[Using the SHiPA with the elderly: a person-centered approach].
Qualitative differences in control, distance and relationship with other people were examined using multidimensional and configurational analyses with data from the SHiPA. The SHiPA, developed by Bouisson (2005), contributes to inform on psychological functioning the elderly, using open responses, no limited into choices, and assesses some aspects of distress and adaptative resources in common daily life events that are frequently causes of difficulties. Based on scores in differential weighting of SHiPA dimensions, multivariate analyses revealed five psychological functioning profiles, characterized by anxiety, depression, cognition, internality, satisfaction with life, and routinization levels. Analyse of the differences between SHiPA profiles suggested a first discrimination depending on the individuals, psychological resources level, and the situation of subjects in third and fourth age.


Adherence to Antihypertensive Medications and Stroke Risk: A Dose-Response Meta-Analysis.
Inconsistent findings have been obtained for previous studies evaluating the association between antihypertensive medication (AHM) adherence and the risk of stroke. This dose-response meta-analysis was designed to investigate the association between AHM adherence and stroke risk. MEDLINE and Embase databases were systematically searched to identify relevant studies. The quantification of adherence to AHM was calculated as the percentage of the sum of days with AHM actually taken divided by the total number of days in a specific period. Summary relative risks (RR) and 95% CIs were estimated using a random-effects model. Stratified and dose-response analyses were also performed. A total of 18 studies with 1 356 188 participants were included. The summary RR of stroke for the highest compared with the lowest AHM adherence level was 0.73 (95% CI, 0.67-0.79). Stratified by stroke subtype, a higher AHM adherence was associated with lower risks of ischemic stroke (RR, 0.74; 95% CI, 0.69-0.79) and hemorrhagic stroke (RR, 0.55; 95% CI, 0.42-0.72). Moreover, both fatal (RR, 0.51; 95% CI, 0.36-0.73) and nonfatal stroke (RR, 0.52; 95% CI, 0.28-0.94) were lower in participants with higher AHM adherence. The results of a dose-response analysis indicated that a 20% increment in AHM adherence level was associated with a 9% lower risk of stroke (RR, 0.91; 95% CI, 0.86-0.96). Higher AHM adherence is dose-dependently associated with a lower risk of stroke in patients with hypertension.


The road to deforestation: Edge effects in an endemic ecosystem in Sumatra, Indonesia.
Worldwide, roads are a main driver of deforestation and degradation as they increase forest access along the forest edge. In many tropical areas, unofficial roads go unreported and unrecorded, resulting in inaccurate estimates of intact forested areas. This is the case in central Sumatra, which boasts populations of critically endangered Sumatran elephants (Elephas maximus sumatrensis), tigers (Panthera tigris sumatrae) and other endemic flora and fauna that make the area globally unique. However, maps do not reflect the reality of forest loss in the area. Here we present new maps from 2002 and 2016 of digitized and ground-truthed roads in one of Sumatra's unique lowland tropical protected areas, Tesso Nilo National Park. Using our newly created roads dataset, we examine the distribution of forest with respect to distance to roads. Our data show >2,400 km of roads within the national park in 2016 -nearly a 10-fold increase from roads known in 2002. Most forest (82-99%) within Tesso Nilo falls within 100 m, 500 m, and 1000 m of road edges. Length of road increased 157% and road density increased from 1.06 km/km2 to 2.63 km/km2 from 2002-2016. Our results suggest that this endemic ecosystem is facing substantial threat from roads and their associated impacts. Without swift management action, such as road closures and increased enforcements by park management, this ecosystem, and its endemic wildlife, could be lost. It is imperative that protected areas worldwide more rigorously consider roads and road effects on ecosystem fragmentation in their conservation plans.


Trends and outcomes of concomitant aortic valve replacement and coronary artery bypass grafting in the UK and a survey of practices.
Concomitant revascularization of coronary artery disease at the same time as treatment for aortic valvopathy favourably impacts survival. However, combined surgery may be associated with increased adverse outcomes compared to aortic valve replacement (AVR) or coronary artery bypass grafting in isolation. We retrospectively analyzed all patients who underwent AVR with bypass grafting between February 1996 and March 2019 using data from the National Adult Cardiac Surgery Audit. We used a generalized mixed-effects model to assess the effect of the number and type of bypass grafts associated with surgical AVR on in-hospital mortality, postoperative stroke, and the need for renal dialysis. Furthermore, we conducted an international cross-sectional survey of cardiac surgeons to explore their views about concomitant AVR with coronary bypass grafting interventions. Fifty-one thousand two hundred and seventy-two patients were included in the study. Patients receiving 2 or more bypass grafts demonstrated more significant preoperative comorbidity and disease severity. Patients undergoing 2 and >2 grafts in addition to AVR had increased mortality as compared to patients undergoing AVR and only 1 graft [odds ratio (OR) 1.17, 95% confidence interval (CI) [1.05-1.30], P = 0.005 and OR 1.15, 95% CI [1.02-1.30], P = 0.024 respectively]. A single arterial conduit was associated with a reduction in mortality (OR 0.75, 95% CI [0.68-0.82], P < 0.001) and postoperative dialysis (OR 0.87, 95% CI [0.78-0.96], P = 0.006), but this association was lost with >1 arterial conduit. One hundred and three surgeons responded to our survey, with only a small majority believing that the number of bypass grafts can influence short- or long-term postoperative outcomes in these patients, and an almost equal split in responders supporting the use of staged or hybrid interventions for patients with concomitant pathology. The number of grafts performed during combined AVR and coronary artery bypass grafting is associated with increased morbidity and mortality. The use of an arterial graft was also associated with reduced mortality. Future studies are needed to assess the effect of incomplete revascularization and measure long-term outcomes. Based on our data, current published evidence, and the collective expert opinion we gathered, we endorse future work to investigate the short and long-term efficacy and safety of hybrid intervention for patients with concomitant advanced coronary and aortic valve disease.


Paeonol Ameliorates Abdominal Aortic Aneurysm Progression by the NF-κB Pathway.
Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by localized progressive dilatation. Currently, paeonol has been shown to possess anti-inflammatory and protective cardiovascular properties. Our study aimed to investigate the potential influences of paeonol on AAA progression. Experimental AAAs were created in C57BL/6J mice by intra-aortic infusion of porcine pancreatic elastase, and then intragastrically administered paeonol (20 mg/kg/day) for 14 days. The effects of paeonol on experimental AAA were measured by ultrasound imaging, histopathology, and western blot analyses. Paeonol treatment limited the enlargement of the aneurysmal diameter and alleviated the depletion of elastic fibers and vascular smooth muscle cells (VSMCs). Furthermore, the infiltration of CD68+ macrophages and CD8+ lymphocytes was obviously attenuated after paeonol administration, along with mural neoangiogenesis. Western blot results showed that paeonol inhibited the expression of matrix metalloproteinase (MMP) and the NF-κB pathway activation. Paeonol might prevent experimental AAA progression by inhibiting the NF-κB pathway, which suggests that it is a potential drug for AAA.


Anti-biofilm properties of a mupirocin spray formulation against Escherichia coli wound infections.
Mupirocin ointment is a widely used topical drug for the treatment of bacterial skin infections. However, ointments have some limitations which motivated the development of a film forming spray of mupirocin. Mupirocin spray (2%) was formulated with Eudragit E100 as a film forming agent and tested for its antibacterial and anti-biofilm activities against Escherichia coli, a skin pathogen causing wound and surgical site infections. Treatment with mupirocin spray resulted in significant antibacterial and anti-biofilm activities (inhibition and disruption) with single spray and sub-actual dose concentrations at par with the commercial ointment concentration. The spray formulation was found to be non-toxic to fibroblast cells and greatly resisted removal from the site of application upon washing, in contrast to the ointment which was significantly removed after a single wash. This is the first study to develop and evaluate a spray formulation for mupirocin that forms a stable thin film for sustained release of the drug.


Uncovering financial distress conditions and its determinant factors on insurance companies in Ethiopia.
The study examines the financial distress situation and its determinants in insurance sectors in Ethiopia. To achieve study objectives, revised Altman's 2000 is adopted to measure the financial distress situation. The study adopted an explanatory research design with an arrangement of secondary data analysis via document analysis, quantitative approach, and deductive method of inquiry. The study used panel data from ten insurance companies over the study period 2010/11-2020/21. Descriptive and regression analyses were performed to analyze the data using STATA 14. Econometric model estimation procedures and multiple regression assumptions were tested accordingly. The random effect regression result revealed that firm-specific factors (liquidity and profitability) have a significant positive association, whereas firm size significantly negatively impacts financial distress. While the random effect regression result also proposed inflation has a positive and significant association with financial distress. However, firm-specific factors (revenue growth and leverage) have positive and negative, respectively, and macroeconomic factors (Gross Domestic Product) have positive but statically insignificant to the financial distress situation of insurance sectors in Ethiopia.


Inferring Evolutionary Process From Neuroanatomical Data.
Brain evolution has interested neuroanatomists for over a century. These interests often fall on how free the brain is to evolve independently of the body, how free brain regions are to evolve independently of each other, and how different environmental and ecological factors affect the brain over evolutionary time. But despite major advances in phylogenetic methods, comparative neuroanatomists have tended to limit their macroevolutionary toolbox to regression-based analyses and ignored the scope of evolutionary process-based models at their disposal. This Review summarizes the history of comparative neuroanatomy and highlights the pitfalls of the methodologies traditionally used. It provides an overview of evolutionary process-based modeling approaches for investigating univariate and multivariate data, as well as more sophisticated methods that incorporate hypotheses about biotic and abiotic pressures that may drive brain evolution. The benefits of evolutionary process-based models, and shortcomings of regression-based ones, are illustrated with widely used neuroanatomical data. Ultimately, the intent of this Review is to be a guide for subsuming macroevolutionary methods not typically used in comparative neuroanatomy, in order to improve our understanding of how the brain evolves.


Socio-economic predictors of stillbirths in Nepal (2001-2011).
Stillbirth has a long-lasting impact on parents and families. This study examined socio-economic predictors associated with stillbirth in Nepal for the year 2001, 2006 and 2011. The Nepalese Demographic and Health Survey (NDHS) data for the period (2001-2011) were pooled to estimate socio-economic predictors associated with stillbirths in Nepal using binomial logistic regression while taking clustering and sampling weights into account. A total of 18,386 pregnancies of at least 28 weeks gestation were identified. Of these pregnancies, 335 stillbirths were reported. Stillbirth increased significantly among women that lived in the hills ecological zones (aRR 1.38, 95% CI 1.02, 1.87) or in the mountains ecological zones (aRR 1.71, 95% CI 1.10, 2.66). Women with no schooling (aRR 1.72, 95% CI 1.10, 2.69), women with primary education (aRR 1.81, 95% CI 1.11, 2.97); open defecation (aRR 1.48, 95% CI 1.00, 2.18), and those whose major occupation was agriculture (aRR 1.80, 95% CI 1.16, 2.78) are more likely to report higher stillbirth. Low levels of education, ecological zones and open defecation were found to be strong predictors of stillbirth. Access to antenatal care services and skilled birth attendants for women in the mountainous and hilly ecological zones of Nepal is needed to further reduce stillbirth and improved services should also focus on women with low levels of education.


Proteomic analysis of grapevine (Vitis vinifera L.) tissues subjected to herbicide stress.
Two-dimensional gel electrophoresis coupled to mass spectrometry analysis was used to examine for the first time the effect of a herbicide (flumioxazin) on a crop species (Vitis vinifera L.) at the proteome level. Examination of 2-D maps derived from chemically stressed tissues revealed the presence of 33 spots displaying a differential expression pattern. The presence of stress responsive proteins in the different plant organs analysed suggests that flumioxazin could act systemically. Among the responsive proteins, some photosynthesis-related proteins, including several fragments of the enzyme Rubisco, were identified. This effect suggests that photosynthesis could be impaired by the herbicide. The induction of several enzymatic antioxidant systems was also observed, probably as a result of an oxidative stress. Moreover, the photorespiration pathway was stimulated, as suggested by the induction of some key enzymes involved in this process. Changes in carbon metabolism-associated proteins presumably reflect altered patterns of carbon flux in response to impaired photosynthesis and an increased need for osmotic adjustment in affected tissues. Finally, plant defences were stimulated as revealed by the induction of a set of proteins belonging to the pathogenesis-related 10 class, suggesting that they could play an essential role in cell defence mechanisms against flumioxazin.


Biomaterial Wettability Affects Fibrin Clot Structure and Fibrinolysis.
Thrombosis on blood-contacting medical devices can cause patient fatalities through device failure and unstable thrombi causing embolism. The effect of material wettability on fibrin network formation, structure, and stability is poorly understood. Under static conditions, fibrin fiber network volume and density increase in clots formed on hydrophilic compared to hydrophobic polystyrene surfaces. This correlates with reduced plasma clotting time and increased factor XIIa (FXIIa) activity. These structural differences are consistent up to 50 µm away from the material surface and are FXIIa dependent. Fibrin forms fibers immediately at the material interface on hydrophilic surfaces but are incompletely formed in the first 5 µm above hydrophobic surfaces. Additionally, fibrin clots on hydrophobic surfaces have increased susceptibility to fibrinolysis compared to clots formed on hydrophilic surfaces. Under low-flow conditions, clots are still denser on hydrophilic surfaces, but only 5 µm above the surface, showing the combined effect of the surface wettability and coagulation factor dilution with low flow. Overall, wettability affects fibrin fiber formation at material interfaces, which leads to differences in bulk fibrin clot density and susceptibility to fibrinolysis. These findings have implications for thrombus formed in stagnant or low-flow regions of medical devices and the design of nonthrombogenic materials.


Crossing fitness canyons by a finite population.
We consider the Wright-Fisher model of the finite population evolution on a fitness landscape defined in the sequence space by a path of nearly neutral mutations. We study a specific structure of the fitness landscape: One of the intermediate mutations on the mutation path results in either a large fitness value (climbing up a fitness hill) or a low fitness value (crossing a fitness canyon), the rest of the mutations besides the last one are neutral, and the last sequence has much higher fitness than any intermediate sequence. We derive analytical formulas for the first arrival time of the mutant with two point mutations. For the first arrival problem for the further mutants in the case of canyon crossing, we analytically deduce how the mean first arrival time scales with the population size and fitness difference. The location of the canyon on the path of sequences has a crucial role. If the canyon is at the beginning of the path, then it significantly prolongs the first arrival time; otherwise it just slightly changes it. Furthermore, the fitness hill at the beginning of the path strongly prolongs the arrival time period; however, the hill located near the end of the path shortens it. We optimize the first arrival time by applying a nonzero selection to the intermediate sequences. We extend our results and provide a scaling for the valley crossing time via the depth of the canyon and population size in the case of a fitness canyon at the first position. Our approach is useful for understanding some complex evolution systems, e.g., the evolution of cancer.


Clearance of gentamicin during hemodialysis: comparison of four artificial kidneys.
The effects of four types of artificial kidney on dialyzer clearance rates and serum pharmacokinetics of gentamicin were compared. In 19 patients undergoing chronic hemodialysis, the mean (+/-SE) interdialysis half-life of gentamicin in serum was 49.3 +/- 3.5 hr, whereas during dialysis this value was reduced to 10.0 +/- 0.7 hr. The mean half-life of gentamicin in serum at conventional flow rates for the Hollow Fiber Kidney, Kiil, Gambro, and Coil dialyzers was 11.3, 10.9, 8.2, and 7.4 hr, respectively, and the mean values for clearance of gentamicin were 26,28,42, and 48 ml per min, respectively. For all dialyzers, rates of clearance of gentamicin increased linearly with plasma flow rate over the flow range studied. The Gambro and Coil dialyzers had significantly higher rates of clearance of gentamicin from serum (P less than 0.05) than the Hollow Fiber Kidney and Kiil dialyzers over a wide range of clinically useful plasma flow rates (119-300 ml per min), whereas the Kiil dialyzer cleared gentamicin more effectively (P less than 0.05) than the Hollow Fiber Kidney dialyzer over a more limited interval (117-177 ml per min). Therapeutic recommendations for patients undergoing hemodialysis were made in light of current findings.


Ginseng Saponin Rb1 Attenuates Cigarette Smoke Exposure-Induced Inflammation, Apoptosis and Oxidative Stress via Activating Nrf2 and Inhibiting NF-κB Signaling Pathways.
Cigarette smoke exposure is one of the major risk factors for the development of chronic obstructive pulmonary disease (COPD). Ginseng saponin Rb1 (Rb1) is a natural extract from ginseng root with anti-inflammatory and anti-oxidant effects. However, the underlying mechanism of the Rb1 in COPD remains unknown. Therefore, we sought to explore the role of Rb1 in cigarette smoke-induced damage and to reveal the potential mechanism. The cell viability and lactose dehydrogenase (LDH) activity were analyzed using cell counting kit-8 (CCK-8) and LDH release assays. We further investigated the inflammation, apoptosis and oxidative stress markers and analyzed the nuclear factor-kappa B (NF-κB) and nuclear factor erythroid-2-related factor 2 (Nrf2) pathways in BEAS-2B cells and COPD rat model following cigarette smoke extract (CSE) exposure. Our results showed that CSE promoted inflammation, apoptosis and oxidative stress in BEAS-2B cells. Rb1 suppressed the inflammatory response by inhibiting expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β and inhibiting the NF-κB signaling pathway. Rb1 possessed the ability to hinder cell apoptosis induced by CSE. In addition, Rb1 concurrently reduced CSE-induced oxidative reactions and promoted Nrf2 translocation to nucleus. For in vivo study, Rb1 treatment alleviated CSE-induced lung injury, apoptosis, reactive oxygen species (ROS) release and inflammatory reactions. Also, Rb1 treatment activated Nrf2 signaling and inactivated NF-κB signaling in COPD rats. Rb1 attenuates CSE-induced inflammation, apoptosis and oxidative stress by suppressing NF-κB and activating Nrf2 signaling pathways, which provides novel insights into the mechanism underlying CSE-induced COPD.


Video Analysis of Primary Shoulder Dislocations in Rugby Tackles.
Characteristics of rugby tackles that lead to primary anterior shoulder dislocation remain unclear. To clarify the characteristics of tackling that lead to shoulder dislocation and to assess the correlation between the mechanism of injury and morphological damage of the glenoid. Case series; Level of evidence, 4. Eleven elite rugby players who sustained primary anterior shoulder dislocation due to one-on-one tackling between 2001 and 2014 were included. Using an assessment system, the tackler's movement, posture, and shoulder and head position were evaluated in each phase of tackling. Based on 3-dimensional computed tomography, the glenoid of the affected shoulder was classified into 3 types: intact, erosion, and bone defect. Orientation of the glenoid defect and presence of Hill-Sachs lesion were also evaluated. Eleven tackles that led to primary shoulder dislocation were divided into hand, arm, and shoulder tackle types based on the site at which the tackler contacted the ball carrier initially. In hand and arm tackles, the tackler's shoulder joint was forcibly moved to horizontal abduction by the impact of his upper limb, which appeared to result from an inappropriate approach to the ball carrier. In shoulder tackles, the tackler's head was lowered and was in front of the ball carrier at impact. There was no significant correlation between tackle types and the characteristics of bony lesions of the shoulder. Although the precise mechanism of primary anterior shoulder dislocation could not be estimated from this single-view analysis, failure of individual tackling leading to injury is not uniform and can be caused by 2 main factors: failure of approach followed by an extended arm position or inappropriate posture of the tackler at impact, such as a lowered head in front of the opponent. These findings indicate that injury mechanisms should be assessed for each type of tackle, as it is unknown whether external force to the glenoid is different in each mechanism during shoulder dislocation.


The 2019 novel coronavirus disease (COVID-19) pandemic: A review of the current evidence.
A novel coronavirus (nCoV) spillover event, with its epicenter in Wuhan, People's Republic of China, has emerged as a public health emergency of international concern. This began as an outbreak in December 2019, and till February 28, 2020, there have been 83,704 confirmed cases of novel coronavirus disease 2019 (COVID-19) globally, with 2,859 deaths, resulting in an overall case fatality rate of 3.41 per cent (95% confidence interval 3.29-3.54%). By this time (February 28, 2020) 58 countries or territories and one international conveyance (Diamond Princess Cruise Ship) were affected. As a part of the global response to manage and contain the pandemic, major emphasis was placed on generating research intelligence to guide evidence-based responses to contain the virus, which was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), owing to its genetic similarities with the SARS virus. This review summarizes the emerging evidence which can help guide the public health response, particularly in India. Key areas have been identified in which research needs to be conducted to generate critical intelligence for advising prevention and control efforts. The emergence of SARS-CoV-2 has once again exposed the weaknesses of global health systems preparedness, ability to respond to an infectious threat, the rapidity of transmission of infections across international borders and the ineffectiveness of knee-jerk policy responses to emerging/re-emerging infectious disease threats. The review concludes with the key learning points from the ongoing efforts to prevent and contain COVID-19 and identifies the need to invest in health systems, community-led response mechanisms and the need for preparedness and global health security.


De Novo Design and Synthesis of Polypeptide Immunomodulators for Resetting Macrophage Polarization.
Modulating the extracellular matrix microenvironment is critical for achieving the desired macrophage phenotype in immune investigations or tumor therapy. Combining de novo protein design and biosynthesis techniques, herein, we designed a biomimetic polypeptide self-assembled nano-immunomodulator to trigger the activation of a specific macrophage phenotype. It was intended to be made up of (GGSGGPGGGPASAAANSASRATSNSP)n, the RGD motif from collagen, and the IKVAV motif from laminin. The combination of these domains allows the biomimetic polypeptide to assemble into extracellular matrix-like nanofibrils, creating an extracellular matrix-like milieu for macrophages. Furthermore, changing the concentration further provides a facile route to fine-tune macrophage polarization, which enhances antitumor immune responses by precisely resetting tumor-associated macrophage immune responses into an M1-like phenotype, which is generally considered to be tumor-killing macrophages, primarily antitumor, and immune-promoting. Unlike metal or synthetic polymer-based nanoparticles, this polypeptide-based nanomaterial exhibits excellent biocompatibility, high efficacy, and precise tunability in immunomodulatory effectiveness. These encouraging findings motivate us to continue our research into cancer immunotherapy applications in the future.


Laboratory investigations of the role of the grain surface in astrochemical models.
The rich chemistry often detected in star forming regions is now recognized to be a consequence of solid-state astrochemistry and the thermal desorption of its products. In recent experimental studies, desorption of a range of ices from a gold surface was investigated using temperature programmed desorption (TPD). These data were then used in astrochemical models. In this paper we investigate the sensitivity of these models to the inclusion of TPD data obtained from different surfaces (simulating different dust grains) and different thicknesses of the icy mantles. Detailed laboratory TPD studies of the desorption of ices from a highly oriented pyrolytic graphite (HOPG) surface have been performed. Desorption temperatures and kinetic parameters have been determined directly from the TPD data and have been used to determine the expected desorption temperature for the ices from grain surfaces. The results of these experiments have been incorporated into astrochemical models of high mass star forming regions and have then been compared with the results of previous experiments. From this comparison, we are able to determine whether the nature and composition of the grain surface is important in dictating the chemistry that occurs in star forming regions.


Research advance of Nrf2 on atherosclerosis by regulating vascular smooth muscle cell.
Atherosclerosis is a common pathological change in cardiovascular disease. Vascular smooth muscle cell is the main source of plaque cell and extracellular matrix, and nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating the function of vascular smooth muscle cell. In the process of atherosclerosis, Nrf2 signaling pathway has the following regulatory effects on vascular smooth muscle cell: regulating the phenotype of vascular smooth muscle cell to change to the direction conducive to the alleviation of disease progression; inhibiting the proliferation and migration of vascular smooth muscle cell; mitigating the level of blood lipid; alleviating vascular smooth muscle cell calcification, aging and apoptosis process. This article reviews the specific mechanisms of Nrf2 regulating atherosclerosis, such as phenotypic transformation, proliferation and migration, lipid metabolism, calcification, aging and apoptosis in atherosclerosis, in order to provide a basis for understanding the molecular mechanism of atherosclerosis development and finding therapeutic targets.


Highly condensed fluorinated methacrylate hybrid material for transparent low-kappa passivation layer in LCD-TFT.
Photocurable and highly condensed fluorinated methacrylate oligosiloxane, with a low dielectric constant (kappa = 2.54), was prepared by a nonhydrolytic sol-gel condensation reaction. The oligosiloxane resin was then spin-coated, photocured, and thermally baked in order to fabricate a fluorinated methacrylate hybrid material (FM hybrimer) thin film. This study investigated the application of this FM hybrimer film as a low-kappa passivation layer in LCD-based thin film transistors (TFT). It was found that a dielectric constant as low as kappa = 2.54 could be obtained, without introducing pores in the dense FM hybrimer films. This study compares FM hybrimer film characteristics with those required for passivation layers in LCD-TFTs, including thermal stability, optical transmittance, hydrophobicity, gap fill, and planarization effects as well as electrical insulation.


Nodular thyroid disease and thyroid malignancy: Experience at Polokwane Mankweng Hospital Complex, Limpopo Province, South Africa.
Nodular thyroid disease is common throughout the world. Numbers of patients with goitre are increasing worldwide, as also noted in Limpopo Province, South Africa (SA). Globally, thyroid nodules have been reported in 4-7% of the population on neck palpation and in 30-50% by ultrasonography. To review the profile of thyroid disease in patients with goitre presenting to the Department of Surgery at Polokwane Mankweng Hospital Complex (PMHC), Limpopo, SA, to characterise the pattern of malignancy in patients with goitre, and to determine the most common thyroid cancer. A 6-year retrospective study (2003-2008) of all patients with thyroid nodules who underwent thyroid surgery at PMHC. The study group included 90 patients (mean age 45 years, range 4-80). The male-to-female ratio was 1:17 (5 men, 85 women). Of these patients, 80 (89.9%) had benign lesions, of which 52 (57.8% of the total) were adenomas, 25 (27.8%) multinodular goitres (MNGs), 2 (2.2%) hyperplastic nodules and 1 (1.1%) Hashimoto's thyroiditis. Ten patients (11.1%) had malignant lesions (7 follicular carcinomas and 3 papillary carcinomas), of which 2 were found in MNGs. Adenoma and MNG were the predominant non-malignant conditions (85.6%). The prevalence of thyroid cancer in our study was 11.1%, and of all 90 patients, 7.8% had follicular carcinoma. The risk of malignancy in MNG was 8.9%. Rates of thyroid nodules and carcinoma were highest in women aged 41-60 years. We advocate that total thyroidectomy be considered for MNG, because MNG can harbour incidental carcinoma.


Urinary tract infections in older adults.
Upper and lower urinary tract infections are common and frequently recurring problems encountered by clinicians who manage the health care of older adults. Due to the multiplicity of diseases in this population, it is sometimes difficult to identify symptoms and diagnose urinary tract infections. Evaluating the presenting symptoms, collecting specimens and interpreting laboratory data can present a challenge. Identifying clients at risk, knowing the client's prior health status, recognizing the symptoms and maintaining updated knowledge of antibiotic therapy remain essential care components. This article reviews the current literature on urinary tract infections and provides guidelines for the treatment of urinary tract infections in the older adult.


Postoperative Vasoplegic Syndrome Is Associated With Impaired Endothelial Vasomotor Response in Cardiac Surgery: A Prospective, Observational Study.
Vasoplegic syndrome (VS) affects up to 30% of cardiac surgery patients. Onset of VS may be associated with overproduction of nitric oxide (NO). The response of the brachial artery to NO can be assessed using flow-mediated vasodilation (FMD). The aim of this study was to assess brachial artery diameter and FMD response immediately after cardiac surgery. Prospective, observational study. Single-center study in a tertiary teaching hospital. Patients older than 18 years undergoing elective cardiac surgery with cardiopulmonary bypass who provided informed consent. Brachial artery diameter and FMD response were measured before cardiac surgery and just after surgery on admission to the intensive care unit. Patients were screened for VS for the following 48 hours. Eleven (39%) of the 28 patients included in the study developed VS. Brachial artery diameter and FMD differed between VS and non-VS patients. On intensive care unit admission, mean (± standard deviation) brachial artery diameter was greater in VS patients than in non-VS patients (3.9 ± 0.7 mm v 3.0 ± 0.8 mm, respectively; p = 0.002). Similarly, the FMD response after surgery was greater in VS patients than in non-VS patients (42% ± 8% v 31% ± 1%, respectively; p = 0.014). Brachial artery diameter and FMD response after surgery were both predictive of VS, with an area under the curve (95% confidence interval) of 0.850 (0.705-0.995) (p = 0.002) and 0.755 (0.56-0.95) (p = 0.047), respectively. Cardiac surgery with cardiopulmonary bypass appears to alter the NO-mediated endothelial vasomotor response.


[Simple in vitro test systems for determining the toxicity of environmental chemicals: microcultures of human lymphocytes and monoxenic ciliate cultures].
Two test methods were developed to assess (I) the cytotoxicity, (II) the environmental toxicity of chemicals. Test parameter for (I) is the growth inhibition of human T-lymphocytes stimulated by PHA (test period 6-7 days), for (II) the inhibition of cell multiplication of the ciliate Tetrahymena pyriformis grown monoxenically in a chemically defined medium which contained glucose and citrate as only carbon source (test period 13-14 days). The EC50 values (mol/l) of Pb, Cd, Hg, dichlorvos, atrazine and lindane were for (I): greater than or equal to 10(-2,5), 10(-5,4), 10(-5,6), 10(-5,0), 10(-4,75) and 10(-3,95) respectively, for (II): 10(-6,72), less than or equal to 10(-6,66), 10(-7,84), 10(-3,61), 10(-3,93) and 10(-4,75) respectively. The advantages of the described bioassays are simple handling and high sensitivity.


Protein structure determination with paramagnetic solid-state NMR spectroscopy.
Many structures of the proteins and protein assemblies that play central roles in fundamental biological processes and disease pathogenesis are not readily accessible via the conventional techniques of single-crystal X-ray diffraction and solution-state nuclear magnetic resonance (NMR). On the other hand, many of these challenging biological systems are suitable targets for atomic-level structural and dynamic analysis by magic-angle spinning (MAS) solid-state NMR spectroscopy, a technique that has far less stringent limitations on the molecular size and crystalline state. Over the past decade, major advances in instrumentation and methodology have prompted rapid growth in the field of biological solid-state NMR. However, despite this progress, one challenge for the elucidation of three-dimensional (3D) protein structures via conventional MAS NMR methods is the relative lack of long-distance data. Specifically, extracting unambiguous interatomic distance restraints larger than ∼5 Å from through-space magnetic dipole-dipole couplings among the protein (1)H, (13)C, and (15)N nuclei has proven to be a considerable challenge for researchers. It is possible to circumvent this problem by extending the structural studies to include several analogs of the protein of interest, intentionally modified to contain covalently attached paramagnetic tags at selected sites. In these paramagnetic proteins, the hyperfine couplings between the nuclei and unpaired electrons can manifest themselves in NMR spectra in the form of relaxation enhancements of the nuclear spins that depend on the electron-nucleus distance. These effects can be significant for nuclei located up to ∼20 Å away from the paramagnetic center. In this Account, we discuss MAS NMR structural studies of nitroxide and EDTA-Cu(2+) labeled variants of a model 56 amino acid globular protein, B1 immunoglobulin-binding domain of protein G (GB1), in the microcrystalline solid phase. We used a set of six EDTA-Cu(2+)-tagged GB1 mutants to rapidly determine the global protein fold in a de novo fashion. Remarkably, these studies required quantitative measurements of only approximately four or five backbone amide (15)N longitudinal paramagnetic relaxation enhancements per residue, in the complete absence of the usual internuclear distance restraints. Importantly, this paramagnetic solid-state NMR methodology is general and can be directly applied to larger proteins and protein complexes for which a significant fraction of the signals can be assigned in standard 2D and 3D MAS NMR chemical shift correlation spectra.


CRISPR-Cas9 generated Pompe knock-in murine model exhibits early-onset hypertrophic cardiomyopathy and skeletal muscle weakness.
Infantile-onset Pompe Disease (IOPD), caused by mutations in lysosomal acid alpha-glucosidase (Gaa), manifests rapidly progressive fatal cardiac and skeletal myopathy incompletely attenuated by synthetic GAA intravenous infusions. The currently available murine model does not fully simulate human IOPD, displaying skeletal myopathy with late-onset hypertrophic cardiomyopathy. Bearing a Cre-LoxP induced exonic disruption of the murine Gaa gene, this model is also not amenable to genome-editing based therapeutic approaches. We report the early onset of severe hypertrophic cardiomyopathy in a novel murine IOPD model generated utilizing CRISPR-Cas9 homology-directed recombination to harbor the orthologous Gaa mutation c.1826dupA (p.Y609*), which causes human IOPD. We demonstrate the dual sgRNA approach with a single-stranded oligonucleotide donor is highly specific for the Gaac.1826 locus without genomic off-target effects or rearrangements. Cardiac and skeletal muscle were deficient in Gaa mRNA and enzymatic activity and accumulated high levels of glycogen. The mice demonstrated skeletal muscle weakness but did not experience early mortality. Altogether, these results demonstrate that the CRISPR-Cas9 generated Gaac.1826dupA murine model recapitulates hypertrophic cardiomyopathy and skeletal muscle weakness of human IOPD, indicating its utility for evaluation of novel therapeutics.


The nature of the rate-limiting steps in the refolding of the cofactor-dependent protein aspartate aminotransferase.
The refolding of mitochondrial aspartate aminotransferase (mAAT; EC 220.127.116.11) has been studied following unfolding in 6 m guanidine hydrochloride for different periods of time. Whereas reactivation of equilibrium-unfolded mAAT is sigmoidal, reactivation of the short term unfolded protein displays a double exponential behavior consistent with the presence of fast and slow refolding species. The amplitude of the fast phase decreases with increasing unfolding times (k approximately 0.75 min(-1) at 20 degrees C) and becomes undetectable at equilibrium unfolding. According to hydrogen exchange and stopped-flow intrinsic fluorescence data, unfolding of mAAT appears to be complete in less than 10 s, but hydrolysis of the Schiff base linking the coenzyme pyridoxal 5'-phosphate (PLP) to the polypeptide is much slower (k approximately 0.08 min(-1)). This implies the existence in short term unfolded samples of unfolded species with PLP still attached. However, since the disappearance of the fast refolding phase is about 10-fold faster than the release of PLP, the fast refolding phase does not correspond to folding of the coenzyme-containing molecules. The fast refolding phase disappears more rapidly in the pyridoxamine and apoenzyme forms of mAAT, both of which lack covalently attached cofactor. Thus, bound PLP increases the kinetic stability of the fast refolding unfolding intermediates. Conversion between fast and slow folding forms also takes place in an early folding intermediate. The presence of cyclophilin has no effect on the reactivation of either equilibrium or short term unfolded mAAT. These results suggest that proline isomerization may not be the only factor determining the slow refolding of this cofactor-dependent protein.


Osteoporosis Is the Most Important Risk Factor for Odontoid Fractures in the Elderly.
Traumatic odontoid fractures (TOFs) have been described as the most common injury affecting the C-spine in the elderly. Previous studies have identified degenerative changes and bone loss as important predisposing factors. However, their interaction and respective age-adjusted impact needs further clarification. We conducted a retrospective analysis of 5303 patients (aged ≥60 years) admitted to a level I trauma center between January 2008 and January 2016 who underwent CT imaging of the C-spine. Ninety-two patients with TOF and 80 patients with other cervical spine fractures (OCSF) were identified and a respective 3:1 age- and sex-matched control group without fractures after trauma was built. In all groups, cervical bone mineral density (cBMD) was determined using phantom calibration, and degenerative changes were evaluated in a qualitative manner. In all groups, the severity of degenerative changes of the C-spine increased with age (all p < 0.05) and was inversely correlated with cBMD (all p < 0.05). cBMD was the only significant predictor of a TOF in a multivariate logistic regression model (adjusted odds ratio [OR] = 3.066, 95% confidence interval [CI] 1.432-6.563 for cervical osteoporosis). An association between odontoid cysts and TOF reached significance only in Anderson and D'Alonzo (A&D) type II TOFs (aOR = 1.383; 95% CI 1.012-1.890). Patients with OCSFs, compared with patients with TOFs, were younger (median 74 versus 83 years) and had a higher cBMD (median 208 mg/mL versus 172 mg/mL). No differences were observable when comparing cBMD and grades of degenerative changes between OCSFs and their control group (all p >0.1). Decreased cBMD is the major predisposing factor for the occurrence of TOF but not for OCSF in the elderly. The severity of odontoid cysts was found to be a cBMD-independent factor associated with A&D type II TOFs. However, degenerative changes in the odontoid neighboring joints seem to be an epiphenomenon of bone loss and older age but do not independently predispose for TOF. © 2017 American Society for Bone and Mineral Research.


[Spectral characteristics of electrogastrography in gastric cancer. Possibilities of screening].
A standardised application of electrogastrography (EGG) using spectral analysis was used in 182 subjects (72 normals, 74 cancerous and 36 ulcerous) in a large range of the aging (10 to 70 years). The conditions of derivations from the abdominal surface electrodes (n = 6) are following: bipolar distance 14 cm around the pyloric point at 0 degrees (antrum axis), 60 degrees and 120 degrees. In fasting situation in normal subjects the gastric frequency (N) and the spectral amplitude (Y) of the most energetic component of EGG was 2.89 +/- 0.2 c/min for N and 54 +/- 44 microV for Y in antropyloric axis. In the cancerous group a significative increase of mean amplitude is observed (P = 0.01). On the contrary any mean change of frequency was observed (2.89 +/- 0.3 c/min). The individual comparison with normal parameters leads to following selection: neoplasia, n = 42/74 cases (57%); ulcer, n = 13/36 (36%); however 7/72 normal subjects (10%) fall in this abnormal class as false positive. After an ingestion of tea (120 ml) giving a volumetric stimulation, the modifications of frequency are not significative contrary to the amplitude increase. Finally, the association of one or two abnormalities leads to the following percentages: 66% in cancerous, 45% in ulcerous and 23% in normal subjects. Thus a better proportion of abnormalities was observed in cancerous subjects with the stimulation but this procedure may lead to an increase of false abnormality in the non-neoplastic subjects.


Can Medicare prospective payment survive the ICD-9-CM disease classification system?
The Medicare prospective payment system represents a fundamental change in hospital payment. The diagnosis-related group (DRG) patient classification scheme serves as the modifier of payment for this system. The DRG definitions are, in turn, based on the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM). Deficiencies in the ICD-9-CM coding system directly affect the equity of the Medicare payment system. A review of the ICD-9-CM system identifies three principal problems: the inability of the system to reflect clinically important patient attributes adequately; the use of outcome, rather than approach, to code surgical procedures; and the blurring of clinical specificity by the adoption of certain coding rules. If these deficits in coding specificity are not corrected, it is unlikely that DRGs will adequately distinguish clinically unique types of patients. This inability to differentiate among patients threatens to undermine the equity of Medicare payments. Physicians must become more aware of disease coding and more involved in its development and implementation.


Amylase polymorphism: studies of sera and duodenal aspirates in normal individuals and in cystic fibrosis.
Prior genetic studies of the human pancreatic amylase (Amy2) locus have been directed principally to the electrophoretic analysis of serum and urine, on the assumption that these fluids receive negligible contributions from the salivary (Amy 1) locus. In support of that assumption was the observation that the isozyme bands were lacking in patients with cystic fibrosis and in a postpancreatectomy patient. We have examined the sera of 97 patients having cystic fibrosis and find normal levels of serum amylase. On electrophoresis, three-quarters of the cystic fibrosis patients have a pattern (F-pattern) not observed in normal sera. The pattern is characterized by the absence of Pa 1. Comparative electrophoresis and mixing experiments indicate that the F-pattern is of salivary origin and is unmasked in cystic fibrosis by the absence of a pancreatic contribution. The normal serum pattern is considered to be an admixture of salivary and pancreatic amylase. On the assumption that duodenal fluids might more closely reflect the pancreatic (Amy 2) locus, electrophoretic studies were performed on 148 normal individuals and 37 individuals with cystic fibrosis. Electrophoretic phenotypes in duodenal aspirates are more complex than previously reported in studies of urine and serum; presumably because of the higher concentrations of amylase in the aspirates. Comparative electrophoresis and mixing experiments indicate that the phenotypes observed in duodenal aspirates also reflect admixture of pancreatic and salivary amylase. This recognition of pancreatic and salivary admixture in sera fortunately does not alter our prior understanding of the genetics of the Amy 2 polymorphism. The extensive studies which led to the delineation of the Amy 2 polymorphism were essentially based on the presence or absence of a variant band which proves now to be outside the zone of admixture.


Pectus excavatum: historical background, clinical picture, preoperative evaluation and criteria for operation.
Pectus excavatum is a depression of the sternum and costal cartilages which may present at birth, or more commonly during the teenage growth spurt. Symptoms of lack of endurance, shortness of breath with exercise, or chest pain are frequent. Although pectus excavatum may be a component of some uncommon syndromes, patients usually are healthy. Evaluation should include careful anatomic description with photographs, radiography to demonstrate the depth of the depression, extent of cardiac compression, or displacement, measurement of pulmonary function, and echocardiography to look for mitral valve prolapse (in 15%) or diminished right ventricular volume. Indications for surgical treatment include two or more of the following: a severe, symptomatic deformity; progression of deformity; paradoxical respiratory chest wall motion; computer tomography scan with a pectus index greater than 3.25; cardiac compression/displacement and/or pulmonary compression; pulmonary function studies showing restrictive disease; mitral valve prolapse, bundle branch block, or other cardiac pathology secondary to compression of the heart; or failed previous repair(s). The developmental factors, genetics, and physiologic abnormalities associated with the condition are reviewed.


Metabolic Interactions between Bacteria and Fungi in Commensal Oral Biofilms.
Oral health is more than just the absence of disease. The key to oral health is a diverse microbiome in an ecological balance. The oral microbiota is one of the most complex and diverse microbial communities in the human body. To maintain oral health, balance between the human host and the intrinsic microorganisms is essential. The healthy oral cavity is represented by a great microbial diversity, including both bacteria and fungi. The bacterial microbiome is very well studied. In contrast, fungi inhabiting the oral cavity are often overlooked. All microbial species in the oral cavity form communities which establish a variety of micro-niches and inter- and intra-species interactions. These interactions can be classified into three main groups: physical, chemical and metabolic interactions. Different metabolic interactions are reviewed in this report, among which are the metabolism of sugars, carbon, lactate and oxygen. This review set out with the aim of assessing the importance of metabolic interactions between fungi and bacteria in the healthy oral cavity.


American Society of Clinical Oncology Position Statement: Strategies for Reducing Cancer Health Disparities Among Sexual and Gender Minority Populations.
ASCO is committed to addressing the needs of sexual and gender minority (SGM) populations as a diverse group at risk for receiving disparate care and having suboptimal experiences, including discrimination, throughout the cancer care continuum. This position statement outlines five areas of recommendations to address the needs of both SGM populations affected by cancer and members of the oncology workforce who identify as SGM: (1) patient education and support; (2) workforce development and diversity; (3) quality improvement strategies; (4) policy solutions; and (5) research strategies. In making these recommendations, the Society calls for increased outreach and educational support for SGM patients; increased SGM cultural competency training for providers; improvement of quality-of-care metrics that include sexual orientation and gender information variables; and increased data collection to inform future work addressing the needs of SGM communities.


Cost of home and hospital care for patients with cystic fibrosis followed up in two reference medical centers in France.
In France, new guidelines for clinical practices concerning cystic fibrosis came out in 2002, underscoring the need for early and intensive management of this disease. Because no recent health economic studies on cystic fibrosis in France were available, we conducted a cost-analysis study before the new guidelines were put into practice, with a view to a later study on the medical and economic impact of these guidelines. A cost-analysis study was performed of the inpatient and outpatient costs of patients with cystic fibrosis for the 2000-2001 period. The various direct costs were estimated on a sample of sixty-five adult and pediatric patients managed for cystic fibrosis in two reference medical centers. Data were obtained from medical records, and questionnaires were filled out by the patients. Analysis was made from the perspective of the French healthcare system. We studied sixty-five patients, 54 percent male patients and 72 percent children under 18 years of age. The total cost of cystic fibrosis care totaled 16,189 euros per year and per patient. Outpatient costs accounted for 88 percent of the total cost versus 12 percent for inpatient costs; medication costs were the highest with 21 percent of the total cost for home intravenous antibiotic treatments and 49 percent of the total cost for chronic medications. The results show that outpatient costs were higher than inpatient costs, which could be related to the importance granted to home health care in France, notably for intravenous antibiotic treatments given for pulmonary complications.


Stochastic approaches for modelling in vivo reactions.
In recent years, stochastic modelling has emerged as a physically more realistic alternative for modelling in vivo reactions. There are numerous stochastic approaches available in the literature; most of these assume that observed random fluctuations are a consequence of the small number of reacting molecules. We review some important developments of the stochastic approach and consider its suitability for modelling intracellular reactions. We then describe recent efforts to include the fluctuation effects caused by the structural organisation of the cytoplasm and the limited diffusion of molecules due to macromolecular crowding.


Inhibition of platelet aggregation ex vivo is repressed in apolipoprotein E deficient mice.
In the present study, we assessed whether the endogenous platelet inhibitory mechanisms are altered in the early to moderate stages of the atherosclerotic process. Apolipoprotein E deficient mice (ApoE-/-), a mouse model of atherosclerosis, and their wild-type (WT) counterparts were used to assess agonist-stimulated synthesis of prostacyclin (PGI2), inhibition of platelet aggregation ex vivo, and intra-platelet cAMP levels. Basal U46619 and ADP -induced platelet aggregation in vitro were increased in ApoE-/- mice at 18-20 weeks in comparison with 8-10 weeks of age. Systemically administered endothelin-1 (ET-1) or bradykinin (BK) inhibited platelet aggregation in a similar fashion in 8- to 10-week-old ApoE-/- and WT mice, but not in the ApoE-/- mice at 18-20 weeks of age, although both peptides maintained their capacity to increase plasma levels of the PGI2. Intravenous infusion of PGI2 also failed to inhibit platelet aggregation ex vivo in 18- to 20-week-old ApoE-/- mice. Interestingly, both BK and PGI2 retained their ability to increase intraplatelet cAMP in WT and ApoE-/- mice. Our results suggest that a loss of activity of endogenous inhibitorymechanisms could contribute to the increased platelet reactivity in ApoE-/- mice, and that this phenomenon occurs early in the intermediate stage of the atherosclerotic process.


Growth factor induced mitogenic effects and inositol phosphate responses in primary hepatocyte cultures from normal rat liver and rat liver nodules.
In our studies of normal and neoplastic growth regulation, we have compared growth factor induced second messenger response and mitogenic activity in a rat hepatocarcinogenesis model. Inositol phosphate (IP) turnover was measured by incubating the cells with [3H]inositol and stimulating them with either epidermal growth factor, diferric transferrin, ferricyanide, vasopressin, norepinephrine, angiotensin II or bombesin for 2 min. The IPs formed were separated on HPLC. Mitogenic responses were monitored by bromodeoxyuridine uptake and labeling index. IP turnover was stimulated by vasopressin, norepinephrine and angiotensin II in both normal and nodular cells, but not by the other four agonists tested. The IP response was somewhat lower in cells from liver nodules. All compounds except bombesin were mitogenic to both nodular cells and cells from normal rats of different ages, with epidermal growth factor inducing the largest mitogenic response. Bombesin, on the other hand, had only a minor effect on normal cells, but induced a pronounced mitogenic response in nodular cells. In normal rats, the cells' ability to respond to growth stimulation decreased with increasing rat age. In this respect, nodular cells behaved in a way more like young normal cells than their age-matched controls. Taken together, these data support the view of liver nodules being a more autonomous cell population, with increased sensitivity to growth factors and possibilities for autocrine growth stimulation.


Application of occupational exposure limits to unusual work schedules.
A one-compartment exponential models is described which predicts "equal protection", based on biological uptake rates, for unusual air contaminant exposure situations as compared to a "normal" exposure of five 8-hour days per week. This is done by equating peak body burdens resulting from a normal and an unusual exposure, in terms of an adjustment factor applied to the normal exposure limit for an air contaminant. This factor predicts the highest allowable concentration in an unusual exposure situation which will not result in a higher-than normal body accumulation of the inhaled substance. Graphs and formulae are provided for determining adjustment factors for anticipated unusual exposure schedules. The model's predictions and published data are compared.


Disruption of the NMDA receptor-PSD-95 interaction in hippocampal neurons with no obvious physiological short-term effect.
PSD-95 binds to and co-localizes with NMDA receptors at postsynaptic sites. Their co-expression in COS7 cells induces the formation of aggregates containing both proteins. These findings have lead to the hypothesis that PSD-95 helps to cluster NMDA receptors at postsynaptic sites. In addition, PSD-95 binds various regulatory proteins including Src, Pyk2, SynGAP, and nNOS and may recruit signaling proteins to NMDA receptors. We tested whether synaptic transmission or plasticity was affected by acute dissociation of the PSD-95-NMDA receptor interaction with various peptides that bound to the first two PDZ domains of PSD-95 and its homologs and with antibodies directed against the very C-terminus of the NR2A and NR2B subunits of the NMDA receptor. Membrane-impermeable peptides injected via whole cell patch electrodes distributed within minutes throughout dendritic branches into spines in acute hippocampal slices and membrane-permeable peptides containing 11 arginine residues effectively accumulated in neurites in slices and primary hippocampal cultures. Neither peptides nor antibodies showed any effect on basal synaptic transmission or induction of long-term potentiation (LTP) in hippocampal slices. Pharmacologically isolated NMDA receptor activity was also not affected. However, the membrane-permeable peptide disrupted the NMDA receptor-PSD-95 interaction in slices as tested by immunoprecipitation and subsequent immunoblotting. These findings suggest that acute dissociation of PSD-95 and its homologs from the NMDA receptor and likely from other protein complexes does not result in any easily detectable physiological effects in hippocampal slices. However, we cannot exclude a role of PSD-95 in early events that lead to clustering of NMDA receptors or of other proteins including stargazin and AMPA receptors at postsynaptic sites nor do these experiments address the possibility of long-term changes in the slices. In fact, incubation of primary hippocampal cultures with the membrane-permeable peptide lead to a moderate decrease in the number of dendritic clusters of PSD-95 and NMDA receptors and their colocalization by 20-30%, suggesting some role of PSD-95 and its homologs in NMDA receptor clustering.


Virologic, immunologic, and clinical follow-up of a couple infected by the human immunodeficiency virus type one, group O.
The pathogenic course (virologic, immunologic, and clinical changes) of infection due to human immunodeficiency virus type one (HIV-1) group O viruses is unknown at present. To address this issue, serial HIV-1 isolates from a married couple (patients A and B) infected with a group O virus were analyzed to determine the temporal association between disease status and alterations in several parameters including plasma viral burden as measured by semiquantitative polymerase chain reaction, changes in CD4+ T cells, presence of neutralizing antibodies, and the ability to induce syncytia on the MT2 cells. For patient A who has been asymptomatic for at least 8 years, both the absence of syncytium-inducing (SI) variants and the presence of autologous and heterologous neutralizing antibodies correlated with a clinically healthier status. In contrast, a switch from NSI to SI variants was observed in patient B in 1990, followed by an expanded in vitro host range, increased viral burden, and a sharp decrease in CD4+ T cells 4 years later. Moreover, plasma obtained from this patient uniformly failed to neutralize both autologous and heterologous viruses. These observations in patient B correlated with a slightly unfavorable clinical status. Based on our preliminary results, it appears that the pathogenic course of infections due to group O viruses is similar to that reported previously for infections due to group M viruses.


Survey of the effectiveness of masking noises during dental treatment--a pilot study.
The aim of this study was to test the effectiveness of a newly developed system, using masking noises with specific frequencies and amplitudes, adjusted to typical noises experienced during dental treatment such as the high-speed hand-held drill. In accordance with an analysis of typical noises experienced during dental treatment, masking noises with specific frequencies (frequency range 0.02 to 20 kHz) and amplitudes were created, with the aim of reducing the patients' awareness of typical treatment noises by overlaying frequencies. Two hundred fifty-four outpatients (113 males, 141 females) with a mean age of 32 years (+/- 10.5 years) were enrolled in this study. Patients were treated 15 minutes with and 15 minutes without the masking noise. Patients and practitioners filled out questionnaires aimed to evaluate the effectiveness of the system, sensitivity to noise (scale 0 to 10; 0 = effective, 10 = noneffective), psychologic aspects, and statements of fear. There was a significant reduction in patients' awareness of noise using this system during dental treatment. Most of the patients regarded the masking noise as a pleasureable supplementation to common treatment and would select this manner of dental treatment employing the device again (81.5%); 48.2% said they were more relaxed. The system does not, in principle, interfere with dental treatment, and in most instances, the device does not impede the communication between practitioners and patients. The present study demonstrates that using masking noises during dental treatment reduces the sensitivity to drill noise, reduces fear and stress, and may be useful in dental practice as an adjunct to common dental treatment.


Optimal PET protection for streaming scalably compressed video streams with limited retransmission based on incomplete feedback.
For streaming scalably compressed video streams over unreliable networks, Limited-Retransmission Priority Encoding Transmission (LR-PET) outperforms PET remarkably since the opportunity to retransmit is fully exploited by hypothesizing the possible future retransmission behavior before the retransmission really occurs. For the retransmission to be efficient in such a scheme, it is critical to get adequate acknowledgment from a previous transmission before deciding what data to retransmit. However, in many scenarios, the presence of a stochastic packet delay process results in frequent late acknowledgements, while imperfect feedback channels can impair the server's knowledge of what the client has received. This paper proposes an extended LR-PET scheme, which optimizes PET-protection of transmitted bitstreams, recognizing that the received feedback information is likely to be incomplete. Similar to the original LR-PET, the behavior of future retransmissions is hypothesized in the optimization objective of each transmission opportunity. As the key contribution, we develop a method to efficiently derive the effective recovery probability versus redundancy rate characteristic for the extended LR-PET communication process. This significantly simplifies the ultimate protection assignment procedure. This paper also demonstrates the advantage of the proposed strategy over several alternative strategies.


Multivariate analysis of morphometric traits of Malaimadu cattle-autochthonous draft cattle of south India.
Malaimadu cattle is a less explored indigenous cattle germplasm reared in the Western Ghats area of Tamil Nadu, south India. This study aimed to analyze the morphological structure of the Malaimadu cattle using a multivariate approach that explains and best represents body conformation. Sixteen body measurements were obtained from 156 adult female cattle from their native breeding tract. The Nearest Neighbor Method of Hierarchical Cluster analysis was used to group the morphometric traits into clusters. Pearson's coefficients of correlation (r) were estimated to determine the phenotypic correlations between different body measurements. Traits were analyzed using varimax rotated principal component analysis (PCA) with Kaiser normalization. Cluster analysis categorizes morphometric traits into two distinct clusters with the first cluster formed by traits related to horns and face, while the second cluster denotes general body conformation. Out of 120 phenotypic correlations, 55 were significant of which 51 were positive correlations. The estimated correlation coefficient ranges between - 0.50 (body length and face width) to 0.85 (chest girth and body weight). PCA extracted six components representing 70.19% of the total variance, while the first principal component comprises chest girth (CG), body weight (BW), height at wither (HW), and Paunch girth (PG) alone accounts for 23.70% thereby describing the general size and shape of the animal. The multivariate approach has proven to be effective in differentiating Malaimadu cattle from other indigenous breeds of south India with clear morphometric differences that help in identifying the pure phenotype for future propagation and also for devising breeding strategies.


Pentanoic acid induces thymic stromal lymphopoietin production through Gq/11 and Rho-associated protein kinase signaling pathway in keratinocytes.
Thymic stromal lymphopoietin (TSLP) plays an important role in allergic skin inflammation. Short-chain fatty acids (SCFAs), including pentanoic acid, are products of bacterial metabolism and are associated with allergic skin disorders. However, whether SCFAs induce TSLP production is still unclear. In this study, we evaluated the effect of SCFAs on TSLP production and found that pentanoic acid was the most efficacious of the tested SCFAs. The Gq/11 inhibitor YM-254890 and the Rho-associated protein kinase (ROCK) inhibitor Y-27632 inhibited pentanoic acid-induced TSLP production, as did transfection with Gq/11 siRNA. These results suggested that pentanoic acid-induced TSLP production was mediated by Gq/11 and ROCK, providing insights into a novel TSLP production pathway in keratinocytes. The novel mechanism of TSLP production is expected to support the development of TSLP-regulating approaches in allergic skin disorders.


Deletion of VPS50 protein in mice brain impairs synaptic function and behavior.
VPS50, is an accessory protein, involved in the synaptic and dense core vesicle acidification and its alterations produce behavioral changes in C.elegans. Here, we produce the mosaic knock out (mKO) of VPS50 using CRISPR/Cas9 system in both cortical cultured neurons and whole animals to evaluate the effect of VPS50 in regulating mammalian brain function and behavior. While mKO of VPS50 does not change the number of synaptic vesicles, it produces a mislocalization of the V-ATPase pump that likely impact in vesicle acidification and vesicle content to impair synaptic and neuronal activity in cultured neurons. In mice, mKO of VPS50 in the hippocampus, alter synaptic transmission and plasticity, and generated robust cognitive impairments associate to memory formation. We propose that VPS50 is an accessory protein that aids the correct recruitment of the V-ATPase pump to synaptic vesicles, thus having a crucial role controlling synaptic vesicle acidification and hence synaptic transmission.


Oxidative modification of neurofilament-L by copper-catalyzed reaction.
Neurofilament-L (NF-L) is a major element of neuronal cytoskeletons and known to be important for neuronal survival in vivo. Since oxidative stress might play a critical role in the pathogenesis of neurodegenerative diseases, we investigated the role of copper and peroxide in the modification of NF-L. When disassembled NF-L was incubated with copper ion and hydrogen peroxide, then the aggregation of protein was proportional to copper and hydrogen peroxide concentrations. Dityrosine crosslink formation was obtained in copper-mediated NF-L aggregates. The copper-mediated modification of NF-L was significantly inhibited by thiol antioxidants, Nacetylcysteine, glutathione, and thiourea. A thioflavin-T binding assay was performed to determine whether the copper/H2O2 system-induced in vitro aggregation of NF-L displays amyloid-like characteristics. The aggregate of NF-L displayed thioflavin T reactivity, which was reminiscent of amyloid. This study suggests that copper-mediated NF-L modification might be closely related to oxidative reactions which may play a critical role in neurodegenerative diseases.


Catalytic reduction of CN-, CO, and CO2 by nitrogenase cofactors in lanthanide-driven reactions.
Nitrogenase cofactors can be extracted into an organic solvent to catalyze the reduction of cyanide (CN(-)), carbon monoxide (CO), and carbon dioxide (CO2) without using adenosine triphosphate (ATP), when samarium(II) iodide (SmI2) and 2,6-lutidinium triflate (Lut-H) are employed as a reductant and a proton source, respectively. Driven by SmI2, the cofactors catalytically reduce CN(-) or CO to C1-C4 hydrocarbons, and CO2 to CO and C1-C3 hydrocarbons. The C-C coupling from CO2 indicates a unique Fischer-Tropsch-like reaction with an atypical carbonaceous substrate, whereas the catalytic turnover of CN(-), CO, and CO2 by isolated cofactors suggests the possibility to develop nitrogenase-based electrocatalysts for the production of hydrocarbons from these carbon-containing compounds.


Development of a clinical scoring model to predict the overall and relapse‑free survival of patients with hepatocellular carcinoma following a hepatectomy.
Hepatocellular carcinoma (HCC) is a highly lethal disease, and surgical resection is one of the major treatment methods used. However, to date, at least to the best of our knowledge, there is no effective prognostic scoring system for the overall survival (OS) and relapse-free survival (RFS) of patients following hepatectomy. The present study developed a low-cost and easy-to-use model based on the clinicopathological characteristics of patients with HCC for assessment of outcome prediction and risk stratification. A total of 690 patients with HCC undergoing surgery were included and randomly divided into two cohorts (n=345). Cox regression analysis was conducted to investigate the association between the clinicopathological and treatment features, and patient survival. Multivariate analysis revealed that ascites, vascular tumor thrombus, low tumor differentiation and extrahepatic metastasis were independent risk factors for OS. Extrahepatic metastasis and multiple tumors were independent risk factors to predict tumor recurrence. These variables were weighted to construct the ascites, vascular tumor thrombus, low tumor differentiation, extrahepatic metastasis and multiple tumors (AVLEM) score based on the cumulative incidence (CuI) of the aforementioned variables, and the patients were classified into grade 0 (CuI=0), grade 1 (CuI=1 for OS and CuI ≥1 for RFS), and grade 2 (CuI ≥2) subgroups, respectively. Kaplan-Meier analysis revealed that the OS and RFS differed significantly among the subgroups; however, the survival rate between the two cohorts did not exhibit any marked differences. On the whole, the present study demonstrates that with this AVLEM scoring system, patients with HCC with a high score had a poor OS and RFS; thus, it is suggested that such patients undergo imaging examinations following a hepatectomy more frequently.


Comparison of CT images with average intensity projection, free breathing, and mid-ventilation for dose calculation in lung cancer.
The purpose of this study was to compare three computed tomography (CT) images under different conditions-average intensity projection (AIP), free breathing (FB), mid-ventilation (MidV)-used for radiotherapy contouring and planning in lung cancer patients. Two image sets derived from four-dimensional CT (4DCT) acquisition (AIP and MidV) and three-dimensional CT with FB were generated and used to plan for 29 lung cancer patients. Organs at risk (OARs) were delineated for each image. AIP images were calculated with 3D conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT). Planning with the same target coverage was applied to the FB and MidV image sets. Plans with small and large tumors were compared regarding OAR volumes, geometrical center differences in OARs, and dosimetric indices. A gamma index analysis was also performed to compare dose distributions. There were no significant differences (P > 0.05) in OAR volumes, the geometrical center differences, maximum and mean doses of the OARs between both tumor sizes. For 3DCRT, the gamma analysis results indicated an acceptable dose distribution agreement of 95% with 2%/2 mm criteria. Although, the gamma index results show distinct contrast of dose distribution outside the planning target volume (PTV) in IMRT, but within the PTV, it was acceptable. All three images could be used for OAR delineation and dose calculation in lung cancer. AIP image sets seemed to be suitable for dose calculation while patient movement between series acquisition of FB images should be considered when defining target volumes on 4DCT images.


Estrogen Receptor and Signal Transducer and Activator of Transcription 3 Expression in Equine Mammary Tumors.
Equine mammary tumors are uncommon, and relatively sparse histopathologic and molecular data exist. The present study describes the histopathologic features of 7 such tumors, which exhibited infiltrative growth, intermediate to high mitotic rates, and focally extensive necrosis. The tumors exhibited variably strong staining for vimentin and cytokeratin 14, as well as frequently weak cytoplasmic staining for pan-cytokeratin. E-cadherin expression was strong. Interestingly, a subgroup of the tumors exhibited strong nuclear staining for estrogen receptor α. Three of 7 tumors exhibited nuclear expression of the transcription factor STAT3, suggesting that STAT3 was transcriptionally active. Rare to absent nuclear STAT3 expression was observed in carcinomas exhibiting moderate to intense staining for cytokeratin 14. This investigation confirms previous investigators' assertions that equine mammary tumors have a malignant phenotype. A subset of the equine mammary tumors exhibited estrogen receptor α expression, suggesting that these tumors may potentially have similar molecular characteristics to their feline and canine counterparts.


SAGA Complex Subunits in Candida albicans Differentially Regulate Filamentation, Invasiveness, and Biofilm Formation.
SAGA (Spt-Ada-Gcn5-acetyltransferase) is a highly conserved, multiprotein co-activator complex that consists of five distinct modules. It has two enzymatic functions, a histone acetyltransferase (HAT) and a deubiquitinase (DUB) and plays a central role in processes such as transcription initiation, elongation, protein stability, and telomere maintenance. We analyzed conditional and null mutants of the SAGA complex module components in the fungal pathogen Candida albicans; Ngg1, (the HAT module); Ubp8, (the DUB module); Tra1, (the recruitment module), Spt7, (the architecture module) and Spt8, (the TBP interaction unit), and assessed their roles in a variety of cellular processes. We observed that spt7Δ/Δ and spt8Δ/Δ strains have a filamentous phenotype, and both are highly invasive in yeast growing conditions as compared to the wild type, while ngg1Δ/Δ and ubp8Δ/Δ are in yeast-locked state and non-invasive in both YPD media and filamentous induced conditions compared to wild type. RNA-sequencing-based transcriptional profiling of SAGA mutants reveals upregulation of hyphal specific genes in spt7Δ/Δ and spt8Δ/Δ strains and downregulation of ergosterol metabolism pathway. As well, spt7Δ/Δ and spt8Δ/Δ confer susceptibility to antifungal drugs, to acidic and alkaline pH, to high temperature, and to osmotic, oxidative, cell wall, and DNA damage stresses, indicating that these proteins are important for genotoxic and cellular stress responses. Despite having similar morphological phenotypes (constitutively filamentous and invasive) spt7 and spt8 mutants displayed variation in nuclear distribution where spt7Δ/Δ cells were frequently binucleate and spt8Δ/Δ cells were consistently mononucleate. We also observed that spt7Δ/Δ and spt8Δ/Δ mutants were quickly engulfed by macrophages compared to ngg1Δ/Δ and ubp8Δ/Δ strains. All these findings suggest that the SAGA complex modules can have contrasting functions where loss of Spt7 or Spt8 enhances filamentation and invasiveness while loss of Ngg1 or Ubp8 blocks these processes.


Infective endocarditis due to Acinetobacter baumannii complex--a case report.
We report a case of infective endocarditis caused by Acinetobacter baumannii complex in a 27-year-old male patient. The patient presented with fever of five days duration, palpitation, dyspnea, cough and chest pain. He had undergone a surgical repair of ruptured aneurysm of sinus of valsalva a month before. The transthoracic echocardiogram revealed a large vegetation on the aortic valve. Three samples of blood for culture grew gram-negative pleomorphic coccobacilli within 24 hours which were identified by cultural and biochemical characteristics to be Acinetobacter baumannii complex. Antimicrobial susceptibility was performed by Kirby-Bauer method and the isolate were found to be resistant to ampicillin, Ciprofloxacin, Ceftriaxone, Gentamicin, Amikacin, Augmentin, Levofloxacin, Piperacillin-Tazobactam, Netilimicin and sensitive to Imipenem. Patient was initially treated with Ceftraixone and Gentamicin and subsequently with Ampicillin and Amikacin but did not respond to treatment and died of sepsis before therapy with Imipenem could be started.


Measurement and control of quality determining properties of clinical dextrans.
For plasma substitutes a main requirement is that they give plasma volume expansion. For dextran this property has been shown to be molecular weight dependent. The magnitude and duration of the volume effect, and the magnitude and rate of the excretion of dextrans have been carefully studied with regard to the correlation with molecular weight. Other clinically important effects like flow promotion and disaggregation of erythrocytes also have shown correlation with molecular weight. The measurement and control of the molecular weight distribution (MWD) of clinical dextrans thus is an important quality measure. The tolerance limits must be so set that a clinically relevant discriminating effect is obtained. In most of the current official monographs methods give only average figures of the MWDs or of broad fractions of the MWDs. In some cases these figures are not even molecular weight figures but viscosity figures. In the 1960's gel permeation chromatography (GPC) methods were developed for quality control of dextran. These methods are now suggested and considered for some pharmacopoeias, and are already introduced into one, namely the Nordic Pharmacopoeia. With these methods information of the total MWD is obtained. The proportion of dextran in a desirable molecular weight range can be directly seen, and presence of dextran with undesirable molecular weight can be revealed.


Evaluation of burn severity in vivo in a mouse model using spectroscopic optical coherence tomography.
Clinical management of burn injuries depends upon an accurate assessment of the depth of the wound. Current diagnostic methods rely primarily on subjective visual inspection, which can produce variable results. In this study, spectroscopic optical coherence tomography was used to objectively evaluate burn injuries in vivo in a mouse model. Significant spectral differences were observed and correlated with the depth of the injury as determined by histopathology. The relevance of these results to clinical burn management in human tissues is discussed.


Myxedema Coma with Reversible Cardiopulmonary Failure: a Rare Entity in 21St Century.
Myxedema coma, a rare entity in 21st century in developed nations, is a decompensated phase of hypothyroidism with high mortality rates. We describe a young woman with myxedema, who developed respiratory failure, congestive heart failure and significant pericardial effusion, some of the uncommon manifestations. Decreased cardiac contractility can result in cardiomyopathy and heart failure. As illustrated by this case, myxedema can also result in significant pericardial effusion due to increased vascular permeability. Myxedema can further be complicated by alveolar hypoventilation and respiratory failure secondary to the lack of central drive as well as respiratory muscle weakness. Prompt therapy with thyroid hormone replacement, glucocorticoid therapy, aggressive supportive care and management of the precipitating event can save lives and reverse the cardiopulmonary symptoms, as in our patient. Hence, physicians should have a high index of suspicion for myxedema coma in patients with unexplained cardiopulmonary failure. Our report is, therefore, aimed at bringing awareness about the rare but fatal manifestations of myxedema coma.


[Detection of memory T cells, follicular T cells and relevant cytokines in the peripheral blood of patients with myasthenia gravis during treatment].
Objective The variations in T cell subset composition and levels of inflammatory cytokines and acetylcholine receptor (AChR) antibody during the interval for myasthenia gravis (MG) patients were evaluated to investigate regulatory roles of in the pathogenesis of MG. Methods Thirty patients with MG and 20 healthy controls (HCs) were recruited. Flow cytometry was employed to detect the frequencies of CD4+ T cells, CD8+ T cells, central memory T cells (CD4+CD45RO+CCR7+, Tcm), effector memory T cells (CD4+CD45RO+CCR7-, Tem), follicular helper T cells (CD4+CXCR5+, Tfh) and follicular regulatory T cells (CD4+CXCR5+ FOXP3 +, Tfr) in the peripheral blood. The levels of interleukin 2(IL-2), IL-4, IL-12, IL-17 and interferon γ (IFN-γ) in the peripheral blood were determined by cytometric beads array (CBA). The levels of IL-7 and anti-AChR antibody were measured with ELISA. Results No obvious differences were observed in the frequencies of Tfh, Tem, CD8+ T cells and CD4+ T cells, and the ratio of CD4/CD8 in the peripheral blood of MG patients, compared with HCs. MG subjects presented notably decreased frequencies of Tcm and increased frequencies of Tfr compared with HCs. In addition, elevated levels of IL-2, IL-4, IL-12, IL-17 and IFN-γ and lowered levels of IL-7 were observed in the plasma of MG individuals, compared with HCs. No significant correlations were found among the levels of cytokines and frequencies of T cell subsets. No significant changes were found in AChR antibody levels. Conclusion The results suggest a unique spectrum of the memory T cells and follicular T cells, together with a unique cytokine profile in the MG individuals during treatment.


What underlies the perception that a medical intervention is effective? An exploratory study among smokers.
The perceived ineffectiveness of medical interventions is a key predictor of their underuse. This study explores the nature of this perception with regards to a range of medical interventions. Adult smokers (n = 18) completed interviews and questionnaires using the repertory grid technique to elicit personal constructs underlying perceptions of effectiveness of a range of medical interventions (three to stop smoking, three to prevent heart disease, one to reduce pain, one to lose weight, and one to treat depression). Principle components analysis was applied to identify the key underlying dimensions within the constructs. Numerical estimates of the effectiveness of the interventions were also collected from participants to compare them with the published evidence. Constructs clustered around three dimensions: "therapeutic impact," "behavior-dependent impact," and "impact facilitates general health." Smokers perceived impacts that are dependent on the individuals' behavior to offer small therapeutic impacts, while facilitating individuals' general health. These three characteristics were attributed to nonbiomedical interventions (e.g., talk-based interventions), while the opposite characteristics were attributed to biomedical interventions (i.e., medication and surgery). Numerical estimates showed that the effectiveness of stop-smoking interventions was underestimated relative to interventions to prevent heart disease. The elicited dimensions provide a basis for communicating evidence concerning the effectiveness of medical interventions, with a view to increasing their use.


Ornithine decarboxylase supports ILC3 responses in infectious and autoimmune colitis through positive regulation of IL-22 transcription.
Group 3 innate lymphoid cells (ILC3s) are RORγT+ lymphocytes that are predominately enriched in mucosal tissues and produce IL-22 and IL-17A. They are the innate counterparts of Th17 cells. While Th17 lymphocytes utilize unique metabolic pathways in their differentiation program, it is unknown whether ILC3s make similar metabolic adaptations. We employed single-cell RNA sequencing and metabolomic profiling of intestinal ILC subsets to identify an enrichment of polyamine biosynthesis in ILC3s, converging on the rate-limiting enzyme ornithine decarboxylase (ODC1). In vitro and in vivo studies demonstrated that exogenous supplementation with the polyamine putrescine or its biosynthetic substrate, ornithine, enhanced ILC3 production of IL-22. Conditional deletion of ODC1 in ILC3s impaired mouse antibacterial defense against Citrobacter rodentium infection, which was associated with a decrease in anti-microbial peptide production by the intestinal epithelium. Furthermore, in a model of anti-CD40 colitis, deficiency of ODC1 in ILC3s markedly reduced the production of IL-22 and severity of inflammatory colitis. We conclude that ILC3-intrinsic polyamine biosynthesis facilitates efficient defense against enteric pathogens as well as exacerbates autoimmune colitis, thus representing an attractive target to modulate ILC3 function in intestinal disease.


Educating vocationally trained family physicians: a survey of graduates from a postgraduate medical education programme.
INTRODUCTION Since 1991 the University of Otago, Dunedin, New Zealand has offered postgraduate qualifications specifically designed to educate general practitioners (GPs) about their unique work environment. AIM To determine motivations and impacts of postgraduate education for practising GPs. METHODS Survey of the 100 graduates of the University of Otago, Dunedin postgraduate general practice programme. Ninety five living graduates were approached and 70 (73.7%) responded. Quantitative data about disposition of respondents before enrolling and after completion of the programme were analysed using chi-square and paired t-tests. Free text responses about motivations, impacts and outcomes of the program were thematically analysed. RESULTS 64 GPs graduated with a postgraduate diploma and 36 with a masters degree in general practice. Although the mean number of graduates was 3.5 and 2.0 (respectively), annual enrolments averaged 25.1. Most graduates (60.9%) were aged in their 40s when they started studying and most (94.3%) had a spouse and/or children at home. DISCUSSION This voluntary postgraduate medical education complements traditional medical training but has low external value despite personal, practising and professional benefits. Graduates valued engagement above completion of a qualification. KEYWORDS Medical education; general practitioners; scholarship; professionalism.


[The overdiagnosis of bacterial endocarditis].
The diagnosis of bacterial endocarditis (BE) is analyzed in 255 patients. After examination, the diagnosis of BE was verified but in 92 patients (36.1%). Of these, BE was overdiagnosed in 163 patients (63.9%). The main causes of the overdiagnosis were body temperature rise in 134 patients (52.6%), heart murmur in 163 patients (63.9%), and positive hemoculture in 57 patients (22.3%). Three cases of BE overdiagnosis are provided. Exaggeration of the specificity of body temperature rise in patients with heart murmur often leads to BE overdiagnosis. Mitral valve prolapse is one of the predisposing BE factors. At the same time it is a cause of overdiagnosis of BE in patients with fever, BE overdiagnosis often results in unbased long-term antibacterial therapy, while other causes of the symptoms are not considered. Ineffectiveness of antibacterial treatment (no clinical improvement, continuous or recurrent fever) points to the necessity of further diagnostic search.


Peripheral neuropathy: differential diagnosis and management.
Peripheral neuropathy has a variety of systemic, metabolic, and toxic causes. The most common treatable causes include diabetes mellitus, hypothyroidism, and nutritional deficiencies. The diagnosis requires careful clinical assessment, judicious laboratory testing, and electrodiagnostic studies or nerve biopsy if the diagnosis remains unclear. A systematic approach begins with localization of the lesion to the peripheral nerves, identification of the underlying etiology, and exclusion of potentially treatable causes. Initial blood tests should include a complete blood count, comprehensive metabolic profile, and measurement of erythrocyte sedimentation rate and fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels; specialized tests should be ordered if clinically indicated. Lumbar puncture and cerebrospinal fluid analysis may be helpful in the diagnosis of Guillain-Barré syndrome and chronic inflammatory demyelinating neuropathy. Electrodiagnostic studies, including nerve conduction studies and electromyography, can help in the differentiation of axonal versus demyelinating or mixed neuropathy. Treatment should address the underlying disease process, correct any nutritional deficiencies, and provide symptomatic treatment.


Nordic walking versus walking without poles for rehabilitation with cardiovascular disease: Randomized controlled trial.
With Nordic walking, or walking with poles, one can travel a greater distance and at a higher rate than with walking without poles, but whether the activity is beneficial for patients with cardiovascular disease is unknown. This randomized controlled trial was undertaken to determine whether Nordic walking was more effective than walking without poles on walk distance to support rehabilitation training for patients with acute coronary syndrome (ACS) and peripheral arterial occlusive disease (PAOD). Patients were recruited in a private specialized rehabilitation centre for cardiovascular diseases. The entire protocol, including patient recruitment, took place over 2 months, from September to October 2013. We divided patients into 2 groups: Nordic Walking Group (NWG, n=21) and Walking Group without poles (WG, n=21). All patients followed the same program over 4 weeks, except for the walk performed with or without poles. The main outcome was walk distance on the 6-min walk test. Secondary outcomes were maximum heart rate during exercise and walk distance and power output on a treadmill stress test. We included 42 patients (35 men; mean age 57.2±11 years and BMI 26.5±4.5kg/m2). At the end of the training period, both groups showed improved walk distance on the 6-min walk test and treatment stress test as well as power on the treadmill stress test (P<0.05). The NWG showed significantly greater walk distance than the WG (P<0.05). Both ACS and PAOD groups showed improvement, but improvement was significant for only PAOD patients. After a 4-week training period, Nordic walking training appeared more efficient than training without poles for increasing walk distance on the 6-min walk test for patients with ACS and PAOD.


Onset of industrial pollution recorded in Mumbai mudflat sediments, using integrated magnetic, chemical, 210Pb dating, and microscopic methods.
The onset and rise of urban and industrial pollution in the Mumbai region was reconstructed from an anthropogenically contaminated mudflat sediment profile from the adjacent Thane creek using magnetic parameters, polycyclic aromatic hydrocarbon (PAH) data, metal contents, and the (210)Pb dating technique. The 1.8 m vertical section at Airoli (Navi Mumbai) reveals an increase of magnetic susceptibility (χ) from background values of (20-50) to (75-100) × 10(-8) [m(3) kg(-1)] in the anthropogenically affected zone above ∼93 cm. A sharp rise of χ from (75-100) to (130-215) × 10(-8) [m(3) kg(-1)] subdivides the anthropogenically affected zone at a depth of ∼63 cm. Characterization with rock magnetic parameters (SIRM, Soft IRM, and S-ratio) reveals a significant contribution of ferri(o)magnetic phases in the upper zone. Based on the magnetic classification sampling intervals for cost-intensive PAH and metal analyses were determined. Steadily increasing contents of PAH and metals of anthropogenic origin are observed above the boundary depth at ∼93 cm. A sediment accumulation rate of 1.2 ± 0.3 cm/yr provided by (210)Pb dating dates the ∼63 cm boundary to 1951. Increasing industrial activity, including the establishment of a coal-fired power plant in 1956, and refineries between 1955 and 1960, correlates well with the substantial increase of χ, PAH, and metal contents. Scanning electron microscopy (SEM) investigation on magnetic extracts from the contaminated zone reveals the presence of magnetic spherules derived from industrial high-temperature processes.


Defect-mediated saturable absorption and carrier dynamics in tin (II) monosulfide quantum dots.
Tin (II) monosulfide (SnS) has attracted considerable attention in emerging photonics and optoelectronics because of high carrier mobility, large absorption coefficient, anisotropic linear and nonlinear optical properties, and long-time stability. In this Letter, we report third-order nonlinear absorption and refraction of SnS quantum dots (QDs). Under excitation with 800-nm femtosecond pulses, QDs exhibit saturable absorption (saturation intensity ∼ 47.69 GW/cm2) and positive refractive nonlinearity (nonlinear refraction coefficient ∼ 1.24 × 10-15 cm2/W). Nonetheless, we investigate charge carrier dynamics using femtosecond transient absorption spectroscopy and propose the presence of midgap defect states which not only dictate carrier dynamics but also give rise to nonlinear optical properties in SnS QDs.


[Gemcitabine augments major histocompatibility complex class I-related chain A expression in pancreatic cancer].
Major histocompatibility complex(MHC)class I related chain A( MICA) expressed on the cell surface of tumor cells functions as a ligand for natural killer group 2, member D (NKG2D), an important immunoreceptor expressed on natural killer ( NK ), CD8, and γδT cells. The interaction of MICA and NKG2D stimulates NK cell-mediated cytotoxicity. Gemcitabine (GEM), a key drug for pancreatic cancer treatment, stimulates the expression of cell surface MICA in tumor cells to enhance the cytotoxicity of NK cells. The combination of GEM and S-1 is used as a neoadjuvant chemotherapy (NAC) drug for pancreatic cancer in our department. We investigated the effect of GEM on pancreatic cancer. On immunohistochemistry, MICA expression was positive in 11 of 13 (85%) pancreatic ductal adenocarcinomas in the NAC group, and in 4 of 11 (36%) in the placebo control group. There was a greater proportion of NKG2D-positive cells in 5 random samples taken from both the NAC groups( 10 of 13, 77%) than in equivalent samples taken from the placebo control group( 3 of 11, 27%). In addition, CD16-positive cells were more prevalent among NK, CD8, and γδT cells in the NAC group( 9 of 13, 69%) than in the placebo control group( 3 of 11, 27%). Therefore, GEM may induce MICA expression on the surface of pancreatic cells and thus cause the accumulation of NKG2D and CD16-positive cells around tumors.