Lean body mass can predict lung function in underweight and normal weight sedentary female young adults.
A previous cross-sectional study found reduced lung function among over weight and obese students in Zanjan city. However, there is no reliable evidence about the respiratory function of underweight and normal weight students. The objective of this study was to evaluate lung function and develop prediction equations in underweight and normal weight female young adults residing in Soltanieh city near Zanjan. A cross sectional study was conducted on underweight (n=29, mean age=16±0.84 years) and normal weight (n=38, mean age=15.9±0.86 years) sedentary female young adults. Fat mass (FM) was measured by Omron Body Fat Monitor FB-3002. Lean body mass (LBM), waist to hip ratio (WHR), body mass index (BMI) and waist circumference (WC) were calculated. Maximum oxygen uptake was calculated using Queen's College step test. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were recorded, using Spirolab III spirometer. Independent t test, Pearson's correlation test and stepwise linear regression analysis were used for data analysis. FVC and FEV1 were significantly lower than the reference values in both groups (P<0.05). LBM was significantly correlated with FVC and FEV1 in underweight and normal weight groups (P<0.05). Regression equations were derived to predict FVC and FEV1 using LBM. This study suggests that dynamic lung functions are poor in underweight and normal weight sedentary female young adults residing in Soltanieh city and LBM plays a significant role in their lung function.


Thunderclap headache without subarachnoid hemorrhage associated with regrowth of previously coil-occluded aneurysms.
Thunderclap headache is a sudden, high-intensity headache often associated with subarachnoid hemorrhage secondary to a ruptured intracerebral aneurysm. A variety of less common causes have now been described. This report presents the cases of 2 patients who experienced thunderclap headache after regrowth of an aneurysm, without hemorrhage of previously coiled aneurysms. Thunderclap headache after endovascular occlusion of a ruptured intracranial aneurysm may be a symptom of aneurysm regrowth and may warrant angiographic investigation.


Structure of the acetylcholine-gated channel.
The structure of the acetylcholine-gated channel, trapped in open as well as closed states, has been analysed by electron crystallographic methods. The channel has large vestibules extending from the membrane which shape the acetylcholine-binding pockets and facilitate selective transport of cations across a narrow membrane-spanning pore. When acetylcholine enters these pockets it triggers a concerted conformational change that opens the pore by destabilizing a gate in the middle of the membrane made by a ring of pore-lining alpha-helical segments. The alternative 'open' configuration of porelining segments reshapes the lumen and creates new surfaces, allowing the ions to pass through. Recent results, at nearly 4A resolution, have defined more precisely the structure of the pore and the design of the vestibular entrances.


Pregabalin for peripheral neuropathic pain.
Pregabalin is an anticonvulsant drug that is under review for use in Canada. It was recently approved in the US and Europe for the treatment of adults with peripheral neuropathic pain (NeP). In most short-term randomized controlled trials (RCTs) of pregabalin in patients with diabetic peripheral neuropathy (DPN) and or post-herpetic neuralgia (PHN), there were early and significant decreases in mean pain scores. The number of subjects with > 50% reduction in pain score was increased when pregabalin was compared to placebo. The most common adverse effects were dizziness and sleepiness. Withdrawal due to adverse events was also more frequent with pregabalin than with placebo. While pregabalin appears to be an effective treatment for NeP, there is no evidence that it offers advantages over treatments being used in Canada.


Serodiagnosis by fluorescent antibody staining of an outbreak of trichinosis in Lebanon.
The opportunity offered by a recent outbreak of trichinosis in Lebannon was utilized to evaluate the applicability of an indirect fluorescent antibody (IFA) test for early diagnosis. Freeze-dried T. spiralis sonicated larval antigen fragments were used, together with human test serum and monospecific anti-human IgG, IgM and IgA fluorescein conjugates. Diagnostic IgG levels of 1/100 and above were observed in serum obtained some time during the acute phase of illness from nine out of ten patients. Diagnosis was made in seven cases within 30 days after the onset of symptoms. IgM antibodies were demonstrated in occasional samples. No IgA antibodies were detected. IgG levels of 1/100 were present in only four out of ten samples obtained 150 days after the clinical onset. These observations suggest that freeze-dried larval antigens make the IFA test an easy and useful procedure in the diagnosis of acute trichinosis. In chronic cases the efficacy of the method appears to be poor.


[Metabolomic profiling in patients with metabolic syndrome].
To identify biomarkers, which are most specific for patients with metabolic syndrome (MS) using metabolomic profiling. Metabolomic profiling of patients with MS and comparison of their profile with the profile of volunteers was performed using high-performance liquid chromatography-mass-spectrometry. The metabolomic profile of MS patients differed in several amino acids, including choline, cysteine, and serine and in the acylcarnitine group (р<0.05 for all comparisons). The metabolites most specific for MS patients were identified. Increased concentrations of a combination of amino acids and carnitines can be considered as possible additional risk factors for cardiovascular diseases.


The implications of different approaches to evaluating intervention: evidence from the study of language delay/disorder.
There is a pressure to both identify and expand the evidence base with regard to the treatment of speech and language disorders in children, as there is in other areas of speech and language therapy. This paper addresses two sources of evidence, a systematic review and meta-analysis of early language interventions and the monitoring of an early language target for socially disadvantaged children in Sure Start programmes in England. There is a growing number of efficacy studies in the field of speech and language disorders in children. For example, in a recent review for the Cochrane Collaboration in the UK 36 articles reporting a total of 33 different trials. Twenty-five of these articles provided sufficient information for use in a series of meta-analyses. The results indicate that speech and language therapy may be effective for children with phonological or expressive vocabulary difficulties. There is mixed evidence concerning the effectiveness of intervention for children with expressive syntax difficulties and little evidence available considering the effectiveness of intervention for children with receptive language difficulties. No significant differences were found between interventions administered by trained parents and clinicians. A number of gaps in the evidence base are identified. But such reviews are essentially retrospective and, while the results may be interesting for practitioners, they do not provide the whole picture. The paper then turns to a very different data set and the role of population monitoring, an approach to assessing the value of interventions which has not hitherto been used in any area of speech and language therapy. The data are derived from a year-on-year monitoring of the language output of 2-year-olds in Sure Start programmes in England. This is a programme funded by central government in the UK to reduce the impact of social disadvantage on children, parents and their communities. The practice and policy implications of these two different sources of information are considered. Who is the consumer of such information and what can they do with it once they have it?


Total synthesis of (-)-aurantioclavine.
The concise total synthesis of (-)-aurantioclavine has been achieved by taking advantage of strategies for the asymmetric alkenylation of N-tert-butanesulfinyl imines. The enantiomerically pure natural product was prepared in 6 steps and 27% overall yield by using Rh-catalyzed addition of a N-methyliminodiacetic acid (MIDA) boronate and in 5 steps and 29% yield by employing a Grignard reagent addition sequence.


Long-term protection in children with meningococcal C conjugate vaccination: lessons learned.
Owing to an increase in group C disease, extensive prelicensure studies have been funded by both the UK Department of Health and vaccine manufacturers. These demonstrated the safety and immunogenicity of three candidate meningococcal group C conjugate (MCC) vaccines (two conjugated to CRM(197) and one to tetanus toxoid) in the targeted age groups. Induction of immunological memory in infants and young children was also demonstrated by either a low dose of polysaccharide challenge following primary immunization with MCC or by an increase in avidity indices post-primary to pre-challenge. Immune memory after infant immunization persisted to at least 4 years of age, although antibody persistence in this age group was poor. MCC vaccine was introduced into the UK routine immunization schedule at 2, 3 and 4 months of age in 1999, with a catch-up as a single dose to all children aged 1-18 years with two doses for infants aged 5-11 months. The number of group C cases fell rapidly in the targeted age groups and early analyzes showed high vaccine effectiveness in all age groups together with significant herd immunity. However, when effectiveness was measured again more than 1 year after vaccination, there was a significant decline in all age groups, most marked in infants vaccinated in the routine infant immunization program, for whom there was no demonstrable efficacy after only 1 year and then in toddlers for whom efficacy declined to 61% (95% confidence interval: -327-94) from 88% (95% confidence interval: 65-96) in the first year. However, good disease control was maintained in the UK with only low numbers of vaccine failures. The assumption that immune memory was predictive of long-term protection is incorrect, at least after vaccination in infancy. Persistence of antibody and herd immunity may be more relevant for long-term disease control.


Examining the interplay among family, culture, and latina teen suicidal behavior.
In this article, we explore the relationships among culture, family, and attempted suicide by U.S. Latinas. We analyzed qualitative interviews conducted with Latina teen suicide attempters (n = 10) and their parents. We also incorporated data collected from adolescents with no reported history of self-harm (n = 10) and their parents to examine why some individuals turned to suicide under similar experiences of cultural conflict. Our results reveal that Latina teens who attempted suicide lacked the resources to forge meaningful social ties. Without the tools to bridge experiences of cultural contradiction, the girls in our study described feeling isolated and alone. Under such conditions, adolescents turned to behaviors aimed at self-destruction. Unlike their peers who attempted suicide, adolescent Latinas with no lifetime history of attempted suicide were able to mobilize resources in ways that balanced experiences of acculturative tension by creating supportive relationships with other individuals.


Factors affecting peer-reviewed publication of abstracts presented at meetings of the European College of Veterinary Ophthalmologists (2008-2012).
To review abstracts presented at five consecutive meetings of the European College of Veterinary Ophthalmologists (ECVO), and identify abstract characteristics that affect the probability of their publication in peer-reviewed journals. An online search was conducted for peer-reviewed publications (PRPs) stemming from abstracts from five ECVO meetings (2008-2012). Time to publication and journal were noted. Effects of ocular tissue/discipline, species, type of presentation and study, funding acknowledgment and affiliation, professional qualifications, and nationality of the first and last authors on probability of publication were analyzed. Of presented abstracts, 29% (87/299) were published as PRPs in Veterinary Ophthalmology (n = 50), other veterinary journals (n = 22), and nonveterinary journals (n = 15). During the 5 years studied, there was no significant difference between the impact factor of Veterinary Ophthalmology and the 25 other journals in which PRPs were published (P = 0.369). Median time to PRP acceptance or publication was 468 days. Independent variables most significant in determining the probability of PRP were oral presentation (P = 0.002), resident authorship (P < 0.0001), and species (P = 0.002), with food animal abstracts having the highest odds ratio. Ocular tissue/discipline (P = 0.13) and type of study (P = 0.33) did not affect publication probability. Funding acknowledgment (P = 0.02), author nationality (P = 0.02), and academic affiliation (P = 0.04) were also significant factors. Publication rate of ECVO abstracts is lower, but time to publication is similar, compared with most biomedical meetings.


Priorities for research on environment, climate and health, a European perspective.
Climate change, urbanisation, chemical pollution and disruption of ecosystems, including biodiversity loss, affect our health and wellbeing. Research is crucial to be able to respond to the current and future challenges that are often complex and interconnected by nature. The HERA Agenda, summarised in this commentary, identifies six thematic research goals in the environment, climate and health fields. These include research to 1) reduce the effects of climate change and biodiversity loss on health and environment, 2) promote healthy lives in cities and communities, 3) eliminate harmful chemical exposures, 4) improve health impact assessment and implementation research, 5) develop infrastructures, technologies and human resources and 6) promote research on transformational change towards sustainability. Numerous specific recommendations for research topics, i.e., specific research goals, are presented under each major research goal. Several methods were used to define the priorities, including web-based surveys targeting researchers and stakeholder groups as well as a series of online and face-to-face workshops, involving hundreds of researchers and other stakeholders. The results call for an unprecedented effort to support a better understanding of the causes, interlinkages and impacts of environmental stressors on health and the environment. This will require breakdown of silos within policies, research, actors as well as in our institutional arrangements in order to enable more holistic approaches and solutions to emerge. The HERA project has developed a unique and exciting opportunity in Europe to consensuate priorities in research and strengthen research that has direct societal impact.


Cooperative action of alpha-glucanotransferase and maltogenic amylase for an improved process of isomaltooligosaccharide (IMO) production.
Maltogenic amylase and alpha-glucanotransferase (alpha-GTase) were employed in an effort to develop an efficient process for the production of isomaltooligosaccharides (IMOs). Bacillus stearothermophilus maltogenic amylase (BSMA) and alpha-GTase from Thermotoga maritima were overexpressed in Escherichia coli using overexpression vectors. An IMO mixture containing 58% of various IMOs was produced from liquefied corn syrup by the hydrolyzing and transglycosylation activities of BSMA alone. When BSMA and alpha-GTase were reacted simultaneously, the IMO content increased to 68% and contained relatively larger IMOs compared with the products obtained by the reaction without alpha-GTase. Time course analysis of the IMO production suggested that BSMA hydrolyzed maltopentaose and maltohexaose most favorably into maltose and maltotriose and transferred the resulting molecules simultaneously to acceptor molecules to form IMOs. alpha-GTase transferred donor sugar molecules to the hydrolysis products such as maltose and maltotriose to form maltopentaose, which was then rehydrolyzed by BSMA as a favorable substrate.


Investigation of physiologic leukopenia in Belgian Tervuren dogs.
Physiologic leukopenia in Tervuren dogs was reported in North America with a higher frequency in aged Tervurens. If not recognized, physiologic leukopenia can provoke unnecessary clinical investigations. The primary objective was to compare Tervurens and control dogs in Belgium with respect to the numbers of dogs with physiologic leukopenia. The secondary objectives were to compare Tervurens with control dogs and age classes within Tervurens and controls for parameters related to physiologic leukopenia. Tervurens (n = 94) and control dogs (n = 48, maximum of 5 dogs per breed and 5 mixed breed dogs) were entered into the study. Dogs were 1-11 years old and healthy on routine physical examination. Dogs had no history of disease or drug administration in the previous 2 months. Hematologic analyses were performed by an automated device within 30 hours of sampling. Blood smears were evaluated for cellular morphologic anomalies. Only 1 of the 94 Tervuren dogs had physiologic leukopenia (1.06%; 95% confidence interval, 0.05-5.22). Furthermore, the white blood cell (WBC) count in Tervuren dogs (median, 10.00 x 109/L; range, 5.90-20.80) was not significantly different (P = .55) from that of control dogs (median, 9.75 x 109/L; range, 5.20-20.90). The WBC count decreased significantly (P < .001) with age in Tervuren dogs. Physiologic leukopenia is uncommon in the Belgian Tervuren dog. Differences with earlier data published in North America might be due to genetic or environmental differences.


Exosomal IDH1 increases the resistance of colorectal cancer cells to 5-Fluorouracil.
Chemoresistance challenges the clinical treatment of colorectal cancer and requires an urgent solution. Isocitrate dehydrogenase 1 (IDH1) is a key enzyme involved in glucose metabolism that mediates the malignant transformation of tumors. However, the mechanisms by which IDH1 is involved in colorectal cancer cell proliferation and drug resistance induction remain unclear. In this study, we found that IDH1 was highly expressed in human colorectal cancer tissues and could be used to indicate a high-grade tumor. In vitro gene overexpression and knockdown were used to determine whether IDH1 promoted the proliferation of the colorectal cancer cell line HCT8 and resistance to 5-Fluorouracil (5FU). Further studies have shown that the 5FU-resistant cell line, HCT8FU, secreted exosomes that contained a high level of IDH1 protein. The exosomal IDH1 derived from 5FU-resistant cells enhanced the resistance of 5FU-sensitive cells. Metabolic assays revealed that exosomes derived from 5FU-resistant cells promoted a decrease in the level of IDH1-mediated NADPH, which is associated with the development of 5FU resistance in colorectal cancer cells. Therefore, exosomal IDH1 may be the transmitter and driver of chemoresistance in colorectal cancer and a potential chemotherapy target.


The short life of an aortic cusp aneurysm: a case report.
This report describes a 42-year-old man with a history of lymphoma who is admitted with symptoms of chest pain, ST elevation changes, and elevated troponins. Immediate bedside echocardiographic evaluation led to an aborted urgent coronary angiography and a diagnosis of presumed endocarditis. Transesophageal echocardiography (TTE) subsequently revealed an aortic noncoronary cusp aneurysm masking as vegetation. The rapid assessment by TTE and transesophageal echocardiogram prevented an alternate course for this patient's management. We reviewed the necessity of heart catheterization in patients with significantly elevated troponins, pericarditis symptoms, and the rare sighting of aortic valve cusp aneurysms.


Fin whale acoustic presence and song characteristics in seas to the southwest of Portugal.
Fin whales were once abundant in the seas to the southwest of Portugal, but whaling activities decreased their numbers considerably. Acoustic data from ocean bottom seismometers provide an opportunity to detect fin whales from their notes, data that would otherwise be logistically challenging and expensive to obtain. Based on inter-note interval and frequency bandwidth, two acoustic patterns produced by fin whales were detected in the study area: pattern 1, described from fin whales in the Mediterranean Sea, and pattern 2, associated with fin whales from the northeast North Atlantic Ocean (NENA). NENA fin whales travel into the western Mediterranean Sea, but the Mediterranean population has not been documented to travel regularly into the NENA. In this study, 11 months of acoustic data recorded southwest of Portugal in the NENA were used to characterize 20-Hz fin whale notes into these patterns. Pattern 2 was the most common and occurred mostly in November-January. Pattern 1 occurred less frequently and mostly in September-December, February and April, which suggested a limited excursion of whales from the Mediterranean Sea. There were also occasions when the two patterns were recorded simultaneously. Results suggest that fin whales from the NENA and Mediterranean Sea might mix in the area during part of the year.


Wearable Microneedle-Based Array Patches for Continuous Electrochemical Monitoring and Drug Delivery: Toward a Closed-Loop System for Methotrexate Treatment.
Wearable devices based on microneedle (MN) technology have recently emerged as tools for in situ transdermal sensing or delivery in interstitial fluid (ISF). Particularly, MN-based electrochemical sensors allow the continuous monitoring of analytes in a minimally invasive manner through ISF. Exogenous small molecules found in ISF such as therapeutic drugs are ideal candidates for MN sensors due to their correlation with blood levels and their relevance for the optimal management of personalized therapies. Herein, a hollow MN array patch is modified with conductive pastes and functionalized with cross-linked chitosan to develop an MN-based voltammetric sensor for continuous monitoring of methotrexate (MTX). Interestingly, the chitosan coating avoids biofouling while enabling the adsorption of MTX at the electrode's surface for sensitive analysis. The MN sensor exhibits excellent analytical performance in vitro with protein-enriched artificial ISF and ex vivo under a Franz diffusion cell configuration. The MN sensor shows a linear range from 25 to 400 μM, which fits within the therapeutic range of high-dose MTX treatment for cancer patients and an excellent continuous operation for more than two days. Moreover, an iontophoretic hollow MN array patch is developed with the integration of both the anode and cathode in the single MN array patch. The ex vivo characterization demonstrates the transdermal on-demand drug delivery of MTX. Overall, the combination of both MN patches represents impactful progress in closed-loop systems for therapeutic drug management in disorders such as cancer, rheumatoid arthritis, or psoriasis.


Ring A-seco mosquito larvicidal limonoids from Turraea wakefieldii.
Five novel limonoids, 1-5, were isolated from the root bark of Turraea wakefieldii and were characterized as tecleaninoid derivatives. This is the first report of the natural occurrence of tecleanin-type limonoids with a five-membered-ring A-seco structure for which we propose the name neotecleanins. The relative stereochemical structures of compounds 1-5 were established on the basis of NMR spectroscopy. The absolute stereochemical structure of 5 was confirmed by X-ray diffraction methods. In mosquito larvicidal assays, compounds 1, 2 and 4 showed dose-dependent larvicidal activity against larvae of Anopheles gambiae s.s.


Biochemical Markers in the Prediction of Contrast-induced Acute Kidney Injury.
For many years clinicians have been searching for "kidney troponin"- a simple diagnostic tool to assess the risk of acute kidney injury (AKI). Recently, the rise in the variety of contrast-related procedures (contrast computed tomography (CT), percutaneous coronary intervention (PCI) and angiography) has resulted in the increased number of contrast-induced acute kidney injuries (CI-AKI). CIAKI remains an important cause of overall mortality, prolonged hospitalisation and it increases the total costs of therapy. The consequences of kidney dysfunction affect the quality of life and they may lead to disability as well. Despite extensive worldwide research, there are no sensitive and reliable methods of CI-AKI prediction. Kidney Injury Molecule 1 (KIM-1) and Neutrophil Gelatinase Lipocalin (NGAL) have been considered as kidney-specific molecules. High concentrations of these substances before the implementation of contrast-related procedures have been suggested to enable the estimation of kidney vulnerability to CI-AKI and they seem to have the predictive potential for cardiovascular events and overall mortality. According to other authors, routine determination of known inflammation factors (e.g., CRP, WBC, and neutrophil count) may be helpful in the prediction of CIAKI. However, the results of clinical trials provide contrasting results. The pathomechanism of contrast- induced nephropathy remains unclear. Due to its prevalence, the evaluation of the risk of acute kidney injury remains a serious problem to be solved. This paper reviews pathophysiology and suggested optimal markers facilitating the prediction of contrast-induced acute kidney injury.


The incidence and management of complications of venous access in home parenteral nutrition (HPN): A 19 year longitudinal cohort series.
Long term central venous access for Home Parenteral Nutrition (HPN) is associated with catheter related complications. The most studied and well known of these is Catheter Related Blood Stream Infection (CRBSI). This paper looks at other venous access complications, including blocked and damaged catheters, catheter related thrombosis and CRBSI. This paper will also present treatment outcomes for each of these complications. This paper will also examine if there are any correlating patient or catheter related factors that can help predict future catheter related complications. By demonstrating the treatment outcomes for each line complication, it is hoped this will contribute to the literature that could be used for standard setting in complications related to long term central venous access. HPN data were analysed from the Greater Glasgow and Clyde (GGC) Home Parenteral Nutrition Database (HPN) which is a comprehensive, prospectively maintained electronic record of all HPN patients treated in GGC. The time period of data collection was 1998-2017. Descriptive statistics were used to report data frequency, age, and catheter days' distributions. Data were not normally distributed and so non-parametric tests were used. Spearman's Rho correlation was used to measure correlation between two numeric groups. Catheter complications were reported as a rate in count data, meaning that more than one event could be recorded per patient, with 1000 catheter days as the person-time denominator. Poisson means test and Fisher exact tests were used to compare different rates, as complications were treated as count data increasing over variable total time periods. P < 0.05 with 95% confidence interval (CI) was considered significant in all tests. Comparisons between binary data sets used two sample t-tests to compare the groups. From 169 patients, 101 (59.8%) were female and 68 (40.2%) were male. The age when first starting HPN ranged from 16 to 79 years old with a median of 56 years. Total catheter days was 173,151 derived from 408 catheter insertions on 169 patients. 282 complications occurred in 85 patients over the study period. An overall catheter complication rate of 1.62/1000 days was found. 84 patients did not experience a single complication. There were 171 proven catheter infections in 66 patients over the study period. Infection rate from the entire period of report was 1.35 infections/1000 catheter days. This decreased over time. Infection was found to be correlated with length of time on HPN, catheter location, catheter diameter and use of Taurolock-Hep100. Thrombosis (n = 16) was associated with total time on HPN (r2 = 0.187, P < 0.05) and the number of infections (r2 = 0.207, P < 0.05). Damage was strongly associated with increasing time on HPN with (r2 of 0.494 and P < 0.005). Blockage was not associated with any patient or catheter factors. Overall catheter salvage rate for CRBSI by antibiotic treatment was 61.87%. Success varied according to organism cultured. Catheter salvage was less successful in other complications and overall catheter salvage rate was 41,115 catheters were salvaged from 282 complications. This study has provided a baseline for rates of less common venous access complications in HPN and their management. Catheter salvage is possible after at least 41% of complications. It is likely that experience is helpful whether that of individual patient, the team or a clinical network. Our results support the use of smaller central venous catheters, in upper body veins, and the use of Taurolock-Hep100 in patients who have recurrent infections.


Efficacy of Long-lasting Insecticidal Nets With Declining Physical and Chemical Integrity on Aedes aegypti (Diptera: Culicidae).
Fitting long-lasting insecticidal nets (LLIN) as screens on doors/windows has a significant impact on indoor-adult Aedes aegypti (L.), with entomological reductions measured in a previous study being significant for up to 2 yr post-installation, even in the presence of pyrethroid-resistant Aedes populations. To better understand the mode of LLIN protection, bioassays were performed to evaluate the effects of field deployment (0, 6, and 12 mo) and damage type (none, central, lateral, and multiple) on LLIN efficacy. Contact bioassays confirmed that LLIN residual activity (median knockdown time, in minutes, or MKDT) decreased significantly over time: 6.95 (95% confidence interval [CI]: 5.32-8.58) to 9.24 (95% CI: 8.69-9.79) MKDT at 0- and 12-mo age, respectively, using a pyrethroid-susceptible Aedes strain. Tunnel tests (exposing human forearm for 40 min as attractant) showed that deployment time affected negatively Aedes passage inhibition from 54.9% (95% CI: 43.5-66.2) at 0 mo to 35.7% (95% CI: 16.3-55.1) at 12 mo and blood-feeding inhibition from 65.2% (95% CI: 54.2-76.2) to 48.9% (95% CI: 26.4-71.3), respectively; both the passage/blood-feeding inhibition increased by a factor of 1.8-2.9 on LLINs with multiple and central damages compared with nets with lateral damage. Mosquito mortality was 74.6% (95% CI: 65.3-83.9) at 0 mo, 72.3% (95% CI: 64.1-80.5) at 6 mo, and 59% (95% CI: 46.7-71.3) at 12 mo. Despite the LLIN physical integrity could be compromised over time, we demonstrate that the remaining chemical effect after field conditions would still contribute to killing/repelling mosquitoes.


[Cervical epidural injection technic under computed tomography guidance in the treatment of cervicobrachial neuralgia].
Epidural injections of corticosteroids in the cervical spine can provide effective treatment of cervicobrachial neuralgia. This technique is mainly described by anesthesiologists who perform injections without imaging control. We demonstrate that this infiltration can be easily performed under CT-guidance by radiologists.


Sex Differences in Adult Facial Three-Dimensional Morphology: Application to Gender-Affirming Facial Surgery.
Background: Gender-affirming facial surgery (GFS) is pursued by transgender individuals who desire facial features that better reflect their gender identity. Currently, there are a few objective guidelines to justify and facilitate effective surgical decision making. Objective: To quantify the effect of sex on adult facial size and shape through an analysis of three-dimensional (3D) facial surface images. Materials and Methods: Facial measurements were obtained by registering an atlas facial surface to 3D surface scans of 545 males and 1028 females older than 20 years of age. The differences between male and female faces were analyzed and visualized for a set of predefined surgically relevant facial regions. Results: On average, male faces are 7.3% larger than female faces (Cohen's D = 2.17). Sex is associated with significant facial shape differences (p < 0.0001) in the entire face as well as in each sub-region considered in this study. The facial regions in which sex has the largest effect on shape are the brow, jaw, nose, and cheek. Conclusions: These findings provide biologic data-driven anatomic guidance and justification for GFS, particularly forehead contouring cranioplasty, mandible and chin alterations, rhinoplasty, and cheek modifications.


Acute and delayed effects of prolonged exercise on serum lipoproteins. II. Concentration and composition of low-density lipoprotein subfractions and very low-density lipoproteins.
To investigate the effects of a single period of prolonged exercise on lipoprotein concentration and composition, 13 healthy endurance-trained men were examined before and after (1 h, 20 h) a cross-country run [30 km, time: 130 (SD 7.4) min]. The data show that following acute exercise, serum triglyceride (TG) concentration were reduced (36%) as a consequence of a reduced number (31%) of very low density lipoprotein (VLDL) particles. Changes in composition of VLDL were present but less evident. In contrast to this, acute exercise did not induce significant changes in the average concentration of individual low-density lipoprotein (LDL) subfractions. However, changes in dense LDL [density (d) > 1.044 g.ml-1] concentration were significantly correlated to changes in serum TG: a reduction of dense LDL occurred in subjects with large reductions in serum TG. In addition, LDL composition changed significantly. Immediately (1 h) after exercise the TG content of all LDL subfractions was reduced. These reductions were significant in large (d = 1.006-1.037 g.ml-1) and small LDL (1.044-1.063 g.ml-1). It can be concluded therefore from our study that acute exercise primarily altered the composition of LDL subfractions while their concentration remained stable.


Effects of geometric confinement on the adhesive debonding of soft elastic solids.
The effect of increasing confinement on soft elastic gel layers has been investigated and a means of analyzing the behavior of such systems has been developed. A probe tack test was used to study the behavior of thin elastic layers during interfacial debonding from a cylindrical glass indenter. For this gel-indenter system, confinement is defined as the ratio of a(0), the radius of the indenter, to h, the thickness of the elastic layer. In order to investigate geometric effects, the adhesion energy of the gel was kept constant while the thickness and modulus of the gels were varied. A fracture mechanics approach, based on the compliance of the layer, has been employed in analyzing the experimental data. It is shown that a fracture mechanics analysis is appropriate for these systems, allowing quantitative results to be obtained, despite very irregular contacts. It has also been shown that the interfacial instabilities observed during debonding maximize the compliance of the elastic layer. Additionally, four dimensionless parameters that dictate the behavior of confined systems have been defined, offering a general guide to understanding and characterizing the mechanical behavior of thin elastic layers.


Dalitz plot analysis of Coulomb exploding O3 in ultrashort intense laser fields.
The three-body Coulomb explosion of O3, O3(3+)-->O++O++O+, in ultrashort intense laser fields (2x10(15) W/cm2) is studied with two different pulse durations (9 and 40 fs) by the coincidence momentum imaging method. In addition to a decrease in the total kinetic energy release, a broadening in the Dalitz plot distribution [Philos. Mag. 44, 1068 (1953)] is observed when the pulse duration is increased from 9 to 40 fs. The analysis based on a simple Coulomb explosion model shows that the geometrical structure of O3 remains almost unchanged during the interaction with the few-cycle intense laser fields, while a significant structural deformation along all the three vibrational coordinates, including the antisymmetric stretching coordinate, is identified in the 40 fs intense laser fields. The observed nuclear dynamics are discussed in terms of the population transfer to the excited states of O3.


Intramolecular-Catalyzed Vitrimers with White-Light Emission for Light-Emitting Diode Encapsulation.
Currently available encapsulating materials for white light-emitting diodes (WLEDs) have certain limitations, such as the toxicity of phosphors and the non-recyclable nature of the encapsulating materials. In this study, relatively promising encapsulating materials with two significant advantages are developed. First, the chips can be directly encapsulated without phosphors using luminescent encapsulating materials. Second, the encapsulating materials can be reprocessed for recycling via intramolecular catalysis. To this end, blue-light-emitting vitrimers (BEVs) are prepared by the reaction of epoxy resin with amines and are found to exhibit strong blue emission and fast stress relaxation via internal catalysis. To obtain white-light emission, a well-designed yellow component, perylenetetracarboxylic dianhydride, is grafted into the BEVs to generate white-light-emitting vitrimers (WEVs). A rare synergy of blue- and yellow-light emission affords white-light emission. When the WEV is used as an encapsulating adhesive for 365 nm LED chips without inorganic phosphors, stable white light with CIE coordinates (0.30, 0.32) is successfully achieved, indicating a promising future for WLED encapsulation.


Biphasic Dissolution as an Exploratory Method During Early Drug Product Development.
Dissolution testing is a major tool used to assess a drug product's performance and as a quality control test for solid oral dosage forms. However, compendial equipment and methods may lack discriminatory power and the ability to simulate aspects of in vivo dissolution. Using low buffer capacity media combined with an absorptive phase (biphasic dissolution) increases the physiologic relevance of in vitro testing. The purpose of this study was to use non-compendial and compendial dissolution test conditions to evaluate the in vitro performance of different formulations. The United States Pharmacopeia (USP)-recommended dissolution method greatly lacked discriminatory power, whereas low buffer capacity media discriminated between manufacturing methods. The use of an absorptive phase in the biphasic dissolution test assisted in controlling the medium pH due to the drug removal from the aqueous medium. Hence, the applied non-compendial methods were more discriminative to drug formulation differences and manufacturing methods than conventional dissolution conditions. In this study, it was demonstrated how biphasic dissolution and a low buffer capacity can be used to assess in vitro drug product performance differences. This can be a valuable approach during the early stages of drug product development for investigating in vitro drug release with improved physiological relevance.


A blockchain-based computerized network infrastructure for the transparent, immutable calculation and dissemination of quantitative, measurable parameters of academic and medical research publications.
Digital transformation of healthcare systems should rely on decentralized computer networks and take advantage of the unique characteristics of blockchain technology. Decentralization ensures process transparency and data transparency for all relevant stakeholders. These values are essential in the realms of populations' healthcare information communications and processing, control and tracking of medical logistics supply chains, clinical research management, and control of certified healthcare services organizations. Mounting decentralized processes onto a blockchain-based computerized network will endow the values of immutability, improved cybersecurity, and potential for incentivizing stakeholders for relevant, pre-determined activities. One of the most relevant processes that would benefit from a decentralized, blockchain-based architecture is the submission, review, and publishing of scientific manuscripts. Current structures and processes in this world are non-transparent, poorly incentivizing significant stakeholders such as manuscripts' reviewers, and many are potentially corrupted. In this review, we suggest a blockchain-based architecture for such systems and advocate further research and development in several domains of modern healthcare systems-offering medicine to become "the new guy on the block (chain)."


Gray matter volume differences between transgender men and cisgender women: A voxel-based morphometry study.
Gender dysphoria (GD) is characterized by distress due to inconsistency between gender identity and biological sex. Individuals with GD often desire to be the other gender, which is called transgender. Although altered brain volumes in transgender people, particularly transgender women, have been reported, the particular brain regions have been inconsistent among studies. This study aimed to investigate neuroanatomical differences in transgender men without physical interventions. T1-weighted magnetic resonance images (MRIs) were acquired in 21 transgender men and 21 cisgender women matched for biological sex and age. Whole-brain comparisons using voxel-based morphometry (VBM) were performed to identify gray matter volume (GMV) differences between transgender men and cisgender women. Transgender men showed greater GMV in the right posterior cingulate gyrus (PFWE-corr = 3.06×10-6) and the left occipital pole (PFWE-corr = 0.017) and lower GMV in the left middle temporal gyrus (PFWE-corr = 0.017) than cisgender women. Even after including serum sex hormone levels as covariates, the posterior cingulate gyrus was still significant (PFWE-corr < 0.05). In contrast, the occipital pole and the middle temporal gyrus were not significant after controlling for the sex hormone levels (PFWE-corr > 0.05), especially affected by testosterone but not estradiol. These findings suggest that transgender men have altered brain structure. We suggest that larger posterior midline structures may contribute to sensitivity to self-referential processing through altered visual perception in transgender people.


[Changes in intracardiac hemodynamics after percutaneous catheter balloon valvuloplasty in different types of valvular stenosis of the pulmonary artery].
Percutaneous catheter balloon valvuloplasty was carried out in 75 patients with valvular pulmonary stenosis (VPS), whose ages ranged from 18 months to 38 years. In 40 of them (53.3%) VPS was complicated by infundibular stenosis of the right ventricle. After percutaneous catheter balloon valvuloplasty 13 patients received out-patient treatment with beta-adrenergic blocking agents in doses of 20 to 120 mg/24 hours. Control examination in periods of 6 months to 2 years after the operation was conducted in 35 patients among whom 10 patients had been given beta-adrenergic blocking agents in the postoperative period. A stable reduction of the right ventricle-pulmonary artery (RV-PA) gradient and positive dynamics of the cardiac volume indices were recorded in 25 patients after correction of isolated VPS and in 6 patients after percutaneous catheter balloon valvuloplasty and treatment with beta-adrenergic blocking agents. The residual RV-PA gradient in 4 patients after treatment with beta-adrenergic blocking agents remained within a range of 30 mm Hg. Percutaneous catheter balloon valvuloplasty is an effective method for the correlation of isolated VPS. Coexistence of VPS with infundibular right-ventricular stenosis is not a contraindication for the use of this method for correcting the anomaly. In such a case the roentgenosurgical intervention should be supplemented by treatment with beta-adrenergic blocking agents in individual doses.


Proteomic analyses of nucleus laminaris identified candidate targets of the fragile X mental retardation protein.
The avian nucleus laminaris (NL) is a brainstem nucleus necessary for binaural processing, analogous in structure and function to the mammalian medial superior olive. In chickens (Gallus gallus), NL is a well-studied model system for activity-dependent neural plasticity. Its neurons have bipolar extension of dendrites, which receive segregated inputs from two ears and display rapid and compartment-specific reorganization in response to unilateral changes in auditory input. More recently, fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates local protein translation, has been shown to be enriched in NL dendrites, suggesting its potential role in the structural dynamics of these dendrites. To explore the molecular role of FMRP in this nucleus, we performed proteomic analysis of NL, using micro laser capture and liquid chromatography tandem mass spectrometry. We identified 657 proteins, greatly represented in pathways involved in mitochondria, translation and metabolism, consistent with high levels of activity of NL neurons. Of these, 94 are potential FMRP targets, by comparative analysis with previously proposed FMRP targets in mammals. These proteins are enriched in pathways involved in cellular growth, cellular trafficking and transmembrane transport. Immunocytochemistry verified the dendritic localization of several proteins in NL. Furthermore, we confirmed the direct interaction of FMRP with one candidate, RhoC, by in vitro RNA binding assays. In summary, we provide a database of highly expressed proteins in NL and in particular a list of potential FMRP targets, with the goal of facilitating molecular characterization of FMRP signaling in future studies.


Active oscillations in microscale navigation.
Living organisms routinely navigate their surroundings in search of better conditions, more food, or to avoid predators. Typically, animals do so by integrating sensory cues from the environment with their locomotor apparatuses. For single cells or small organisms that possess motility, fundamental physical constraints imposed by their small size have led to alternative navigation strategies that are specific to the microscopic world. Intriguingly, underlying these myriad exploratory behaviours or sensory functions is the onset of periodic activity at multiple scales, such as the undulations of cilia and flagella, the vibrations of hair cells, or the oscillatory shape modes of migrating neutrophils. Here, I explore oscillatory dynamics in basal microeukaryotes and hypothesize that these active oscillations play a critical role in enhancing the fidelity of adaptive sensorimotor integration.


Introducing medical students to deep learning through image labelling: a new approach to meet calls for greater artificial intelligence fluency among medical trainees.
Our approach addresses the urgent need for AI experience for the doctors of tomorrow. Through a medical education-focused approach to data labelling, we have fostered medical student competence in medical imaging and AI. We envision our framework being applied at other institutions and academic groups to develop robust labelling programs for research endeavours. Application of our approach to core visual modalities within medicine (e.g. interpretation of ECGs, diagnostic imaging, dermatologic findings) can lead to valuable student experience and competence in domains that feature prominently in clinical practice, while generating much needed data in fields that are ripe for AI integration.


Probabilistically Perfect Cloning of Two Pure States: Geometric Approach.
We solve the long-standing problem of making n perfect clones from m copies of one of two known pure states with minimum failure probability in the general case where the known states have arbitrary a priori probabilities. The solution emerges from a geometric formulation of the problem. This formulation reveals that cloning converges to state discrimination followed by state preparation as the number of clones goes to infinity. The convergence exhibits a phenomenon analogous to a second-order symmetry-breaking phase transition.


Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms.
Biologics have the potential to induce an immune response when used therapeutically. A number of in vitro assays are currently used preclinically to predict the risk of immunogenicity, but the validation of these preclinical tools suffers from the relatively small number of accessible immunogenic molecules and the limited understanding of the mechanisms underlying the immunogenicity of biologics. Here, we present the post-hoc analysis of three monoclonal antibodies with high immunogenicity in the clinic. Two of the three antibodies elicited a CD4 T cell proliferative response in multiple donors in a peripheral blood mononuclear cell assay, but required different experimental conditions to induce these responses. The third antibody did not trigger any T cell response in this assay. These distinct capacities to promote CD4 T cell responses in vitro were mirrored by different capacities to stimulate innate immune cells. Only one of the three antibodies was capable of inducing human dendritic cell (DC) maturation; the second antibody promoted monocyte activation while the third one did not induce any innate cell activation in vitro. All three antibodies exhibited a moderate to high internalization by human DCs and MHC-associated peptide proteomics analysis revealed the presence of potential T cell epitopes that were confirmed by a T-cell proliferation assay. Collectively, these findings highlight the existence of distinct immune stimulatory mechanisms for immunogenic antibodies. These findings have implications for the preclinical immunogenicity risk assessment of biologics.


Experimental meridian line of stomach and its low impedance nature.
Applying electrical impulse stimuli at the Jing point (St. 45) and then tapping on the skin surface along the vertical lines crossing the channel of the stomach, the line of latent propagated sensation along channel (LPSC) was determined in 51 patients at the acupuncture clinic. Of the cases examined, 98 percent were found to have positive LPSC lines which were basically coincident with the classical stomach channel. Using a low frequency skin impedance detector, the skin impedance of the entire lines of LPSC was found to be lower than its adjacent areas.


[Effect of grapefruit pulp on the pharmacokinetics of the dihydropyridine calcium antagonists nifedipine and nisoldipine].
The effect of the intake of 200 g of grapefruit pulp (corresponding to one grapefruit) on the pharmacokinetics of the calcium antagonists nifedipine (NF) and nisoldipine (NS) were investigated in 8 healthy Japanese male volunteers. A crossover design was used for the study: group I did not ingest any grapefruit (control group); group II ingested grapefruit 1 h after drug administration; and group III ingested grapefruit 1 h before drug administration. The intake of grapefruit pulp increased the plasma concentrations of both NF and NS, an effect that has previously been reported with grapefruit juice. The increase was most marked when grapefruit was eaten before drug administration. For both NF and NS, subjects who ingested grapefruit 1 h before drug administration exhibited a greater Cmax and AUC0-24 than did subjects in the control group. For NF, the Cmax was 1.4 times higher and the AUC0-24 1.3 times larger in group III than in group I. For NS, the Cmax was 1.5 times higher and the AUC0-24 1.3 times larger in group III than in group I. The increase in the AUC0-24 was significant for both drugs (p < 0.05). The finding that the ratios of Cmax and AUC0-24 for unchanged drug and metabolites did not vary greatly among the three groups for either drug suggests that the increase in serum concentration produced by grapefruit intake may be due to other factors than an inhibitory effect on drug metabolism. Also, the increases in Cmax and AUC0-24 of NS produced by grapefruit intake were smaller than those produced by grapefruit juice intake, indicating that grapefruit pulp and juice have different effects on the pharmacokinetics.


Influence of prognostic features on the final outcome in rheumatoid arthritis: a review of the literature.
The literature on prognostic features on the final outcome in RA is reviewed. It is generally agreed that female sex and a positive RF are variables indicating a poor prognosis. Longstanding increased ESR and CRP values, decreased Hb, or the appearance of subcutaneous nodules are indicators of a less favorable clinical course. No conclusions can be drawn regarding other factors due to the incomplete and heterogeneous study designs.


Word frequency effects in priming performance in young and older adults.
The present study examined word frequency effects on implicit priming in older adults compared with younger adults. In Experiment 1 participants performed a spelling test consisting of primed and unprimed homophones (e.g., mourning) and nonhomophones (e.g., militant). Older adults spelled more unprimed, low-frequency homophones than did younger adults, suggesting that there are age-related differences in base-rate spelling of lower frequency homophones. Experiment 2 involved a word-fragment completion task that primed both high- and low-frequency words. Young adults showed larger priming effects for low-frequency words, whereas older adults showed smaller and similar priming effects for high- and low-frequency words. Experiment 3 replicated the finding that word frequency has no effect on priming performance in older adults on a word-fragment completion task. These studies found differential word frequency effects on priming performance between young and older adults.


Self-Punishment Promotes Forgiveness in the Direct and Indirect Reciprocity Contexts.
Most previous studies regarding self-punishment have focused on the correlation between moral emotion and self-punishment. Only a few studies have attempted to understand self-punishment from the perspective of seeking forgiveness, and no study has yet directly tested whether wrongdoers' self-punishment promotes others to forgive the wrongdoers. In three studies, the participants judged the wrongdoers' self-punishment behaviors following an unfair allocation and reported the extent to which they forgave the wrongdoers. The results demonstrated that self-punishment did promote forgiveness in both the direct (Studies 1 and 2) and indirect reciprocity (Study 3) contexts. Consistent with costly signaling theory, the costlier the self-punishment was, the stronger the effect it had on forgiveness. Moreover, communicative self-punishment had a better effect than silent self-punishment when the cost was relatively high in the direct-reciprocity studies. These findings can guide us regarding how to address a damaged relationship via self-punishment when compensation is not feasible or acceptable.


The constituents of essential oil in leaves of Karaj accession of Trigonella foenum graecum.
The chemical composition of the essential oils of Karaj accession of Trigonella foenum graecum leaves was detected by hydro-distillation and analysed by gas chromatography (GC-FID) and gas chromatography-mass spectroscopy (GC-MS) apparatuses for first time. Thirty-six compounds representing 95.3% of the total components were identified. The patterns of the main compounds were (2E)-Hexenal (26.61%), n-Hexadecanoic acid (10.14%) and (E)-b-Ionone (7.99%). Other notable constituents were Thymol (4.79%), 6,10,14-trimethyl-2-Pentadecanone (4.59%), Carvacrol (3.40%), (E)-Nerolidol (3.32%) and (2E,6Z)-Nonadienal (3.30%). (2E)-Hexenal was found as the most dominant component in this study.


Cellulase adsorption and an evaluation of enzyme recycle during hydrolysis of steam-exploded softwood residues.
The sugar yield and enzyme adsorption profile obtained during the hydrolysis of SO2-catalyzed steam-exploded Douglas-fir and posttreated steam-exploded Douglas-fir substrates were determined. After hot alkali peroxide posttreatment, the rates and yield of hydrolysis attained from the posttreated Douglas-fir were significantly higher, even at lower enzyme loadings, than those obtained with the corresponding steam-exploded Douglas-fir. The enzymatic adsorption profiles observed during hydrolysis of the two substrates were significantly different. Ultrafiltration was employed to recover enzyme in solution (supernatant) and reused in subsequent hydrolysis reactions with added, fresh substrate. These recycle findings suggested that the enzyme remained relatively active for three rounds of recycle. It is likely that enzyme recovery and reuse during the hydrolysis of posttreated softwood substrates could lead to reductions in the need for the addition of fresh enzyme during softwood-based bioconversion processes.


10-Year prospective study of noise exposure and hearing damage among construction workers.
To characterise the effects of noise exposure, including intermittent and peaky exposure, on hearing damage as assessed by standard pure-tone thresholds and otoacoustic emissions, a longitudinal study was conducted on newly hired construction apprentices and controls over a 10-year period. Among the 456 subjects recruited at baseline, 316 had at least two (mean 4.6) examinations and were included in this analysis. Annual examinations included hearing threshold levels (HTLs) for air conducted pure tones and distortion product otoacoustic emission (DPOAE) amplitudes. Task-based occupational noise exposure levels and recreational exposures were estimated. Linear mixed models were fit for HTLs and DPOAEs at 3, 4 and 6 kHz in relation to time since baseline and average noise level since baseline, while controlling for hearing level at baseline and other risk factors. Estimated L(EQ) noise exposures were 87±3.6 dBA among the construction workers. Linear mixed modelling demonstrated significant exposure-related elevations in HTL of about 2-3 dB over a projected 10-year period at 3, 4 or 6 kHz for a 10 dB increase in exposure. The DPOAE models (using L1=40) predicted about 1 dB decrease in emission amplitude over 10 years for a 10 dB increase in exposure. The study provides evidence of noise-induced damage at an average exposure level around the 85 dBA level. The predicted change in HTLs was somewhat higher than would be predicted by standard hearing loss models, after accounting for hearing loss at baseline. Limited evidence for an enhanced effect of high peak component noise was observed, and DPOAEs, although similarly affected, showed no advantage over standard hearing threshold evaluation in detecting effects of noise on the ear and hearing.


Directed aerosol writing of ordered silica nanostructures on arbitrary surfaces with self-assembling inks.
This paper reports the fabrication of micro- and macropatterns of ordered mesostructured silica on arbitrary flat and curved surfaces using a facile robot-directed aerosol printing process. Starting with a homogenous solution of soluble silica, ethanol, water, and surfactant as a self-assembling ink, a columnated stream of aerosol droplets is directed to the substrate surface. For deposition at room temperature droplet coalescence on the substrates and attendant solvent evaporation result in continuous, highly ordered mesophases. The pattern profiles are varied by changing any number of printing parameters such as material deposition rate, printing speed, and aerosol-head temperature. Increasing the aerosol temperature results in a decrease of the mesostructure ordering, since faster solvent evaporation and enhanced silica condensation at higher temperatures kinetically impede the molecular assembly process. This facile technique provides powerful control of the printed materials at both the nanoscale and microscale through chemical self-assembly and robotic engineering, respectively.


Vandetanib for the treatment of lung cancer.
VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). Once considered to be separate targets, VEGF and EGFR are now shown to have interconnected downstream pathways, potentiating the effectiveness of their dual signaling inhibition in cancer therapy. Molecules such as vandetanib that inhibit VEGFR and EGFR have also been reported to inhibit other receptors, including RET and additional kinases, and may be beneficial in treating patients with solid tumors. This review covers the significance of targeting VEGF and EGFR in the treatment of NSCLC and the rationale behind their dual inhibition. Clinical trials that evaluate the use of vandetanib in the setting of refractory NSCLC are also explored. Vandetanib is currently not approved in the setting of NSCLC. However, its approval for medullary thyroid cancer makes it promising for identifying markers and potentially a NSCLC patient population who will benefit from the treatment.


Reducing patient distress: a model for dementia care.
More than 750000 people in the UK have some form of dementia; with a rise expected over the next 25 years. With early diagnosis of cancer, more patients with dementia will attend for cancer treatment. Immobilisation masks, used to ensure accurate head and neck radiotherapy, may trigger panic in patients, even without prior mental health problems. This single case study reports on the care provided to a patient with dementia and his carer, his wife Betty, during cancer treatment. Bert was diagnosed with dementia 10 years prior to his cancer diagnosis. The use of sedation appeared to trigger confusion rather than facilitate procedures. Bert's case illustrates how an individualised contract of care could be developed to help maximise interactions, ensure ongoing consent and maintain dignity during difficult and challenging medical procedures.


The "Fully Catalytic System" in Mitsunobu Reaction Has Not Been Realized Yet.
An investigation of the recently reported "fully catalytic Mitsunobu reaction" using catalytic amounts of a phosphine reagent and an azo reagent has shown that although benzyl 4-nitrobenzoate is formed under the fully catalytic conditions, the same result is obtained if the hydrazine catalyst is omitted, indicating that this is not a Mitsunobu reaction. In addition, when the reaction between (-)-ethyl lactate and 4-nitrobenzoic acid was carried out using the "fully catalytic" method, the corresponding ester was formed but in very low yield and with predominant retention of configuration. Unfortunately, the system catalytic in phosphine reagent is incompatible with that in the azo reagent.


Underwater wireless optical communication system using a 16-QAM modulated 450-nm laser diode based on an FPGA.
An underwater wireless optical communication (UWOC) system with a 450-nm laser diode and a 150-MHz PIN photodiode is presented. The 16-ary quadrature amplitude modulation scheme is employed and realized on a field-programmable gate array (FPGA) to efficiently provide a high data rate. Experimental results show that this system can achieve data rates up to 50 Mbps over a distance of 3 m underwater with a bit error rate (BER) of 7.11×10-4 in artificial seawater at 35‰ salinity, where the attenuation coefficient is 0.481. This BER is below the forward error correction target of 3.8×10-3. Thus, this system can provide reliable high-speed communications over short to moderate distance point-to-point UWOC links.


[Disseminated peritoneal leiomyomatosis. Light and electron microscopic study].
The rare case of disseminated peritoneal leiomyomatosis is reported. A 41 year old non-gravid patient had a laparotomy for uterine fibroids and numerous subperitoneal nodules were found in the abdominal cavity. The light and electron microscopic examinations showed disseminated peritoneal leiomyomatosis. The nodular proliferation of the sub-peritoneal stroma is characteristic for this disease. The patient is free of problems three years following the initial diagnosis of disseminated peritoneal leiomyomatosis.


A Receptor Story: Insulin Resistance Pathophysiology and Physiologic Insulin Resensitization's Role as a Treatment Modality.
Physiologic insulin secretion consists of an oscillating pattern of secretion followed by distinct trough periods that stimulate ligand and receptor activation. Apart from the large postprandial bolus release of insulin, β cells also secrete small amounts of insulin every 4-8 min independent of a meal. Insulin resistance is associated with a disruption in the normal cyclical pattern of insulin secretion. In the case of type-2 diabetes, β-cell mass is reduced due to apoptosis and β cells secrete insulin asynchronously. When ligand/receptors are constantly exposed to insulin, a negative feedback loop down regulates insulin receptor availability to insulin, creating a relative hyperinsulinemia. The relative excess of insulin leads to insulin resistance (IR) due to decreased receptor availability. Over time, progressive insulin resistance compromises carbohydrate metabolism, and may progress to type-2 diabetes (T2D). In this review, we discuss insulin resistance pathophysiology and the use of dynamic exogenous insulin administration in a manner consistent with more normal insulin secretion periodicity to reverse insulin resistance. Administration of insulin in such a physiologic manner appears to improve insulin sensitivity, lower HgbA1c, and, in some instances, has been associated with the reversal of end-organ damage that leads to complications of diabetes. This review outlines the rationale for how the physiologic secretion of insulin orchestrates glucose metabolism, and how mimicking this secretion profile may serve to improve glycemic control, reduce cellular inflammation, and potentially improve outcomes in patients with diabetes.


Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial.
Although the use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown. In this study, we evaluated bortezomib in combination with dexamethasone (BD) for induction chemotherapy prior to HDM/SCT. This was a single-center, prospective, randomized controlled trial comparing induction therapy consisting of two BD cycles followed by HDM/SCT (BD + HDM/SCT) with HDM/SCT alone in the treatment of patients with newly diagnosed AL amyloidosis. The hematological and organ responses of the patients were assessed every three months post HDM/SCT. Fifty-six patients newly diagnosed with renal (100%), cardiac (57.1%), liver (7.1%), or nervous system (8.9%) AL amyloidosis were enrolled in this study; 28 patients were assigned to each arm. Two patients died within 100 days of HDM/SCT (3.6% treatment-related mortality). The overall hematologic response rates in the BD + HDM/SCT arm and HDM/SCT arm at three, six and twelve months were 78.5% versus 50%, 82.1% versus 53.5% and 85.7% versus 53.5%, respectively. In the BD + HDM/SCT arm, 15 (53.5%) patients achieved a hematologic response after BD and before HDM/SCT. An intention-to-treat analysis revealed a higher rate of complete remission in the BD + HDM/SCT arm at both 12 and 24 months (67.9% and 70%, respectively) than with the HDM/SCT-only therapy (35.7% and 35%, respectively, P = 0.03). After a median follow-up of 28 months, the survival rates at 24 months post-treatment start were 95.0% in the BD + HDM/SCT group and 69.4% in the HDM/SCT alone group (P = 0.03). Our preliminary data suggest that the outcome of treating AL amyloidosis with BD induction and HDM/SCT was superior to the outcome of the HDM/SCT treatment alone. This trial has been registered at clinicaltrials.gov with the number NCT01998503.


Acute optic neuritis and the prognosis for multiple sclerosis.
In a retrospective survey of acute optic neuritis 144 cases in adults were found and, of these, 127 were reviewed, five had died of causes related to multiple sclerosis, and 12 were lost to follow-up. There was a statistically significant seasonal variation in the incidence of optic neuritis. When the life-table method of analysis was used, the probability of developing multiple sclerosis rises to 78% 15 years after an episode of optic neuritis. At review, 49 (73%) of the 67 patients with multiple sclerosis were independent and leading active lives.


Association of monoclonal gammopathy of undetermined significance and C3 glomerulopathy.
Monoclonal gammopathy of undetermined significance (MGUS) is usually an asymptomatic pre-malignant condition caused by the proliferation of clonal plasma cells. Often considered a benign condition, it has the potential to progress to malignant plasma cell or lymphoproliferative disorders. Moreover, MGUS can rarely cause glomerular disease by activating the alternative complement pathway resulting in immunoglobulin-negative C3-positive glomerulonephritis called C3 glomerulopathy. Because of its rarity, the diagnosis might not be considered by the treating physicians, leading to delayed diagnosis or misdiagnosis. Untreated C3 glomerulopathy can lead to irreversible glomerular damage and end-stage renal failure, and a high index of suspicion is essential for timely diagnosis and management. Here, we present the case of a patient with a prior diagnosis of MGUS who presented with proteinuria and microscopic haematuria and was diagnosed with C3 glomerulopathy. The patient had complete resolution of the disease after receiving treatment with a combination of dexamethasone, lenalidomide and bortezomib for the underlying MGUS.


Lipiarmycin targets RNA polymerase and has good activity against multidrug-resistant strains of Mycobacterium tuberculosis.
The aim of this study was to determine the in vitro activity of lipiarmycin against drug-resistant strains of Mycobacterium tuberculosis (MTB) and to establish the resistance mechanism of MTB against lipiarmycin using genetic approaches. MIC values were measured against a panel of drug-resistant strains of MTB using the broth microdilution method. Spontaneous lipiarmycin-resistant mutants of MTB were tested for cross-resistance to standard anti-TB drugs, and their rpoB and rpoC genes were sequenced to identify mutations. Lipiarmycin exhibited excellent inhibitory activity against multidrug-resistant strains of MTB with MIC values of <0.1 mg/L. Sequence analysis of the rpoB and rpoC genes from spontaneous lipiarmycin-resistant mutants of MTB revealed that missense mutations in these genes caused resistance to lipiarmycin. Although both lipiarmycin and rifampicin are known to inhibit the bacterial RNA polymerase, the sites of mutation in the rpoB gene were found to be different in MTB strains resistant to these inhibitors. Whereas all six rifampicin-resistant MTB strains tested had mutation in the 81 bp hotspot region of the rpoB gene spanning codons 507-533, 16 of 18 lipiarmycin-resistant strains exhibited mutation between codons 977 and 1150. The remaining two lipiarmycin-resistant strains had mutation in the rpoC gene. Lipiarmycin has excellent bactericidal activity against MTB and lacks cross-resistance to standard anti-TB drugs. Furthermore, rifampicin-resistant strains remained fully susceptible to lipiarmycin, and none of the lipiarmycin-resistant MTB strains became resistant to rifampicin, highlighting the lack of cross-resistance.


Control of Cellular Aging, Tissue Function, and Cancer by p53 Downstream of Telomeres.
Telomeres, the nucleoprotein complex at the ends of eukaryotic chromosomes, perform an essential cellular role in part by preventing the chromosomal end from initiating a DNA-damage response. This function of telomeres can be compromised as telomeres erode either as a consequence of cell division in culture or as a normal part of cellular ageing in proliferative tissues. Telomere dysfunction in this context leads to DNA-damage signaling and activation of the tumor-suppressor protein p53, which then can prompt either cellular senescence or apoptosis. By culling cells with dysfunctional telomeres, p53 plays a critical role in protecting tissues against the effects of critically short telomeres. However, as telomere dysfunction worsens, p53 likely exacerbates short telomere-driven tissue failure diseases, including pulmonary fibrosis, aplastic anemia, and liver cirrhosis. In cells lacking p53, unchecked telomere shortening drives chromosomal end-to-end fusions and cycles of chromosome fusion-bridge-breakage. Incipient cancer cells confronting these telomere barriers must disable p53 signaling to avoid senescence and eventually up-regulate telomerase to achieve cellular immortality. The recent findings of highly recurrent activating mutations in the promoter for the telomerase reverse transcriptase (TERT) gene in diverse human cancers, together with the widespread mutations in p53 in cancer, provide support for the idea that circumvention of a telomere-p53 checkpoint is essential for malignant progression in human cancer.


Unravelling the structural plasticity of stretched DNA under torsional constraint.
Regions of the genome are often held under torsional constraint. Nevertheless, the influence of such constraint on DNA-protein interactions during genome metabolism is still poorly understood. Here using a combined optical tweezers and fluorescence microscope, we quantify and explain how torsional constraint influences the structural stability of DNA under applied tension. We provide direct evidence that concomitant basepair melting and helical unwinding can occur in torsionally constrained DNA at forces >∼50 pN. This striking result indicates that local changes in linking number can be absorbed by the rest of the DNA duplex. We also present compelling new evidence that an overwound DNA structure (likely P-DNA) is created (alongside underwound structures) at forces >∼110 pN. These findings substantiate previous theoretical predictions and highlight a remarkable structural plasticity of torsionally constrained DNA. Such plasticity may be required in vivo to absorb local changes in linking number in DNA held under torsional constraint.


Hereditary hemochromatosis in children, adolescents, and young adults.
Hereditary hemochromatosis is the most common cause of iron overload in adults and is probably the second most common cause of iron overload in children in the United States next to transfusional overload. Serious morbidity from this disorder of iron absorption can occur in early as well as in middle and advanced age, iron overload having been reported in children with hereditary hemochromatosis as early as 2 years of age. Younger persons differ from older persons in that the risk for iron loading in females appears to be equal to the risk for males, in contrast to a preponderance of males among older patients. Also, younger patients frequently demonstrate cardiac and gonadal involvement, with cardiac failure commonly leading to death, whereas older patients are more likely to have liver involvement and diabetes mellitus, with liver failure and hepatoma commonly leading to death. Because early diagnosis and treatment can prevent the toxicities of iron overload, appropriate screening can be lifesaving. Transferrin saturation is the most reliable screening test. Liver biopsy with objective measurement of hepatic iron stores is the most important diagnostic criterion at present, although reliable noninvasive methods for quantitating body iron are being developed. Young individuals who should be screened for iron overload include patients with cardiac myopathies, hypogonadism, amenorrhea, loss of libido, diabetes mellitus, other endocrine disorders, cirrhosis of the liver, and arthritis, as well as the siblings, parents, and children of patients with hereditary hemochromatosis or iron loading of unknown cause.


Effect of exocrine pancreatic function on resting energy expenditure in cystic fibrosis.
To prove the hypothesis that exocrine pancreatic function determines resting energy expenditure (REE) in cystic fibrosis (CF). Thirty-eight CF individuals, 9-34 (19.98 +/- 1.0) years, were divided into three groups: Six pancreatic sufficient patients (PS; group A), 21 pancreatic insufficient patients (PI), whose pulmonary function was comparable to that of group A (group B1) and 11 PI patients, whose pulmonary function was significantly worse than that of group A (group B2). REE was estimated by indirect calorimetry. Predicted REE was based on Schofield equations. Measured REE was expressed as % of the predicted. BMI, BMI z-scores, serum albumin, cholesterol and triglycerides levels were related to REE. Results were expressed as mean +/- standard error. Groups B1 and B2 had significantly higher REE% (111.7 +/- 2.75% and 119.94 +/- 3.8, respectively) as opposed to group A (98.9 +/- 3.81%; p = 0.022 and 0.035, respectively) whose REE% was similar to that predicted. REE% between group B1 and B2 was not statistically significant. In groups A, B1 and B, mean FEV1% was 86.33 +/- 10.1%, 90.24 +/- 4.39%, 44.54 +/- 3.47%, respectively, mean BMI was 25.6 +/- 2.06, 19.48 +/- 0.64 and 20.09 +/- 8.8, respectively, BMI z-scores were 0.75 +/- 0.51, -0.52 +/- 0.24 and -1.07 +/- 0.37, respectively. Significant correlation was demonstrated between REE%, BMI z-scores and cholesterol levels in group A. Clinically stable CF patients, who had comparable pulmonary function, exhibited increased REE% only in the presence of exocrine pancreatic insufficiency. REE% strongly correlated with BMI z-scores in pancreatic sufficiency. These findings support the hypothesis that pancreatic rather than pulmonary function may determine nutritional status as well as REE in CF.


Sexual function one year after transurethral prostatic resection. Patients' own assessments.
One year after transurethral resection of the prostate for benign hyperplasia, 127 men received a questionnaire requesting personal evaluation of sexual function, including erection, ejaculation, libido and satisfaction. Significant postoperative dysfunction was reported in all these respects: 54% of the responders claimed deterioration and half of them blamed the operation. Decline in sexual function had a multifactorial background, including advancing age, morbidity, and changed marital and social conditions. Although other examinations with preoperative and postoperative evaluation report a lower incidence of impotence development, which may be more reliable, it is psychologically interresting that the patients themselves suspect the transurethral resection as the cause of impaired sexuality.


Clinical study of anatomical ACL reconstruction with adjustable oval shaped bone tunnels: a CT evaluation.
The purpose of this article was to demonstrate an adjustable oval bone tunnel ACLR technique. Aim of this technique was to fit the direction and shape of the footprint and tendon-bone healing passage (TBHP) which was defined as the passage of the normal ACL insertion embedded in the bone as closely as possible. 30 fresh-frozen human cadaveric knees were used to do the ACL anatomical insertions research. 20 patients underwent adjustable oval bone tunnel surgery and 20 patients were in round tunnel group. The tunnel of the presented technique was first drilled with a small diameter round drill bit. Then according to the direction and area of the remnant insersion fibers, the major axes of oval tunnels were expanded to theoretical value with a bone file. Major and minor axes, positions of bone apertures, and areas were evaluated on CT scans. These results were compared with cadaveric and theoretical values. The distance of major axis of oval femoral and tibial tunnel apertures were 10.42 ± 0.55 mm and 12.63 ± 0.5 mm respectively. There're no statistical significance compared with theoretical distance (femoral: P = 0.068, tibial: P = 0.058). The distance of minor axis of oval femoral and tibial tunnel apertures were 6.79 ± 0.28 mm and 6.02 ± 0.29 mm respectively. Both of them were longer than theoretical values (P < 0.001). Compared with the round femoral tunnel, the major/minor axis ratio of oval tunnel (1.53) was more close to the cadaveric results (1.83, P < 0.001). The areas of femoral and tibial apertures were 53.12 ± 1.87 mm2 and 54.22 ± 3.21 mm2 respectively. Both of them were smaller than the round tunnel area and lager than theoretical areas (P < 0.001). We successfully developed the adjustable single oval bone tunnel ACLR technique, which mimic the direction and shape of the tibial and femoral footprints together with the BTHP better than single round tunnel.


Human immunodeficiency virus and other sexually transmitted infections among female sex workers in two major cities in Papua New Guinea.
Treatable sexually transmitted infections are very common in developing countries and quite often are inadequately treated or remain untreated despite the fact that they enhance the transmission of human immunodeficiency virus (HIV). To estimate the prevalence of HIV, syphilis, chlamydial infection, gonorrhea, and trichomoniasis among female sex workers in Port Moresby and Lae, Papua New Guinea, and to collect data on associated behaviors. Self-identified female sex workers recruited through our peer-mediated sexually transmitted disease (STD)/HIV risk-reduction community outreach program were invited to participate in the study. Participants underwent pretest counseling, were interviewed, and were asked to self-collect vaginal swab specimens for the detection of STDs and to provide 10 mL of blood for HIV and syphilis testing. A total of 407 female sex workers, 207 in Port Moresby and 200 in Lae, were enrolled in the study. The overall prevalence rates of HIV, syphilis, genital chlamydial infection, gonorrhea, and trichomoniasis among these women were estimated to be 10%, 32%, 31%, 36%, and 33%, respectively. The sex workers in Port Moresby had a significantly higher HIV infection rate (17%) than those in Lae (3%) and a significantly lower trichomoniasis rate (21%) than those in Lae (44%). Mixed infections were common, occurring in 45% of the cases. Despite a high rate of symptoms, the rate of treatment-seeking was low. Condom use among the sex workers was very inconsistent; 85% reported that they did not use condoms at all times when having sex with their clients. Common reasons cited were dislike by clients, unavailability, alcohol use, and familiarity with a client. STDs are very common among female sex workers in Port Moresby and Lae and very often present as multiple infections. Despite STD/HIV awareness campaigns, unsafe sex-particularly irregular use of condoms-continues among sex workers and their clients. Barriers to safer sexual behavior need to be addressed, as do improvements in provision of STD services.


Spatiotemporal Variation of Osmanthus fragrans Phenology in China in Response to Climate Change From 1973 to 1996.
Climate change greatly affects spring and autumn plant phenology around the world consequently, and significantly impacts ecosystem function and the social economy. However, autumn plant phenology, especially autumn flowering phenology, has not been studied so far. In this study, we examined the spatiotemporal pattern of Osmanthus fragrans phenology, including both leaf phenology (the date of bud-bust, BBD; first leaf unfolding, FLD; and 50% of leaf unfolding, 50 LD) and flowering phenology (the date of first flowering, FFD; peak of flowering, PFD; and end of flowering, EFD). Stepwise multiple linear regressions were employed to analyze the relationships between phenophases and climatic factors in the long term phenological data collected by the Chinese Phenological Observation Network from 1973 to 1996. The results showed that spring leaf phenophases and autumn flowering phenophases were strongly affected by latitude. BBD, FLD, and 50LD of O. fragrans were delayed by 3.98, 3.93, and 4.40 days as per degree of latitude increased, while FFD, PFD and EFD in O. fragrans advanced 3.11, 3.26, and 2.99 days, respectively. During the entire study period, BBD was significantly delayed across the region, whereas no significant trends were observed either in FLD or 50LD. Notably, all flowering phenophases of O. fragrans were delayed. Both leaf and flowering phenophases negatively correlated with growing degree-days (GDD) and cold degree-days (CDD), respectively. BBD and FLD were negatively correlated with total annual precipitation. In addition to the effects of climate on autumn flowering phenology, we found that earlier spring leaf phenophases led to delayed autumn flowering phenophases. Our results suggest that future climate change and global warming might delay the phenological sequence of O. fragrans. Our findings also advanced the flowering mechanism study of autumn flowering plants, and facilitated the accurate prediction of future phenology and climate change.


Role of TGF-β activated kinase-1 inhibitor on the interaction between macrophages and mesangial cells on the condition of high glucose.
To investigate the effect of TGF-β activated kinase-1(TAK1) inhibitor 5Z-7-oxozeaenol on the interaction between macrophages and mesangial cells exposed to high glucose. The macrophages and mesangial cells were cultured separately or co-cultured and divided into seven groups: inhibitor control group, mannitol control group, normal control group, high glucose group and inhibitor groups. The expression of p-TAK1, TAK1 binding protein (TAB1), transcription factor NF - κ B (NF-κB p65) of macrophages were analyzed by Western blotting. The intracellular localization of NF-κB p65 was analyzed by immunofluorescence. The levels of inflammation cytokines and extracellular matrix were determined by enzyme-linked immune sorbent assay. Migration of macrophages was observed by microscope. Compared with control group, the expression of p-TAK1, TAB1, NF-κB p65 were significantly higher in high glucose group (P < 0.05). Both in co-culture group and single culture group, the levels of inflammation cytokines and extracellular matrix (P < 0.05) in high glucose group were higher than that in control group. Exposed to high glucose, the levels of inflammation cytokines and extracellular matrix in co-cultured group were higher than that in single culture group (P < 0.05). 5Z-7-oxozeaenol can decrease those cytokines secretion, comparing with high glucose group (P < 0.05). The number of macrophages migration were decreased by 5Z-7-oxozeaenol (P < 0.05). Exposed to high glucose, macrophages and mesangial cells can interact with each other to promote the secretion of inflammation cytokines and extracellular matrix. TAK1 inhibitor can reduce the secretion of inflammation cytokines and extracellular matrix components by intervening NF-κB p65 nuclear transfer and inhibiting macrophage migration.


Critical shoulder angle is associated with full-thickness rotator cuff tears in patients with glenohumeral osteoarthritis.
Higher critical shoulder angle (CSA) is correlated with rotator cuff tears (RCTs), whereas lower CSA is associated with glenohumeral osteoarthritis (OA). Our goal was to investigate whether patients with concurrent glenohumeral OA and full-thickness RCTs demonstrate a higher CSA than patients with OA alone. Using a 2-surgeon shoulder arthroplasty registry, we identified 31 patients with glenohumeral OA and full-thickness RCTs confirmed by plain radiography and magnetic resonance imaging, respectively. Sixty-two age- and gender-matched controls (1:2 ratio) with glenohumeral OA and an intact rotator cuff were identified from the same registry. Two independent observers evaluated the radiographs for CSA and acromiohumeral index. The average CSA was 30° in the OA control group and 35° in the concurrent RCT and OA group (P < .0001). Acromiohumeral index was comparable between the groups (P = .13). Interobserver reliability of the independent reviewers was excellent (κ = 0.89; Ρ = 0.95). The receiver operating characteristic curve for CSA demonstrated that a value >35° was 90% specific and 52% sensitive for a full-thickness RCT in the setting of OA (area under curve = 0.84). Concurrent glenohumeral OA and full-thickness RCT are associated with greater CSA values compared with patients with glenohumeral OA alone. The CSA measurement may be useful in determining the need for magnetic resonance imaging to assess rotator cuff integrity in the arthritic population.


The impact of leadership development on GP mental health commissioning.
Purpose This paper aims to explore the learning needs of general practitioners (GPs) involved in commissioning mental health provision in England, and offer an evaluation of a leadership and commissioning skills development programme for Mental Health Commissioners. Design/methodology/approach Retrospective mixed method, including online mixed method survey, rating participants' knowledge, skills, abilities, semi-structured telephone interviews and third-party questionnaires were used. Results were analysed for significant differences using the Wilcoxon Signed Ranks test. Open-ended responses and interview transcripts were analysed thematically. Findings Indicative results showed that participants perceived significant impacts in ability across eight key question groups evaluated. Differences were found between the perceived and observed impact in relation to technical areas covered within the programme which were perceived as the highest scoring impacts by participants. Research limitations/implications The indicative results show a positive impact on practice has been both perceived and observed. Findings illustrate the value of this development programme on both the personal development of GP Mental Health Commissioners and commissioning practice. Although the findings of this evaluation increase understanding in relation to an important and topical area, larger scale, prospective evaluations are required. Impact evaluations could be embedded within future programmes to encourage higher participant and third-party engagement. Future evaluations would benefit from collection and analysis of attendance data. Further research could involve patient, service user and carer perspectives on mental health commissioning. Originality value Results of this evaluation could inform the development of future learning programmes for mental health commissioners as part of a national approach to improve mental health provision.


Effects of female urine on growth and sexual maturation in male rabbits.
Urine of adult males or adult females, or distilled water (control), was applied to the oro-nasal grooves of Dutch-belted male rabbits after weaning. The body and testicular weights of males treated with urine of females were significantly less than those of controls between 88 and 125, and 96 and 109 days, respectively. Sperm counts and the pattern of androgen-dependent production of gel-plugs in semen also differed significantly between treatments during the critical maturation period. These suppressant effects of urine of females on male development in rabbits may represent a mechanism by which females may manipulate the reproductive success of neighbouring conspecifics in free-living colonies.


Thiazolidinediones in type 2 diabetes--have they lived up to expectations?
The thiazolidinediones have been in clinical use for the management of type 2 diabetes for the past five years. These agents reduce insulin resistance by acting as ligands that regulate gene expression related to the proliferation and differentiation of adipose tissue. Overall, data from several clinical studies suggest that their hypoglycaemic efficacy is slightly less than sulphonylureas and metformin but greater than acarbose and the glinides. In the short term, treatment with thiazolidinediones is associated with weight gain, expansion of plasma volume, fluid retention, peripheral oedema, an increased risk of congestive heart failure when combined with insulin, and an idiosyncratic hepatotoxic reaction to troglitazone. The long term consequences of these effects are not known. Contrary to expectations, despite being insulin sensitisers these agents do not favourably influence the other components of the metabolic syndrome that are believed to be aggravated by insulin resistance. Dyslipidaemia and elevated blood pressure, which are major risk factors of cardiovascular disease in type 2 diabetes, are not favourably improved with thiazolidinedione treatment. Unlike the sulphonylureas and metformin, which have been shown in recent long term randomised studies to reduce cardiovascular risk substantially, there is no data on the long term cardiovascular safety of the thiazolidinediones. At present, in the absence of long term data, the thiazolidinediones in clinical use are moderately effective hypoglycaemic drugs with no particular advantage over existing treatments in type 2 diabetes.


Digital Transformation in Ophthalmic Clinical Care During the COVID-19 Pandemic.
COVID-19 has placed unprecedented pressure on health systems globally, whereas simultaneously stimulating unprecedented levels of transformation. Here, we review digital adoption that has taken place during the pandemic to drive improvements in ophthalmic clinical care, with a specific focus on out-of-hospital triage and services, clinical assessment, patient management, and use of electronic health records. We show that although there have been some successes, shortcomings in technology infrastructure prepandemic became only more apparent and consequential as COVID-19 progressed. Through our review, we emphasize the need for clinicians to better grasp and harness key technology trends such as telecommunications and artificial intelligence, so that they can effectively and safely shape clinical practice using these tools going forward.


Functional characterization of a soluble NADPH-cytochrome P450 reductase from Fusarium graminearum.
Fusarium head blight is a devastating disease in wheat caused by some fungal pathogens of the Fusarium genus mainly F. graminearum, due to accumulation of toxic trichothecenes. Most of the trichothecene biosynthetic pathway has been mapped, although some proteins of the pathway remain uncharacterized, including an NADPH-cytochrome P450 reductase. We subcloned a F. graminearum cytochrome P450 reductase that might be involved in the trichothecene biosynthesis. It was expressed heterologously in E. coli as N-terminal truncated form with an octahistidine tag for purification. The construct yielded a soluble apoprotein and its incubation with flavins yielded the corresponding monomeric holoprotein. It was characterized for activity in the pH range 5.5-9.5, using thiazolyl blue tetrazolium bromide (MTT) or cytochrome c as substrates. Binding of the small molecule MTT was weaker than for cytochrome c, however, the rate of MTT reduction was faster. Contrary to other studies of cytochrome reductase proteins, MTT reduction proceeded in a cooperative manner in our studies. Optimum kinetic activity was found at pH 7.5-8.5 for bothMTT and cytochrome c. This is the first paper presenting characterization of a cytochrome P450 reductase from F. graminearum which most likely is involved in mycotoxin biosynthesis or some primary metabolic pathway such as sterol biosynthesis in F. graminearum.


Spatial effects in supercontinuum generation in waveguides.
An economic, space- and time-resolved method to model ultra-short, intense pulse propagation in waveguides is described. Simulations of supercontinuum generation on a chip demonstrate the utility of the approach. Comparisons with the generalized nonlinear Schrödinger equation elucidate spatial effects, which influence pulse dynamics and the generation of new spectral components.


Lithium toxicity precipitated by profound hypothyroidism.
Many patients who have undergone surgical treatment for thyroid cancer are treated with postoperative radioactive iodine ablation. Thyroid hormone is generally stopped for several weeks prior to treatment. We report the case of a woman on long-standing treatment with lithium for bipolar disorder who, after 3 weeks of withdrawal from thyroid hormone, presented to the hospital with severe lithium toxicity. She required admission to the intensive care unit and was treated with hemodialysis and supportive care with resolution of her illness. In this patient, renal dysfunction associated with her hypothyroid state was likely the precipitating event leading to the lithium toxicity. We review the effect of hypothyroidism on renal function and the association of hypothyroidism with drug toxicities. This case illustrates the potential for hypothyroid-induced renal dysfunction to lead to adverse clinical consequences in patients taking medications cleared by the kidneys.


Isolated Actinic Lichen Planus of the Lower Lip.
Oral lichen planus (LP) is a common manifestation in patients with LP; however, isolated lip LP is rare and may mimic other conditions such as lichenoid drug eruptions, actinic cheilitis, and early carcinoma in situ in the absence of typical skin lesions. Actinic lichen planus (ALP) is a variant of LP occurring on light-exposed areas in patients with dark skin. We report the case of a Chinese female with isolated ALP of the lower lip, mimicking herpes simplex infection at presentation. The presence of prognathism, involvement of the lower lip, and flares associated with sunlight reinforces the role of sun exposure in the development of this condition.