Mycosis fungoides and Sézary syndrome.
Mycosis fungoides and Sézary syndrome are the most common of the cutaneous T-cell lymphomas, which are a heterogeneous group of neoplasms that affect the skin as a primary site. Although the aetiologies of mycosis fungoides and Sézary syndrome are unknown, important insights have been gained in the immunological and genetic perturbations that are associated with these diseases. Unlike some B-cell lymphomas, cutaneous T-cell lymphomas as a group are rarely if ever curable and hence need chronic-disease management. New approaches to treatments are being investigated and include biological and cytotoxic drugs, phototherapy, and monoclonal antibodies that are directed towards novel molecular targets. New molecular technologies such as complementary-DNA microarray have the potential to increase the accuracy of diagnosis and provide important prognostic information. Treatments can be combined to greatly improve clinical outcome without substantially increasing toxic effects in advanced disease that is otherwise difficult to treat. Although present treatment strategies are generally not curative, there is hope that experimental treatments, particularly immunotherapy, might eventually reverse or suppress the abnormalities of mycosis fungoides and Sézary syndrome to the point at which they become non-life-threatening, chronic diseases.


Increasing sucrose uptake capacity of wheat grains stimulates storage protein synthesis.
Increasing grain sink strength by improving assimilate uptake capacity could be a promising approach toward getting higher yield. The barley (Hordeum vulgare) sucrose transporter HvSUT1 (SUT) was expressed under control of the endosperm-specific Hordein B1 promoter (HO). Compared with the wild type, transgenic HOSUT grains take up more sucrose (Suc) in vitro, showing that the transgene is functional. Grain Suc levels are not altered, indicating that Suc fluxes are influenced rather than steady-state levels. HOSUT grains have increased percentages of total nitrogen and prolamins, which is reflected in increased levels of phenylalanine, tyrosine, tryptophan, isoleucine, and leucine at late grain development. Transcript profiling indicates specific stimulation of prolamin gene expression at the onset of storage phase. Changes in gene expression and metabolite levels related to carbon metabolism and amino acid biosynthesis suggest deregulated carbon-nitrogen balance, which together indicate carbon sufficiency and relative depletion of nitrogen. Genes, deregulated together with prolamin genes, might represent candidates, which respond positively to assimilate supply and are related to sugar-starch metabolism, cytokinin and brassinosteroid functions, cell proliferation, and sugar/abscisic acid signaling. Genes showing inverse expression patterns represent potential negative regulators. It is concluded that HvSUT1 overexpression increases grain protein content but also deregulates the metabolic status of wheat (Triticum aestivum) grains, accompanied by up-regulated gene expression of positive and negative regulators related to sugar signaling and assimilate supply. In HOSUT grains, alternating stimulation of positive and negative regulators causes oscillatory patterns of gene expression and highlights the capacity and great flexibility to adjust wheat grain storage metabolism in response to metabolic alterations.


The direct effects of inattention and hyperactivity/impulsivity on peer problems and mediating roles of prosocial and conduct problem behaviors in a community sample of children.
This study tested whether children's symptoms of inattention and hyperactivity/impulsivity were associated with peer problems and whether these associations were mediated by conduct problems and prosocial behaviors. A community sample of 500 children, including 245 boys and 255 girls, who ranged in age from 6 to 9 years (M = 7.6, SD = 0.91) were recruited. Teachers' report of children's inattention, hyperactivity/impulsivity, conduct problems, prosocial behaviors, and peer problems was collected. Symptoms of inattention and hyperactivity/impulsivity were significantly positively associated with peer problems. Conduct problems were associated with more peer problems and prosocial behaviors with less peer problems. Conduct problems and prosocial behaviors partially mediated the association between hyperactivity/impulsivity and peer problems and fully mediated the inattention-peer problems association. Findings show that prosocial behaviors and conduct problems are important variables that account for some of the negative impact of symptoms of inattention and hyperactivity/impulsivity on peer functioning.


Urinary dysfunction in early and untreated Parkinson's disease.
Urinary dysfunction is common in Parkinson's disease (PD); however, little is known about urinary dysfunction in early and untreated PD patients. Fifty consecutive untreated PD patients (mean age, 66.7; mean disease duration, 23.6 months; and mean Hoehn & Yahr scale, 1.9) were recruited; those with other conditions that might have influenced urinary function were excluded. Patients were evaluated using a urinary questionnaire and urodynamic studies. Sixty-four per cent complained of urinary symptoms (storage, 64.0%; voiding, 28.0%). Urodynamic studies showed abnormal findings in the storage phase in 84%, with detrusor overactivity (DO) and increased bladder sensation without DO in 58.0% and 12.0% of patients, respectively. In the voiding phase, detrusor underactivity, impaired urethral relaxation such as detrusor sphincter dyssynergia, and bladder outlet obstruction were present in 50.0%, 8.0% and 16% of patients, respectively. In patients with both storage and voiding phase abnormalities, DO+detrusor underactivity was the most common finding. Few patients experienced urge incontinence and/or quality-of-life impairment owing to urinary dysfunction; none had low-compliance bladder or abnormal anal-sphincter motor unit potential. These urinary symptoms and urodynamic findings were not correlated with gender, disease severity or motor symptom type. Urinary dysfunction, manifested primarily as storage disorders with subclinical voiding disorders and normal anal-sphincter electromyography, occurs in early and untreated PD patients. In cases with severe voiding disorder and/or abnormal anal-sphincter electromyography, other diagnoses should be considered.


An update on sickle cell nephropathy.
Sickle cell disease (SCD) is a major health problem in many countries. Sickle cell nephropathy (SCN) is now a well-characterized entity with specific manifestations, risk factors and prognosis. The presence of sickled erythrocytes in the renal medullary vessels is the hallmark of the disease with a variety of renal complications. Renal manifestations of SCD include renal ischemia, microinfarcts, renal papillary necrosis and renal tubular abnormalities with variable clinical presentations. Proximal tubule dysfunction generally impairs urinary concentration, while more distal tubule dysfunction may impair potassium excretion, leading to hyperkalemia. Glomerular disease with proteinuria may develop due to ischemia and results in a compensatory increase in the renal blood flow and glomerular filtration rate; such hyperfiltration, combined with glomerular hypertrophy, probably contributes to glomerulosclerosis. Acute and chronic kidney disease are the expected outcomes of the disease. Both dialysis and kidney transplantation are effective renal replacement therapies for end-stage renal disease due to SCN, with a higher advantage for transplantation. Whether bone marrow transplantation in the early stage of the disease can halt the progression of SCN is unknown and awaits clinical studies.


Abnormal cytokine serum levels correlate with impaired cellular immune responses after surgery.
Serum levels of the interleukins (IL)-2, -1 beta, and -6, tumor-necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2) were measured serially before and after operation in patients undergoing various surgical procedures. Peripheral blood mononuclear cells (PBMC) from the same patients were analyzed before and after surgery for proliferative responses in the autologous mixed lymphocyte reaction (AMLR) and for cytolytic activity against the natural killer (NK)-sensitive K562 cell line. In patients who had major surgery, a decrease in IL-2 levels and increases in IL-1 beta, TNF-alpha, IL-6, and PGE2 levels were observed up to 9 days after the operation compared to those of the preoperative values. Decreased AMLR responses and NK activity were also observed in PBMC collected 5 days after surgery. All these changes were more intense in patients who had undergone major surgical procedures of increasing severity (i.e., cancer patients). Similar, although weaker, changes in cytokine serum levels, AMLR responses, and NK activity were also observed in patients undergoing minor surgery. Our data suggest that changes in cytokine serum levels may cause cellular immune dysfunctions, particularly in patients undergoing major surgery, and provide the basis for immune intervention in order to avoid infections occurring after major surgery.


Novel energy conservation strategies and behaviour of Pelotomaculum schinkii driving syntrophic propionate catabolism.
Under methanogenic conditions, short-chain fatty acids are common byproducts from degradation of organic compounds and conversion of these acids is an important component of the global carbon cycle. Due to the thermodynamic difficulty of propionate degradation, this process requires syntrophic interaction between a bacterium and partner methanogen; however, the metabolic strategies and behaviour involved are not fully understood. In this study, the first genome analysis of obligately syntrophic propionate degraders (Pelotomaculum schinkii HH and P. propionicicum MGP) and comparison with other syntrophic propionate degrader genomes elucidated novel components of energy metabolism behind Pelotomaculum propionate oxidation. Combined with transcriptomic examination of P. schinkii behaviour in co-culture with Methanospirillum hungatei, we found that formate may be the preferred electron carrier for P. schinkii syntrophy. Propionate-derived menaquinol may be primarily re-oxidized to formate, and energy was conserved during formate generation through newly proposed proton-pumping formate extrusion. P. schinkii did not overexpress conventional energy metabolism associated with a model syntrophic propionate degrader Syntrophobacter fumaroxidans MPOB (i.e., CoA transferase, Fix and Rnf). We also found that P. schinkii and the partner methanogen may also interact through flagellar contact and amino acid and fructose exchange. These findings provide new understanding of syntrophic energy acquisition and interactions.


Exploring risk perception and attitudes to miscarriage and congenital anomaly in rural Western Kenya.
Understanding the socio-cultural context and perceptions of adverse pregnancy outcomes is important for informing the best approaches for public health programs. This article describes the perceptions, beliefs and health-seeking behaviours of women from rural western Kenya regarding congenital anomalies and miscarriages. Ten focus group discussions (FGDs) were undertaken in a rural district in western Kenya in September 2010. The FGDs included separate groups consisting of adult women of childbearing age, adolescent girls, recently pregnant women, traditional birth attendants and mothers of children with a birth defect. Participants were selected purposively. A deductive thematic framework approach using the questions from the FGD guides was used to analyse the transcripts. There was substantial overlap between perceived causes of miscarriages and congenital anomalies and these were broadly categorized into two groups: biomedical and cultural. The biomedical causes included medications, illnesses, physical and emotional stresses, as well as hereditary causes. Cultural beliefs mostly related to the breaking of a taboo or not following cultural norms. Mothers were often stigmatised and blamed following miscarriage, or the birth of a child with a congenital anomaly. Often, women did not seek care following miscarriage unless there was a complication. Most reported that children with a congenital anomaly were neglected either because of lack of knowledge of where care could be sought or because these children brought shame to the family and were hidden from society. The local explanatory model of miscarriage and congenital anomalies covered many perceived causes within biomedical and cultural beliefs. Some of these fuelled stigmatisation and blame of the mother. Understanding of these beliefs, improving access to information about the possible causes of adverse outcomes, and greater collaboration between traditional healers and healthcare providers may help to reduce stigma and increase access to formal healthcare providers.


The influence of surround suppression on adaptation effects in primary visual cortex.
Adaptation, the prolonged presentation of stimuli, has been used to probe mechanisms of visual processing in physiological, imaging, and perceptual studies. Previous neurophysiological studies have measured adaptation effects by using stimuli tailored to evoke robust responses in individual neurons. This approach provides an incomplete view of how an adapter alters the representation of sensory stimuli by a population of neurons with diverse functional properties. We implanted microelectrode arrays in primary visual cortex (V1) of macaque monkeys and measured orientation tuning and contrast sensitivity in populations of neurons before and after prolonged adaptation. Whereas previous studies in V1 have reported that adaptation causes stimulus-specific suppression of responsivity and repulsive shifts in tuning preference, we have found that adaptation can also lead to response facilitation and shifts in tuning toward the adapter. To explain this range of effects, we have proposed and tested a simple model that employs stimulus-specific suppression in both the receptive field and the spatial surround. The predicted effects on tuning depend on the relative drive provided by the adapter to these two receptive field components. Our data reveal that adaptation can have a much richer repertoire of effects on neuronal responsivity and tuning than previously considered and suggest an intimate mechanistic relationship between spatial and temporal contextual effects.


How do supply-side factors influence informal payments for healthcare? The case of HIV patients in Cameroon.
Direct out-of-pocket payments for healthcare continue to be a major source of health financing in low-income and middle-income countries. Some of these direct payments take the form of informal charges paid by patients to access the needed healthcare services. Remarkably, however, little is known about the extent to which these payments are exercised and their determinants in the context of Sub-Saharan Africa. This study attempts therefore to shed light on the role of supply-side factors in the occurrence of informal payments while accounting for the demand-side factors. The study relies on data taken from a nationally representative survey conducted among people living with HIV/AIDS in Cameroon. A multilevel mixed-effect logistic model is employed to identify the factors associated with the incidence of informal payments. Results reveal that circa 3.05% of the surveyed patients incurred informal payments for the consultations made on the day of the survey. The amount paid informally represents up to four times the official tariff. Factors related to the following: (i) human resource management of the health facilities (e.g., task shifting); (ii) health professionals' perceptions vis-à-vis the remunerations of HIV care provision; and (iii) reception of patients (e.g., waiting time) significantly influence the probability of incurring informal payments. Also of note, the type of healthcare facilities is found to play a role: informal payments appear to be significantly lower in private non-profit facilities compared with those belonging to public sector. Our findings allude to some policy recommendations that can help reduce the incidence of informal payments.


Comparison of targeted peptide quantification assays for reductive dehalogenases by selective reaction monitoring (SRM) and precursor reaction monitoring (PRM).
Targeted absolute protein quantification yields valuable information about physiological adaptation of organisms and is thereby of high interest. Especially for this purpose, two proteomic mass spectrometry-based techniques namely selective reaction monitoring (SRM) and precursor reaction monitoring (PRM) are commonly applied. The objective of this study was to establish an optimal quantification assay for proteins with the focus on those involved in housekeeping functions and putative reductive dehalogenase proteins from the strictly anaerobic bacterium Dehalococcoides mccartyi strain CBDB1. This microbe is small and slow-growing; hence, it provides little biomass for comprehensive proteomic analysis. We therefore compared SRM and PRM techniques. Eleven peptides were successfully quantified by both methods. In addition, six peptides were solely quantified by SRM and four by PRM, respectively. Peptides were spiked into a background of Escherichia coli lysate and the majority of peptides were quantifiable down to 500 amol absolute on column by both methods. Peptide quantification in CBDB1 lysate resulted in the detection of 15 peptides using SRM and 14 peptides with the PRM assay. Resulting quantification of five dehalogenases revealed copy numbers of <10 to 115 protein molecules per cell indicating clear differences in abundance of RdhA proteins during growth on hexachlorobenzene. Our results indicated that both methods show comparable sensitivity and that the combination of the mass spectrometry assays resulted in higher peptide coverage and thus more reliable protein quantification.


Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice.
Mesenchymal stem cells (MSCs) have the inherent ability to migrate to multiple organs and to exert immunosuppressive activity. The aim of this study was to investigate the anti-arthritogenic effects of interleukin (IL)-10-transduced MSCs (IL-10-MSC) on the development of inflammatory arthritis. DBA/1 mice were immunized with type II collagen (CII) to induce inflammatory arthritis and then injected weekly three times with IL-10-MSCs 21 days after primary immunization. Control mice received vehicle or MSCs alone. Serum anti-CII antibody and T cell response to CII were determined. The results showed that cultured IL-10-MSCs were able to secrete high amounts of IL-10 in vitro. Injection of IL-10-MSCs decreased the severity of arthritis significantly. However, there was no difference in arthritis severity between mice treated with MSC and vehicle alone. Anti-CII antibody titres in the sera and T cell proliferative response to CII in lymph node cells were decreased significantly in mice treated with IL-10-MSCs compared with vehicle-treated mice. Serum IL-6 level was also decreased by the administration of IL-10-MSCs. In contrast, spleen cells of IL-10-MSC-treated mice produced higher amounts of IL-4 than those of control mice. Interestingly, although not as potent as IL-10-MSCs, injection of naive MSCs alone decreased serum levels of IL-6 and anti-CII antibody, while increasing IL-4 production from cultured splenic cells. Taken together, systemic administration of genetically modified MSCs overexpressing IL-10 inhibits experimental arthritis not only by suppressing autoimmune response to CII but also by regulating cytokine production, and thus would be a new strategy for treating rheumatoid arthritis.


Increased slow wave sleep with 5-HT2 receptor antagonists: detection by ambulatory EEG recording and automatic sleep stage analysis.
The effect on slow wave sleep (SWS) of 5-HT antagonists with different affinities for 5-HT(1) and 5-HT(2) receptors was investigated using ambulatory EEG monitoring in normal volunteers. The selective 5-HT( 2) antagonists, ritanserin and cypropheptadine, increased SWS while the non-selective 5-HT antagonist metergoline did not. The histamine H( 1)-receptor antagonist, mepyramine, was similarly without effect on SWS. These findings suggest that home ambulatory monitoring with automatic sleep stage analysis may be useful in detecting the effect of selective 5-HT( 2) receptor antagonists on SWS.


Misreporting of dietary energy intake in adolescents.
To examine the prevalence of under and overreporting of energy intake in adolescents and their associated factors. Cross-sectional study with 96 postpubertal adolescents (47 normal-weight and 49 obese), mean age of 16.6±1.3 years. Weight and height were measured, and body mass index was calculated. Body composition was assessed by dual energy X-ray absorptiometry. Dietary intake was evaluated by a 3-day dietary record. Biochemical assessment was performed (serum total cholesterol, LDL-cholesterol, HDL-cholesterol, plasma glucose, and insulin). Underreporters reported energy intake < 1.35 x basal metabolic rate (BMR), whereas overreporters reported energy intake > 2.4 x BMR. Energy intake misreporting (under or overreporting) was identified in 65.6% of adolescents (64.6 and 1% of under and overreporting, respectively). Obese adolescents were 5.0 times more likely to underreport energy intake (95%CI 2.0-12.7) than normal-weight participants. Underreporters showed higher rates of insufficient intake of carbohydrate (19.3 vs. 12.1%, p = 0.046) and lipids (11.3 vs. 0%, p < 0.001) than plausible reporters. Cholesterol intake was also lower in underreporters (p = 0.017). There were no significant differences in body composition and biochemical parameters in relation to misreporting. The results obtained demonstrated a high percentage of misreporting of energy intake among adolescents, especially among obese subjects, which suggests that energy-adjusted nutrient intake values should be employed in diet-disease risk analysis in order to contribute to a reduction in errors associated with misreporting.


Stereotyped behaviour in children with autism and intellectual disability: an examination of the executive dysfunction hypothesis.
Increasing attention has been paid to the executive dysfunction hypothesis argued to underpin stereotyped behaviour in autism. The aim of this study is to investigate one component of this model, that stereotyped behaviours are related to impaired generativity and compromised behavioural inhibition, by examining whether episodes of these behaviours terminate naturally without external intervention. Using a naturalistic observational methodology the stereotyped behaviours of six participants with autism were recorded in real time over periods ranging from 3.59 to 9.20 h. Data were also recorded for teaching staff interactions with participants and environmental settings (one-to-one, group and freetime). In comparison with one-to-one settings stereotyped behaviours were more frequent when participants were in freetime settings with the exception of one participant. For the termination of stereotyped behaviours these behaviours stopped with no ongoing physical or verbal adult contact being evident for a median of 73.25% of the time. Additionally, for a median of 89.40% of the time stereotyped behaviour stopped without the initiation of adult contact. The termination of bouts of stereotyped behaviour was frequently not associated with any adult contact and thus this form of external intervention. This finding warrants explanation by extending the hypothesis that compromised impaired generativity and behavioural inhibition offers a complete explanation of stereotyped behaviours.


Descartes the doctor: rationalism and its therapies.
During the Scientific Revolution one important gauge of the quality of reformed natural philosophical knowledge was its ability to produce a more effective medical practice. Indeed, it was sometimes thought that philosophers who pretended to possess new and more potent philosophical knowledge might display that possession in personal health and longevity. Rene Descartes repeatedly wrote that a better medical practice was a major aim of his philosophical enterprise. He said that he had made important strides towards achieving that aim, on that basis, he offered practical medical advice to others and advertised the expectation that, taking his own advice, he would live a very long time. This paper describes what Cartesian medicine looked like in practice and what that practice owed to the power of modernist Reason.


Development and phenotypic characterization of a high density in vitro model of auricular chondrocytes with applications in reconstructive plastic surgery.
Cultivation of phenotypically stable auricular chondrocytes will have applications in autologous chondrocyte transplantation and reconstructive surgery of cartilage. Chondrocytes grown in monolayer culture rapidly dedifferentiate assuming a fibroblast-like morphology and lose their cartilage-specific pattern of gene expression. Three-dimensional high-density culture models mimic more closely the in vivo conditions of cartilage. Therefore, this study was undertaken to test whether the high-density cultures might serve as a suitable model system to acquire phenotypically and functionally differentiated auricular chondrocytes from porcine cartilage. Freshly isolated porcine auricular chondrocytes were cultured for 7 passages in monolayer culture. From each passage (passage 0 and 1-7) cells were introduced to high-density cultures and examined by transmission electron microscopy. Western blotting was used to analyse the expression of cartilage-specific markers, such as collagen type II and cartilage specific proteoglycan, fibronectin, cell adhesion and signal transduction receptor beta1-integrin, matrix metalloproteinases (MMP-9, MMP-13), cyclo-oxygenase (COX)-2 and the apoptosis commitment marker, activated caspase-3. When dedifferentiated auricular chondrocytes from monolayer passages 0-4 were cultured in high-density culture, they recovered their chondrocytic phenotype and formed cartilage nodules surrounded by fibroblast-like cells and synthesised collagen type II, proteoglycans, fibronectin and beta1-integrins. However, chondrocytes from monolayer passages 5-7 did not redifferentiate to chondrocytes even when transferred to high-density culture, and did not synthesize a chondrocyte-specific extracellular matrix. Instead, they produced increasing amounts of MMP-9, MMP-13, COX-2, activated caspase-3 and underwent apoptosis. Three-dimensional high-density cultures may therefore be used to obtain sufficient quantities of fully differentiated auricular chondrocytes for autologous chondrocyte transplantation and reconstructive plastic surgery.


Interaction between a coating-borne peptide of the Brassica pollen grain and stigmatic S (self-incompatibility)-locus-specific glycoproteins.
Methods are described for the removal of the sporophytic pollen grain coating of Brassica oleracea and for the isolation of coat polypeptides. The coat contains a small number of proteins ranging from 6 to 45 kDa. Many of the larger proteins are glycosylated, while all carry high positive charges resulting in pI values from 8.5 to 11. Polypeptides with pI values of 9.5, 9.0, and 8.5 possess strong esterase activity. No major differences could be detected in either pI values or molecular masses of pollen-coating polypeptides from grains carrying different sporophytically expressed S (self-incompatibility) alleles. Mixing pollen coat proteins with stigmatic extracts results in a conspicuous binding interaction involving female S-locus-specific and perhaps S-locus-related glycoproteins. This interaction, which is reversed by heating in the presence of SDS, results in an apparent charge shift of the female glycoprotein(s) of up to 2 pI units. The male participant in this interaction has been isolated by using a combination of fast protein liquid chromatography and reverse-phase HPLC and was shown to be a 7-kDa nonglycosylated peptide. Experiments with whole pollen cultured in vitro show challenge with stigmatic extracts to stimulate the release of gametophytic and sporophytic polypeptides and to result in the formation of a conspicuous interaction product, demonstrating the 7-kDa peptide to be freely available within the coating of pollen in vivo.


The Journey of Cultures Taken During Revision Joint Arthroplasty: Preanalytical Phase.
Background: Microbiological culture has been considered the standard for pathogen identification for decades. However, culture is a laborious, time consuming, imperfect and outdated process. This study aims to inform the orthopedic community of the steps and timing of routine culture processing. Methods: We prospectively tracked 103 cultures from 33 revision hip and knee arthroplasty patients between September 2017-February 2018. Times were recorded at intraoperative collection; time of pick up from OR, transportation time; arrival at the laboratory; culture processing and plating time; and time to final result reporting. Results: Of the 103 cultures, 45.6% were processed and incubated in less than two hours, and 54.4% greater than or equal to two hours. The mean time spent in the OR, during transport, and within the laboratory prior to incubation was 0:53, 0:06 and 1:12. The range of time that samples remained at each stage varied considerably in the OR (0:03-3:33), in transit(0:04-0:16), and in the lab prior to incubation(0:26-3:01). The proportion of the total time to incubation attributed to idle time samples spent in the OR after initial sampling was 40.0%. In contrast, transport to the laboratory represented 5.1% of the total time. Idle time in the laboratory represented the greatest share at 54.9%. Conclusion: There is significant variability in the time to transport, process and incubate culture samples. Almost half of the specimens were processed outside the 2-hour recommended window. Surgeons should be aware of idle time during processing and seek to optimize their institutional pathways to maximize culture yield.


Pilot testing of methods for evaluation of acupuncture for emesis during radiotherapy: a randomised single subject experimental design.
Many acupuncture studies are of weak methodological quality, possibly due to lack of pilot testing. This pilot study tested design features, including test of feasibility, compliance to treatment and data collection, level of blinding success and the patients' potential perceived effects of the treatment, in preparation for an efficacy study. A modified single subject experimental design was conducted. 10 cancer patients were randomised to verum penetrating acupuncture or non-penetrating sham needles for 30 min 2-3 times/week during radiotherapy over abdomen/pelvis. They answered test-retested emesis questions (r=0.527-1.0) covering nausea, vomiting, use of antiemetics, wellbeing and activities of daily living. Overall, the patients completed 98% of the 345 emesis-questionnaire days and 101 of the 115 offered treatments. All patients believed they received verum acupuncture. 10 patients experienced antiemetic effects, seven relaxation, five pain-reduction and five experienced sleep improvement. Two types of nausea questions showed absolute concordance (r=1.0) (n of observations=456). Nausea was experienced by one of five verum acupuncture treated patients (duration median 0% of the radiotherapy-days) and four of five sham acupuncture treated patients (duration median 24% of the radiotherapy-days). Patients experiencing nausea rated decreased wellbeing and performance of daily activities compared to patients free from nausea. All patients were blinded, complied with verum/sham treatments and data-collection, and believed they had effects of the received treatment. The methods for verum/sham treatment and data collection may thus be used in an adequately powered randomised controlled study of the effect of acupuncture for radiotherapy-induced emesis.


Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma.
Programmed death 1 (PD-1) pathway inhibitors have not been prospectively evaluated in patients with non-clear cell renal cell carcinoma (nccRCC). The phase II KEYNOTE-427 study (cohort B) was conducted to assess the efficacy and safety of single-agent pembrolizumab, a PD-1 inhibitor, in advanced nccRCC. Patients with histologically confirmed, measurable (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) nccRCC and no prior systemic therapy received pembrolizumab 200 mg intravenously once every 3 weeks for ≤ 24 months. The primary end point was objective response rate (ORR) per RECIST v1.1. Among enrolled patients (N = 165), 71.5% had confirmed papillary, 12.7% had chromophobe, and 15.8% had unclassified RCC histology. Most patients (67.9%) had intermediate or poor International Metastatic RCC Database Consortium risk status and tumors with programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (61.8%). The median time from enrollment to database cutoff was 31.5 months (range, 22.7-38.8). In all patients, the ORR was 26.7%. The median duration of response was 29.0 months; 59.7% of responses lasted ≥ 12 months. The ORR by CPS ≥ 1 and CPS < 1 status was 35.3% and 12.1%, respectively. The ORR by histology was 28.8% for papillary, 9.5% for chromophobe, and 30.8% for unclassified. Overall, the median progression-free survival was 4.2 months (95% CI, 2.9 to 5.6); the 24-month rate was 18.6%. The median overall survival was 28.9 months (95% CI, 24.3 months to not reached); the 24-month rate was 58.4%. Overall, 69.7% of patients reported treatment-related adverse events, most commonly pruritus (20.0%) and hypothyroidism (14.5%). Two deaths were treatment related (pneumonitis and cardiac arrest). First-line pembrolizumab monotherapy showed promising antitumor activity in nccRCC. The safety profile was similar to that observed in other tumor types.


Committee report: Considerations and recommendations for national guidance regarding the retention and use of residual dried blood spot specimens after newborn screening.
Newborn screening programs are state based with variable policies. Guidance regarding the retention, storage, and use of portions of newborn screening dried blood spots that remain after screening (residual specimens) was first published in 1996. Since then, newborn screening programs have paid increased attention to specimen storage and usage issues. Standard residual specimen uses include quality assurance and program evaluation, treatment efficacy, test refinement, and result verification. In all cases, privacy and security are primary concerns. In general, two distinct state practices regarding the storage and use of residual newborn screening specimens exist: (1) short-term storage (<3 years), primarily for standard program uses and (2) long-term storage (>18 years), for standard program uses and possible important public health research uses. Recently, there have been concerns in some consumer communities regarding both the potential uses of residual specimens and patient (newborn and family) privacy. To assist in policy improvements that can protect the individual's privacy and allow for important public health uses of residual newborn screening specimens, the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children has developed recommendations (with requested action by the Secretary where applicable). This report presents the Committee's recommendations and reviews the pertinent associated issues.


Evolution of Bradyrhizobium-Aeschynomene mutualism: living testimony of the ancient world or highly evolved state?
Until recently it had been well established that the initial step in legume-rhizobia symbioses was flavonoid and Nod factor (NF) signaling. However, NF-independent symbiosis is now known to occur between Bradyrhizobium and some species of Aeschynomene. Since its discovery, this unusual symbiotic system has attracted attention, and efforts have been devoted to revealing the NF-independent symbiotic mechanism, although the molecular mechanisms of nodule initiation still remain to be elucidated. NF-independent symbiosis is also interesting from the perspective of the evolution of legume-rhizobia symbiosis. In this mini-review, we discuss the current literature on the NF-independent symbiotic system in terms of phylogeny of the partners, infection, bacteroid differentiation, nodule structure, photosynthesis, endophytic features and model host plant. We also discuss NF-independent symbiosis, which is generally regarded to be more primitive than NF-dependent symbiosis, because the bacteria invade host plants via 'crack entry'. We propose three possible scenarios concerning the evolution of NF-independent symbiosis, which do not exclude the possibility that the NF-independent system evolved from NF-dependent interactions. Finally, we examine an interesting question on Bradyrhizobium-Aeschynomene mutualism, which is how do they initiate symbiosis without NF. Phylogenetic and genomic analyses of symbiotic and non-symbiotic bradyrhizobia with A. indica may be crucial to address the question, because of the very narrow phylogeny of natural endosymbionts without nod genes compared with other legume-rhizobia symbioses.


Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle.
The broad nature of insulin resistant glucose metabolism in skeletal muscle of patients with type 2 diabetes suggests a defect in the proximal part of the insulin signaling network. We sought to identify the pathways compromised in insulin resistance and to test the effect of moderate exercise on whole-body and cellular insulin action. We conducted euglycemic clamps and muscle biopsies on type 2 diabetic patients, obese nondiabetics and lean controls, with and without a single bout of exercise. Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1-association with PI 3-kinase defines a key step in insulin resistance.


Segment 4 and the left lateral segment regeneration pattern after resection of the middle hepatic vein in a living donor right hepatectomy.
Inclusion of the middle hepatic vein (MHV) with a right hepatectomy (RH) in live donor liver transplantation improves venous drainage of the anterior sector of the graft. Its long-term effects on donor left liver (LL) regeneration are not well described. Donors who underwent RH with MHV (MHV+, n = 12) were compared with donors who underwent RH with preservation of the MHV (MHV-, n = 24). Peri-operative complications and volume of the entire liver and individual segments were evaluated at 1 year post-donation. There was a trend towards a higher complication rate in the MHV+ group (41% versus 25%), without reaching statistical significance (P = 0.3). Males, high body mass index (BMI) and a smaller residual liver volume (RLV) were predictors for greater LL regeneration. MHV+ donors had impaired regeneration of segment 4 (S4) at 1 year, and compensatory greater left lateral segment regeneration. The absence of venous drainage of S4 (V4) to left hepatic vein (LHV) was a predictor of impaired S4 regeneration. Regeneration of S4 is impaired in MHV+ donors. Caution should be taken when considering MHV removal on donors with dominant S4, especially on those with potential increased demand for liver regeneration, such as males, higher BMI and a smaller RLV.


Poisson-like fluctuation patterns of revertants of leucine auxotrophy (leu-500) in Salmonella typhimurium caused by delay in mutant cell division.
Leu+ mutants from Salmonella typhimurium leu-500 strain MA412 arise at high frequencies and mutant colonies appear over a broad range of time on selective plates. This observation suggested that these Leu+ mutants might be induced or "directed."= If such a mechanism was responsible, mutants should originate on selective plates rather than in the preceding culture in nonselective conditions and should give rise to Poisson-like fluctuation curves upon plating of sister cultures on selective medium. Poisson-like distribution profiles were indeed observed for Leu+ mutants of S. typhimurium MA412. However, an explanation for the observed Poisson-like fluctuation patterns without a need for selection-induced mutations was found. Microscopical analysis and cell mass/viable count measurements showed that the size of Leu+ mutant cells was often much larger than those of nonmutants. This size difference was a stable characteristic of a large proportion of Leu+ mutants, was observed both in stationary and growing culture and did not measurably affect the division rates of the cells in nutrient broth. As the transition from normal-sized nonmutant to oversized mutant cells during the nonselective culture phase of the fluctuation experiment may have been accompanied by a period with no or few completed cell division cycles, the number of mutant offspring may have been smaller than that of sibling nonmutants. Such underrepresentation of mutants in the final culture is expected to give rise to Poisson-like fluctuation patterns without invoking "directed" mutations.


Habitus of home and traditional drinking: a qualitative analysis of reported middle-class alcohol use.
There is evidence that alcohol consumption among those in middle-class occupations consistently exceeds safe levels, yet there has been little research into why this occurs. This article explores the meanings associated with alcohol use among professional, managerial and clerical workers. Qualitative data were collected from five focus groups of male and female employees aged 21-55 (N =49: 32 male, 17 female). Each focus group was conducted on the premises of a medium-scale or large-scale employer, four public sector and one private sector, in the north-east of England. Using Bourdieu's concepts of 'habitus', 'capitals' and 'fields' we found that, among these middle-class occupational groups, alcohol use was associated with two habitus: a 'home drinking' habitus and a 'traditional drinking' habitus. Those of the home drinking habitus particularly used wine as a source of cultural capital and a means of distinction, whereas those in the traditional habitus consumed lager, beer and spirits to have fun in social settings. A small minority appeared to belong to a third, omnivorous, habitus where a wide range of alcoholic drinks were consumed in a variety of contexts. Existing public health initiatives to reduce alcohol consumption may require modification to accommodate a range of drinking cultures.


Combined spatial and non-spatial prior for inference on MRI time-series.
When modelling FMRI and other MRI time-series data, a Bayesian approach based on adaptive spatial smoothness priors is a compelling alternative to using a standard generalized linear model (GLM) on presmoothed data. Another benefit of the Bayesian approach is that biophysical prior information can be incorporated in a principled manner; however, this requirement for a fixed non-spatial prior on a parameter would normally preclude using spatial regularization on that same parameter. We have developed a Gaussian-process-based prior to apply adaptive spatial regularization while still ensuring that the fixed biophysical prior is correctly applied on each voxel. A parameterized covariance matrix provides separate control over the variance (the diagonal elements) and the between-voxel correlation (due to off-diagonal elements). Analysis proceeds using evidence optimization (EO), with variational Bayes (VB) updates used for some parameters. The method can also be applied to non-linear forward models by using a linear Taylor expansion centred on the latest parameter estimates. Applying the method to FMRI with a constrained haemodynamic response function (HRF) shape model shows improved fits in simulations, compared to using either the non-spatial or spatial-smoothness prior alone. We also analyse multi-inversion arterial spin labelling data using a non-linear perfusion model to estimate cerebral blood flow and bolus arrival time. By combining both types of prior information, this new prior performs consistently well across a wider range of situations than either prior alone, and provides better estimates when both types of prior information are relevant.


A Randomized Controlled Pilot Trial of Different Mobile Messaging Interventions for Problem Drinking Compared to Weekly Drink Tracking.
Recent evidence suggests that text messaging may help to reduce problem drinking as an extension to in-person services, but very little is known about the effectiveness of remote messaging on problem drinking as a stand-alone intervention, or how different types of messages may improve drinking outcomes in those seeking to moderate their alcohol consumption. We conducted an exploratory, single-blind randomized controlled pilot study comparing four different types of alcohol reduction-themed text messages sent daily to weekly drink self-tracking texts in order to determine their impact on drinking outcomes over a 12-week period in 152 participants (≈ 30 per group) seeking to reduce their drinking on the internet. Messaging interventions included: weekly drink self-tracking mobile assessment texts (MA), loss-framed texts (LF), gain-framed texts (GF), static tailored texts (ST), and adaptive tailored texts (TA). Poisson and least squares regressions were used to compare differences between each active messaging group and the MA control. When adjusting for baseline drinking, participants in all messaging groups except GF significantly reduced the number of drinks consumed per week and the number of heavy drinking days compared to MA. Only the TA and GF groups were significantly different from MA in reducing the number of drinking days. While the TA group yielded the largest effect sizes on all outcome measures, there were no significant differences between active messaging groups on any outcome measure. 79.6% of individuals enrolled in the study wanted to continue receiving messages for an additional 12 weeks at the end of the study. Results of this pilot study indicate that remote automated text messages delivered daily can help adult problem drinkers reduce drinking frequency and quantity significantly more than once-a-week self-tracking messages only, and that tailored adaptive texts yield the largest effect sizes across outcomes compared to MA. Larger samples are needed to understand differences between messaging interventions and to target their mechanisms of efficacy.


Comparative study of phase II biotransformation in rabbit ocular tissues.
To assess the biotransformational capability of ocular tissues in the rabbit, representative phase II enzymes were assayed in five tissues from the eye, and in the liver, kidney, and intestine. Within the eye, the iris/ciliary body exhibited the highest glutathione S-transferase activity, whereas the cornea possessed the highest specific activities for N-acetyl-, sulfo-, and UDP-glucuronosyl-transferases. Cornea, iris/ciliary body, choroid, and retina exhibited significant activities of p-aminobenzoic acid N-acetyltransferase, 2-naphthol sulfotransferase, and 1-chloro-2,4-dinitrobenzene glutathione S-transferase. Despite its size and protein content, lens displayed little or no biotransformational activity. Only the iris/ciliary body conjugated sulfobromophthalein with glutathione. UDP-glucuronsyltransferase activity varied depending on tested substrates and tissues. When compared to liver, kidney, or intestine, N-acetyltransferase activity in the iris/ciliary body nearly matched the rate measured in kidney, glutathione S-transferase activity in cornea and iris/ciliary body was nearly 70 and 89%, respectively, of the rate in intestine, and corneal sulfotransferase activity was greater than that in kidney. These data suggest that biotransformation pathways are present in the eye, and particularly in ocular tissues having adequate blood supply or interfacing with the external environment.


Suppression of hapten-specific delayed-type hypersensitivity responses in mice by idiotype-specific suppressor T cells after administration of anti-idiotypic antibodies.
Delayed-type hypersensitivity (DTH) responses specific for the phosphorylcholine (PC) hapten were induced in BALB/c mice by immunization with syngeneic peritoneal exudate cells (PEC) coupled with diazotized phenyl-phosphoryl-choline. PC-specific DTH responses were elicited in such immunized mice after footpad challenge with PC-derivatized syngeneic spleen cells. Moreover, PC-immune lymph node cells could passively transfer PC-specific DTH responses to naive BALB/c mice and it was possible to demonstrate that the cells responsible for such passively transferred responses were T lymphocytes. Because the T-15 idiotypic determinant displayed on the TEPC-15 PC-binding myeloma protein is known to be a dominant idiotype associated with anti-PC antibody responses in BALB/c mice, an analysis was made of the effects of anti-T-15 idiotypic antibodies on the induction and expression of murine PC-specific DTH responses. Repeated injections of anti-T-15 idiotypic antiserum, raised in A/J mice by immunization with TEPC-15 myeloma protein, into recipient BALB/c mice both immediately before and after sensitization with PC-PEC virtually abolished the development of PC-specific DTH responses. Although administration of anti-T-15 antiserum effectively inhibited the induction phase of PC-specific DTH responses, these anti-idiotypic antibodies had no suppressive activity at the effector phase of these responses. The inhibition observed with anti-T-15 antibodies was highly specific for the PC hapten, and for PC-specific DTH responses of BALB/c but not A/J mice. Studies were conducted to address the possibility that anti-Id treatment induced suppressor T lymphocytes capable of specifically inhibiting the activity of PC-specific T cells participating in DTH responses. The results demonstrate that idiotype-specific suppressor T cells are, indeed, induced by treatment with anti-Id; moreover, such suppressor T cells, once induced, are highly effective in abrogating both the induction and the effector phases of PC-specific T cell-mediated DTH responses in BALB/c mice.


Light control in a multicore fiber using the memory effect.
Endoscopic imaging through a multicore fiber (MCF) is widely used but is affected by pixelated images, which limits its resolution to a few micrometers. This is due to the spacing between the cores in the MCF, which is large enough to avoid core-to-core light coupling. Wavefront shaping techniques have been shown to focus light to a resolution finer than the inter core spacing, however a long calibration procedure is needed. Moreover the calibration depends on the optical fiber conformation. Here, we show a calibration method using only one digital hologram. The method is based on digital phase conjugation and the memory effect of the MCF to focus and scan a spot. In addition, we show how simple patterns can be projected using the same multicore fiber.


Long-wavelength properties of phase-field-crystal models with second-order dynamics.
The phase-field-crystal (PFC) approach extends the notion of phase-field models by describing the topology of the microscopic structure of a crystalline material. One of the consequences is that local variation of the interatomic distance creates an elastic excitation. The dynamics of these excitations poses a challenge: pure diffusive dynamics cannot describe relaxation of elastic stresses that happen through phonon emission. To this end, several different models with fast dynamics have been proposed. In this article we use the amplitude expansion of the PFC model to compare the recently proposed hydrodynamic PFC amplitude model with two simpler models with fast dynamics. We compare these different models analytically and numerically. The results suggest that in order to have proper relaxation of elastic excitations, the full hydrodynamical description of the PFC amplitudes is required.


64-slice computed tomographic angiography for the diagnosis of intermediate risk coronary artery disease: an evidence-based analysis.
In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html The objective of this report is to determine the accuracy of computed tomographic angiography (CTA) compared to the more invasive option of coronary angiography (CA) in the detection of coronary artery disease (CAD) in stable (non-emergent) symptomatic patients. CT ANGIOGRAPHY: CTA is a cardiac imaging test that assesses the presence or absence, as well as the extent, of coronary artery stenosis for the diagnosis of CAD. As such, it is a test of cardiac structure and anatomy, in contrast to the other cardiac imaging modalities that assess cardiac function. It is, however, unclear as to whether cardiac structural features alone, in the absence cardiac function information, are sufficient to determine the presence or absence of intermediate pretest risk of CAD. CTA technology is changing rapidly with increasing scan speeds and anticipated reductions in radiation exposure. Initial scanners based on 4, 8, 16, 32, and 64 slice machines have been available since the end of 2004. Although 320-slice machines are now available, these are not widely diffused and the existing published evidence is specific to 64-slice scanners. In general, CTA allows for 3-dimensional (3D) viewing of the coronary arteries derived from software algorithms of 2-dimensional (2D) images. The advantage of CTA over CA, the gold standard for the diagnosis of CAD, is that it is relatively less invasive and may serve as a test in determining which patients are best suited for a CA. CA requires insertion of a catheter through an artery in the arm or leg up to the area being studied, yet both tests involve contrast agents and radiation exposure. Therefore, the identification of patients for whom CTA or CA is more appropriate may help to avoid more invasive tests, treatment delays, and unnecessary radiation exposure. The main advantage of CA, however, is that treatment can be administered in the same session as the test procedure and as such, it's recommended for patients with a pre-test probability of CAD of ≥80%. The progression to the more invasive CA allows for the diagnosis and treatment in one session without the added radiation exposure from a previous CTA. The visibility of arteries in CTA images is best in populations with a disease prevalence, or pre-test probabilities of CAD, of 40% to 80%, beyond which patients are considered at high pre-test probability. Visibility decreases with increasing prevalence as arteries become increasingly calcified (coronary artery calcification is based on the Agaston score). Such higher risk patients are not candidates for the less invasive diagnostic procedures and should proceed directly to CA, where treatment can be administered in conjunction with the test itself, while bypassing the radiation exposure from CTA. CTA requires the addition of an ionated contrast, which can be administered only in patients with sufficient renal function (creatinine levels >30 micromoles/litre) to allow for the clearing of the contrast from the body. In some cases, the contrast is administered in patients with creatinine levels less than 30 micromoles/litre. A second important criterion for the administration of the CTA is patient heart rate, which should be less than 65 beats/min for the single source CTA machines and less than 80 beats/min for the dual source machines. To decrease heart rates to these levels, beta-blockers are often required. Although the accuracy of these two machines does not differ, the dual source machines can be utilized in a higher proportion of patients than the single source machines for patients with heart beats of up to 80 beats/min. Approximately 10% of patients are considered ineligible for CTA because of this inability to decrease heart rates to the required levels. Additional contra-indications include renal insufficiency as described above and atrial fibrillation, with approximately 10% of intermediate risk patients ineligible for CTA due these contraindications. The duration of the procedure may be between 1 and 1.5 hours, with about 15 minutes for the CTA and the remaining time for the preparation of the patient. CTA is licensed by Health Canada as a Class III device. Currently, two companies have licenses for 64-slice CT scanners, Toshiba Medical Systems Corporation (License 67604) and Philips Medical Systems (License 67599 and 73260). How does the accuracy of CTA compare to the more invasive CA in the diagnosis of CAD in symptomatic patients at intermediate risk of the disease?How does the accuracy for CTA compare to other modalities in the detection of CAD? A literature search was performed on July 20, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 until July 20, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any relevant studies not identified through the search. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. English language articles and English or French-language HTAs published from January 1, 2004 to July 20, 2009.Randomized controlled trials (RCTs), non-randomized clinical trials, systematic reviews and meta-analyses.Studies of symptomatic patients at intermediate pre-test probability of CAD.Studies of single source CTA compared to CA for the diagnosis of CAD.Studies in which sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) could be established. HTAs, SRs, clinical trials, observational studies. Non-English studies.Pediatric populations.Studies of patients at low or high pre-test probability of CAD.Studies of unstable patients, e.g., emergency room visits, or a prior diagnosis of CAD.Studies in patients with non-ischemic heart disease.Studies in which outcomes were not specific to those of interest in this report.Studies in which CTA was not compared to CA in a stable population. OUTCOMES OF INTEREST): CAD defined as ≥50% stenosis. COMPARATOR: Coronary angiography. MEASURES OF INTEREST: Sensitivity, specificity;Negative predictive value (NPV), positive predictive value (PPV);Area under the curve (AUC) and diagnostic odds ratios (DOR). RESULTS OF LITERATURE SEARCH AND EVIDENCE-BASED ANALYSIS: The literature search yielded two HTAs, the first published by MAS in April 2005, the other from the Belgian Health Care Knowledge Centre published in 2008, as well as three recent non-randomized clinical studies. The three most significant studies concerning the accuracy of CTA versus CA are the CORE-64 study, the ACCURACY trial, and a prospective, multicenter, multivendor study conducted in the Netherlands. Five additional non-randomized studies were extracted from the Belgian Health Technology Assessment (2008). (ABSTRACT TRUNCATED)


Adult obese mice suffer from chronic secondary brain injury after mild TBI.
A traumatic brain injury (TBI) event is a devastating injury to the brain that may result in heightened inflammation, neurodegeneration, and subsequent cognitive and mood deficits. TBI victims with co-morbidities such as heart disease, diabetes, or obesity may be more vulnerable to the secondary brain injury that follows the initial insult. Compared to lean individuals, obese subjects tend to have worse clinical outcomes and higher mortality rates after trauma. To elucidate whether obesity predisposes individuals to worse outcomes after TBI, we subjected adult lean and obese male/female mice to a mild TBI. The injury was administered using a controlled skull impact (CSI) device. Lean or obese 6-month-old C57 BL/6 mice were subjected once to a mild TBI. Additionally, at day 30 after injury, both the lean and obese mice were tested for increased anxiety using the open field test. At day 30 after TBI, compared to the lean mice, we found heightened microglial (MG) activation in the cerebral cortex, corpus callosum, and hypothalamus. Another compelling finding was that, compared to the non-injured obese male control mice, the obese TBI mice had a decrease in the rate of weight gain and serum corticosterone levels at day 30 after injury. Additionally, the injured obese mice displayed higher levels of anxiety as determined by a significant decrease in time spent in the non-peripheral zones in the open field test. In contrast to the obese males, the obese female mice did not exhibit increases in the number of active MG in the brain, changes in weight gain/corticosterone levels, or increased anxiety at day 30 after TBI. The data presented here suggests that obese mice have worse outcomes compared to lean mice after mild TBI. Also, the obese males have worse outcomes than the injured female mice. This data may explain the sequela of chronic secondary brain injury in obese adults after a single mild TBI. Also, this report may help shape how the overweight/obese populations are monitored over the days and months following a TBI.


The effect of omega-3 polyunsaturated fatty acid supplementation on emotional dysregulation, oppositional behaviour and conduct problems in ADHD: A systematic review and meta-analysis.
A number of randomised controlled trials report a beneficial effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on emotional lability (EL) and related domains (e.g. oppositional behaviour, conduct problems). Given that n-3 PUFA supplementation shows a significant effect on reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) and that EL and related behaviours commonly co-occurs with ADHD, it is important that there is a more conclusive picture as to the effect of n-3 PUFA on these co-occurring clinical domains. Databases (Ovid Medline, Embase, Psychinfo) were searched for trials assessing the effects of n-3 PUFA on EL, oppositional behaviour, aggression and conduct problems. We included trials in children who had ADHD or a related neurodevelopmental disorder. Of the 1775 identified studies, 10 were included in the meta-analysis. In the primary analyses n-3 PUFA supplementation did not show improvements in measures of EL, oppositional behaviour, conduct problems or aggression. However subgroup analyses of higher quality studies and those meeting strict inclusion criteria found a significant reduction in EL and oppositional behaviour. A number of treatment effects may have failed to reach statistical significance due to small sample sizes and within and between study heterogeneity in terms of design and study participants. These results exclude the possibility of moderate to large effects. They provide suggestive evidence of small effects of n-3 PUFA on reducing EL and oppositional behaviour in subgroups of children with ADHD.


Phlebotomine sand flies (Diptera: Psychodidae) of the Palestinian West Bank: potential vectors of leishmaniasis.
Two forms of leishmaniasis are endemic to the Jenin district in the northern region of the West Bank. Visceral leishmaniasis (VL), caused by Leishmania infantum, mainly affects infants. Cutaneous leishmaniasis (CL) affects a broader age group and is probably caused by L. tropica. Although the Jenin district is the most important focus of leishmaniasis in the West Bank, the sand fly fauna of the area has never been studied in a systematic manner. We collected base-line data on sand fly species, their distribution, and their feeding preferences to facilitate risk assessments for contracting leishmaniasis. Light traps, sticky traps, insecticide knockdown collections, aspirator, and human-landing collections were used. A total of 4,082 sand flies was collected in foci of confidence limits and/or VL between June and December 1998. Nine Phlebotomus species representing seven subgenera were identified: P. (Larroussius) perfiliewi transcaucasicus Perfil'ev, P. (La.) tobbi Adler & Theodor, P. (La.) mascitti canaaniticus Adler & Theodor, P. (La.) mascitti mascitti Grassi, P. (La.) syriacus Adler & Theodor, P. (Phlebotomus) papatasi Scopoli, P. (Synphlebotomus) s.p., P. (Paraphlebotomus) sergenti Parrot, P. (Par.) jacusieli Theodor, P. (Adlerius) halepensis Theodor. Two other Phlebotomus subspecies, P. (La.) major major Annandale, P. (La .) neglectus Tonnoir, require confirmation. In addition, four species of the closely related genus, Sergentomyia were also found: S. (Sergentomyia) theodori Parrot, S. (S.) fallax Parrot, S. (Sintonitus) tiberiadis Adler, Theodor & Lourie, S. (Sin.) christophersi Sinton. Among five species of sand flies collected on human bait, P. papatasi constituted approximately 90% followed by P. major syriacus (8%) and P. mascitti (2%). Sand fly human-biting activity occurred through the night and it was highest between 2400 and 0300 hours. P. papatasi. P. perfiliewi, P. major and P. tobbi were the more endophilic species constituting 93% of all flies caught indoors. Seven Phlebotomus spp. constitute potential vectors of leishmaniasis but the most probable ones are as follows: P. papatasi the main human-biting species, a recognized vector of L. major (CL), P. sergenti, L. tropica (CL) and P. syriacus, L. infantum (VL).


Characterization of four plasma membrane aquaporins in tulip petals: a putative homolog is regulated by phosphorylation.
We suggested previously that temperature-dependent tulip (Tulipa gesneriana) petal movement that is concomitant with water transport is regulated by reversible phosphorylation of an unidentified plasma membrane intrinsic protein (PIP). In this study, four full-length cDNAs of PIPs from tulip petals were identified and cloned. Two PIPs, namely TgPIP1;1 and TgPIP1;2, are members of the PIP1 subfamily, and the remaining two PIPs, namely TgPIP2;1 and TgPIP2;2, belong to the PIP2 subfamily of aquaporins and were named according to the nomenclature of PIP genes in plants. Of these four homologs, only TgPIP2;2 displayed significant water channel activity in the heterologous expression assay using Xenopus laevis oocytes. The water channel activity of this functional isoform was abolished by mercury and was affected by inhibitors of protein kinase and protein phosphatase. Using a site-directed mutagenesis approach to substitute several serine residues with alanine, and assessing water channel activity using the methylotrophic yeast Pichia pastoris expression assay, we showed that Ser35, Ser116 and Ser274 are the putative phosphorylation sites of TgPIP2;2. Real-time reverse transcription-PCR analysis revealed that the transcript levels of TgPIP1;1 and TgPIP1;2 in tulip petals, stems, leaves, bulbs and roots are very low when compared with those of TgPIP2;1 and TgPIP2;2. The transcript level of TgPIP2;1 is negligible in roots, and TgPIP2;2 is ubiquitously expressed in all organs with significant transcript levels. From the data reported herein, we suggest that TgPIP2;2 might be modulated by phosphorylation and dephosphorylation for regulating water channel activity, and may play a role in transcellular water transport in all tulip organs.


Triage of women with low-grade cervical lesions--HPV mRNA testing versus repeat cytology.
In Norway, women with low-grade squamous intraepithelial lesions (LSIL) are followed up after six months in order to decide whether they should undergo further follow-up or be referred back to the screening interval of three years. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures. At the University Hospital of North Norway, repeat cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in triage of women with ASC-US and LSIL. In this study, women with LSIL cytology in the period 2005-2008 were included (n = 522). Two triage methods were evaluated in two separate groups: repeat cytology only (n = 225) and HPV mRNA testing in addition to repeat cytology (n = 297). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as the study endpoint. Of 522 women with LSIL, 207 had biopsies and 125 of them had CIN2+. The sensitivity and specificity of repeat cytology (ASC-US or worse) were 85.7% (95% confidence interval (CI): 72.1, 92.2) and 54.4 % (95% CI: 46.9, 61.9), respectively. The sensitivity and specificity of the HPV mRNA test were 94.2% (95% CI: 88.7, 99.7) and 86.0% (95% CI: 81.5, 90.5), respectively. The PPV of repeat cytology was 38.4% (95% CI: 29.9, 46.9) compared to 67.0% (95% CI: 57.7, 76.4) of the HPV mRNA test. HPV mRNA testing was more sensitive and specific than repeat cytology in triage of women with LSIL cytology. In addition, the HPV mRNA test showed higher PPV. These data indicate that the HPV mRNA test is a better triage test for women with LSIL than repeat cytology.


Global conservation outcomes depend on marine protected areas with five key features.
In line with global targets agreed under the Convention on Biological Diversity, the number of marine protected areas (MPAs) is increasing rapidly, yet socio-economic benefits generated by MPAs remain difficult to predict and under debate. MPAs often fail to reach their full potential as a consequence of factors such as illegal harvesting, regulations that legally allow detrimental harvesting, or emigration of animals outside boundaries because of continuous habitat or inadequate size of reserve. Here we show that the conservation benefits of 87 MPAs investigated worldwide increase exponentially with the accumulation of five key features: no take, well enforced, old (>10 years), large (>100 km(2)), and isolated by deep water or sand. Using effective MPAs with four or five key features as an unfished standard, comparisons of underwater survey data from effective MPAs with predictions based on survey data from fished coasts indicate that total fish biomass has declined about two-thirds from historical baselines as a result of fishing. Effective MPAs also had twice as many large (>250 mm total length) fish species per transect, five times more large fish biomass, and fourteen times more shark biomass than fished areas. Most (59%) of the MPAs studied had only one or two key features and were not ecologically distinguishable from fished sites. Our results show that global conservation targets based on area alone will not optimize protection of marine biodiversity. More emphasis is needed on better MPA design, durable management and compliance to ensure that MPAs achieve their desired conservation value.


Madness, fear, and control in Bangladesh: clashing bodies of power/knowledge.
This article presents an understanding of how Bangladeshis cope with madness in relation to two assumptions: that systems of knowledge and of power are coterminous, and that actors in medical encounters draw on incompatible and unequal bodies of knowledge-power I first offer a perspective on psychiatry, emotion, and discourse in Bangladesh as a society increasingly caught up in globalizing modernity. Then I present two types of data to illumine tensions between various attempts to control the fears associated with schizophrenia. The first is a set of exchanges in the advice column of a new popular psychiatry magazine in Bangladesh that inculcate new perspectives on self Those who write to the editors signal their fears of what might, in the end, be impossible to control. Answers from the psychiatrists who edit the magazine reflect discourses circulating on the web, at international conferences, and at the institutions in the United Kingdom and the United States where one of them received his training. The second data set consists of video recordings of persons diagnosed with schizophrenia interacting with families and/or psychiatrists. In part because of knowledge-power asymmetries, attempts at controlling fears surrounding schizophrenia in these four cases fail to address the depths, tacitness, embodiment, and narrative embedding of anxieties experienced by all parties. I close with an argument about the implications for theories of culture and of medical pluralism that arise from cases in which the local Self is experienced from the perspective of powerful Others.


Percutaneous core needle biopsy versus open biopsy in diagnostics of bone and soft tissue sarcoma: a retrospective study.
Biopsy is a crucial step within the diagnostic cascade in patients with suspected bone or soft tissue sarcoma. Open biopsy is still considered the gold standard. However, recent literature suggests similar results for percutaneous biopsy techniques. Therefore, the aim of this retrospective analysis was to compare open and percutaneous core needle biopsy (CNB) regarding their accuracy in diagnosis of malignant musculoskeletal lesions. From January 2007 to December 2009, all patients with suspected malignant primary bone or soft tissue tumour undergoing a percutaneous CNB or open biopsy and a subsequent tumour resection at our department were identified and enrolled. Sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV) and diagnostic accuracy were calculated for both biopsy techniques and compared using Fisher's exact test. A total of 77 patients were identified and enrolled in this study. Sensitivity, specificity, PPV, NPV and diagnostic accuracy were 100% for CNB in bone tumours. Sensitivity (95.5%), NPV (91.7%) and diagnostic accuracy (93.3%) for open biopsy in bone tumours showed slightly inferior results without statistical significance (p > 0.05). In soft tissue tumours favourable results were obtained in open biopsies compared to CNB with differences regarding sensitivity (100% vs. 81.8%, p = 0.5), NPV (100% vs. 50%, p = 0.09) and diagnostic accuracy (100% vs. 84.6%, p = 0,19) without statistical significance. The overall diagnostic accuracy was 92.9% for CNB and 98.0% for open biopsy (p = 0.55). A specific diagnosis could be obtained in 84.2% and 93.9%, respectively (p = 0.34). In our study we found moderately inferior results for the percutaneous biopsy technique compared to open biopsy in soft tissue tumours whereas almost equal results were obtained for both biopsy techniques for bone tumours. Thus, CNB is a safe, minimal invasive and cost-effective technique for diagnosing bony lesions. In soft tissue masses, the indication for percutaneous core needle biopsy needs to be made carefully by an experienced orthopaedic oncologist with respect to the suspected entity, size of necrosis and location of the lesion to avoid incorrect or deficient results.


Stress responses of Synechocystis sp. strain PCC 6803 mutants impaired in genes encoding putative alternative sigma factors.
In the complete genome sequence of the cyanobacterium SYNECHOCYSTIS: sp. strain PCC 6803 [Kaneko et al. (1996 ). DNA Res 3, 109-136] genes were identified encoding putative group 3 sigma-factors SigH (Sll-0856), SigG (Slr-1545) and SigF (Slr-1564) and the regulatory protein RsbU (Slr-2031). Mutations in these genes were generated by interposon mutagenesis to study their importance in stress acclimation. For the genes sigH, sigF and rsbU, the loci segregated completely. However, attempts to mutagenize the sigG locus resulted in merodiploids. Under standard growth conditions only minor differences were detected between the mutants and wild-type. However, cells of the RsbU mutant showed a clear defect in regenerating growth after a nitrogen- and sulphur-starvation-induced stationary phase. After applying salt, heat and high-light shocks, stress protein synthesis was analysed by means of one- and two-dimensional electrophoresis. Cells of the SigF mutant showed a severe defect in the induction of salt stress proteins. Although the acclimation to moderate salt stress up to 684 mM NaCl was not significantly changed in this mutant, its ability to acclimate to higher concentrations of NaCl was reduced. Northern blot experiments showed a constitutive expression of the rsbU and sigF genes. The expression of the sigH gene was found to be stress-stimulated, particularly in heat-shocked cells, whilst that of sigG was transiently decreased under stress conditions. Possible functions of these regulatory proteins in stress acclimation of Synechocystis cells are discussed.


The fabrication of white light-emitting diodes using the n-ZnO/NiO/p-GaN heterojunction with enhanced luminescence.
Cheap and efficient white light-emitting diodes (LEDs) are of great interest due to the energy crisis all over the world. Herein, we have developed heterojunction LEDs based on the well-aligned ZnO nanorods and nanotubes on the p-type GaN with the insertion of the NiO buffer layer that showed enhancement in the light emission. Scanning electron microscopy have well demonstrated the arrays of the ZnO nanorods and the proper etching into the nanotubes. X-ray diffraction study describes the wurtzite crystal structure array of ZnO nanorods with the involvement of GaN at the (002) peak. The cathodoluminescence spectra represent strong and broad visible emission peaks compared to the UV emission and a weak peak at 425 nm which is originated from GaN. Electroluminescence study has shown highly improved luminescence response for the LEDs fabricated with NiO buffer layer compared to that without NiO layer. Introducing a sandwich-thin layer of NiO between the n-type ZnO and the p-type GaN will possibly block the injection of electrons from the ZnO to the GaN. Moreover, the presence of NiO buffer layer might create the confinement effect.


Explaining the Association between Early Adversity and Young Adults' Diabetes Outcomes: Physiological, Psychological, and Behavioral Mechanisms.
Previous studies have documented that early adversity increases young adults' risk for diabetes resulting in morbidity and comorbidity with adverse health conditions. However, less is known about how inter-related physiological (e.g., body mass index [BMI]), psychological (e.g., depressive symptoms), and behavioral mechanisms (e.g., unhealthy eating and sedentary behavior) link early adversity to young adults' diabetes outcomes, although these mechanisms appear to stem from early stressful experiences. The current study tested the patterning of these longitudinal pathways leading to young adults' diabetes using a nationally representative sample of 13,286 adolescents (54% female) over a period of 13 years. The findings indicated that early adversity contributed to elevated BMI, depressive symptoms, and stress-related health behaviors. The impact of these linking mechanisms on hierarchical diabetes outcomes (i.e., prediabetes and diabetes) remained significant after taking their associations with each other into account, showing that these mechanisms operate concurrently. The findings emphasize the importance of early detection for risk factors of young adults' diabetes in order to minimize their detrimental health effects.


The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.
Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.


Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to areas of highest pressure: cohort observations at baseline and twelve months.
Plantar pressures are commonly used as clinical measures, especially to determine optimum foot orthotic design. In rheumatoid arthritis (RA) high plantar foot pressures have been linked to metatarsophalangeal (MTP) joint radiological erosion scores. However, the sensitivity of foot pressure measurement to soft tissue pathology within the foot is unknown. The aim of this study was to observe plantar foot pressures and forefoot soft tissue pathology in patients who have RA. A total of 114 patients with established RA (1987 ACR criteria) and 50 healthy volunteers were assessed at baseline. All RA participants returned for reassessment at twelve months. Interface foot-shoe plantar pressures were recorded using an F-Scan® system. The presence of forefoot soft tissue pathology was assessed using a DIASUS musculoskeletal ultrasound (US) system. Chi-square analyses and independent t-tests were used to determine statistical differences between baseline and twelve months. Pearson's correlation coefficient was used to determine interrelationships between soft tissue pathology and foot pressures. At baseline, RA patients had a significantly higher peak foot pressures compared to healthy participants and peak pressures were located in the medial aspect of the forefoot in both groups. In contrast, RA participants had US detectable soft tissue pathology in the lateral aspect of the forefoot. Analysis of person specific data suggests that there are considerable variations over time with more than half the RA cohort having unstable presence of US detectable forefoot soft tissue pathology. Findings also indicated that, over time, changes in US detectable soft tissue pathology are out of phase with changes in foot-shoe interface pressures both temporally and spatially. We found that US detectable forefoot soft tissue pathology may be unrelated to peak forefoot pressures and suggest that patients with RA may biomechanically adapt to soft tissue forefoot pathology. In addition, we have observed that, in patients with RA, interface foot-shoe pressures and the presence of US detectable forefoot pathology may vary substantially over time. This has implications for clinical strategies that aim to offload peak plantar pressures.


Simplified method for ultra high-resolution photoacoustic microscopy via transient absorption.
Photoacoustic microscopy (PAM) is a hybrid imaging modality that combines optical illumination with ultrasonic detection to achieve absorption contrast imaging of endogenous and exogenous chromophores. Optical resolution PAM achieves high lateral-resolution by tightly focusing the excitation light; however the axial resolution is still dependent upon the bandwidth of the ultrasonic transducer. As a result, PAM images have highly asymmetric voxels with submicron lateral resolution and axial resolution typically limited to tens of microns. We have previously reported on a resonant multiphoton approach to PAM called transient absorption ultrasonic microscopy (TAUM), which enables high axial resolution by frequency encoding the photoacoustic signal at the overlap of a pump and a probe beam. This approach enables photoacoustic imaging with subcellular resolution on par with other multiphoton microscopy techniques. Here, we report on an innovation that enables TAUM imaging with a much less sophisticated optical system than previously reported. If we allow the time delay between the pump and probe to collapse to zero, the pump and probe optical paths can be combined. An amplitude modulator in the single beam path is sufficient to encode the TAUM signal at the second harmonic of the modulation frequency. The resulting system is essentially a standard optical resolution PAM system that incorporates an amplitude modulator and utilizes a Fourier post processing algorithm to improve the axial resolution by approximately an order of magnitude. A prototype system based on this approach has been assembled and tested on fixed bovine erythrocytes.


Prevalence of Hepatitis B Virus Infection among Pregnant Women Attending Antenatal Clinics in Vientiane, Laos, 2008-2014.
The Lao People's Democratic Republic (PDR) is still considered a highly endemic country for hepatitis B, mainly due to perinatal transmission of hepatitis B virus (HBV), despite efforts made since 2004 for universal immunization of newborns. The prevalence of HBV surface antigen (HBsAg) carriage in pregnant women is a relevant marker for the risk of mother-to-child HBV transmission. This study aimed to assess the changes in prevalence of HBV infection among pregnant women attending the Mahosot Prenatal Clinic (Vientiane Capital). Methods. A retrospective study was performed in the Mahosot Hospital Laboratory to collect and analyze all the results of HBsAg testing in pregnant women from 2008 to 2014. Results. Of a total of 13,238 tested women of mean age of 26 years, 720 women (5,44% [95 CI: 5.1-5.8%]) were found HBsAg positive, the annual prevalence ranging from 4.6% to 6.2%. A slight but steady and significant decrease in prevalence over the 7 years of the study could be documented. Conclusion. Although below the 8% hyperendemic threshold, the HBsAg prevalence observed in pregnant women in Vientiane reflects a high risk of HBV perinatal transmission and call for a widespread infant immunization with an HBV vaccine birth dose.


Osteomyelitis secondary to trauma involving the proximal end of the radius in horses: five cases (1987-2001).
To determine clinical, radiographic, and scintigraphic abnormalities in and treatment and outcome of horses with trauma-induced osteomyelitis of the proximal aspect of the radius. Retrospective study. 5 horses. Data collected from the medical records included signalment; history; horse use; degree of lameness; radiographic, ultrasonographic, and scintigraphic findings; treatment; and outcome. Duration of lameness prior to referral ranged from 14 to 60 days. Mean severity of lameness was grade 3 of 5, and all horses had a single limb affected. All horses had signs of pain during elbow joint manipulation and digital palpation over the lateral aspect of the proximal end of the radius. Radiographic lesions consisted of periosteal proliferation, osteolysis, and subchondral bone lysis. Scintigraphy in 3 horses revealed intense pharmaceutical uptake diffusely involving the proximal end of the radius. Two horses had sepsis of the elbow joint. All horses were treated with antimicrobials long-term; 1 horse was also treated by local perfusion of the radial medullary cavity through an indwelling cannulated screw. At follow-up, all horses had returned to their previous function. Results suggest that osteomyelitis of the proximal end of the radius can result from a traumatic injury to the antebrachium. Because lesions may be an extension of septic arthritis, a thorough examination of the wound area and elbow joint is recommended. Prolonged systemic antimicrobial treatment can result in a successful outcome.


Glenohumeral joint injections: a review.
Intra-articular injections into the glenohumeral joint are commonly performed by musculoskeletal providers, including orthopaedic surgeons, family medicine physicians, rheumatologists, and physician assistants. Despite their frequent use, there is little guidance for injectable treatments to the glenohumeral joint for conditions such as osteoarthritis, adhesive capsulitis, and rheumatoid arthritis. We performed a comprehensive review of the available literature on glenohumeral injections to help clarify the current evidence-based practice and identify deficits in our understanding. We searched MEDLINE (1948 to December 2011 [week 1]) and EMBASE (1980 to 2011 [week 49]) using various permutations of intra-articular injections AND (corticosteroid OR hyaluronic acid) and (adhesive capsulitis OR arthritis). We identified 1 and 7 studies that investigated intra-articular corticosteroid injections for the treatment of osteoarthritis and adhesive capsulitis, respectively. Two and 3 studies investigated the use of hyaluronic acid in osteoarthritis and adhesive capsulitis, respectively. One study compared corticosteroids and hyaluronic acid injections in the treatment of osteoarthritis, and another discussed adhesive capsulitis. Based on existing studies and their level of evidence, there is only expert opinion to guide corticosteroid injection for osteoarthritis as well as hyaluronic acid injection for osteoarthritis and adhesive capsulitis.


A noninvasive measure of physical maturity as a predictor of bone mass in children.
The purpose of this study was to describe the accumulation of whole body bone mass in a longitudinal study of prepubertal boys and girls using Roche's physical maturity index as a measure of developmental age. We measured 561 children (39% white, 61% African-American) from a suburban school district, representing an ethnically mixed, middle-class community adjacent to Detroit. Anthropometric measures taken for the present study included recumbent length (cm), stature (cm), weight (kg), whole body bone mineral content (WBBMC in g) and a noninvasive measure of physical maturity (PM%). PM% was calculated from published formulae derived from data from the Fels Longitudinal Study, using recumbent length, weight, midparental stature, age, and age- and gender-specific regression coefficients. At average age 9.9 (+/-0.6) years, there were no significant gender differences in stature, recumbent length, weight, or WBBMC in either ethnic group. Average PM for girls was significantly greater than that for boys within each ethnic group. There were no significant ethnic differences in PM in either gender. Stature and WBBMC were significantly different in the two ethnic groups for both boys and girls. Regressions of WBBMC on PM and chronological age indicated that PM explained more of the variance in WBBMC than did age (r2 ranging from 0.28 to 0.75 for PM versus 0.01 to 0.06 for age). In the case of African-American boys, r2 was similar (0.09 for PM and 0.06 for age). PM is a useful, noninvasive measure of developmental age that is significantly correlated with bone mass in children. Our study also indicates that PM is a better predictor of WBBMC than chronological age. Because PM can be calculated without using invasive and potentially expensive methods, PM may be useful in some clinical as well as research settings.


Mode locking of electron spin coherences in singly charged quantum dots.
The fast dephasing of electron spins in an ensemble of quantum dots is detrimental for applications in quantum information processing. We show here that dephasing can be overcome by using a periodic train of light pulses to synchronize the phases of the precessing spins, and we demonstrate this effect in an ensemble of singly charged (In,Ga)As/GaAs quantum dots. This mode locking leads to constructive interference of contributions to Faraday rotation and presents potential applications based on robust quantum coherence within an ensemble of dots.


Vaccine delivery using nanoparticles.
Vaccination has had a major impact on the control of infectious diseases. However, there are still many infectious diseases for which the development of an effective vaccine has been elusive. In many cases the failure to devise vaccines is a consequence of the inability of vaccine candidates to evoke appropriate immune responses. This is especially true where cellular immunity is required for protective immunity and this problem is compounded by the move toward devising sub-unit vaccines. Over the past decade nanoscale size (<1000 nm) materials such as virus-like particles, liposomes, ISCOMs, polymeric, and non-degradable nanospheres have received attention as potential delivery vehicles for vaccine antigens which can both stabilize vaccine antigens and act as adjuvants. Importantly, some of these nanoparticles (NPs) are able to enter antigen-presenting cells by different pathways, thereby modulating the immune response to the antigen. This may be critical for the induction of protective Th1-type immune responses to intracellular pathogens. Their properties also make them suitable for the delivery of antigens at mucosal surfaces and for intradermal administration. In this review we compare the utilities of different NP systems for the delivery of sub-unit vaccines and evaluate the potential of these delivery systems for the development of new vaccines against a range of pathogens.


Biochemical monitoring of the early endocytic traffic of the type I interferon receptor.
The type I interferon (IFN) receptor consists of two transmembrane chains IFNAR1 and IFNAR2, associated with the tyrosine kinases Tyk2 and Jak1, respectively. Binding of IFN to this receptor complex induces activation of Jak/Stat and non-Stat signaling pathways. Ligand binding also drives receptor internalization and sorting toward degradation or recycling. To gain insights into receptor trafficking and its relation to signaling, we performed subcellular organelle fractionation from IFN-stimulated Daudi cells and defined biochemically an early endosomal antigen-1 (EEA1)-positive compartment bearing the activated IFN receptor. Endosomes were thus purified by immunoaffinity isolation on anti-EEA1 antibodies-coated beads. The content of these purified endosomal fractions was analyzed by Western blot and proteomics. Shortly after IFN stimulation, robustly ubiquitinated IFNAR1 and a small amount of IFNAR2 were found in this endosomal compartment, which also contained tyrosine-phosphorylated Tyk2 and Jak1. These data strongly point to the prolonged interaction during traffic of the tyrosine kinases, still in an activated configuration, with the receptors. Among the major constituents of this EEA1-positive compartment, some proteins that have been implicated in IFN signaling were identified. Altogether, these observations suggest that trafficking of the IFN receptor through endosomes may regulate signaling pathways.