectively, in response to altered community composition. As a consequence, net production remained constant. Light and dark calcification rates both gradually declined by 20%, and low or negative daily net calcification rates were observed at an aragonite saturation state of <2.3. The study demonstrates that ocean acidification as predicted for the end of this century will strongly alter reef communities, and will significantly change rates of community metabolism.


Resveratrol metabolism in a non-human primate, the grey mouse lemur (Microcebus murinus), using ultra-high-performance liquid chromatography-quadrupole time of flight.
The grey mouse lemur (Microcebus murinus) is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 mg.kg-1 of oral resveratrol) by ultra-high performance liquid chromatography (UHPLC), coupled to a quadrupole-time-of-flight (Q-TOF) mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives) and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives). The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism.


Ownership of knowledge--the role of patents in pharmaceutical R&D.
Both the public and the private sectors contribute to research and development (R&D) in pharmaceuticals. The public sector originates many of the discoveries of new drugs. The private sector, which focuses on development, is heavily reliant on patents. Though patents are presumed to reward genuine inventions, lax rules on patentability and shortcomings in procedures permit protection to be obtained on a myriad of minor developments. These patents, though weak and possibly invalid in many cases, are used to restrain competition and delay the entry of generic competition. Developing countries should design and implement their patent laws so as to prevent strategic patenting and promote competition and access to medicines.


Burnout and safety outcomes - a cross-sectional nationwide survey of EMS-workers in Germany.
The association between burnout and patient safety has been analyzed in many studies for nurses, physicians, and residents. However, studies concerning prehospital emergency medical services (EMS) workers are limited, although they are particularly under risk for emotional stress. This study aims to descriptively analyze the overall degree of burnout among EMS-workers, and potential adverse events that might harm patients as well as the relationship between burnout and perceived safety outcomes for EMS-workers in Germany. EMS-workers were recruited via German EMS-journals, social media and a professional association to participate in an online survey. The questionnaire includes the ´Maslach Burnout Inventory´ (MBI), the 'Emergency Medical Services Safety Inventory' (EMS-SI), and items about job satisfaction and the individual person. Data was descriptively analyzed by calculating frequencies, means, percentages and Pearson correlation coefficients. The association between burnout and patient safety was analyzed using linear and logistic regression models. A total of n = 1101 questionnaires were considered for data analysis. The vast majority of participants were male, younger than 40 years old, and full-time employees with an EMS-experience of 12 years on average. Between 19.9 and 40% of the participants showed a high degree of burnout in one of the burnout dimensions. Safety compromising behavior was the outcome measure with the highest percentage of participants reporting a negative outcome measure. The dimensions emotional exhaustion and depersonalization were positively associated with the safety outcomes injury and safety compromising behavior. Additionally, experiences, job satisfaction and the intention to leave the current job were significantly associated with the outcome measures. This is the first study that examines the association between the degree of burnout and patient safety for EMS-workers. The results suggest that an expansion of psychological support for EMS-workers should be considered. Further research should concentrate on the complex relations between working conditions, burnout and patient safety.


Aluminium and breast cancer: Sources of exposure, tissue measurements and mechanisms of toxicological actions on breast biology.
This review examines recent evidence linking exposure to aluminium with the aetiology of breast cancer. The human population is exposed to aluminium throughout daily life including through diet, application of antiperspirants, use of antacids and vaccination. Aluminium has now been measured in a range of human breast structures at higher levels than in blood serum and experimental evidence suggests that the tissue concentrations measured have the potential to adversely influence breast epithelial cells including generation of genomic instability, induction of anchorage-independent proliferation and interference in oestrogen action. The presence of aluminium in the human breast may also alter the breast microenvironment causing disruption to iron metabolism, oxidative damage to cellular components, inflammatory responses and alterations to the motility of cells. The main research need is now to investigate whether the concentrations of aluminium measured in the human breast can lead in vivo to any of the effects observed in cells in vitro and this would be aided by the identification of biomarkers specific for aluminium action.


Survival of splinted mini-implants after contamination with stainless steel.
Dental practitioners are instructed to avoid any type of contact with implant surfaces prior to their insertion. However, the probability of contaminating the surface is high, especially when placement of implants necessitates the use of precise surgical guides. The aim of this study was to evaluate the 2-year survival rate of splinted mini-implants that came into contact with stainless steel prior to their insertion. During the clinical portion of the study, initiated over a 3-day period, 90 mini-implants were inserted into the anterior mandible of 45 totally edentulous patients; 46 were inserted using a prefabricated stainless steel guide (group 1, bar) and 44 were placed without a guide (group 2, ball). A flapless surgical protocol was used. All implants were immediately loaded with mandibular overdentures, and follow-up was conducted for up to 2 years. The Kaplan-Meier method was used to analyze implant survival in each group, with a confidence level of 95%. In the in vitro phase of the study, five mini-implants were contaminated for 20 seconds with a stainless steel surgical guide. They were then observed using scanning electron microscopy and energy dispersive spectroscopy to identify contaminants and to determine qualitatively the chemical composition of the surface. As a control, five mini-implants recently extracted from their original containers were analyzed. During the 2-year follow-up, one implant failed (97.8% survival rate) in group 1 and four failed in group 2 (90.9% survival rate). The in vitro analysis revealed carbon and oxygen on all implants. On the implants that were in contact with stainless steel, additional elements were identified, including silica, calcium, iron, and chromium. Contact between mini-implants and stainless steel surgical guides does not seem to generate contamination that compromises the survival of splinted mini-implants.


Monochromatic heterodyne fiber-optic profile sensor for spatially resolved velocity measurements with frequency division multiplexing.
Investigating shear flows is important in technical applications as well as in fundamental research. Velocity measurements with high spatial resolution are necessary. Laser Doppler anemometry allows nonintrusive precise measurements, but the spatial resolution is limited by the size of the measurement volume to approximately 50 microm. A new laser Doppler profile sensor is proposed, enabling determination of the velocity profile inside the measurement volume. Two fringe systems with contrary fringe spacing gradients are generated to determine the position as well as the velocity of passing tracer particles. Physically discriminating between the two measuring channels is done by a frequency-division-multiplexing technique with acousto-optic modulators. A frequency-doubled Nd:YAG laser and a fiber-optic measuring head were employed, resulting in a portable and flexible sensor. In the center of the measurement volume of approximately 1-mm length, a spatial resolution of approximately 5 microm was obtained. Spatially resolved measurements of the Blasius velocity profile are presented. Small velocities as low as 3 cm/s are measured. The sensor is applied in a wind tunnel to determine the wall shear stress of a boundary layer flow. All measurement results show good agreement with the theoretical prediction.


Lymphocyte subpopulation in healthy and diseased gingival tissue.
In this study, infiltrating lymphocytes subpopulation in gingival sections of healthy, inflamed, and periodontitis lesions was investigated. A set of cluster of differentiation (CD) antigen specific monoclonal/polyclonal antibodies to detect different cell types within the tissues was used. These included anti-CD3 (pan T-cell), anti-CD45RO (memory T-cell), anti-CD20 (B-cell), and kappa light chain (plasma cells). Biopsies of gingival tissue were obtained from 17 patients who had clinically healthy gingiva, from 18 patients with gingivitis, and 17 patients with periodontitis.A significantly greater proportion of T-cells (P < 0.00) was observed in healthy gingival and gingivitis tissue samples compared to periodontitis tissue samples. In addition, a greater proportion of B-cells was observed in periodontitis lesions than in the gingival lesions (P < 0.00). The memory T-cells and the kappa light-chain plasma cells were present in both healthy and diseased tissues, suggestive of previous activation by periodontal pathogenic microorganisms.In conclusion, these differences in the relative proportions of B- and T-cells may reflect a difference in the immunopathology of periodontitis and gingivitis lesions.


Distribution of Thelastomatoid Nematodes (Nematoda: Oxyurida) in Endemic and Introduced Cockroaches on the Galápagos Island Archipelago, Ecuador.
The thelastomatoid pinworm fauna (Nematoda: Oxyurida: Thelastomatoidea) was surveyed in 3 endemic species and 6 introduced species of cockroach hosts (Insecta: Blattaria) in the Galápagos Islands, Ecuador. A total of 658 host specimens were examined from preserved collections that had been collected between 1966 and 2003 from 7 islands in the archipelago. Eight species of pinworms were identified from these cockroach hosts, including the dominant species Cephalobellus ovumglutinosus and a Severianoia sp. as well as Leidynema appendiculata, Hammerschmidtiella diesingi, an unidentified Cephalobellus species resembling Cephalobellus magalhaesi, an unidentified Protrellus species closely resembling Protrellus shamimi, and an undescribed Blattophila sp. Five new host records are identified for C. ovumglutinosus including the endemic Galápagos cockroaches Chorisoneura carpenteri, Ischnoptera snodgrassii, and Ischnoptera santacruzensis. These endemics were also infected with an undescribed Blatticola sp. Other species recorded resemble known pinworms from other hosts around the world. Prevalence between islands and between host species was variable, but total prevalence for individual pinworm species was consistently low (<10%). A single host specimen examined was infected with more than 1 pinworm species; otherwise only a single species was observed in each infected host. At least 1 introduced pinworm species carried to the islands via invasive cockroach hosts was present in endemic host species, but several globally widespread introduced pinworm species were absent from endemic cockroaches. Santa Cruz was inhabited by the greatest number of pinworm species, likely due to a higher rate of invasive host introduction. This survey, the first from this region, showed that the distribution and transmission of pinworms in the Galápagos Islands is complex and may provide future models of invertebrate dispersal and speciation in an ecosystem already rich with examples of evolution.


Domestic, peridomestic and wild hosts in the transmission of Trypanosoma cruzi in the Caatinga area colonised by Triatoma brasiliensis.
The role played by different mammal species in the maintenance of Trypanosoma cruzi is not constant and varies in time and place. This study aimed to characterise the importance of domestic, wild and peridomestic hosts in the transmission of T. cruzi in Tauá, state of Ceará, Caatinga area, Brazil, with an emphasis on those environments colonised by Triatoma brasiliensis. Direct parasitological examinations were performed on insects and mammals, serologic tests were performed on household and outdoor mammals and multiplex polymerase chain reaction was used on wild mammals. Cytochrome b was used as a food source for wild insects. The serum prevalence in dogs was 38% (20/53), while in pigs it was 6% (2/34). The percentages of the most abundantly infected wild animals were as follows: Thrichomys laurentius 74% (83/112) and Kerodon rupestris 10% (11/112). Of the 749 triatomines collected in the household research, 49.3% (369/749) were positive for T. brasiliensis, while 6.8% were infected with T. cruzi (25/369). In captured animals, T. brasiliensis shares a natural environment with T. laurentius, K. rupestris, Didelphis albiventris, Monodelphis domestica, Galea spixii, Wiedomys pyrrhorhinos, Conepatus semistriatus and Mus musculus. In animals identified via their food source, T. brasiliensis shares a natural environment with G. spixii, K. rupestris, Capra hircus, Gallus gallus, Tropidurus oreadicus and Tupinambis merianae. The high prevalence of T. cruzi in household and peridomiciliar animals reinforces the narrow relationship between the enzootic cycle and humans in environments with T. brasiliensis and characterises it as ubiquitous.


Associations between personal exposures and fixed-site ambient measurements of fine particulate matter, nitrogen dioxide, and carbon monoxide in Toronto, Canada.
A longitudinal study investigating personal exposures to PM(2.5), nitrogen dioxide (NO(2)), and carbon monoxide (CO) for cardiac compromised individuals was conducted in Toronto, Canada. The aim of the study was (1) to examine the distribution of exposures to PM(2.5), NO(2), and CO; and (2) to investigate the relationship between personal exposures and fixed-site ambient measurements of PM(2.5), NO(2), and CO. In total, 28 subjects with coronary artery disease wore the Rupprecht & Patashnick ChemPass Personal Sampling System one day a week for a maximum of 10 weeks. The mean (SD) personal exposures were 22 microg m(-3) (42), 14 p.p.b. (6), and 1.4 p.p.m (0.5) for PM(2.5), NO(2), and CO, respectively. PM(2.5) and CO personal exposures were greater than central fixed-site ambient measurements, while the reverse pattern was observed for NO(2). Ambient PM(2.5) and NO(2) were correlated with personal exposures to PM(2.5) and NO(2) with median Spearman's correlation coefficients of 0.69 and 0.57, respectively. The correlations between personal exposures and ambient measurements made closest to the subjects' homes or the average of all stations within the study were not stronger than the correlation between personal exposures and central fixed-site measurements. Personal exposures to PM(2.5) were correlated with personal exposures to NO(2) (median Spearman's correlation coefficient of 0.43). This study suggests that central fixed-site measurements of PM(2.5) and NO(2) may be treated as surrogates for personal exposures to PM(2.5) and NO(2) in epidemiological studies, and that NO(2) is a potential confounder of PM(2.5).


Group Therapy Use and Its Impact on the Outcomes of Inpatient Rehabilitation After Traumatic Brain Injury: Data From Traumatic Brain Injury-Practice Based Evidence Project.
To describe the amount and content of group therapies provided during inpatient rehabilitation for traumatic brain injury (TBI), and to assess the relations of group therapy with patient, injury, and treatment factors and outcomes. Prospective observational cohort. Inpatient rehabilitation. Consecutive admissions (N=2130) for initial TBI rehabilitation at 10 inpatient rehabilitation facilities (9 in the United States, 1 in Canada) from October 2008 to September 2011. Not applicable. Proportion of sessions that were group therapy (≥2 patients were treated simultaneously by ≥1 clinician); proportion of patients receiving group therapy; type of activity performed and amount of time spent in group therapy, by discipline; rehabilitation length of stay; discharge location; and FIM cognitive and motor scores at discharge. Of the patients, 79% received at least 1 session of group therapy, with group therapy accounting for 13.7% of all therapy sessions and 15.8% of therapy hours. On average, patients spent 2.9h/wk in group therapy. The greatest proportion of treatment time in group format was in therapeutic recreation (25.6%), followed by speech therapy (16.2%), occupational therapy (10.4%), psychology (8.1%), and physical therapy (7.9%). Group therapy time and type of treatment activities varied among admission FIM cognitive subgroups and treatment sites. Several factors appear to be predictive of receiving group therapy, with the treatment site being a major influence. However, group therapy as a whole offered little explanation of differences in the outcomes studied. Group therapy is commonly used in TBI rehabilitation, to varying degrees among disciplines, sites, and cognitive impairment subgroups. Various therapeutic activities take place in group therapy, indicating its perceived value in addressing many domains of functioning. Variation in outcomes is not explained well by overall percentage of therapy time delivered in groups.


The Society for Vascular Surgery practice guidelines on follow-up after vascular surgery arterial procedures.
Although follow-up after open surgical and endovascular procedures is generally regarded as an important part of the care provided by vascular surgeons, there are no detailed or comprehensive guidelines that specify the optimal approaches with regard to testing methods, indications for reintervention, and follow-up intervals. To provide guidance to the vascular surgeon, the Clinical Practice Council of the Society for Vascular Surgery appointed an expert panel and a methodologist to review the current clinical evidence and to develop recommendations for follow-up after vascular surgery procedures. For those procedures for which high-quality evidence was not available, recommendations were based on observational studies, committee consensus, and indirect evidence. Recognizing that there are numerous published reports on the role of duplex ultrasound for surveillance of infrainguinal vein bypass grafts, the Society commissioned a systematic review and meta-analysis on this topic. The panel classified the strength of each recommendation and the corresponding quality of evidence on the basis of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system: recommendations were graded either strong or weak, and the quality of evidence was graded high, moderate, or low. The resulting recommendations represent a wide variety of open surgical and endovascular procedures involving the extracranial carotid artery, thoracic and abdominal aorta, mesenteric and renal arteries, and lower extremity arterial revascularization. The panel also identified many areas in which there was a lack of high-quality evidence to support their recommendations. This suggests that there are opportunities for further clinical research on testing methods, threshold criteria, and the role of surveillance as well as on the modes of failure and indications for reintervention after vascular surgery procedures.


Finding the sources of septicemia at a neonatal intensive care unit: newborns and infants can be contaminated while being fed.
This study was conducted to determine whether the hospital devices and materials used for the examination and treatment of patients play a role in the outbreaks of infection in hospitals. Environmental sampling was performed to find the possible sources of septicemia at the neonatal intensive care unit (NICU). Environmental sampling results and blood culture records from the outbreak areas were compared to determine if they had any relationship with each other. Semisolid and solid samples were compared with liquid samples for positive cultures using a chi-square test. Statistical significance was accepted at P<0.05. The results showed that liquid sources were more frequent media for infectious agents (OR, 8.75; chi-square, 0.0278). The most common cultured microorganisms were coagulase negative Staphylococcus and Klebsiella pneumoniae, which were responsible for septicemias at NICU. There were strong relationships between environmental culture results and the agents responsible for the outbreak of septicemia at the NICU. The formula heater at the pediatrics clinic also revealed the same microorganisms with the blood cultures of 3 patients in the same clinic. Although there are matches between the environmental sampling and blood culture records in our study, there is a need for further studies. We conclude that moist areas and liquid environments must be regularly checked for pathogen microorganisms. Instead of using heated water to sterilize infant formula, dry air sterilization should be used. Liquid media like oxygen reservoir solution and antiseptic solutions must be checked for contamination and should be changed periodically.


Bu-Shen-Ning-Xin decoction suppresses osteoclastogenesis via increasing dehydroepiandrosterone to prevent postmenopausal osteoporosis.
Bu-Shen-Ning-Xin decoction (BSNXD), a traditional Chinese medicine, has been used to prevent and treat age-related diseases such as postmenopausal osteoporosis (PMO) for decades. This study sought to investigate the underlying mechanisms of BSNXD in terms of receptor activation of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro because of the critical roles of bone resorption in the development and progression of osteoporosis. In mice, serum levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and 17-β-estradiol (E2) were evaluated with an enzyme immunoassay kit after ovariectomy. Levels of DHEA and DHEAS increased significantly following administration of BSNXD while the level of E2 did not. In addition, tartrate-resistance acid phosphatase staining showed that DHEA profoundly inhibited RANKL-induced osteoclastogenesis in vitro in a dose-dependent manner via estrogen receptor α (ERα) but not via estrogen receptor β or androgen receptors. Cytotoxicity was not detected in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. These data suggest that BSNXD prevents PMO by increasing DHEA via the ERαpathway to suppress osteoclastogenesis.


Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia.
Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant antileukemia activity. A multicenter phase II study of cloretazine was conducted in patients 60 years of age or older with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Cloretazine 600 mg/m2 was administered as a single intravenous infusion. Patients were stratified by age, performance score, cytogenetic risk category, type of AML, and comorbidity. One hundred four patients, median age 72 years (range, 60 to 84 years), were treated on study. Performance status was 2 in 31 patients (30%) and no patient had a favorable karyotype. Forty-seven patients (45%) had cardiac disease, 25 patients (24%) had hepatic disease, and 19 patients (18%) had pulmonary disease, defined as per the Hematopoietic Cell Transplantation-Specific Comorbidity Index, at study entry. The overall response rate was 32%, with 29 patients (28%) achieving complete response (CR) and four patients (4%) achieving CR with incomplete platelet recovery. Response rates in 44 de novo AML patients, 45 secondary AML patients, and 15 high-risk MDS patients were 50%, 11%, and 40%, respectively. Response by cytogenetic risk category was 39% in 56 patients with intermediate cytogenetic risk and 24% in 46 patients with unfavorable cytogenetic risk. Nineteen (18%) patients died within 30 days of receiving cloretazine therapy. Median overall survival was 94 days, with a 1-year survival of 14%; the median duration of survival was 147 days, with a 1-year survival of 28% for those who achieved CR. Cloretazine has significant activity and modest extramedullary toxicity in elderly patients with AML or high-risk MDS. Response rates remain consistent despite increasing age and comorbidity.


Predicting marsh vulnerability to sea-level rise using Holocene relative sea-level data.
Tidal marshes rank among Earth's vulnerable ecosystems, which will retreat if future rates of relative sea-level rise (RSLR) exceed marshes' ability to accrete vertically. Here, we assess the limits to marsh vulnerability by analyzing >780 Holocene reconstructions of tidal marsh evolution in Great Britain. These reconstructions include both transgressive (tidal marsh retreat) and regressive (tidal marsh expansion) contacts. The probability of a marsh retreat was conditional upon Holocene rates of RSLR, which varied between -7.7 and 15.2 mm/yr. Holocene records indicate that marshes are nine times more likely to retreat than expand when RSLR rates are ≥7.1 mm/yr. Coupling estimated probabilities of marsh retreat with projections of future RSLR suggests a major risk of tidal marsh loss in the twenty-first century. All of Great Britain has a >80% probability of a marsh retreat under Representative Concentration Pathway (RCP) 8.5 by 2100, with areas of southern and eastern England achieving this probability by 2040.


Neuropeptide release augments serum albumin loss and reduces ultrafiltration in peritoneal dialysis.
The triggers of the acute local inflammatory response to peritoneal dialysis (PD) fluid exposure remain unknown. In the present study, we investigated the effects of neurogenic inflammation and mast cell degranulation on water and solute transport in experimental PD. Single 2-hour dwells in rats with PD catheters were studied. Histamine and the neuropeptides substance P and calcitonin gene-related peptide (CGRP) were measured in PD fluid samples by ELISA. Radiolabeled albumin ((125)I and (131)I respectively) was used as an intraperitoneal (IP) and intravascular tracer. Glucose and urea concentrations were measured in plasma and PD fluid. The effects of varying the volume and osmolarity of a lactate-buffered PD fluid were compared and related to the effects of pharmacologic intervention. Application of 20 mL 3.9% glucose PD fluid induced an IP histamine release during the first 30 minutes, blockable by the mast cell stabilizer doxantrazole and the substance P neurokinin-1 receptor (NK1R)-blocker spantide. Histamine release was also inhibited at a reduced PD volume (14 mL), but was not affected by normalizing the PD fluid osmolarity. Blockade of NK1R also reduced plasma albumin leakage to the peritoneal cavity. Inhibition of CGRP receptors by CGRP8-37 improved osmotic (transcapillary) and net ultrafiltration and reduced the dialysate urea concentration. Neuropeptide release was not clearly related to activation of the TrpV1 receptor, the classic trigger of neurogenic inflammation. Neuropeptide release exaggerated albumin loss and reduced ultrafiltration in this rat PD model. Intervention aimed at the neuropeptide action substantially improved PD efficiency.


STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1.
Store-operated Ca(2+) channels activated by the depletion of Ca(2+) from the endoplasmic reticulum (ER) are a major Ca(2+) entry pathway in nonexcitable cells and are essential for T cell activation and adaptive immunity. After store depletion, the ER Ca(2+) sensor STIM1 and the CRAC channel protein Orai1 redistribute to ER-plasma membrane (PM) junctions, but the fundamental issue of how STIM1 activates the CRAC channel at these sites is unresolved. Here, we identify a minimal, highly conserved 107-aa CRAC activation domain (CAD) of STIM1 that binds directly to the N and C termini of Orai1 to open the CRAC channel. Purified CAD forms a tetramer that clusters CRAC channels, but analysis of STIM1 mutants reveals that channel clustering is not sufficient for channel activation. These studies establish a molecular mechanism for store-operated Ca(2+) entry in which the direct binding of STIM1 to Orai1 drives the accumulation and the activation of CRAC channels at ER-PM junctions.


Hair analysis provides a historical record of cortisol levels in Cushing's syndrome.
The severity of Cushing's Syndrome (CS) depends on the duration and extent of the exposure to excess glucocorticoids. Current measurements of cortisol in serum, saliva and urine reflect systemic cortisol levels at the time of sample collection, but cannot assess past cortisol levels. Hair cortisol levels may be increased in patients with CS, and, as hair grows about 1 cm/month, measurement of hair cortisol may provide historical information on the development of hypercortisolism. We attempted to measure cortisol in hair in relation to clinical course in six female patients with CS and in 32 healthy volunteers in 1 cm hair sections. Hair cortisol content was measured using a commercially available salivary cortisol immune assay with a protocol modified for use with hair. Hair cortisol levels were higher in patients with CS than in controls, the medians (ranges) were 679 (279-2500) and 116 (26-204) ng/g respectively (P<0.001). Segmental hair analysis provided information for up to 18 months before time of sampling. Hair cortisol concentrations appeared to vary in accordance with the clinical course. Based on these data, we suggest that hair cortisol measurement is a novel method for assessing dynamic systemic cortisol exposure and provides unique historical information on variation in cortisol, and that more research is required to fully understand the utility and limits of this technique.


Medication discussion between nurse prescribers and people with diabetes: an analysis of content and participation using MEDICODE.
This paper is a report of a study to identify the content of, and participation in, medicine discussion between nurse prescribers and people with diabetes in England. Diabetes affects 246 million people worldwide and effective management of medicines is an essential component of successful disease control. There are now over 20,000 nurse independent prescribers in the UK, many of whom frequently prescribe for people with diabetes. With this responsibility comes a challenge to effectively communicate with patients about medicines. National guidelines on medicines communication have recently been issued, but the extent to which nurse prescribers are facilitating effective medicine-taking in diabetes remains unknown. A purposive sample of 20 nurse prescribers working with diabetes patients audio-recorded 59 of their routine consultations and a descriptive analysis was conducted using a validated coding tool: MEDICODE. Recordings were collected between January and July 2008. The unit of analysis was the medicine. A total of 260 instances of medicine discussion identified in the audio-recordings were analysed. The most frequently raised themes were 'medication named' (raised in 88·8% of medicines), 'usage of medication' (65·4%) and 'instructions for taking medication' (48·5%). 'Reasons for medication' (8·5%) and 'concerns about medication' were infrequently discussed (2·7%). Measures of consultation participation suggest largely dyadic medicine discussion initiated by nurse prescribers. MEDICODE discussion themes linked to principles of recent guidelines for effective medicine-taking were infrequently raised. Medicine discussion was characterized by a one statement-one response style of communication led by nurses. Professional development is required to support theoretically informed approaches to effective medicines management.


Evaluation of Efficacy of Transvaginal Sonography with Hysteroscopy for Assessment of Tubal Patency in Infertile Women Regarding Diagnostic Laparoscopy.
Infertility, as one of the most common gynecological disorders, affects many people worldwide. To choose the clinical treatment, correct assessment of tubal patency can provide an important clue; therefore, it is considered as one of the major steps in workup examinations of infertile women. In this study, we aimed to compare the results of transvaginal ultrasonography (TVS) after hysteroscopy (HSC) with laparoscopy, as a gold standard, for assessing the fallopian tubal patency in infertile women. This is a cross-sectional study which included 49 infertile women referred to Shahid Beheshti Hospital affiliated with Isfahan University of Medical Sciences during the years 2015 and 2016. At first, patients who met the inclusion criteria were examined through HSC in by a specialist in gynecology and obstetrics in operating room because laparoscopy was performed after TVS with HSC, but HSC was performed without anesthesia. TVS was performed before and after of HSC to observe fluid in the pouch of Douglas. The findings of TVS with HSC and laparoscopy were compared. There was a strong agreement between TVS after HSC and laparoscopy (kappa coefficient = 0.935, 95% confidence interval [CI]: 0.81, 1.00). The sensitivity of TVS after HSC was 100% (95% CI: 66.37, 100) and specificity was 97.50% (95% CI: 86.84, 99.94) with a positive predictive value of 90% (95% CI: 55.50, 99.75) and negative predictive value of 100% (95% CI: 90.97, 100). TVS after HSC is an accurate diagnostic tool for examination of fallopian tubal patency in infertile women.


Risk of fractures in patients with multiple sclerosis: a population-based cohort study.
To examine the risk of fracture in patients with multiple sclerosis (MS) compared with population-based controls. A population-based cohort study was performed in the Dutch PHARMO Record Linkage System (1998-2008). Patients with MS (n = 2,415) were matched by year of birth, sex, and practice to up to 6 patients without MS (controls). We used Cox proportional hazards models to estimate the hazard ratio (HR) of fracture in MS. Time-dependent adjustments were made for age, history of disease, and drug use. During follow-up, there were 59 fractures among patients with MS (2.4%) and 227 fractures among controls (1.8%). Patients with MS had a 1.7-fold increased risk of osteoporotic fracture (HR 1.73 [95% confidence interval (CI) 1.18-2.53]) and a 4-fold increased risk of hip fracture (HR 4.08 [95% CI 2.21-7.56]). The risk of osteoporotic fracture was significantly greater for patients with MS who had been prescribed antidepressants (HR 3.25 [95% CI 1.77-5.97]) or hypnotics/anxiolytics (HR 3.40 [95% CI 2.06-5.63]) in the previous 6 months, compared with controls. Increased awareness of the risk of hip fracture is warranted in patients with MS, especially in those who have recently been prescribed antidepressants or hypnotics/anxiolytics.


Secretory pathway stress responses as possible mechanisms of disease involving Golgi Ca2+ pump dysfunction.
In mammalian tissues, uptake of Ca(2+) and Mn(2+) by Golgi membranes is mediated by the secretory pathway Ca(2+) -ATPases, SPCA1 and SPCA2, encoded by the ATP2C1 and ATP2C2 genes. Loss of one copy of the ATP2C1 gene, which causes SPCA1 haploinsufficiency, leads to squamous cell tumors of keratinized epithelia in mice and to Hailey-Hailey disease, an acantholytic skin disease, in humans. Although the disease phenotypes resulting from SPCA1 haploinsufficiency in mice and humans are quite different, each species-specific phenotype is remarkably similar to those arising as a result of null mutations in one copy of the ATP2A2 gene, encoding SERCA2, the endoplasmic reticulum (ER) Ca(2+) pump. SERCA2 haploinsufficiency, like SPCA1 haploinsufficiency, causes squamous cell tumors in mice and Darier's disease, also an acantholytic skin disease, in humans. The phenotypic similarities between SPCA1 and SERCA2 haploinsufficiency in the two species, and the general functions of the two pumps in consecutive compartments of the secretory pathway, suggest that the underlying disease mechanisms are similar. In this review, we discuss evidence supporting the view that chronic Golgi stress and/or ER stress resulting from Ca(2+) pump haploinsufficiencies leads to activation of cellular stress responses in keratinocytes, with the predominance of proapoptotic pathways (although not necessarily apoptosis itself) leading to acantholytic skin disease in humans and the predominance of prosurvival pathways leading to tumors in mice.


Simultaneous estimation of phase and phase derivative using a difference equation representation of the interference field.
A computationally efficient technique for fringe analysis in digital holographic interferometry using a difference equation representation of the interference field is presented. The spatially varying coefficient of the difference equation is estimated accurately by constraining it in the subspace spanned by the linearly independent basis functions. The coefficient estimated provides an accurate estimation of the interference phase derivative and enables the linear estimation of the interference field. Thereupon, the interference phase is estimated using a simple unwrapping algorithm. The performance of the proposed method is validated with the help of simulation and experimental results.


Response of the ubiquitous pelagic diatom Thalassiosira weissflogii to darkness and anoxia.
Thalassiosira weissflogii, an abundant, nitrate-storing, bloom-forming diatom in the world's oceans, can use its intracellular nitrate pool for dissimilatory nitrate reduction to ammonium (DNRA) after sudden shifts to darkness and anoxia, most likely as a survival mechanism. T. weissflogii cells that stored 4 mM (15)N-nitrate consumed 1.15 (±0.25) fmol NO3 (-) cell(-1) h(-1) and simultaneously produced 1.57 (±0.21) fmol (15)NH4 (+) cell(-1) h(-1) during the first 2 hours of dark/anoxic conditions. Ammonium produced from intracellular nitrate was excreted by the cells, indicating a dissimilatory rather than assimilatory pathway. Nitrite and the greenhouse gas nitrous oxide were produced at rates 2-3 orders of magnitude lower than the ammonium production rate. While DNRA activity was restricted to the first few hours of darkness and anoxia, the subsequent degradation of photopigments took weeks to months, supporting the earlier finding that diatoms resume photosynthesis even after extended exposure to darkness and anoxia. Considering the high global abundance of T. weissflogii, its production of ammonium and nitrous oxide might be of ecological importance for oceanic oxygen minimum zones and the atmosphere, respectively.


Transport Evidence for Sulfur Vacancies as the Origin of Unintentional n-Type Doping in Pyrite FeS2.
Pyrite FeS2 has long been considered a potential earth-abundant low-cost photovoltaic material for thin-film solar cells but has been plagued by low power conversion efficiencies and open-circuit voltages. Recent efforts have identified a lack of understanding and control of doping, as well as uncontrolled surface conduction, as key roadblocks to the development of pyrite photovoltaics. In particular, while n-type bulk behavior in unintentionally doped single crystals and thin films is speculated to arise from sulfur vacancies (VS), proof remains elusive. Here, we provide strong evidence, from extensive electronic transport measurements on high-quality crystals, that VS are deep donors in bulk pyrite. Otherwise identical crystals grown via chemical vapor transport under varied S vapor pressures are thoroughly characterized structurally and chemically, and shown to exhibit systematically different electronic transport. Decreased S vapor pressure during growth leads to reduced bulk resistivity, increased bulk Hall electron density, reduced transport activation energy, onset of positive temperature coefficient of resistivity, and approach to an insulator-metal transition, all as would be expected from increased VS donor density. Impurity analyses show that these trends are uncorrelated with metal impurity concentration and that extracted donor densities significantly exceed total impurity concentrations, directly evidencing a native defect. Well-controlled, wide-range n-doping of pyrite is thus achieved via the control of VS concentration, with substantial implications for photovoltaic and other applications. The location of the VS state within the gap, the influence of specific impurities, unusual aspects to the insulator-metal transition, and the influence of doping on surface conduction are also discussed.


Cryopreservation of spermatozoa from wild-born Namibian cheetahs (Acinonyx jubatus) and influence of glycerol on cryosurvival.
Sperm cryopreservation is a valuable tool for the genetic management of ex situ populations. This study was conducted to assess: (1) semen characteristics of wild-born cheetahs; and (2) the impact of three types of glycerol influence (duration of exposure, temperature, and method of addition) on sperm cryosensitivity. To evaluate the impact of duration of glycerol exposure, spermatozoa were incubated in Test Yolk Buffer (TYB) with 4% glycerol at ambient temperature (approximately 22 degrees C) for 15 vs. 60 min before cryopreservation. To evaluate the influence of temperature and method of glycerol addition, spermatozoa were resuspended at ambient temperature either in TYB with 0% glycerol followed by addition of 8% glycerol (1:1 v/v; at ambient temperature vs. 5 degrees C) or directly in TYB with 4% glycerol. All samples were cryopreserved in straws over liquid nitrogen vapor and evaluated for sperm motility and acrosomal integrity after thawing. Semen samples (n = 23; n = 13 males) contained a high proportion (78%) of pleiomorphic spermatozoa. Ejaculates also contained a high proportion of acrosome-intact (86%) and motile spermatozoa (78%). Immediately after thawing, a significant proportion of spermatozoa retained intact acrosomes (range, 48-67%) and motility (range, 40-49%). After thawing, incubation in glycerol for 60 min at ambient temperature before freezing decreased (p < 0.05) sperm motility and acrosomal integrity at one time-point each (pre-centrifugation and post-centrifugation, respectively). However, method or temperature of glycerol addition had no (p > 0.05) impact on sperm cryosurvival. In summary, (1) wild-born cheetahs produce high proportions of pleiomorphic spermatozoa but with a high proportion of intact acrosomes; and (2) resuspension in 4% glycerol, followed by exposure for up to 60 min at ambient temperature, had minimal effect on sperm motility and acrosomal integrity after cryopreservation. Results indicate the feasibility of cryopreserving cheetah spermatozoa under field conditions, providing a user-friendly method to capture and store gametes to enhance genetic management.


Gene expression profiling of human cancers.
DNA microarrays allow us to visualize simultaneously the expression of potentially all genes within a cell population or tissue sample-revealing the "transcriptome." The analysis of this type of data is commonly called "gene expression profiling" (GEP) because it provides a comprehensive picture of the pattern of gene expression in a particular biological sample. For this reason microarrays are revolutionizing life sciences research and are leading to the development of novel and powerful methods for investigating cancer biology, classifying cancers, and predicting clinical outcome of cancers. Several recent high-profile reports have revealed how clustering of GEP data can clearly identify clinically (and prognostically) important subtypes of cancer among patients considered by established clinicopathological criteria to have similar tumors. Accurate "prognostic signatures" can be obtained from GEP data, which represent relatively small numbers of genes. These signatures can be valuable in directing appropriate treatment and in predicting clinical outcome, and they generally outperform other systems based on clinical and histological criteria. In this paper the basic principles of DNA microarray technology and the different types of microarray platforms available will be introduced, and the power of the technique will be illustrated by reviewing some recent GEP studies on selected cancers, including a preliminary analysis of hepatocellular carcinoma from our Palermo laboratory. GEP is likely to be adopted in the future as a key decision-making tool in the clinical arena. However, several issues relating to data analysis, reproducibility, cross-comparability, validation, and cost need to be resolved before the technology can be adopted broadly in this context.


1.5:1 meshed AlloDerm bolsters for stapled rectal anastomoses does not provide any advantage in anastomotic strength in a porcine model.
The most feared complication of colorectal anastomoses is leaks resulting in severe morbidity. The concept of staple-line reinforcement is a growing area of interest. In this study, the authors evaluated the feasibility and effect of using 1.5:1 meshed AlloDerm to bolster end-to-end stapled rectal anastomoses in a porcine model. A total of 30 female 45-kg domestic pigs were studied, and each served as its own control by creating a bolstered and unbolstered anastomosis in each animal. All anastomoses were created with a 29-mm end-to-end stapling device. Bolstered anastomoses were randomized to proximal and distal positions along the rectum, and each rectorectal anastomosis was separated by an average of 10 cm. The animals were survived to 3, 5, and 30 days. Barium enemas were then performed and the 2 anastomotic sites harvested. Each anastomosis underwent burst testing. The internal diameter of each anastomosis was measured, and a biochemical analysis was performed for elastin and collagen content. Bolstered anastomoses offered no strength advantage as burst pressures were no different when compared with unbolstered anastomoses. There was also no difference in anastomotic internal diameter, biochemical analysis of elastin or collagen, or presence of adhesions when comparing bolstered with unbolstered anastomoses. There were 4 subclinical leaks-1 in the unbolstered group and 3 in the bolstered group. The routine use of 1.5:1 meshed AlloDerm sandwich bolsters in stapled rectal anastomosis does not confer any detectable advantage in anastomotic strength. Further studies are needed to determine equivalence to traditional stapled anastomoses.


Using Web-based interventions to support caregivers of patients with cancer: a systematic review.
To explore the literature to examine the physical, social, psychological, financial, usability, and feasibility outcomes of Web-based interventions on caregivers of people with cancer and to identify potential trends in this body of evidence. PubMed, CINAHL®, PsycINFO®, and Inspec. Six articles met inclusion criteria. Across studies, most caregivers were middle-aged female spouses with some college attendance who felt "somewhat comfortable" using the Internet. Caregiver interventions used single- and multicomponent services and reduced negative mood. Web-based caregiver interventions can be beneficial in offering information and support and may positively influence the social and psychological outcomes in this population. Many studies described caregiver Internet usage and interventional perceptions and needs, but few have examined the impact of web-based interventions on caregivers. More research is needed to produce high-quality evidence in this population.


Chronic graft-versus-host disease after allogeneic stem cell transplantation: challenges in prevention, science, and supportive care.
Chronic GVHD (cGVHD) remains one of the most significant complications affecting the quality of life of long-term survivors of allogeneic stem cell transplant (SCT). Recent advancements in SCT, including the adoption of reduced-intensity conditioning regimens and improvements in inpatient supportive care, have yielded dramatic reductions in early mortality and led to the expanding use of allogeneic SCT in a broader range of patients, including the elderly. In turn, this development has resulted in a growing number of SCT survivors who remain free of their underlying malignancies but who require care for long-term complications, including cGVHD. cGVHD may have protean manifestations and may pose unique diagnostic and therapeutic challenges. To address inconsistencies in the diagnosis, treatment, and supportive care of cGVHD, experts within the SCT community have worked to develop consensus guidelines; these efforts have yielded more precise definitions and will facilitate more uniform clinical trials. With an increase in SCT survivorship, the management of patients with cGVHD is performed as a partnership between SCT physicians and primary oncologists. This review is designed to help general oncologists understand the current state of cGVHD, including its pathogenesis and treatment. The review places particular emphasis on general principles governing the optimal supportive management of cGVHD and examines recent consensus recommendations regarding its diagnosis and management by organ system.


Epidemiology of invasive candidiasis: a persistent public health problem.
Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.


Spatial inequality through the prism of a pandemic: Covid-19 in South Africa.
In this paper, we examine whether pre-existing socio-economic inequalities relate to inequalities in vulnerability to COVID-19 infection in the context of South Africa using the 2016 Community Survey, which allows for a detailed geographical disaggregation of the analysis. For this purpose, we use a set of indicators of a household's vulnerability to COVID-19 infection and then aggregate these into an index of COVID-19 vulnerability. We use these indicators and their aggregate indices to profile COVID-19 vulnerability at the national, provincial and municipal levels as well providing an urban/rural breakdown. We find that pre-existing socio-economic inequalities are related to inequalities in vulnerability to COVID-19 infection. Poorer households are more vulnerable to infection due to their living conditions. While close to 30% of the population in the poorest two wealth quintiles may be considered vulnerable to the virus due to multiple vulnerability factors, the corresponding figure for the richest two wealth quintiles is less than 2%. There are also stark spatial inequalities in COVID-19 vulnerability. This has implications for budget allocations in response to the COVID-19 pandemic, especially as some of the government relief funding has been and will be apportioned according to municipal need.


Revision surgery after interbody fusion with rhBMP-2: a cautionary tale for spine surgeons.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) promotes the induction of bone growth and is widely used in spine surgery to enhance arthrodesis. Recombinant human BMP-2 has been associated with a variety of complications including ectopic bone formation, adjacent-level fusion, local bone resorption, osteolysis, and radiculitis. Some of the complications associated with rhBMP-2 may be the result of rhBMP-2 induction of the inflammatory host response. In this paper the authors report on a patient with prior transforaminal lumbar interbody fusion (TLIF) using an interbody cage packed with rhBMP-2, in which rhBMP-2 possibly contributed to vascular injury during an attempted anterior lumbar interbody fusion. This 63-year-old man presented with a 1-year history of worsening refractory low-back pain and radiculopathy caused by a Grade 1 spondylolisthesis at L4-5. He underwent an uncomplicated L4-5 TLIF using an rhBMP-2-packed interbody cage. Postoperatively, he experienced marginal improvement of his symptoms. Within the next year and a half the patient returned with unremitting low-back pain and neurogenic claudication that failed to respond to conservative measures. Radiological imaging of the patient revealed screw loosening and pseudarthrosis. He underwent an anterior retroperitoneal approach with a plan for removal of the previous cage, complete discectomy, and placement of a femoral ring. During the retroperitoneal approach the iliac vein was adhered with scarring and fibrosis to the underlying previously operated L4-5 interbody space. During mobilization the left iliac vein was torn, resulting in significant blood loss and cardiac arrest requiring chest compression, defibrillator shocks, and blood transfusion. The patient was stabilized, the operation was terminated, and he was transferred to the intensive care unit. He recovered over the next several days and was discharged at his neurological baseline. The authors propose that the rhBMP-2-induced host inflammatory response partially contributed to vessel fibrosis and scarring, resulting in the life-threatening vascular injury during the reoperation. Spine surgeons should be aware of this potential inflammatory fibrosis in addition to other reported complications related to rhBMP-2.


Phase changes in the upper mantle.
The C-region of the upper mantle has two transition regions 75 to 90 kilometers thick. In western North America these start at depths of 365 kilometers and 620 kilometers and involve velocity increases of about 9 to 10 percent. The locations of these transition regions, their general shape, and their thicknesses are consistent with, first, the transformation of magnesium-rich olivine to a spinel structure and, then, a further collapse of a material having approximately the properties of the component oxides. The velocity increases associated with each transition region are slightly less than predicted for the appropriate phase change. This can be interpreted in terms of an increasing fayalite content with depth. The location of the transition regions and the seismic velocities in their vicinity supply new information regarding the composition and temperature of the upper mantle. The depths of the transition regions are consistent with temperatures near 1500 degrees C at 365 kilometers and 1900 degrees C at 620 kilometers.


Bone loss preventing effect of Sophorae Fructus on ovariectomized rats.
The preventive effects of Sophorae Fructus extracts (I: hot water extract and II: combination product using I) on bone loss in ovariectomized (OVX) rats were investigated. Sophorae Fructus extracts were orally administrated to OVX rats for 9 weeks. Ovariectomy caused the increase of body weight and deoxypyridinoline (Dpd: bone resorption marker) and decrease of calcium (Ca: bone formation marker) level in serum. Dpd level were significantly decreased and Ca levels were elevated at 9 weeks in Sophorae Fructus extracts administered groups after ovariectomy at a dose of 0.556 g/kg/day compared with control group. In administered groups, trabecular bone area (TBA) in the tibia and lumbar were also increased compared with control group in histomorphological analysis. The preventive or treatment effects of Sophorae Fructus extracts on bone loss in OVX rats appears to be due to suppression of bone turnover.


Neural correlates of coherent audiovisual motion perception.
Real-life moving objects are often detected by multisensory cues. We investigated the cortical activity associated with coherent visual motion perception in the presence of a stationary or moving auditory noise source using functional magnetic resonance imaging. Twelve subjects judged episodes of 5-s random-dot motion containing either no (0%) or abundant (16%) coherent direction information. Auditory noise was presented with the displayed visual motion that was moving in phase, was moving out-of-phase, or was stationary. Subjects judged whether visual coherent motion was present, and if so, whether the auditory noise source was moving in phase, was moving out-of-phase, or was not moving. Performance was greatest for a moving sound source that was in phase with the visual coherent dot motion compared with when it was in antiphase. A random-effects analysis revealed that auditory motion activated extended regions in both cerebral hemispheres in the superior temporal gyrus (STG), with a right-hemispheric preponderance. Combined audiovisual motion led to activation clusters in the STG, the supramarginal gyrus, the superior parietal lobule, and the cerebellum. The size of the activated regions was substantially larger than that evoked by either visual or auditory motion alone. The congruent audiovisual motion evoked the most extensive activation pattern, exhibiting several exclusively activated subregions.


Neuroprotective effects of lithium in cultured cells and animal models of diseases.
Lithium, the major drug used to treat manic depressive illness, robustly protects cultured rat brain neurons from glutamate excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptors. The lithium neuroprotection against glutamate excitotoxiciy is long-lasting, requires long-term pretreatment and occurs at therapeutic concentrations of this drug. The neuroprotective mcchanisms involve inactivation of NMDA receptors, decreased expression of pro-apoptotic proteins, p53 and Bax, enhanced expression of the cytoprotective protein, Bcl-2, and activation of the cell survival kinase, Akt. In addition, lithium pretreatment suppresses glutamate-induced loss of the activities of Akt, cyclic AMP-response element binding protein (CREB), c-Jun - N-terminal kinase (JNK) and p38 kinase. Lithium also reduces brain damage in animal models of neurodegenerative diseases in which excitotoxicity has been implicated. In the rat model of stroke using middle cerebral artery occlusion, lithium markedly reduces neurologic deficits and decreases brain infarct volume even when administered after the onset of ischemia. In a rat Huntington's disease model, lithium significantly reduces brain lesions resulting from intrastriatal infusion of quinolinic acid, an excitotoxin. Our results suggest that lithium might have utility in the treatment of neurodegenerative disorders in addition to its common use for the treatment of bipolar depressive patients.


Expired hydrogen peroxide in breath condensate of cystic fibrosis patients.
Stimulated inflammatory cells release large amounts of hydrogen peroxide (H2O2). Breath condensate H2O2 has been shown to be elevated in stable asthmatic children, chronic obstructive pulmonary disease and intubated adult respiratory distress syndrome. In cystic fibrosis airways, where neutrophilic inflammation dominates, it is postulated that H2O2 in breath condensate would be elevated and may be used as a marker of airways inflammation. Expired breath condensate was collected from 16 clinically stable cystic fibrosis (CF) patients (mean age 25.3 yrs, mean forced expiratory volume in one second (FEV1) 50.2%) and 14 normal subjects (mean age 29.9 yrs). Total plasma leukocyte, neutrophil, monocyte and eosinophil counts and lung function were also measured on the day of collection. A method of breath condensate collection excluding the confounding factors of nasal air and saliva contamination was validated and used and H2O2 measured fluorometrically using an optimized assay. The median level of H2O2 concentration in breath condensate of CF patients was lower than that in normal subjects (0.064 versus 0.089 microM), but this did not reach statistical significance (p = 0.20, Mann-Whitney rank sum test). Within the CF group, there was no correlation between H2O2 concentration and lung function. Expired breath condensate H2O2 is not elevated in patients with cystic fibrosis, and is thus not a suitable marker of airways inflammation in these patients. Possible explanations include physical barriers to its detection caused by viscous airways secretions, reaction with other reactive species or increased antioxidant activity caused by trapping of positively charged antioxidants in negatively charged airways secretions.


Gait and balance disorders in older adults.
Gait and balance disorders are common in older adults and are a major cause of falls in this population. They are associated with increased morbidity and mortality, as well as reduced level of function. Common causes include arthritis and orthostatic hypotension; however, most gait and balance disorders involve multiple contributing factors. Most changes in gait are related to underlying medical conditions and should not be considered an inevitable consequence of aging. Physicians caring for older patients should ask at least annually about falls, and should ask about or examine for difficulties with gait and balance at least once. For older adults who report a fall, physicians should ask about difficulties with gait and balance, and should observe for any gait or balance dysfunctions. The Timed Up and Go test is a fast and reliable diagnostic tool. Persons who have difficulty or demonstrate unsteadiness performing the Timed Up and Go test require further assessment, usually with a physical therapist, to help elucidate gait impairments and related functional limitations. The most effective strategy for falls prevention involves a multifactorial evaluation followed by targeted interventions for identified contributing factors. Evidence on the effectiveness of interventions for gait and balance disorders is limited because of the lack of standardized outcome measures determining gait and balance abilities. However, effective options for patients with gait and balance disorders include exercise and physical therapy.


Multiple source generation using air-structured optical waveguides for optical field shaping and transformation within and beyond the waveguide.
In this paper we review recent results describing the generation of optical modes within waveguides based on coherent scattering from artificially structured interfaces. The generation of optical waveguide propagation similar to free space propagation enables possible solutions to controlling and shaping optical field generation in free space using coherent scattering of multiple sources. It is shown that the controlled fabrication of such sources can be done simply with air-material structured waveguides such as air-silica structured fibres. Further, the technique of coherent superposition is well known in Fresnel optics, exploiting zone plates to correct the necessary phase adjustments for a desired lens performance. Similarly, in waveguide form this allows fine control of the interference process resulting in the desired mode field and its properties within the waveguide, at the end of the waveguide in the near field regime and well beyond the waveguide into the far field. A factor that can contribute significantly to the coherent scattering within the Fresnel waveguide is resonant-like scattering inside the low index regions since the critical angle of propagation can be very small, increasing Fresnel reflections between interfaces. The results presented here open up a range of hitherto unexplored possibilities in controlling and shaping at first glance disparate phenomena, including free space diffraction.


Catalytic hydrogenation of carbonyl and nitro compounds using an [N,O]-chelate half-sandwich ruthenium catalyst.
A series of N,O-chelate half-sandwich ruthenium complexes for both carbonyl and nitro compound hydrogenation have been synthesized based on β-ketoamino ligands. All complexes exhibited high activity for the catalytic hydrogenation of a series of ketones and nitroarenes with molecular H2 as the reducing reagent in aqueous medium. Consequently, the catalytic system showed the catalytic TON values of 950 for 1-phenylethanol in acetophenone hydrogenation and 1960 for 1-chloro-4-nitrobenzene in p-chloroaniline hydrogenation. Good catalytic activity was displayed for various kinds of substrates with either electron-donating or electron-withdrawing groups. The neutral ruthenium complexes 1-4 were fully characterized using NMR, IR, and elemental analysis. Molecular structures of complexes 2 and 4 were further confirmed using single-crystal X-ray diffraction analysis.


Eating habits and colorectal cancer.
In order to investigate the relation between the occurrence of colorectal cancer and food consumption in Hokkaido, Japan, etiological factors of colorectal cancer were investigated through an ecologic study using official food consumption and mortality statistics concerning colorectal cancer, and through a community-based case-control study. The ratio of 'animal foods' to 'plant foods' and that of 'animal protein' to 'plant protein' had a significant correlation with the mortality rate in colorectal cancer. The percentage of fat energy was much more contributory than the absolute amount of fat. Traditional Japanese foods tended to prevent while Western foods tended to promote colorectal cancer. Odds ratios for Japanese foods were low for colon cancer, and those for Western foods were high for rectum cancer. Relative amounts of foods are more contributory than their absolute amounts. An increase of colorectal cancer in Japanese people may be attributable to the increase in the relative amounts of Western foods. Reduction of the ratio of animal foods to plant foods (i.e., a reduction in relative amounts of Western foods or an increase in relative amounts of Japanese foods) may lend to the prevention of colorectal cancer.


Effect of Ozone Treatment on Nano-Sized Silver Sulfide in Wastewater Effluent.
Silver nanoparticles used in consumer products are likely to be released into municipal wastewater. Transformation reactions, most importantly sulfidation, lead to the formation of nanoscale silver sulfide (nano-Ag2S) particles. In wastewater treatment plants (WWTP), ozonation can enhance the effluent quality by eliminating organic micropollutants. The effect of ozonation on the fate of nano-Ag2S, however, is currently unknown. In this study, we investigate the interaction of ozone with nano-Ag2S and evaluate the effect of ozonation on the short-term toxicity of WWTP effluent spiked with nano-Ag2S. The oxidation of nano-Ag2S by ozone resulted in a stoichiometric factor (number of moles of ozone required to oxidize one mole of sulfide to sulfate) of 2.91, which is comparable to the results obtained for the reaction of bisulfide (HS(-)) with ozone. The second-order rate constant for the reaction of nano-Ag2S with ozone (k = 3.1 × 10(4) M(-1) s(-1)) is comparable to the rate constant of fast-reacting micropollutants. Analysis of the ozonation products of nano-Ag2S by transmission electron microscopy (TEM) and X-ray absorption spectroscopy (XAS) revealed that ozonation dominantly led to the formation of silver chloride in WWTP effluent. After ozonation of the Ag2S-spiked effluent, the short-term toxicity for the green algae Chlamydomonas reinhardtii increased and reached EC50 values comparable to Ag(+). This study thus reveals that ozone treatment of WWTP effluent results in the oxidation of Ag2S and, hence, an increase of the Ag toxicity in the effluent, which may become relevant at elevated Ag concentrations.


Hydrothermal treatment of municipal solid waste incineration fly ash for dioxin decomposition.
Hydrothermal treatment of MSWI fly ash was performed in this paper with a purpose to reduce its dioxin content. First a hydrothermal reactor was set up with a mixture of ferric sulphate and ferrous sulphate serviced as the reactant, then the effects caused by reaction conditions such as reaction temperature, pre-treatment by water-washing and reactant dosage were checked; the results showed that as a promising technology, hydrothermal treatment exhibited considerable high efficiencies in decomposition of PCDDs/PCDFs and good stabilization of heavy metals as well. Experimental results also showed that for dioxin destruction, higher reaction temperature is the most important influencing factor followed by Fe addition, and pre-treatment of raw fly ash by water-washing increased the destruction efficiencies of dioxins only very slightly. Finally with help of Gaussian software chemical computational simulation was performed to investigate the mechanism of dioxin decomposition based on quantum chemistry calculation. The calculation results were supported by the experimental data. The leaching toxicities of hydrothermal products were higher than upper limits defined in the latest Chinese standard GB 16889-2008 for sanitary landfill disposal, thus an auxiliary process is suggested after the hydrothermal treatment for heavy metal stabilization.


Mathematical model of dynamic protein interactions regulating p53 protein stability for tumor suppression.
In the field of cancer biology, numerous genes or proteins form extremely complex regulatory network, which determines cancer cell fate and cancer cell survival. p53 is a major tumor suppressor that is lost in more than 50% of human cancers. It has been well known that a variety of proteins regulate its protein stability, which is essential for its tumor suppressive function. It remains elusive how we could understand and target p53 stabilization process through network analysis. In this paper we discuss the use of random walk and stationary distribution to measure the compound effect of a network of genes or proteins. This method is applied to the network of nine proteins that influence the protein stability of p53 via regulating the interaction between p53 and its regulator MDM2. Our study identifies that some proteins such as HDAC1 in the network of p53 regulators may have more profound effects on p53 stability, agreeing with the established findings on HDAC1. This work shows the importance of using mathematical analysis to dissect the complexity of biology networks in cancer.


Serum N-glycan profile shift during human ageing.
Biomarkers indicating biological age are of significant interest for prevention, diagnosis and monitoring (and the treatment) of age-related diseases. We previously reported an alteration of serum N-glycan profile in old humans using "DNA Sequencer Adapted-Fluorophore Assisted Carbohydrate Electrophoresis" (DSA-FACE). To validate the shift in serum N-glycan profile during ageing, we studied serum N-glycan profiles in different age groups of healthy volunteers, patients with dementia, and patients with Cockayne syndrome, a genetic DNA repair disorder involving neurodegeneration and premature ageing. We found that the log of the ratio of two glycans (NGA2F and NA2F), named GlycoAgeTest, remained steady up to the age of 40years and thereafter gradually increased to reach its highest level in nonagenarians. Patients with dementia or Cockayne syndrome had a higher GlycoAgeTest level than age-matched healthy individuals. We thus demonstrate that the value of GlycoAgeTest is better than chronological age for estimating the physiological age of a human individual, and that it could be used as an ageing biomarker for healthy humans. Our data indicate that the GlycoAgeTest could be used as a non-invasive surrogate marker for general health, for forecasting disease progression during ageing, and for monitoring the efficacy of anti-ageing food compounds.


The brave new world of older patients: preparing general practice training for an ageing population.
Develop and pilot test evidence-based resources for general practice training practices to enhance older patients' (65+ years) interactions with General Practice Registrars (GPRs). In Australia, general practice trainees, referred to as GPRs, see fewer older patients and patients with chronic conditions than doctors who have completed their specialist GP training. This reduces learning opportunities for GPRs in the management of these important patient groups. Therefore, developing effective strategies to improve GPR-older patient interaction is critical to primary care training, to meet the current and future needs of an ageing population. Adopting a social marketing approach, GPR practice resources were developed to address knowledge and attitudinal barriers at the practice and patient level to improve older patient comfort, and willingness to engage, with GPR care. Two focus groups with older patients (n=18) and interviews with staff of training practices (n=12) were utilised to pre-test resources. Amended resources were pilot tested and evaluated in a naturalistic GPR training practice setting using a structured patient questionnaire (n=44). Pilot evaluation suggests improved comfort and willingness of older patients to interact with GPRs. In all, 54% of survey participants indicated they would be more likely to make an appointment with a Registrar in the future as a result of exposure to the resources. In all, 40% of patients would feel comfortable having a GPR manage a complex or chronic condition, which compares favourably with 28% of similarly aged patients in previous research. The use of tailored, engaging and informative GPR resources for older patients and practice staff may be an important contributor to addressing the growing problem of ensuring GPRs are adequately engaged in treating older patients. The adoption of a social marketing framework was instrumental in enhancing the acceptance and effectiveness of this intervention.


Circumcision and HIV infection among men who have sex with men in Britain: the insertive sexual role.
The objective was to examine the association between circumcision status and self-reported HIV infection among men who have sex with men (MSM) in Britain who predominantly or exclusively engaged in insertive anal intercourse. In 2007-2008, a convenience sample of MSM living in Britain was recruited through websites, in sexual health clinics, bars, clubs, and other venues. Men completed an online survey which included questions on circumcision status, HIV testing, HIV status, sexual risk behavior, and sexual role for anal sex. The analysis was restricted to 1,521 white British MSM who reported unprotected anal intercourse in the previous 3 months and who said they only or mostly took the insertive role during anal sex. Of these men, 254 (16.7 %) were circumcised. Among men who had had a previous HIV test (n = 1,097), self-reported HIV seropositivity was 8.6 % for circumcised men (17/197) and 8.9 % for uncircumcised men (80/900) (unadjusted odds ratio [OR], 0.97; 95 % confidence interval [95 % CI], 0.56, 1.67). In a multivariable logistic model adjusted for known risk factors for HIV infection, there was no evidence of an association between HIV seropositivity and circumcision status (adjusted OR, 0.79; 95 % CI, 0.43, 1.44), even among the 400 MSM who engaged exclusively in insertive anal sex (adjusted OR, 0.84; 95 % CI, 0.25, 2.81). Our study provides further evidence that circumcision is unlikely to be an effective strategy for HIV prevention among MSM in Britain.


Optimized Screw Trajectory for Lumbar Cortical Bone Trajectory Pedicle Screws Based on Clinical Outcome: Evidence Favoring the Buttress Effect Theory.
Cortical bone trajectory (CBT) is a relatively new technique for pedicle screw insertion in the field of spine surgery. Previous studies have demonstrated the significantly better pullout and toggle characteristics the new method offers, and it appears to have certain advantages over the widely used traditional trajectory. The mechanism of the pullout and toggle characteristics still remains unknown. To report the medium- to long-term follow-up findings of patients who underwent posterior lumbar interbody fusion or posterior lumbar fusion (PLIF/PLF) at our institution and to discuss the ideal screw trajectory when using this technique. Retrospective radiologic study. Fifty-five patients who underwent PLIF/PLF for lumbar spondylosis using the new technique between January 2011 and January 2016 were included. Clinical outcome was assessed using the Japanese Orthopaedic Association scores for low back pain and visual analog scale scores. Screw loosening was evaluated via the presence of a translucent zone surrounding the pedicle screw using plain X-radiography (Xp). The screw trajectory was evaluated by measuring the rostral range (RR) and the lateral range score (LRS). The RR is the angle between the line drawn along the distal end plate of the vertebra and the line drawn along the screw on the lateral view. The LRS is the score given depending on the position of the tip of the screw seen on the Xp taken in the anteroposterior (AP) view. The pedicle ring is equally divided into the medial third (zone A), central third (zone B), and the lateral third (zone C) by four vertical lines. A score of 0 to 3 points is given depending on the position of the tip of the screw: 0, outside the pedicle ring; 1, zone A; 2, zone B; and 3, zone C. Bone fusion was recorded in 49 patients (49/55 patients). The total number of screws with a visible translucent zone on Xp was 26 (26/242 screws). When the screws are inserted at a more acute angle in the lateral view (low RR) or when the screws are directed more medially (low LRS), the risk of developing a translucent zone around the pedicle screw increased. With CBT, the pedicle screws are inserted from the pars interarticularis that is rich in cortical bone, strong enough to withstand the substantial forces usually encountered in the region. Our clinical data suggest that the optimal screw trajectory is one where the screw is inserted at an angle > 22.55 degrees (high RR) on the lateral view Xp and where the tip of the screw is directed toward the lateral third of the pedicle on the AP Xp. We believe the naturally occurring buttress effect that exists in the vertebra may give CBT a mechanical and anatomical advantage over the traditional screw trajectory.