Two case reports of deadly Himalayan bites with tertiary level care: A snake and a possible scorpion.
In the Himalayan region, there is a prevalence of unknown bites (not much data except media) including snakes with high range of mortality among victims because hilly terrain leads to delay in transportation and delayed initiation of proper treatment due to lack of developed tertiary care centers. These bites can present from local hypersensitivity reactions to neurological, cardiological, respiratory, hematological, musculoskeletal, and renal manifestations. We highlight two cases that presented with delayed and varied manifestations, recovered but delayed with dedicated supportive care. A 25-year-old female presented 3 days after bite from an unknown snake, possibly krait, developed cardiotoxicity, neuroxotoxicity, rhabdomyolysis, and hemolytic features and was managed with antivenom and anticholinesterase therapy along with medroxyprogesterone to facilitate recovery from bite-associated neurotoxicity. A 75-year-old male subjected to an unknown bite possibly a scorpion developed shock which was most likely cardiogenic in nature secondary to toxin and was managed initially using inotropic support. Prazosin was started, and he recovered completely though at a later time. Hence, apart from krait bite presenting as multisystem involvement, anticholinesterase and medroxyprogesterone acetate are vital for survival. Similarly, prazosin has a vital role in the recovery of scorpion bite-induced cardiotoxicity. Many such unknown venomous bites go unreported. Further case studies and case reports are necessary to help redefine the epidemiology of such bites in the Himalayan region that poses a diagnostic and therapeutic challenge.


Thrombogenicity of sirolimus-eluting stents and bare metal stents: evaluation in the early phase after stent implantation.
Thrombogenicitiy of drug-eluting stents is a matter of controversial debate. The aim of this study was to evaluate the thrombogenicity of sirolimus-eluting stents (SES) compared to bare metal stents (BMS) in a standardised in vitro model. Nine SES and nine BMS were implanted in tubing loops and nine loops without stent served as controls. Initially and after 90 minutes of blood circulation in a modified chandler loop model, thrombin-antithrombin III complex (TAT), PMN-elastase, factor XIIa, SC5b-9, sP-selectin and platelet count were measured. Expression of CD62P, CD45/41 and PAC-1 on platelets were determined by flow cytometry. After 90 minutes, platelet count decreased significantly in the loops with BMS and SES (p<0.05). Levels of TAT, PMN-elastase and SC5b-9 were significantly elevated after 90 minutes in all loops (p<0.05). sP-selectin significantly increased in the loops with BMS and SES after 90 minutes. No significant changes occurred in any flow cytometric data. Platelet count, sP-selectin, TAT, PMN-elastase, SC5b-9, CD62P, CD41/CD45 and PAC-1 showed no significant difference between BMS and SES. These data provide evidence that there is no difference in thrombogenicity of BMS and SES in the in vitro model.


We're not just playing games: Into aging--an aging simulation game.
The elderly represent the largest-growing segment of the population. Specialized training in geriatrics is essential for healthcare professionals to provide optimal health care. As part of an ongoing education program on geriatrics, the game Into Aging: Understanding Issues Affecting the Later Stages of Life, 2nd ed. (1991) was provided to staff members of a facility to help healthcare providers develop personal insight into the aging process through role play. This game has provided the staff members with a better understanding of the issues patients experience as they deal with declines in health.


Syt-7 overexpression predicts poor prognosis and promotes cell proliferation in hepatocellular carcinoma.
Aim: To explore the prognostic significance of Syt-7 in hepatocellular carcinoma (HCC) and the potential mechanisms. Methods: Immunohistochemistry was used to examine the expression of Syt-7. Overall survival and disease-free survival were compared between Syt-7 positive and negative groups. The effects of Syt-7 knockdown on BEL-7404 cells were further evaluated. Results: Syt-7 expression was significantly higher in HCC tumorous tissues compared with paracancerous tissues. Syt-7 was closely associated with α-fetoprotein tumor size, vascular invasion, tumor node metastasis stage and tumor differentiation. Syt-7 was an independent risk factor for overall survival and disease-free survival. Additionally, Syt-7 knockdown inhibited proliferation and colony formation and induced cell cycle arrest in HCC cells. Conclusion: Syt-7 overexpression forecasts unfavorable prognosis and promotes cell proliferation in HCC.


Patients, doctors, and therapists perceptions of professional roles in spinal cord injury rehabilitation: do they agree?
Spinal cord injury is a devastating condition, requiring extensive rehabilitation from a range of health care professionals. However, it is unclear if patients view the professionals' input into their rehabilitation in the same way as those professionals. This paper presents findings from a qualitative study into patient participation in spinal cord injury rehabilitation. The aim of the part of the study reported here was to identify whether there is agreement between health care professionals and patients perceptions of professional roles in spinal cord injury rehabilitation. Results are presented from semi-structured interviews conducted with five doctors, five physiotherapists, three occupational therapists and 20 patients in a spinal cord injury unit in England. Findings suggest considerable agreement between professionals and patients about the role those professionals play in their rehabilitation. Physiotherapists are perceived to be key to rehabilitation, occupational therapists focus on hand function but physiotherapists and occupational therapists complement each other. Doctors coordinate the team yet reduce their input as patients move out of the acute phase into rehabilitation. There are some tensions but the early input of these professionals into patients' rehabilitation may help to develop understanding of roles. Congruence between patients and professionals may mean that patients have realistic expectations and encourage a more equal relationship between them.


Superparamagnetic iron oxide nanoparticles modified with polyethylenimine and galactose for siRNA targeted delivery in hepatocellular carcinoma therapy.
A safe and effective in vivo siRNA delivery system is a prerequisite for liver tumor treatment based on siRNA cancer therapeutics. Nanoparticles based on superparamagnetic iron oxide (SPIO) provide a promising delivery system. In this study, we aimed to explore a novel nanoparticle, which is composed of SPIO. The particles have a core of iron oxide that is modified by galactose (Gal) and polyethylenimine (PEI), which act as shells, providing targeted delivery of therapeutic siRNA to the liver cancer. Gal-PEI-SPIO nanoparticles were synthesized, and the characteristics of the Gal-PEI-SPIO encapsulated with siRNA were analyzed. The particles remained nanoparticles and displayed negligible cytotoxicity when loaded with siRNA. In a serum stability assay, the Gal-PEI-SPIO nanoparticles could shield the siRNA from serum degradation and prolong the half-life of the siRNA in the system. Simultaneously, we found that the mixture could be efficiently taken up by Hepa1-6 cells in a flow cytometry assay. To study the anticancer effect, quantitative polymerase chain reaction and Western blotting were used to validate the silencing efficacy of the complexes in vitro. Subsequently, the nanoparticle mixtures were administered intravenously to tumor-bearing mice to explore the tissue distribution and the effect of the siRNA against cancer. We found that the nanoparticles could provide targeted siRNA delivery, accumulate easily in orthotopic tumors, enhance siRNA accumulation in the tumor tissues for 24 h and protect the siRNA from serum nuclease degradation in comparison with the control group. After these study procedures, the mice were sacrificed, and the tumors were removed to compare the tumor size and analyze the therapeutic effect on tumor growth. The tumor volume and the liver/body weight ratio were significantly reduced in the si-c-Met therapy groups. Additionally, the mRNA levels were also lower than those observed in the controls. Based on these results, we concluded that Gal-PEI-SPIO represents a promising and efficient platform for siRNA delivery in tumor therapy.


Exchange-induced spin polarization in a single magnetic molecule junction.
Many spintronic devices rely on the presence of spin-polarized currents at zero magnetic field. This is often obtained by spin exchange-bias, where an element with long-range magnetic order creates magnetized states and displaces the hysteresis loop. Here we demonstrate that exchange-split spin states are observable and usable in the smallest conceivable unit: a single magnetic molecule. We use a redox-active porphyrin as a transport channel, coordinating a dysprosium-based single-molecule-magnet inside a graphene nano-gap. Single-molecule transport in magnetic field reveals the existence of exchange-split channels with different spin-polarizations that depend strongly on the field orientation, and comparison with the diamagnetic isostructural compound and milikelvin torque magnetometry unravels the role of the single-molecule anisotropy and the molecular orientation. These results open a path to using spin-exchange in molecular electronics, and offer a method to quantify the internal spin structure of single molecules in multiple oxidation states.


Influence of the Fly Ash Material Inoculants on the Tensile and Impact Characteristics of the Aluminum AA 5083/7.5SiC Composites.
The choice of suitable inoculants in the grain refinement process and subsequent enhancement of the characteristics of the composites developed is an important materials research topic, having wide scope. In this regard, the present work is aimed at finding the appropriate composition and size of fly ash as inoculants for grain refinement of the aluminum AA 5083 composites. Fly ash particles, which are by products of the combustion process in thermal power plants, contributing to the large-scale pollution and landfills can be effectively utilized as inoculants and interatomic lubricants in the composite matrix-reinforcement subspaces synthesized in the inert atmosphere using ultrasonic assisted stir casting setup. Thus, the work involves the study of the influence of percentage and size of the fly ash dispersions on the tensile and impact strength characteristics of the aluminum AA 5083/7.5SiC composites. The C type of fly ash with the particle size in the series of 40-75 µm, 76-100 µm, and 101-125 µm and weight % in the series of 0.5, 1, 1.5, 2, and 2.5 are selected for the work. The influence of fly ash as distinct material inoculants for the grain refinement has worked out well with the increase in the ultimate tensile strength, yield strength, and impact strength of the composites, with the fly ash as material inoculants up to 2 wt. % beyond which the tensile and impact characteristics decrease due to the micro coring and segregation. This is evident from the microstructural observations for the composite specimens. Moreover, the role of fly ash as material inoculants is distinctly identified with the X-Ray Diffraction (XRD) for the phase and grain growth epitaxy and the Energy Dispersive Spectroscopy (EDS) for analyzing the characteristic X-Rays of the fly ash particles as inoculant agents in the energy spectrum.


The expression of different superoxide dismutase forms is cell-type dependent in olive (Olea europaea L.) leaves.
Superoxide dismutase (SOD) is a key antioxidant enzyme present in prokaryotic and eukaryotic cells as a first line of defense against the accumulation of superoxide radicals. In olive leaves, the SOD enzymatic system was characterized and was found to be comprised of three isozymes, an Mn-SOD, an Fe-SOD and a CuZn-SOD. Transcript expression analysis of whole leaves showed that the three isozymes represented 82, 17 and 0.8% of the total SOD expressed, respectively. Using the combination of laser capture microdissection (LCM) and real-time quantitative reverse transcription-PCR (RT-PCR), the expression of these SOD isozymes was studied in different cell types of olive leaves, including spongy mesophyll, palisade mesophyll, xylem and phloem. In spongy mesophyll cells, the isozyme proportion was similar to that in whole leaves, but in the other cells the proportion of expressed SOD isozymes was different. In palisade mesophyll cells, Fe-SOD was the most abundant, followed by Mn-SOD and CuZn-SOD, but in phloem cells Mn-SOD was the most prominent isozyme, and Fe-SOD was present in trace amounts. In xylem cells, only the Mn-SOD was detected. On the other hand, the highest accumulation of superoxide radicals was localized in vascular tissue which was the tissue with the lowest level of SOD transcripts. These data show that in olive leaves, each SOD isozyme has a different gene expression depending on the cell type of the leaf.


Influence of ageing on carotid baroreflex peak response latency in humans.
The stability of a physiological control system, such as the arterial baroreflex, depends critically upon both the magnitude (i.e. gain or sensitivity) and timing (i.e. latency) of the effector response. Although studies have examined resting arterial baroreflex sensitivity in older subjects, little attention has been given to the influence of ageing on the latency of peak baroreflex responses. First, we compared the temporal pattern of heart rate (HR) and mean arterial blood pressure (BP) responses to selective carotid baroreceptor (CBR) unloading and loading in 14 young (22 +/- 1 years) and older (61 +/- 1 years) subjects, using 5 s pulses of neck pressure (NP, +35 Torr) and neck suction (NS, -80 Torr). Second, CBR latency was assessed following pharmacological blockade of cardiac parasympathetic nerve activity in eight young subjects, to better understand how known age-related reductions in parasympathetic nerve activity influence CBR response latency. In response to NP, the time to the peak increase in HR and mean BP were similar in young and older groups. In contrast, in response to NS the time to peak decrease in HR (2.1 +/- 0.2 vs. 3.8 +/- 0.2 s) and mean BP (6.7 +/- 0.4 vs. 8.3 +/- 0.2 s) were delayed in older individuals (young vs. older, P < 0.05). The time to peak HR and mean BP were delayed in young subjects following cardiac parasympathetic blockade (glycopyrrolate). Collectively, these data suggest that ageing is associated with delayed peak cardiovascular responses to acute carotid baroreceptor loading that may be, in part, due to age-related reductions in cardiac parasympathetic tone.


Diagnostic Performance of Radiology Residents in Thoracic CT Imaging in Emergency Radiology During The COVID-19 Pandemic.
During the COVID-19 pandemic, the workload of all radiologists and radiology residents, as well as other clinical physicians, has increased. This study aims to determine the diagnostic performance of radiology residents, who effectively contribute to the diagnosis of COVID-19. The thoracic Computed Tomography (CT) images of 135 patients aged 20-83 diagnosed with COVID-19 were evaluated retrospectively by five radiology residents and a radiologist with 10 years of experience. The diagnostic performance of the radiology residents in evaluating COVID-19 was assessed according to their year of residency and the patients' age and gender. Receiver Operating Characteristic (ROC) curve analysis was performed to determine the sensitivity and specificity of radiology residents. The radiology residents' performance in determining COVID-19 using CT findings was evaluated as follows: sensitivity 97.22%, specificity 88.89%, positive predictive value 90.91%, negative predictive value 96.55%, and accuracy 93.33%. According to the year of residency, the sensitivity and specificity of the radiology residents in determining COVID-19 using CT images were between 92.3% and 100%, and 71.43% and 100%, respectively. The high sensitivity and specificity of radiology residents in evaluating thoracic CT images for COVID-19 diagnosis indicate that radiologists are as important as clinical physicians in the diagnosis of COVID-19.


Polymorphism in cytochrome P450 1A2 and their interaction with risk factors in determining risk of squamous cell lung carcinoma in men.
The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma.


The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors.
Acetylcholine activates nicotinic acetylcholine receptors (nAChRs) by binding at an extracellular orthosteric site. Previous studies have described several positive allosteric modulators (PAMs) that are selective for homomeric α7 nAChRs. These include type I PAMs, which exert little or no effect on the rate of receptor desensitisation, and type II PAMs, which cause a dramatic loss of agonist-induced desensitisation. Here we report evidence that transmembrane mutations in α7 nAChRs have diverse effects on receptor activation and desensitisation by allosteric ligands. It has been reported previously that the L247T mutation, located toward the middle of the second transmembrane domain (at the 9' position), confers reduced levels of desensitisation. In contrast, the M260L mutation, located higher up in the TM2 domain (at the 22' position), does not show any difference in desensitisation compared to wild-type receptors. We have found that in receptors containing the L247T mutation, both type I PAMs and type II PAMs are converted into non-desensitising agonists. In contrast, in receptors containing the M260L mutation, this effect is seen only with type II PAMs. These findings, indicating that the M260L mutation has a selective effect on type II PAMs, have been confirmed both with previously described PAMs and also with a series of novel α7-selective PAMs. The novel PAMs examined in this study have close chemical similarity but diverse pharmacological properties. For example, they include compounds displaying effects on receptor desensitisation that are typical of classical type I and type II PAMs but, in addition, they include compounds with intermediate properties.


The Six Item Cognitive Impairment Test (6-CIT) as a screening test for dementia: comparison with Mini-Mental State Examination (MMSE).
The UK national Dementia Strategy clearly outlines a case for early detection and diagnosis of dementia. There is thus a need for a brief screening test for dementia in primary care, which can be administered and scored easily. To compare the performance of two cognitive scales, Mini-Mental State Examination (MMSE) and 6 Item Cognitive Impairment Test (6-CIT), as screening test for dementia in a naturalistic setting. 209 subjects referred to Old Age Psychiatry service were retrospectively studied. Their MMSE and 6-CIT scores were used to compare sensitivity, specificity and the Receiver Operating Characteristic (ROC) Curves for diagnosis of dementia. The correlation between the MMSE score and 6-CIT score is - 0.822. The MMSE has a sensitivity of 79.7% and specificity of 86.4% (cut-off 23/24). The 6-CIT has a sensitivity and specificity of 82.5% and 90.9% respectively (cut-off 10/11). The sensitivity of the 6-CIT increases to 90.2% at a lower cut-off of 9/10, but the corresponding specificity drops to 83.3%. The 6-CIT is a brief and simple test of cognition, which correlates reasonably well with the MMSE in a naturalistic setting. Compared with the MMSE it performs well as a screening instrument for dementia, which makes it a more appropriate test for primary care usage.


Cardiotoxicity with carfilzomib at doses greater than 27 mg/m2: A case series.
Carfilzomib is a second-generation proteasome inhibitor that irreversibly inhibits chymotrypsin-like (CT-L) activities of the proteasome, and is indicated for relapsed or refractory multiple myeloma. Cardiotoxicity is a well-established adverse effect of carfilzomib. The extent of cardiac toxicity in the literature spans anywhere from palpitations to cardiac arrest, with the most commonly reported manifestation being new-onset or worsening heart failure. A pre-clinical study of the pharmacokinetics and pharmacodynamics of carfilzomib given via intravenous bolus or 30-minute infusion in rats showed that carfilzomib can strongly induce apoptosis and potently damage cardiac myocytes at clinically relevant concentrations. Moreover, the mortality rate with the bolus administration was 44% whereas the same dose administered as a 30-minute infusion did not result in mortality. There remains limited clinical data regarding the safety of carfilzomib at doses of 27-56 mg/m2 based on infusion times as these doses have not been well studied. This retrospective review was conducted to evaluate the safety of carfilzomib at doses >27 mg/m2 at all infusion times.


Biodegradation Mechanisms of Patulin in Candida guilliermondii: An iTRAQ-Based Proteomic Analysis.
Patulin, a potent mycotoxin, contaminates fruits and derived products worldwide, and is a serious health concern. Several yeast strains have shown the ability to effectively degrade patulin. However, the mechanisms of its biodegradation still remain unclear at this time. In the present study, biodegradation and involved mechanisms of patulin by an antagonistic yeast Candida guilliermondii were investigated. The results indicated that C. guilliermondii was capable of not only multiplying to a high population in medium containing patulin, but also effectively reducing patulin content in culture medium. Degradation of patulin by C. guilliermondii was dependent on the yeast cell viability, and mainly occurred inside cells. E-ascladiol was the main degradation product of patulin. An iTRAQ-based proteomic analysis revealed that the responses of C. guilliermondii to patulin were complex. A total of 30 differential proteins involved in 10 biological processes were identified, and more than two-thirds of the differential proteins were down-accumulated. Notably, a short-chain dehydrogenase (gi|190348612) was markedly induced by patulin at both the protein and mRNA levels. Our findings will provide a foundation to help enable the commercial development of an enzyme formulation for the detoxification of patulin in fruit-derived products.


Alcohol and hospitalized road traffic injuries in the Philippines.
Each year, there are approximately 1.24 million deaths due to road traffic injuries, the majority of which occur in low- and middle-income countries. Since 2008, 35 countries have passed legislation to implement road safety strategies. However, many countries have yet to pass comprehensive legislation while others lack adequate enforcement of current policies. The annual global mortality rate due to road trauma remains unacceptably high and reflects the need for governments to prioritize the passage and implementation of road safety legislation. Alcohol is a leading risk factor for road trauma globally and the leading cause of death and disability in the Western Pacific region. Despite the overwhelming evidence that strict enforcement of drunk-driving policies can lead to a drastic reduction in alcohol-related road incidents, many countries in the Western Pacific lack sufficient data that could facilitate the design of appropriate drunk-driving interventions. This paper provides an analysis of the current status of policies and attitudes related to alcohol and road injuries throughout the Western Pacific region, with a specific focus on the Philippines. Following the passage of drunk-driving legislation in 2013, a medical records review of alcohol-related road trauma patients in Manila Doctors Hospital was conducted. The findings of this pilot project further highlight the pervasive problem of missing or unreliable data regarding alcohol's role in road trauma. Assessing the burden of drunk driving is an important step in designing effective interventions and systematically changing attitudes about driving under the influence.


Neurofuturity: a theory of change.
Our experience is dominated by familiar sameness and unfamiliar change. This article is about change and why and how people change. The capacity to change is critical to the ability to adapt to a changing environment. Our brains help us to manage change by constructing possible futures and enabling us to behave in a way that prepares us for those futures. Capturing the world outside of us to make it into an internal experience is called perception. Some therapies aim to capture the work as it is. Capturing our world as it has been is termed 'memory'. Therapies which aim to revisit and remould this work so that the present and future are easier to deal with, help adaptation. Capturing the possible worlds to come is described here as neurofuturity. It is much broader than expectations and includes our feelings towards the future as well as our beliefs. Therapies are described in terms of which questions they answer and which time frame they address. Therapies and therapists address these big questions and work in different time frames. Reconstructing patients' experience of the future and acceptance of what cannot change are two of the main tasks of clinicians.


Prevalence and Economic Burden of Epilepsy in the Institutionalized Medicare Fee-for-Service Population.
Based on data from 2003 to 2007, the prevalence of epilepsy was significantly higher in the institutionalized elderly population than in the noninstitutionalized population, but the recent prevalence and economic impact of epilepsy specifically in the institutionalized Medicare population have not been reported. To estimate the prevalence and economic burden of epilepsy and inpatient utilization rates among institutionalized Medicare beneficiaries and to provide a 10-year projection of their population size and the associated costs. We performed a cross-sectional analysis of the institutionalized Medicare population with and without epilepsy using Medicare 5% sample claims data from 2013 and 2014. The identification of epilepsy required ≥1 qualifying claims with an epilepsy diagnosis, or ≥2 qualifying claims ≥30 days apart with a diagnosis of convulsion, in 2014. Institutionalized status was identified by having ≥6 consecutive months of nursing facility claims in 2013 or 2014. Inpatient admissions and 30-day readmissions, average allowed costs, and risk-adjusted incremental costs of epilepsy were calculated and compared between the institutionalized population of Medicare beneficiaries with and without epilepsy. The 2015 Medicare 100% and 5% sample data and inputs from other external sources were used to project the 10-year trends in the size and cost of the institutionalized Medicare population with epilepsy. The prevalence of epilepsy in 2014 was 11.1% in the institutionalized Medicare population. The institutionalized population with epilepsy had significantly higher per-patient per-month (PPPM) costs ($3479 vs $2381, respectively; P <.001), inpatient admissions per 1000 beneficiaries (1105 vs 697, respectively; P <.001), and 30-day readmissions per 1000 beneficiaries (287 vs 145, respectively; P <.001) versus the institutionalized population without epilepsy. The risk-adjusted incremental cost of epilepsy for the institutionalized population was $507.33 PPPM. Based on our model, between 2017 and 2027 an 18% increase in size and a 72% increase in cost are projected for the institutionalized Medicare beneficiaries with epilepsy. The high cost and inpatient resource utilization, as well as the projected growth of the institutionalized Medicare population with epilepsy highlight the need for further investigation of care management opportunities to reduce the cost burden associated with this condition.


Scleroderma in children.
Juvenile systemic scleroderma (jSSc) is a rare childhood disease. In the review period covered within this article, there were few reports devoted exclusively to it. In the past year, there was no breakthrough regarding pathogenesis, classification, or treatment. In the pediatric field, the proposed classification system for jSSc shows significant progress toward a definition of the pediatric population. It should allow better evaluation of this patient group. In adult systemic scleroderma, European efforts to establish indices for disease activity have been published. They should help to assess the disease activity in a standardized way and therefore enable earlier adequate treatment for patients. Biologic markers and new assessment methods for particular organ involvement help to determine disease activity/severity as well. There is still no effective disease-modifying treatment for systemic scleroderma and jSSc. The summarized data of the phase I/II autologous stem cell transplantation trial have been published. The first guidelines for autologous stem cell transplantation for jSSc are proposed. In organ-specific treatment, the introduction of bosentan, a dual endothelin receptor antagonist, to control pulmonary hypertension is a real gain in the therapeutic options. New methods to assess prognosis are evolving and need to be validated in a larger patient population.


A meta-analysis of alcohol drinking and oral and pharyngeal cancers: results from subgroup analyses.
To quantify the magnitude of the association between alcohol and oral and pharyngeal cancer (OPC) by sex, smoking habits, type of alcoholic beverage and other factors. We combined findings from all case-control and cohort studies published until September 2010 and present in this article the results classified by these factors, using a meta-analytic approach. Summary relative risks (RRs) were obtained using random-effects models; heterogeneity was assessed using the χ(2) test. The association between alcohol and OPC risk was similar in men and women, with similar dose-response relationships. No notable differences were found with respect to geographic area and other factors, both for drinking overall and heavy (≥4 drinks/day) drinking. Among never/non-current smokers, the pooled RRs were 1.32 (95% confidence interval, CI, 1.05-1.67) for drinking, and 2.54 (95% CI, 1.80-3.58) for heavy drinking. The corresponding RRs in smokers were 2.92 (95% CI, 2.31-3.70) and 6.32 (95% CI, 5.05-7.90). The pooled RRs for any drinking irrespective of smoking were 2.12 (95% CI, 1.37-3.29) for wine-, 2.43 (95% CI, 1.92-3.07) for beer- and 2.30 (95% CI, 1.78-2.98) for spirits-only drinking. The corresponding RRs for heavy drinking were 4.92 (95% CI, 2.80-8.65), 4.20 (95% CI, 1.43-12.38) and 5.20 (95% CI, 2.77-9.78). The alcohol-related RRs are similar with respect to sex, geographic area and type of alcoholic beverage. The association between alcohol and OPC is stronger in smokers than in non-smokers.


Diabetes in pregnancy: growth of the fetal pancreatic B cells in the rat.
The development of the pancreatic B cells in the offspring of normal (N), subdiabetic (SD), manifest diabetic (MD) and insulin-treated diabetic (MDI) rats was studied with the aid of immunocytochemical staining for insulin. Morphometric evaluation of the B-cell volume density and weight was made by point sampling. The offspring were studied on gestational days 20 and 22 and in the newborn state. In the N offspring the weight of the B-cell parenchyma doubled during the last 2 days of gestation. This rapid increase may be ascribed not only to high mitotic activity but also to differentiation of putative percursor cells to B cells. The mild glucose intolerance of the SD mothers had no major effects on the fetal B-cell development. In the MD group both the volume density and the weight of the B cells were considerably lower than in the N and SD groups at all ages studied. Despite prolonged gestation, the weight of the fetal B cells in the MD newborns was not greater than that in the 20-day-old fetuses of the N group. Insulin treatment of the MD mothers restored the fetal B-cell development towards normal. This study indicates that manifest maternal diabetes in the rat retards the development of the fetal B cells. This is in obvious contrast to the corresponding situation in human diabetic pregnancy, in which hyperinsulinism represents a striking feature of diabetic fetopathy. It is suggested that a milder form of maternal glucose intolerance together with the relatively longer gestational period in man, compared with the rat, may create conditions that favour fetal B-cell hyperplasia.


Template-guided flapless implant insertion and prosthetic rehabilitation with telescopic crowns in a patient with treated generalized aggressive periodontitis: a case report.
Implant therapy offers a wide range of possibilities in prosthetics. Especially for completely edentulous patients with early tooth loss due to periodontitis, implant therapy is an option to regain a comfortable, esthetic dental rehabilitation. Several studies have indicated that osseointegrated implants can be placed successfully in periodontally compromised patients but with lower survival and success rates than in uncompromised patients. This case report describes a patient that received periodontal therapy for generalized aggressive periodontitis and achieved prosthetic rehabilitation 16 years later with telescopic crowns by means of template-guided flapless implant insertion. In particular, in patients with a history of periodontitis in which bone loss makes implant planning more complicated and in whom wound healing might be compromised, the approach presented in this paper describes a method that is predictable and minimally traumatic.


Up-regulation, modification, and translocation of S100A6 induced by exposure to ionizing radiation revealed by proteomics profiling.
The cellular response to genotoxic stress is a complex cascade of events including altered protein expression, interactions, modifications, and relocalization, leading to cell cycle arrest and DNA repair or to apoptosis. p53 protein has a central role in this process, and p53 status is an important factor in the response of a tumor to genotoxic anticancer therapy. We studied p53-related changes postexposure to ionizing radiation using top-down mass spectrometry. Initially two cell lines were compared, HCT116 p53 wild type (wt) and p53(-/-), in a time course study postirradiation. In the p53 wt cell line a striking increase of a 10.2-kDa protein was detected, and this protein was identified with MS/MS analysis as S100A6. Further MS profiling led to detection of two post-translationally modified variants of S100A6, namely glutathionylated and cysteinylated forms. In p53 wt cells, a specific shift from glutathionylated to cysteinylated S100A6 occurred postirradiation. The p53 dependence of this specific change in protein level and modification pattern of S100A6 postirradiation was confirmed in a panel of four lung cancer cell lines (H23, U1810, H69, and A549) with different p53 status and using small interfering RNA against p53. Interestingly the closely related S100 family protein S100A4 showed the same changes in modification pattern post-ionizing radiation in the p53 wt lung cancer cell line, and S100A4 also showed p53-dependent expression. Using confocal microscopy, relocalization of S100A6 from nucleus to cytosol and a colocalization with tropomyosin in stress fibers was detected in A549 cells postirradiation. This relocalization coincided with the change in S100A6 modification pattern. Based on these results, we suggest that S100A6 and S100A4 are regulated via redox modifications in vivo and that these proteins are involved in the cellular response to genotoxic stress.


Regional anesthetic techniques.
Regional anesthesia has several distinct advantages over general anesthesia in the patient scheduled for ambulatory surgery. These include residual analgesia and a lower incidence of postoperative nausea and vomiting. With appropriate choice of regional technique and local anesthetic drug, earlier ambulation and discharge are often possible. These advantages, however, may be negated by the use of excessive sedation. Careful patient selection is required to achieve optimal results. Regional anesthesia requires more time to administer than does general anesthesia, and ideally should be performed in an induction area. However, use of such an area, or employment of techniques with a rapid onset of analgesia (e.g., intravenous regional of spinal anesthesia) may actually reduce the total amount of time a patient spends in the ambulatory unit [16]. Selected application of regional techniques will help convince surgeons, anesthesiologists, and nurses of the advantages of regional blockade and may ultimately lead to greater patient and surgeon satisfaction.


Disparities in Online Use Behaviours and Chinese Digital Inclusion: A 10-Year Comparison.
This study focuses on the disparities in Chinese online use behaviours (frequency and diversity) based on educational background and socioeconomic status over 10 years to reveal the Chinese digital inclusion process. We used the China Family Panel Studies (CFPS) 2010 and 2018 panels and considered the time and cohort effects separately. Ordinary least squares analysis revealed usage frequency. The generalized partial proportional odds model demonstrated participants' prioritization of online study, work, entertainment, and social activity. The results show that the profile of the individuals with the most time spent online has changed from those with high education and income levels to mid-range education and income levels. Individuals with high education and income levels prefer to use the internet for studying and working. There are no clear preference differences between entertainment and social activities amongst most educational backgrounds and socioeconomic statuses. Regarding frequency of internet use, digital inclusion has spread downwards from the upper to the middle classes. Regarding diverse internet uses, upper-class individuals prefer to conduct capital-enhancing activities, and youth remain the main force for diverse online activities; however, over time, middle-aged groups have increased their capital-enhancing activities, and older adults have increased their digital social activities.


Modifiable cardiovascular risk factors in adolescents and adults with congenital heart disease.
Individuals with congenital heart disease (CHD) may be at higher risk of acquired cardiovascular disease than the general population due to their underlying physiology and/or surgical sequelae. We sought to assess the prevalence of cardiovascular disease risk factors in youth and adults with CHD. We assessed cardiovascular health as per the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) health index in patients with CHD aged 15+ years who attended cardiology outpatient clinics. Participants self-reported smoking behavior, fruit and vegetable consumption, physical activity, and whether they had diabetes and hypertension. Individual health indices were categorized into ideal/not ideal, and sum of individual health indices was categorized as poor, intermediate or ideal cardiovascular health as per CANHEART criteria. We included n = 102 adults (35.4 ± 12.9 years, 46% female) and n = 88 youth (17.2 ±1.1 years, 41% female). Most individuals reported to be nonsmokers (88% youth vs 86% adults) and to consume ≥5 servings of fruit and vegetables per day (83% vs 85%, respectively). More adults than youth were overweight/obese (52% vs 22%, p < 0.001) though more adults than youth reported meeting age-specific physical activity guidelines (84% vs 55%, p < 0.001). According to CANHEART health index criteria, 32% of youth and 27% of adults were in ideal cardiovascular health. A low proportion of individuals with CHD are in ideal cardiovascular health, suggesting a need to promote healthy lifestyles during adolescence and throughout adulthood in these individuals.


Metal-organic Framework ZIF-67 Functionalized MXene for Enhancing the Fire Safety of Thermoplastic Polyurethanes.
In this work, a novel functionalization strategy for ZIF-67-modified layered MXene was proposed, aiming at improving the fire safety of thermoplastic polyurethanes (TPU). The ZIF-67@MXene was verified by microscopic morphology, elemental composition, functional group species and crystal structure, and then the successfully prepared ZIF-67@MXene was introduced into the TPU material. When ZIF-67@MXene content was only 0.5 wt%, the peak heat release rate, total heat release rate, peak smoke release rate, total smoke release rate, and CO yield of the TPU/ZIF-67@MXene composites were reduced by 26%, 9%, 50%, and 22%, respectively, compared with the pure TPU. The thermogravimetric tests showed that the residual char of TPU/ZIF-67@MXene composites was the most in all samples. In short, the high-quality carbon layer of TPU/ZIF-67@MXene composites acts as a physical barrier to the transfer of heat and toxic gases, greatly improving the flame retardant properties of the TPU polymer.


Identification and strain differentiation of Vibrio cholerae by using polyclonal antibodies against outer membrane proteins.
Cholera is caused only by O1 and O139 Vibrio cholerae strains. For diagnosis, 3 working days are needed for bacterial isolation from human feces and for biochemical characterization. Here we describe the purification of bacterial outer membrane proteins (OMP) from V. cholerae O1 Ogawa, O1 Inaba, and O139 strains, as well as the production of specific antisera and their use for fecal Vibrio antigen detection. Anti-OMP antisera showed very high reactivity and specificity by enzyme-linked immunosorbent assay (ELISA) and dot-ELISA. An inmunodiagnostic assay for V. cholerae detection was developed; this assay avoids preenrichment and costly equipment and can be used for epidemiological surveillance and clinical diagnosis of cases, considering that prompt and specific identification of bacteria is mandatory in cholera.


'Likelihood to be diagnosed or misdiagnosed': application to meta-analytic data for cognitive screening instruments.
Aim: To extend use of the recently described 'likelihood to be diagnosed or misdiagnosed' (LDM) metric for test accuracy studies through application to recent meta-analytic data of commonly used cognitive screening instruments. Methods: Raw data (true positives and negatives, false positives and negatives) were extracted from meta-analyses (minimum 5 studies or 1000 patients), from which LDM was calculated. LDM values were compared with those previously reported for single test accuracy studies. Results: LDM values for diagnosis of dementia ranged from around two to seven, and for diagnosis of mild cognitive impairment from two to three. LDM values based on meta-analytic data were larger than those reported for individual studies. Conclusion: LDM is an easily calculated and potentially useful unitary, global metric for test accuracy studies.


[Information systems supporting the management work in health].
The article presents some aspects on the relevance of the information systems as tool of support to the management of the work of the health professionals, a time that is a computational resource capable to potential the knowledge search. Know that the information systems available of fast form, easy and insurance the information, allowing that the professionals of the health search knowledge and if become able, creative and competent to inside act with the complexity of the work in health of the Brazilian system of health aiming at to consolidate the politics of the National Health System. It is reflected on what it is the management of the work in health and as the information systems they come contribute for the fortify of action and processes of health in this area.


Developmental expression and differentiation-related neuron-specific splicing of metastasis suppressor 1 (Mtss1) in normal and transformed cerebellar cells.
Mtss1 encodes an actin-binding protein, dysregulated in a variety of tumors, that interacts with sonic hedgehog/Gli signaling in epidermal cells. Given the prime importance of this pathway for cerebellar development and tumorigenesis, we assessed expression of Mtss1 in the developing murine cerebellum and human medulloblastoma specimens. During development, Mtss1 is transiently expressed in granule cells, from the time point they cease to proliferate to their synaptic integration. It is also expressed by granule cell precursor-derived medulloblastomas. In the adult CNS, Mtss1 is found exclusively in cerebellar Purkinje cells. Neuronal differentiation is accompanied by a switch in Mtss1 splicing. Whereas immature granule cells express a Mtss1 variant observed also in peripheral tissues and comprising exon 12, this exon is replaced by a CNS-specific exon, 12a, in more mature granule cells and in adult Purkinje cells. Bioinformatic analysis of Mtss1 suggests that differential exon usage may affect interaction with Fyn and Src, two tyrosine kinases previously recognized as critical for cerebellar cell migration and histogenesis. Further, this approach led to the identification of two evolutionary conserved nuclear localization sequences. These overlap with the actin filament binding site of Mtss1, and one also harbors a potential PKA and PKC phosphorylation site. Both the pattern of expression and splicing of Mtss1 is developmentally regulated in the murine cerebellum. These findings are discussed with a view on the potential role of Mtss1 for cytoskeletal dynamics in developing and mature cerebellar neurons.


Volume of mural thrombus plays a role in the elevation of inflammatory markers after endovascular aortic repair.
Although systemic inflammatory responses are common after endovascular aortic repair (EVAR), its etiology remains uncertain. It is normally well tolerated and has a benign course. This study was undertaken to investigate the possible etiology of post-EVAR inflammation by measuring volumes of chronic mural thrombus and fresh thrombus. The subjects of this study included 34 patients who underwent EVAR from February 2012 to July 2017. Inflammatory markers in all the patients were evaluated before surgery, using the highest value among the laboratory data up to 5 days after surgery, and postoperative computed tomographic angiography (CTA) was taken for all of them before their discharging. Volumes of mural thrombus and fresh thrombus were calculated by CTA. The mean interval from surgery to immediate postoperative CTA was estimated as 6.8 ± 4.0 days. After undergoing EVAR, white blood cell (WBC) (p < 0.01), C-reactive protein (CRP) (p < 0.01) and erythrocyte sedimentation rate (ESR) (p = 0.01) were significantly elevated. Two groups were defined according to the post-implantation syndrome (PIS) by the criteria of systemic inflammatory response syndrome (SIRS);no significant differences were observed in any factors between the two groups. Classification of two groups by the criteria of increasing WBC and CRP revealed that inflammatory markers were significantly enhanced as the volume of mural thrombus increased (p = 0.03). However, no significant risk factor was found in view of aneurysmal growth after EVAR. Volume of mural thrombus is an important risk factor for the elevation of inflammatory markers after EVAR.


Improving accuracy of electrochemical capacitance and solvation energetics in first-principles calculations.
Reliable first-principles calculations of electrochemical processes require accurate prediction of the interfacial capacitance, a challenge for current computationally efficient continuum solvation methodologies. We develop a model for the double layer of a metallic electrode that reproduces the features of the experimental capacitance of Ag(100) in a non-adsorbing, aqueous electrolyte, including a broad hump in the capacitance near the potential of zero charge and a dip in the capacitance under conditions of low ionic strength. Using this model, we identify the necessary characteristics of a solvation model suitable for first-principles electrochemistry of metal surfaces in non-adsorbing, aqueous electrolytes: dielectric and ionic nonlinearity, and a dielectric-only region at the interface. The dielectric nonlinearity, caused by the saturation of dipole rotational response in water, creates the capacitance hump, while ionic nonlinearity, caused by the compactness of the diffuse layer, generates the capacitance dip seen at low ionic strength. We show that none of the previously developed solvation models simultaneously meet all these criteria. We design the nonlinear electrochemical soft-sphere solvation model which both captures the capacitance features observed experimentally and serves as a general-purpose continuum solvation model.


Controlling blood lipids part 2: when and how to use medication.
Drug treatment for abnormal blood lipids includes bile acid sequestrants, fibric acid derivatives, statins, and niacin. Statins generally offer the best combination of safety and effectiveness. Hormone replacement therapy reduces the risk of coronary artery disease in postmenopausal women. The National Cholesterol Education Program offers clear guidelines as to what levels of low-density lipoprotein cholesterol (LDL-C) should trigger consideration of drug treatment, and the authors suggest what levels of high-density lipoprotein cholesterol should prompt treatment. Measurements of small dense LDL-C and lipoprotein(a) may also be helpful in decisions about drug treatment for selected patients.


[Colorimetric assay of perfluorooctanesulfonate based on gold nanoparticles].
For the property of persistent, bioaccumulation and genetic toxicity, perfluorooctanesulfonate (PFOS) is classified as a sort of persistent organic pollutants (POPs). It is significant to develop a novel assay for the determination of PFOS. In this work, we create a new colorimetric assay for PFOS in which the positively-charged gold nanoparticles (AuNPs) work as a nano-probe. This method works on the aggregation of AuNPs induced by PFOS via electrostatic interaction. The stable monodisperse AuNPs coated by cysteamine present color of red wine and the addition of PFOS can make the monodispersed AuNPs aggregated resulting in the color change from wine red to reddish purple with a red-shift in ultraviolet-visible absorption spectrum. The experimental results show that AuNPs has a characteristic absorption peak (524 nm), as well as a wide absorption peak (650 nm) and the absorption signal intensity is proportional to the PFOS content in a range of 0. 8-8. 0 µmo .l L-1. According to these, we developed a method based on ultraviolet-visible absorption and colorimetric to detect PFOS with the detection limit of 80 nmol . L-1. The scanning electron microscope (SEM) was investigated and the photos show that the stable AuNPs are made and the degree of AuNPs aggregation is related with PFOS concentration. The effect tests of coexisting substances in system show that common anions had less impact on the system and inorganic metal ions had some interference, which can be get rid of by cat- ion exchange resin in real sample. This assay was applied to detect PFOS in tap water with a recovery range of 87. 5%-118% and RSD 4. 4%. It is a novel application of AuNPs-based probe for PFOS detection. The proposed method has more advantages such as rapidity, low-cost and simplicity than conventional ones. In addition, it has the visual sensing function and the difference of color can be sensed by naked eyes directly, which produce ideas of real-time colorimetric strategies of nanoprobe application in environmental pollutant detection.


Two-band description of the strong 'spin'-orbit coupled one-dimensional hole gas in a cylindrical Ge nanowire.
The low-energy effective Hamiltonian of the strong 'spin'-orbit coupled one-dimensional hole gas in a cylindrical Ge nanowire in the presence of a strong magnetic field is studied both numerically and analytically. Basing on the Luttinger-Kohn Hamiltonian in the spherical approximation, we show this strong 'spin'-orbit coupled one-dimensional hole gas can be accurately described by an effective two-band HamiltonianHef=ℏ2kz2/(2mh∗)+ασxkz+gh∗μBBσz/2, as long as the magnetic field is purely longitudinal or purely transverse. The explicit magnetic field dependent expressions of the 'spin'-orbit couplingα≡α(B)and the effectiveg-factorgh∗≡gh∗(B)are given. When the magnetic field is applied in an arbitrary direction, the two-band Hamiltonian description is still a good approximation.


Nanoplasmonic multiplex biosensing for COVID-19 vaccines.
The ongoing emergence of severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2) variants requires swift actions in identifying specific antigens and optimizing vaccine development to maximize the humoral response of the patient. Measuring the specificity and the amount of antibody produced by the host immune system with high throughput and accuracy is critical to develop timely diagnostics and therapeutic strategies. Motivated by finding an easy-to-use and cost-effective alternative to existing serological methodologies for multiplex analysis, we develop a proof-of-concept multiplex nanoplasmonic biosensor to capture the humoral response in serums against multiple antigens. Nanoplasmonic sensing relies on the wavelength shift of the localized surface plasmon resonance (LSPR) peak of gold nanostructures upon binding interactions between the antibodies and the immobilized antigens. Here the antigens are first immobilized on different sensing areas by using a mono-biotinylation system based on the high affinity interaction between biotin and streptavidin. We then validate the multiplex platform by detecting the presence of 3 monoclonal antibodies against 3 antigens (2 different hemagglutinins (HAs) from influenza viruses, and the SARS-CoV-2 Spike RBD (receptor binding domain)). We also measure the humoral response in murine sera collected before and after its immunization with the SARS-CoV-2 Spike protein, in good agreement with the results obtained by the ELISA assay. Our nanoplasmonic assays have successfully demonstrated multiple serum antibody profiling, which can be further integrated with microfluidics as an effective high throughput screening platform in future studies for the ongoing SARS-CoV-2 vaccine development.


Blood flow measurement system for fetoscopic laser photocoagulation of chorionic plate anastomosing vessels (FLPC).
Fetoscopic laser photocoagulation of chorionic plate anastomosing vessels (FLPC) applies to the treatment of previable fetuses with severe twin-twin transfusion syndrome (TTTS). The ultimate goal of FLPC is selective blood flow interruption of anastomotic communicating vessels on the placenta fetoscopically. However, there has not been an established method to confirm that the blood flow is blocked, thus, it depends on the operator's experience or intuition to evaluate whether the FLPC was performed successfully or not. For this issue, we have developed a composite-type optical fiberscope (2.2 mm in diameter), which has centrally-located cautery laser fiber and surrounding located fiberglasses for viewing. This fiberscope enables transmission of 50 W Yb fiber laser which can be focused to 10 mm focal length using two lenses on the fiberscope tip. In this study, we combined the fiberscope and a laser blood-flow meter, and irradiated cautery laser to porcine mesenteric vein with measuring blood flow at the same time. From the experimental results, we could quantitatively measure the blood flow before and after laser irradiation, and confirm the blood flow blocking with our system.


Adolescent and young adult tobacco prevention and cessation: current status and future directions.
To summarise the evidence on adolescent and young adult prevention and cessation, and provide future directions for research. Data were collected from published literature. Searches for adolescent prevention were conducted using PubMed, PsycInfo, and ERIC; and for cessation, PubMed, and two major reviews that span January 1978 to May 2002. PubMed, PsychInfo, and SCCI were searched for young adults from January 1990 to May 2002. Data included smoking prevention studies published from January 1990 to May 2002 and conducted in the USA; all identified smoking cessation studies for adolescents. Young adult data were limited to initiation and cessation studies. Extraction of data was by consensus of the authors. Results of the review are qualitative in nature using a consensus approach of the authors. School based curricula alone have been generally ineffective in the long term in preventing adolescents from initiating tobacco use but are effective when combined with other approaches such as media and smoke-free policies. Prevention research should consider multiple approaches and the social conditions that influence the development of youth problem behaviours including tobacco use. Because youth smoking cessation has been understudied to date, scientifically rigorous adolescent smoking cessation studies need to be conducted with attention to high risk smokers and less than daily smokers. Tobacco prevention and cessation for young adults needs focused attention. Prevention and cessation programmes need to address other tobacco products in addition to cigarettes.


How oral environment simulation affects ceramic failure behavior.
Investigating the mechanical behavior of ceramics in a clinically simulated scenario contributes to the development of new and tougher materials, improving the clinical performance of restorations. The optimal in vitro environment for testing is unclear. The purpose of this in vitro study was to investigate the failure behavior of a leucite-reinforced glass-ceramic under compression loading and fatigue in different simulated oral environment conditions. Fifty-three plate-shaped ceramic specimens were produced from computer-aided design and computer-aided manufactured (CAD-CAM) blocks and adhesively cemented onto a dentin analog substrate. For the monotonic test (n=23), a gradual compressive load (0.5 mm/min) was applied to the center of the specimens, immersed in 37ºC water, using a universal testing machine. The initial crack was detected with an acoustic system. The fatigue test was performed in a mechanical cycling machine (37ºC water, 2 Hz) using the boundary technique (n=30). Two lifetimes were evaluated (1×106 and 2×106 cycles). Failure analysis was performed using transillumination. Weibull distribution was used to evaluate compressive load data. A cumulative damage model with an inverse power law (IPL) lifetime-stress relationship was used to fit the fatigue data. A characteristic failure load of 1615 N and a Weibull modulus of 5 were obtained with the monotonic test. The estimated probability of failure (Pf) for 1×106 cycles at 100 N was 31%, at 150 N it was 55%, and at 200 N it was 75%. For 2×106 cycles, the Pf increased approximately 20% in comparison with the values predicted for 1×106 cycles, which was not significant. The most frequent failure mode was a radial crack from the intaglio surface. For fatigue, combined failure modes were also found (radial crack combined with cone crack or chipping). Fatigue affects the fracture load and failure mode of leucite-reinforced glass-ceramic.


Oxidation and aspects of ocular pathology.
Hydrogen peroxide (H2O2), a relatively stable oxidant, is present at low concentrations in the normal eye and is found at elevated concentrations in some patients with maturity-onset cataract. Recently, this laboratory has shown that H2O2 concentrations at levels only slightly above normal physiologic levels cause single-strand breaks in DNA within cultured lens epithelial cells obtained from calf lenses. It is hypothesized that such damage may contribute to the onset of cataract. The major enzyme which metabolizes H2O2 at the concentrations found in the eye is glutathione peroxidase. Since older individuals may have reduced activities of this enzyme and other enzymes involved in oxidative defense, this laboratory is synthesizing low-molecular-weight glutathione peroxidase mimics. It is possible that development of such compounds may improve the capacity of the lens to withstand oxidative stress in vitro.


Clinical significance of symptomatic and silent myocardial ischemia during exercise test in patients with effort angina pectoris--investigation of hemodynamic responses during supine ergometer exercise test.
Thirty one patients with stable effort angina who had no prior myocardial infarctions underwent symptom-limited ergometer exercise test. Hemodynamic responses during exercise were assessed to determine whether or not the limiting symptoms were related to the severity of exercise-induced myocardial ischemia. Twenty-two subjects (Group I) were limited by angina and nine (Group II) were limited by other symptoms. There were no differences in age, sex distribution, prevalence of diabetes mellitus, and left ventricular ejection fraction between the two groups. Multivessel coronary artery diseases, however, were more frequent in group I (16/22 vs 3/9: p less than 0.05). Maximal work load (46.6 +/- 16.0 vs 62.5 +/- 13.4 W: p less than 0.05), exercise duration (4.7 +/- 2.0 vs 7.2 +/- 1.4 min: p less than 0.005), and maximal oxygen consumption (12.4 +/- 4.1 vs 19.3 +/- 3.3 ml/kg/min: p less than 0.005) were significantly lower in group I. The magnitude of ST depression was not different between the two groups (2.0 +/- 0.8 vs 1.8 +/- 0.7 mm: NS). At maximal exercise, heart rate, mean blood pressure, cardiac index, and stroke work index (SWI) were significantly lower in group I (p less than 0.05) and pulmonary capillary wedge pressure was significantly higher in group I (31.1 +/- 6.1 vs 25.1 +/- 5.6 mmHg: p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Conservative strategy for treatment of stable coronary artery disease.
Patients with coronary artery disease vary widely in terms of prognosis, which is mainly dependent on ventricular function. In relation to the major outcomes of death and myocardial infarction, it is not clear in the literature if an invasive strategy of myocardial revascularization is superior to a conservative strategy of optimized medical therapy. Moreover, with the exception of patients with left main coronary disease, this similarity in prognosis also occurs in different subgroups of patients.


Breaking the vicious circle of fatigue in patients with chronic heart failure.
Fatigue is a common symptom in patients with chronic heart failure (CHF). Characteristics of the experience and consequences of fatigue might be unique in these patients. The authors interviewed 15 patients with CHF and analyzed focused online observations of the content discussed in an Internet patient discussion group concerning CHF using grounded theory. The results suggest that fatigue is a circular process in which the consequences of fatigue further exaggerate the experience. However, fatigue could be alleviated by restorative activities. The bodily experience of fatigue was defined as lacking strength and energy and feeling sleepy. Patients reported the mental aspects of fatigue as demoralizing and that they frequently experienced intellectual deficiency. Fatigue leads to sacrificing, which was manifested as refraining, denying oneself, and being isolated. The restoring activities included the categories involuntarily attentive, socially interactive, and mentally absorbed. Interventions aimed to relieve fatigue should focus on restorative activities.


Synthesis and Antibacterial Activity Against MRSA of Pleuromutilin Derivatives Possessing a Mercaptoethylamine Linker.
Methicillin resistant Staphylococcus aureus (MRSA) usually invalidate powerful antibiotics in the clinic. Pleuromutilin derivatives have been reported to possess antibacterial activity against MRSA. The antibacterial activities against MRSA of a series of thirteen synthetic pleuromutilin derivatives were investigated through in vitro models. A series of novel thioehter pleuromutilin derivatives incorporating various aromatic substituents into the C14 side chain have been reported. The in vitro antibacterial activities of these derivatives against MRSA and Escherichia coli were tested by the broth dilution method. Twelve pleuromutilin derivatives were designed, synthesized and evaluated for in vitro antibacterial activities against four Staphylococcus aureus strains. From structure-activity relationship studies, compound 11c was identified as promising compounds with the most potent in vitro antibacterial activity among the series (MIC = 0.0625-0.125 µg/ml) against Staphylococcus aureus strains. The binding of compound 11c to the 50s ribosome was investigated by molecular modeling. It was found that there is a reasonable correlation between the binding free energy and the antibacterial activity.


Effects of dobutamine stimulation on regional myocardial glucose uptake poststunning as measured by positron emission tomography.
The aim was to determine whether dobutamine stimulation of energy expenditure within the postischaemic myocardium would affect regional differences in glucose uptake as measured by positron emission tomography (PET). The metabolic rate of glucose uptake within the myocardium can be assessed with the glucose analog 18F-fluorodeoxyglucose (FDG). Stunning was induced in 14 anaesthetised pigs by partially occluding the left anterior descending coronary artery (LAD) for 20 min (> 80% flow reduction). The metabolic rate of glucose uptake was determined 2 h after reperfusion in the LAD and non-LAD regions in two groups: without (group 1; n = 7) and during (group 2; n = 7) a constant intravenous infusion of dobutamine (4 micrograms.kg-1.min-1). In all pigs, stunning reduced systolic shortening from 16(SD 4)% to 5(5)% (p < 0.05) and slightly lowered myocardial oxygen consumption, from 3.18(1.21) to 2.67(0.93) mumol.min-1.g-1 (p = 0.08). In the postischaemic LAD region of group 1, the metabolic rate of glucose uptake was significantly lower than the non-LAD region (0.11(0.08) and 0.43(0.33) mumol.min-1.g-1 respectively). In group 2, dobutamine induced a sustained increase in both fractional shortening (7(4)% to 16(5)%; p < 0.05) and oxygen consumption (2.34(0.94) to 4.53(1.52) mumol.min-1.g-1; p < 0.05) within the postischaemic LAD region. Despite recruitment of function and oxygen consumption in group 2, the metabolic rate of glucose uptake was similar to that of group 1 (0.11(0.09) and 0.40(0.28) mumol.min-1.g-1 in LAD and remote regions respectively). In this pig model of stunning, uptake of FDG was lower in stunned compared with remote myocardium and was independent of postischaemic changes in oxygen consumption and wall thinning. This supports the contention that after stunning, non-glucose substrates play an important part in maintaining energy expenditure during catecholamine stimulation.


Tenofovir alafenamide for hepatitis B virus infection including switching therapy from tenofovir disoproxil fumarate.
Tenofovir alafenamide (TAF) is a new prodrug of tenofovir, enabling treatment of patients with hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF), via more efficient delivery of tenofovir to the hepatocytes. We compared the efficacy and safety of TDF and TAF and investigated switching from TDF to TAF therapy. Consent for TDF and TAF therapy was obtained from 117 and 67 patients from August 2014 to January 2018. In total, 45 and 14 patients were administered with TDF and TAF, respectively, as naïve therapy, and 36 patients were switched from TDF to TAF. The antiviral effects and renal function safety were assessed. At week 48, the antiviral effects on patients receiving TDF and TAF as naïve therapy were similar in terms of reduction of HBV DNA (-5.6 ± 1.8 logIU/ml vs -5.0 ± 1.7 log IU/ml; P = 0.34) and hepatitis B surface antigen (-0.29 ± 0.64 logIU/ml vs -0.15 ± 0.42 logIU/ml; P = 0.71) levels. A significant decrease in the estimated glomerular filtration rate (eGFR) was seen at 48-week TDF treatment (-5.34 ± 7.69 ml/min/1.73 m2 ; P < 0.001). Switching from TDF to TAF did not increase the HBV DNA or hepatitis B surface antigen at 24 weeks. Although the eGFR worsened during TDF therapy (-7.32 ± 4.87 ml/min/1.73 m2 ), it improved significantly at week 4 (+3.93 ± 6.18 ml/min/1.73 m2 ; P = 0.008) and week 24 (+2.89 ± 4.26 ml/min/1.73 m2 ; P = 0.020) after switching from TDF to TAF. Tenofovir disoproxil fumarate and TAF showed adequate antiviral effects as naïve therapies. Furthermore, switching from TDF to TAF therapy contributed to the maintenance of the antiviral effect and recovery of renal dysfunction.


Recombinant human hyaluronan synthase 3 is phosphorylated in mammalian cells.
Hyaluronan is a ubiquitous component of vertebrate extracellular and cell-associated matrices that serves as a key structural component of skin, cartilage, eyes and joints, and plays important roles in dynamic cellular processes, including embryogenesis, inflammation, wound healing and metastasis. Hyaluronan is synthesized by three homologous hyaluronan synthases designated HAS1, HAS2 and HAS3 that differ in their tissue distribution, regulation and enzymatic characteristics. Some progress has been made in characterizing regulation of HAS transcripts and in distinguishing the enzymatic properties of the various HAS isoforms, but essentially nothing is known about their possible regulation by posttranslational modification. Using [32P]P(i) radiolabelling of a recombinant FLAG (DYKDDDDK) epitope-tagged version of human HAS3 expressed in COS-7 cells, we show that HAS3 is serine-phosphorylated and that this phosphorylation can be enhanced by a number of effectors--most significantly by a membrane-permeable analogue of cAMP. By employing a novel FLAG-tagged phosphorylated reference protein derived from EGFP (enhanced green fluorescent protein), we were able to estimate the stoichiometry of FLAG-HAS3 phosphorylation. It was approx. 0.11 in unstimulated cells and increased to as much as 0.32 in cells stimulated with 8-(4-chlorophenylthio)-cAMP.


Primary hyperaldosteronism treated by radiofrequency ablation.
This is a report of a 57-year-old Jordanian man who had uncontrolled hypertension and hypokalemia. He was diagnosed to have primary hyperaldosteronism with left adrenal adenoma. Traditionally, surgical resection of the adrenal gland whether by laparotomy or laparoscopic procedures would have been considered at this point. However, the treating team elected radiofrequency ablation of the left adrenal in view of the fact that this facility and the expertise was available in the hospital; in addition, this procedure required a shorter duration of hospitalization, was less expensive, and was less invasive. Subsequently, the patients blood pressure improved to 120/75 mm Hg and his anti-hypertensive medications were reduced. Serum aldosterone and computed tomography scan of adrenals improved. We are reporting this case as it is the first time such modalities in the treatment of adrenal adenoma was used.


Transgenic tobacco plants expressing ectopically wheat H⁺-pyrophosphatase (H⁺-PPase) gene TaVP1 show enhanced accumulation and tolerance to cadmium.
Cadmium (Cd) is considered an extremely significant pollutant due to its high toxicity to many organisms. Plants have evolved several mechanisms to cope with Cd, the most important of which is vacuolar sequestration. Cadmium can be directly transported into vacuoles by cations/H(+) exchangers, such as CAXs, which are energized by the pH gradient established by proton pumps. A cDNA (TaVP1) encoding wheat vacuolar H(+)-pyrophosphatase (V-H-PPase) was ectopically expressed in transgenic tobacco to evaluate whether this proton pump expression would enhance Cd tolerance and accumulation in planta. When TaVP1-expressing plants were exposed to various concentrations of Cd, they were found to be more tolerant to Cd compared to wild type plants. Cadmium accumulation in the plant biomass in transgenic plants was higher than that in wild type plants. To the best of our knowledge, this is the first report on the potential for enhancing proton pump expression as a strategy to improve Cd tolerance and accumulation in plants.


A new family handedness sample with findings consistent with X-linked transmission.
A family handedness study of 2632 families and 8605 offspring was conducted. Of the 2632 parental couples, there were 2123 in which both parents were right-handed (RR), 232 in which the mother was left-handed and the father right-handed (LR), 254 in which the mother was right-handed and the father was left-handed (RL), and 23 in which both parents were left-handed (LL). Results showed some important differences from the composite results of four earlier large scale studies that had also employed the same criterion of handedness (writing hand). These had collectively found that the incidence of left-handed offspring, of both sexes, was significantly lower for RR couples than for LR or RL couples, but not lower than for LL couples. Present results, however, suggest an X-linked pattern of genetic influence on handedness. The LR parents produced significantly more left-handed offspring than did RR couples, and this was particularly the case for sons; but while RL couples produced a higher incidence of left-handed daughters than did RR parents, they failed to produce a higher incidence of left-handed sons than did RR couples. Additionally, the present sample showed a significantly greater incidence of left-handed offspring of LL couples than of RR couples, a finding that, while predicted by genetic-influence theories of handedness, was not found in the composite of previous comparison samples. The finding of sex-linkage is potentially important, but will require replicative studies that take special care to preclude possible biasing factors such as selective volunteering of participants and inaccurate offspring ascriptions of parental (particularly paternal) handedness.


Spatial Genomic Resource Reveals Molecular Insights into Key Bioactive-Metabolite Biosynthesis in Endangered Angelica glauca Edgew.
Angelica glauca Edgew, which is an endangered medicinal and aromatic herb, is a rich source of numerous industrially important bioactive metabolites, including terpenoids, phenolics, and phthalides. Nevertheless, genomic interventions for the sustainable utilization and restoration of its genetic resources are greatly offset due to the scarcity of the genomic resources and key regulators of the underlying specialized metabolism. To unravel the global atlas of the specialized metabolism, the first spatial transcriptome sequencing of the leaf, stem, and root generated 109 million high-quality paired-end reads, assembled de novo into 81,162 unigenes, which exhibit a 61.53% significant homology with the six public protein databases. The organ-specific clustering grouped 1136 differentially expressed unigenes into four subclusters differentially enriched in the leaf, stem, and root tissues. The prediction of the transcriptional-interactome network by integrating enriched gene ontology (GO) and the KEGG metabolic pathways identified the key regulatory unigenes that correspond to terpenoid, flavonoid, and carotenoid biosynthesis in the leaf tissue, followed by the stem and root tissues. Furthermore, the stem and root-specific significant enrichments of phenylalanine ammonia lyase (PAL), cinnamate-4-hydroxylase (C4H), and caffeic acid 3-O-methyltransferase (COMT) indicate that phenylalanine mediated the ferulic acid biosynthesis in the stem and root. However, the root-specific expressions of NADPH-dependent alkenal/one oxidoreductase (NADPH-AOR), S-adenosyl-L-methionine-dependent methyltransferases (SDMs), polyketide cyclase (PKC), and CYP72A15 suggest the "root" as the primary site of phthalide biosynthesis. Additionally, the GC-MS and UPLC analyses corresponded to the organ-specific gene expressions, with higher contents of limonene and phthalide compounds in the roots, while there was a higher accumulation of ferulic acid in the stem, followed by in the root and leaf tissues. The first comprehensive genomic resource with an array of candidate genes of the key metabolic pathways can be potentially utilized for the targeted upscaling of aromatic and pharmaceutically important bioactive metabolites. This will also expedite genomic-assisted conservation and breeding strategies for the revival of the endangered A. glauca.


[Ca-dependent modulation of human glycine receptors expressed in cultured cell lines].
Glycine receptors (GlyRs) provide the main inhibitory neurotransmission in spinal cord and brainstem synapses of vertebrates. Fucile et al. (2000) discovered that elevation of intracellular Ca2+ caused rapid potentiation of GlyRs. This modulation develops in less than 100 ms. It is characterized by an increase in GlyR apparent affinity for glycine. It has been suggested that the phenomenon of Ca-induced potentiation involves an unknown Ca2+-binding protein (CaBP). Using the yeast two-hybrid system, screening of human brain cDNA library against the cytoplasmic loop of human alpha 1 subunit (GlyRhl) allowed us to identify five new interactors. One of them belongs to a family of Ca-binding proteins. We analyzed effect of "short" forms of this protein (CaBP-S) on functional properties of GlyRhl expressed in HEK-293 and CHO cells. Using whole-cell recordings and rapid agonist application we constructed concentration dependencies of glycine-induced currents. This analysis revealed statistical differences in EC50s between control cells (expressing only GlyRhl) and those expressing CaBP-S. In HEK-293 cells recorded under conditions of low intracellular Ca concentration (BAPTA 20 mM in the recording pipette), EC50 for glycine in control cells and expressing GlyRhl + CaBP-S were, correspondently, 68+/-49 microM (n = 29) and 409 +/-421 microM (n = 60). In CHO cells EC50 were 54+/-43 microM (n = 25) and 123 +/-104 microM (n = 28). These differences were statistically not significant at recording with intracellular solution containing high Ca concentration (50 microM). In this case EC50 were correspondently 35+/-28 microM (n = 7) and 64 +/-38 microM (n = 7). These results suggest that CaBP-S causes decrease of GlyR sensitivity to agonist through interaction with cytoplasmic domain of GlyR.


Production of the Invasive Aspergillosis Biomarker Bis(methylthio)gliotoxin Within the Genus Aspergillus: In Vitro and in Vivo Metabolite Quantification and Genomic Analysis.
Gliotoxin (GT) is a fungal secondary metabolite that has attracted great interest due to its high biological activity since it was discovered by the 1930s. An inactive derivative of this molecule, bis(methylthio)gliotoxin (bmGT), has been proposed as an invasive aspergillosis (IA) biomarker. Nevertheless, studies regarding bmGT production among common opportunistic fungi, including the Aspergillus genus, are scarce and sometimes discordant. As previously reported, bmGT is produced from GT by a methyl-transferase, named as GtmA, as a negative feedback regulatory system of GT production. In order to analyze the potential of bmGT detection to enable identification of infections caused by different members of the Aspergillus genus we have assessed bmGT production within the genus Aspergillus, including A, fumigatus, A. niger, A. nidulans, and A. flavus, and its correlation with gtmA presence. In order to validate the relevance of our in vitro findings, we compared bmGT during in vitro culture with the presence of bmGT in sera of patients from whom the Aspergillus spp. were isolated. Our results indicate that most A. fumigatus isolates produce GT and bmGT both in vitro and in vivo. In contrast, A. niger and A. nidulans were not able to produce GT or bmGT, although A. niger produced bmGT from a exogenous GT source. The frequency and amount of bmGT production in A. terreus and A. flavus isolates in vitro was lower than in A. fumigatus. Our results suggest that this defect could be related to the in vitro culture conditions, since isolates that did not produce bmGT in vitro were able to synthetize it in vivo. In summary, our study indicates that bmGT could be very useful to specifically detect the presence of A. fumigatus, the most prevalent agent causing IA. Concerning A. terreus and A. flavus a higher number of analyses from sera from infected patients will be required to reach a useful conclusion.


Interpreting functional analysis outcomes using automated nonparametric statistical analysis.
Current methods employed to interpret functional analysis data include visual analysis and post-hoc visual inspection (PHVI). However, these methods may be biased by dataset complexity, hand calculations, and rater experience. We examined whether an automated approach using nonparametric rank-based statistics could increase the accuracy and efficiency of functional analysis data interpretation. We applied Automated Nonparametric Statistical Analysis (ANSA) to a sample of 65 published functional analyses for which additional experimental evidence was available to verify behavior function. Results showed that exact behavior function agreement between ANSA and the publications authors was 83.1%, exact agreement between ANSA and PHVI was 75.4%, and exact agreement across all 3 methods was 64.6%. These preliminary findings suggest that ANSA has the potential to support the data interpretation process. A web application that incorporates the calculations and rules utilized by ANSA is accessible at https://ansa.shinyapps.io/ansa/.


Properties of an Earth-like planet orbiting a Sun-like star: Earth observed by the EPOXI mission.
NASA's EPOXI mission observed the disc-integrated Earth and Moon to test techniques for reconnoitering extrasolar terrestrial planets, using the Deep Impact flyby spacecraft to observe Earth at the beginning and end of Northern Hemisphere spring, 2008, from a range of ∼1/6 to 1/3 AU. These observations furnish high-precision and high-cadence empirical photometry and spectroscopy of Earth, suitable as "ground truth" for numerically simulating realistic observational scenarios for an Earth-like exoplanet with finite signal-to-noise ratio. Earth was observed at near-equatorial sub-spacecraft latitude on 18-19 March, 28-29 May, and 4-5 June (UT), in the range of 372-4540 nm wavelength with low visible resolving power (λ/Δλ=5-13) and moderate IR resolving power (λ/Δλ=215-730). Spectrophotometry in seven filters yields light curves at ∼372-948 nm filter-averaged wavelength, modulated by Earth's rotation with peak-to-peak amplitude of ≤20%. The spatially resolved Sun glint is a minor contributor to disc-integrated reflectance. Spectroscopy at 1100-4540 nm reveals gaseous water and carbon dioxide, with minor features of molecular oxygen, methane, and nitrous oxide. One-day changes in global cloud cover resulted in differences between the light curve beginning and end of ≤5%. The light curve of a lunar transit of Earth on 29 May is color-dependent due to the Moon's red spectrum partially occulting Earth's relatively blue spectrum. The "vegetation red edge" spectral contrast observed between two long-wavelength visible/near-IR bands is ambiguous, not clearly distinguishing between the verdant Earth diluted by cloud cover versus the desolate mineral regolith of the Moon. Spectrophotometry in at least one other comparison band at short wavelength is required to distinguish between Earth-like and Moon-like surfaces in reconnaissance observations. However, measurements at 850 nm alone, the high-reflectance side of the red edge, could be sufficient to establish periodicity in the light curve and deduce Earth's diurnal period and the existence of fixed surface units.


What initiates the pressor effect of salt in salt-sensitive humans? Observations in normotensive blacks.
We tested the traditional hypothesis that an abnormally enhanced renal reclamation of dietary NaCl alone initiates its pressor effect ("salt sensitivity"). Under metabolically controlled conditions, we grouped 23 normotensive blacks as either salt-sensitive (SS) or salt-resistant (SR), depending on whether or not dietary NaCl loading did or did not increase mean arterial blood pressure (MAP) by >or=5 mm Hg. We determined whether dietary NaCl loading induces greater increases in external Na(+) balance, plasma volume, and cardiac output in SS, compared with any in SR subjects, and differential changes in systemic vascular resistance (SVR) that could account for the pressor differences between SS and SR subjects. Using impedance cardiography, we measured cardiac output and SVR daily at 4-hour intervals throughout the last 3 days of a 7-day period of low NaCl intake (30 mmol per day) and throughout a subsequent 7-day period of NaCl loading (250 mmol per day). In the 11 SS subjects, compared with the 12 SR subjects, NaCl loading induced no greater increases in Na(+) balance, body weight, plasma volume, and cardiac output. Yet, from days 2 to 7 of NaCl loading, changes of MAP in SS diverged progressively from those in SR. From days 2 to 4, progressive increases of MAP in SS subjects reflected importantly impaired decreases of SVR, as judged from "normal" decreases of SVR in SR subjects. In SS and SR subjects combined, changes in both MAP and SVR on day 2 strongly predicted changes in MAP on day 7. In many normotensive blacks, vascular dysfunction is critical to the initiation of a pressor response to dietary NaCl.


Temporal and regional trends in IUD insertion: a population-based study in Ontario, Canada.
Intrauterine device (IUD) use is low in Canada and declined between 1985 and 1995. This study examines temporal and regional trends in IUD insertion in Ontario, Canada, from 1996 to 2006. We used physician billing data to determine annual age-adjusted IUD insertion rates for women aged 15-55 years and proportions inserted by gynecologists and family physicians (FPs). We used small area variation statistics to analyze variation in rates across the province. Annual insertion rates followed a U-shaped distribution and were lowest in 2001 and highest in 2006. From 1996 to 2006, the proportion inserted by FPs fell from 38.2% to 31.6% (p<.001). In 2006, women in regions with the highest rates were twice as likely to have an IUD inserted as those in the lowest-rate regions. IUD insertion rates began to increase in 2001, the year of introduction of the levonorgestrel-releasing intrauterine system. Regional variation in rates suggests that access is not equal across the province and that strategies to support FPs to insert IUDs may be important to ensure adequate access.


Overexpression of plastid lipid-associated protein in marine diatom enhances the xanthophyll synthesis and storage.
Plastoglobules, which are lipoprotein structures surrounded by a single hydrophobic phospholipid membrane, are subcellular organelles in plant chromoplasts and chloroplasts. They contain neutral lipids, tocopherols, quinones, chlorophyll metabolites, carotenoids and their derivatives. Proteomic studies indicated that plastoglobules are involved in carotenoid metabolism and storage. In this study, one of the plastid lipid-associated proteins (PAP), the major protein in plastoglobules, was selected and overexpressed in Phaeodactylum tricornutum. The diameter of the plastoglobules in mutants was decreased by a mean of 19.2% versus the wild-type, while the fucoxanthin level was increased by a mean of 51.2%. All mutants exhibited morphological differences from the wild-type, including a prominent increase in the transverse diameter. Moreover, the unsaturated fatty acid levels were increased in different mutants, including an 18.9-59.3% increase in eicosapentaenoic acid content. Transcriptomic analysis revealed that PAP expression and the morphological changes altered xanthophyll synthesis and storage, which affected the assembly of the fucoxanthin chlorophyll a/c-binding protein and expression of antenna proteins as well as reduced the non-photochemical quenching activity of diatom cells. Therefore, metabolic regulation at the suborganelle level can be achieved by modulating PAP expression. These findings provide a subcellular structural site and target for synthetic biology to modify pigment and lipid metabolism in microalgae chassis cells.


[Using ketoprofen in gynaecological practice].
Prophylaxis and treatment of pain syndrome in gynaecology is connected with surgical intrusions. The article presents a critical analysis on characteristics of Ketoprofen, the use of this medication in perspective. The medication had been prescribed in doses 100.00 mg per rectum two hours and 100.00 mg intramuscularly 30 minutes before small-invasive operations (electrocauterizing conization of cervix uteri, diagnostic curettage of the uteri, and abortion in small pregnancy term) started. Ketoprofen has been revealed to have characteristics of adequate analgesia before an operation and prevents the development of pain syndrome in patients after they are operated.


Utility of auscultatory screening for detecting rheumatic heart disease in high-risk children in Australia's Northern Territory.
To evaluate the utility of auscultatory screening for detecting echocardiographically confirmed rheumatic heart disease (RHD) in high-risk children in the Northern Territory, Australia. Cross-sectional screening survey. Twelve rural and remote communities in the NT between September 2008 and June 2010. 1015 predominantly Indigenous schoolchildren aged 5-15 2013s. All children underwent transthoracic echocardiography, using a portable cardiovascular ultrasound machine, and cardiac auscultation by a doctor and a nurse. Sonographers and auscultators were blinded to each others' findings and the clinical history of the children. Echocardiograms were reported offsite, using a standardised protocol, by cardiologists who were also blinded to the clinical findings. Presence of a cardiac murmur as identified by nurses (any murmur) and doctors (any murmur, and "suspicious" or "pathological" murmurs), compared with echocardiogram findings. RHD was defined according to the 2012 World Heart Federation criteria for echocardiographic diagnosis of RHD. Of the 1015 children screened, 34 (3.3%) had abnormalities identified on their echocardiogram; 24 met echocardiographic criteria for definite or borderline RHD, and 10 had isolated congenital anomalies. Detection of any murmur by a nurse had a sensitivity of 47.1%, specificity of 74.8% and positive predictive value (PPV) of 6.1%. Doctor identification of any murmur had 38.2% sensitivity, 75.1% specificity and 5.1% PPV, and the corresponding values for doctor detection of suspicious or pathological murmurs were 20.6%, 92.2% and 8.3%. For all auscultation approaches, negative predictive value was more than 97%, but the majority of participants with cardiac abnormalities were not identified. The results were no different when only definite RHD and congenital abnormalities were considered as true cases. Sensitivity and positive predictive value of cardiac auscultation compared with echocardiography is poor, regardless of the expertise of the auscultator. Although negative predictive value is high, most cases of heart disease were missed by auscultation, suggesting that cardiac auscultation should no longer be used to screen for RHD in high-risk schoolchildren in Australia.


Review of the pleiotropic effects of peroxisome proliferator-activated receptor gamma agonists on platelet function.
The primary target receptor for thiazolidinediones (TZDs) or peroxisome proliferator-activated receptor gamma (PPARgamma) agonists is a transcription factor in the nucleus of adipocytes and other metabolically active cells, where they improve insulin sensitivity and glucose utilization. TZDs are also able to modify gene expression in macrophages, smooth muscle cells, and endothelial cells. Although PPARgamma is considered to be a nuclear receptor, enucleate platelets also highly express this receptor. The aim of this review is to present the current understanding of a direct or indirect effect of TZDs on platelet function. By means of a comprehensive literature search (January 1990-June 2006), publications were obtained that contained specific information about in vitro and in vivo effects of TZDs on platelet function. The effects were studied for different risk biochemical markers, i.e., proteins found to be elevated in the state of procoagulant inflammation and endothelial dysfunction. Improvement of platelet function was reported for all TZDs-troglitazone, pioglitazone, and rosiglitazone. The described effects included reduction of platelet aggregation, suppression of thrombin-induced protein kinase C-alpha and -beta activation, decrease in plasma P-selectin and platelet P-selectin expression, increase in nitric oxide production, inhibition of the Rho/Rho kinase pathway, and inhibition of tissue factor- and platelet-activating factor-induced morphological changes in macrophages. These findings appeared in parallel with reduction of the plasma concentrations of pro-inflammatory risk markers. TZDs seem to have a direct pleiotropic positive influence on platelet function and coagulation and may be helpful in treating the prothrombotic state observed in patients with type 2 diabetes and metabolic syndrome.


A new double elevating osteotomy in management of severe neglected infantile tibia vara using the Ilizarov technique.
Neglected infantile Tibia Vara is a very challenging clinical problem with many technical problems including distorted joint line secondary to the medial tibial plateau depression, obesity leading to difficulty in exposure, performing osteotomies and difficulty in osteotomy fixation. The aim of this study is to evaluate the clinical and radiological results of treatment of severe neglected infantile Tibia Vara using a new osteotomy to elevate the depressed medial tibial plateau in conjunction with the Ilizarov technique. Seven tibias in five patients were included in this study. These were all Stage V and VI according to Langenskiold and Riska classification. The average age at surgery was 11.6 years (ranging from 8 to 15), and the average follow-up was 6.2 years (ranging from 3 to 10). A new double osteotomy technique was used to elevate the depressed medial tibial plateau and correct the varus deformity. Correction was done gradually using the Ilizarov Frame. The results were assessed clinically and radiologically. The femoral shaft -- tibial shaft angle improved from an average of 36 degrees of varus preoperatively to 4 degrees of varus. The femoral condyle-tibial shaft angle improved from an average of 58 degrees to 83 degrees. The angle of depressed medial tibial plateau improved from an average of 53 degrees to 10 degrees. We believe that our new double elevating osteotomy in conjunction with Ilizarov technique is an excellent modality for patients with stage V and VI according to the Langenskiold and Riska classification. The advantages of this technique include correction of the deformity with simultaneous correction of the joint architecture, immediate weight bearing, and avoidance of excessive dissection needed for internal fixation.


Expert googling: best practices and advanced strategies for using google in health sciences libraries.
Google is the search engine of choice for most Internet users. For a variety of reasons, librarians and other expert searchers do not always use Google to its full potential, even though it provides capabilities not possible in traditional bibliographic databases and other search engines. Applying expert searching principles and practices, such as the use of advanced search operators, information retrieval strategies, and search hedges to Google will allow health sciences librarians to find quality information on the Internet more efficiently and effectively.


Phosphorylation of HSP90 by protein kinase A is essential for the nuclear translocation of androgen receptor.
The androgen receptor (AR) is often activated in prostate cancer patients undergoing androgen-ablative therapy because of the activation of cellular pathways that stimulate the AR despite low androgen levels. In many of these tumors, the cAMP-dependent protein kinase A (PKA) pathway is activated. Previous studies have shown that PKA can synergize with low levels of androgen to enhance androgen signaling and consequent cell proliferation, leading to castration-resistant prostate cancer. However, the mechanism by which PKA causes AR stimulation in the presence of low/no androgen is not established yet. Here, using immunofluorescence immunoblotting assays, co-immunoprecipitation, siRNA-mediated gene silencing, and reporter gene assays, we demonstrate that PKA activation is necessary for the phosphorylation of heat shock protein (HSP90) that binds to unliganded AR in the cytoplasm, restricting its entry into the nucleus. We also found that PKA-mediated phosphorylation of the Thr89 residue in HSP90 releases AR from HSP90, enabling AR binding to HSP27 and its migration into the nucleus. Substitution of the Thr89 in HSP90 prevented its phosphorylation by PKA and significantly reduced AR transactivation and cellular proliferation. We further observed that the transcription of AR target genes, such as prostate-specific antigen (PSA), is also lowered in the HSP90 Thr89 variant. These results suggest that using a small-molecule inhibitor against the HSP90 Thr89 residue in conjunction with existing androgen-ablative therapy may be more effective than androgen-ablative therapy alone in the treatment of prostate cancer patients.