Effect of pulmonary autograft transplantation in the surgical treatment of aortic valve disease.
Aortic root replacement with pulmonary autograft (Ross procedure) has the advantages of good haemodynamics and growth potential without the need for anticoagulation. In this study, we reviewed our experience of the Ross procedure for patients with aortic valve disease. From October 1994 to January 2005, 42 Ross procedures were performed in our centre. There were 30 males and 12 females. The mean age was 28 +/- 15 years (range, 5-56 years). Congenital heart disease (CHD) with aortic valve stenosis (AS) and/or aortic valve insufficiency (AI) in 40 cases including one associated with ventricular septal defect (VSD), degenerated aortic valve disease with AS in 1 and subacutive bacterial endocarditis (SBE) with AI in 1 were studied. The diagnosis was made by ultracardiography (UCG) in all patients. The mean aortic valve annulus diameter (AVD) was (2.45 +/- 0.31) cm and pulmonary valve annulus diameter (MPVD) was (2.34 +/- 0.21) cm. All patients had normal pulmonary valves. The New York Heart Association (NYHA) function class was II in 36 cases and III in 6 cases. The operation was performed under moderate hypothermic cardiopulmonary bypass (CPB) with aortic root replacement using pulmonary autograft and pulmonary valve replacement with a homograft. There was no early hospital mortality. Postoperative UCG showed normal aortic valve function in all our patients. The mean gradient across the aortic valve was (6.11 +/- 0.12) mmHg. The left ventricular diastole diameter (LVDD) decreased significantly from (62 +/- 5) mm to (56 +/- 3) mm (P < 0.001). The mean postoperative left ventricular ejective fraction (LVEF) was 0.49 +/- 0.23. All patients were in NYHA class I-II. Follow-up was completed in 38 cases for a mean period of 3.2 years (range 1-10 years). All survivors were in NYHA class I with normal neo-aortic and pulmonary valve function. One patient died after secondary operation due to homograft fungal endocarditis 1 year after the Ross procedure. The cause of death was uncontrolled bleeding. Another patient suffered from cardiogenic shock and was on extracorporeal membrane oxygenation (ECMO) for 10 days postoperatively. This patient was subsequently self-discharged from hospital due to financial issues and he was excluded from follow-up. The Ross procedure is an excellent technique to treat aortic valve disease. Our data show that it can be performed safely with good early and mid-term clinical outcomes.


Evaluation of a prostate biopsy strategy for cancer detection using a computer simulation system with virtual needle biopsy for three-dimensional prostate models.
We evaluated a prostate biopsy strategy for cancer detection using a computer simulation system with virtual needle biopsy for three-dimensional (3D) prostate models. Two 3D prostate models with a volume of 25 cc or 50 cc were constructed from computed tomographic images of radical prostatectomy specimens. The peripheral zone (PZ) and transition zone (TZ) were arranged in the prostate models according to the anatomical information. Four thousand patterns of cancer lesions were automatically inserted into each prostate model with a proportion of 75% in PZ and 25% in TZ. Average hit rates (AHR) in prostate models were evaluated both with an increased number of biopsy cores and various angles of virtual needle biopsy. The influence of adding secondary tumors for hit rates was also evaluated. For both sizes, the laterally angled biopsy in 4-8 core biopsy schemes showed higher AHR than the vertical plane biopsy, while the vertical plane biopsy in 10-18 core biopsy schemes showed higher AHR than the laterally angled biopsy. A higher number of biopsy cores increased the AHR of secondary tumors. Our results suggest that it is important in prostate cancer detection to change the needle placement according to the number of biopsy cores and the size of the prostate.


Light-Driven Water Splitting Mediated by Photogenerated Bromine.
Light-driven water splitting was achieved using a dye-sensitized mesoporous oxide film and the oxidation of bromide (Br- ) to bromine (Br2 ) or tribromide (Br3- ). The chemical oxidant (Br2 or Br3- ) is formed during illumination at the photoanode and used as a sacrificial oxidant to drive a water oxidation catalyst (WOC), here demonstrated using [Ru(bda)(pic)2 ], (1; pic=picoline, bda=2,2'-bipyridine-6,6'-dicarboxylate). The photochemical oxidation of bromide produces a chemical oxidant with a potential of 1.09 V vs. NHE for the Br2 /Br- couple or 1.05 V vs. NHE for the Br3- /Br- couple, which is sufficient to drive water oxidation at 1 (RuV/IV ≈1.0 V vs. NHE at pH 5.6). At pH 5.6, using a 0.2 m acetate buffer containing 40 mm LiBr and the [Ru(4,4'-PO3 H2 -bpy)(bpy)2 ]2+ (RuP2+ , bpy=2,2'-bipyridine) chromophore dye on a SnO2 /TiO2 core-shell electrode resulted in a photocurrent density of around 1.2 mA cm-2 under approximately 1 Sun illumination and a Faradaic efficiency upon addition of 1 of 77 % for oxygen evolution.


Stress overload, influencing factors, and psychological experiences of nurse managers during early stages of the COVID-19 pandemic: a sequential explanatory mixed method study.
Healthcare systems had an exceptionally difficult time during the early COVID-19 pandemic. Nurse managers in particular made enormous contributions to ensuring the safety of patients and front-line nurses while being under excessive psychological stress. However, little is known about their experiences during this time. The aim of this study was thus to assess the level of stress overload and psychological feelings of nurse managers during the early COVID-19 pandemic. A mixed methods sequential explanatory design study with non-random convenience sampling was performed, following the STROBE and COREQ checklists. The study was conducted at the Affiliated Dongyang Hospital, Wenzhou Medical University, with data collected from six provinces in southern China (Zhejiang, Hubei, Shanghai, Jiangsu, Hunan and Jiangxi) during March 2020 and June 2020. A total of 966 nurse managers completed the Stress Overload Scale and Work-Family Support Scale. In addition, a nested sample of nurse managers participated in semi-structured face-to-face interviews. The data were then analyzed using qualitative content analysis, Pearson correlation, and multiple linear regression. The quantitative results showed that nurse managers experienced a moderate level of stress load. There was a significant negative correlation between work-family support and stress load (r = -0.551, p < 0.01). Concerns about protecting front-line nurses and work-family support were the main factors affecting the stress load, which accounted for 34.0% of the total variation. Qualitative analysis identified four main thematic analyses that explained stress load: (1) great responsibility and great stress, (2) unprecedented stress-induced stress response, (3) invisible stress: the unknown was even more frightening, and (4) stress relief from love and support. Taken together these findings indicate that concern about protecting front-line nurses and negative work-family support of nurse managers were the main factors causing stress overload. Implementing measures focused on individual psychological adjustment combined with community and family support and belongingness is one potential strategy to reduce psychological stress among nurse managers.


Outcomes, Approaches, and Challenges to Developing and Passing a Countywide Mandatory Vaccination Policy: St. Louis County's Experience with Hepatitis A Vaccine for Food Service Personnel.
In the early 1990s, St. Louis County had multiple foodservice worker-related hepatitis A outbreaks uncontrolled by standard outbreak interventions. Restaurant interest groups and the general public applied political pressure to local public health officials for more stringent interventions, including a mandatory vaccination policy. Local health departments can enact mandatory vaccination policies, but this has rarely been done. The study objectives were to describe the approach used to pass a mandatory vaccination policy at the local jurisdiction level and illustrate the outcome from this ordinance 15 years later. A case study design was used. In-depth, semi-structured interviews using guided questions were conducted in spring, 2015, with six key informants who had direct knowledge of the mandatory vaccination policy process. Meeting minutes and/or reports were also analyzed. A Poisson distribution analysis was used to calculate the rate of outbreaks before and after mandatory vaccination policy implementation. The policy appears to have reduced the number of hepatitis A outbreaks, lowering the morbidity and economic burden in St. Louis County. The lessons learned by local public health officials in passing a mandatory hepatitis A vaccination policy are important and relevant in today's environment. The experience and lessons learned may assist other local health departments when faced with the potential need for mandatory policies for any vaccine preventable disease.


Skeletal muscle cytokines: regulation by pathogen-associated molecules and catabolic hormones.
This review will update clinicians and basic scientists who study the molecular mechanisms of muscle wasting associated with infection, trauma, cancer cachexia, and AIDS. A special emphasis is placed on recent studies that examine the interaction of insulin-like growth factor 1 and proinflammatory cytokines as positive and negative regulators of muscle mass. Potential mediators of the wasting syndromes include catabolic hormones, such as glucocorticoids, as well as the inflammatory cytokines tumour necrosis factor, IL-1, and IL-6. Cytokines may function either systemically or locally within muscle per se. Lipopolysaccharide and other pathogen-associated molecules stimulate cytokine expression in muscle. The failure to clear pathogen-associated molecules or the introduction of muscle damage may initiate a protracted activation of enzymes and transcription factors that orchestrate a genetic programme that ultimately produces muscle wasting. This review highlights recent advances in our understanding of the expression of the afferent and efferent limbs of the innate immune system in skeletal muscle. A special emphasis is placed on the recognition of pathogen-associated molecules by skeletal muscle cells and how these molecules regulate the expression of inflammatory cytokines and other muscle genes to result in muscle wasting, and when sustained, the erosion of lean body mass.


BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.
The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.


Strong Coupling between the Hydrogen Bonding Environment and Redox Chemistry during the S2 to S3 Transition in the Oxygen-Evolving Complex of Photosystem II.
We have studied the early phase of the S2 → S3 transition in the oxygen-evolving complex (OEC) of photosystem II using the hybrid density functional theory with a quantum mechanical model composed of 338-341 atoms. Special attention is given to the vital role of water molecules in the vicinity of the Mn4CaO5 core. Our results demonstrate how important the dynamic behavior of surrounding water molecules is in mediating critical chemical transformations such as binding and deprotonation of substrates and hydration of the catalytic site and identify a strong coupling of water-chain relocation near the redox-active tyrosine residue Tyr161 (TyrZ) with oxidation of the Mn4CaO5 cluster by TyrZ(•+). The oxidation reaction is further promoted when the catalytic site is more solvated by water. These results indicate the importance of surrounding water molecules in biological catalysts as they ultimately lead to effective catalytic function and/or favorable electron-transfer dynamics.


Evaluation of a multivalent vaccine against lymphatic filariasis in rhesus macaque model.
Lymphatic filariasis affects 120 million people worldwide and another 1.2 billion people are at risk of acquiring the infection. Chemotherapy with mass drug administration is substantially reducing the incidence of the infection. Nevertheless, an effective vaccine is needed to prevent the infection and eradicate the disease. Previously we reported that a multivalent fusion protein vaccine (rBmHAT) composed of small heat shock proteins 12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and large extracellular domain of tetraspanin (TSP LEL) could confer >95% protection against the challenge infection with Brugia malayi infective larvae (L3) in mouse and gerbil models. In this study we evaluated the immunogenicity and efficacy of rBmHAT fusion protein vaccine in a rhesus macaque model. Our results show that rBmHAT is highly immunogenic in rhesus macaques. All the vaccinated monkeys developed significant titers of antigen-specific IgG antibodies against each of the component antigens (16,000 for rBmHSP12.6), (24,000 for rBmALT-2) and (16,000 for rBmTSP-LEL). An in vitro antibody dependent cellular cytotoxicity (ADCC) assay performed using the sera samples from vaccinated monkeys showed that the anti-rBmHAT antibodies are functional with 35% killing of B. malayi L3s. Vaccinated monkeys also had antigen responding cells in the peripheral blood. Vaccine-induced protection was determined after challenging the monkeys with 500 B. malayi L3. Following challenge infection, 3 out of 5 vaccinated macaques failed to develop the infection. These three protected macaques had high titers of IgG1 antibodies and their PBMC secreted significantly high levels of IFN-γ in response to the vaccine antigens. The two vaccinated macaques that picked the infection had slightly low titers of antibodies and their PBMC secreted high levels of IL-10. Based on these findings we conclude that the rBmHAT vaccine is highly immunogenic and safe and can confer significant protection against challenge infections in rhesus macaques.


Investigating phoneme-dependencies of spherical voice directivity patterns.
Dynamic directivity is a specific characteristic of the human voice, showing time-dependent variations while speaking or singing. To study and model the human voice's articulation-dependencies and provide datasets that can be applied in virtual acoustic environments, full-spherical voice directivity measurements were carried out for 13 persons while articulating eight phonemes. Since it is nearly impossible for subjects to repeat exactly the same articulation numerous times, the sound radiation was captured simultaneously using a surrounding spherical microphone array with 32 microphones and then subsequently spatially upsampled to a dense sampling grid. Based on these dense directivity patterns, the spherical voice directivity was studied for different phonemes, and phoneme-dependent variations were analyzed. The differences between the phonemes can, to some extent, be explained by articulation-dependent properties, e.g., the mouth opening size. The directivity index, averaged across all subjects, varied by a maximum of 3 dB between any of the vowels or fricatives, and statistical analysis showed that these phoneme-dependent differences are significant.


Do Health Insurance Schemes Heterogeneously Affect Income and Income Distribution? Evidence from Chinese Agricultural Migrants Survey.
Currently, the particularity of Chinese agricultural migrants groups determines that they can participate in various types of public health insurance schemes, i.e., the New Cooperative Medical Scheme (NCMS), Urban Residents Basic Medical Insurance (URBMI), and Urban Employees Basic Medical Insurance (UEBMI). The goal of this paper is to shed light on whether and how these health insurance schemes affect the agricultural migrants' income and income distribution. A dataset of 86,660 individuals is obtained from China Migrants Dynamic Survey implemented by the National Health Commission. The study uses the basic ordinary least squares regression to assess association between health insurance schemes and income and uses the propensity score matching method to estimate the income effect. In addition, we further use the quantile regression method to explore heterogeneous effects of health insurance schemes on income distribution. We find that UEBMI and URBMI have significant increased monthly net income of agricultural migrants, while NCMS does not. The income-increasing effect of UEBMI is greater than that of URBMI. The income-increasing effect of UEBMI is most obvious in the low-income group. While URBMI has a significant role in increasing income with its income-increasing effect being obvious for the lowest and highest income groups. We suggest that China's health insurance system needs further reforms in order to reduce income inequality of agricultural migrants.


Cytochrome P450 3A5 is highly expressed in normal prostate cells but absent in prostate cancer.
Testosterone is essential for the growth and function of the luminal prostate cells, but it is also critical for the development of prostate cancer, which in the majority of the cases derives from luminal cells. Cytochrome P450 3A (CYP3A) enzymes hydroxylate testosterone and dehydroepiandrosterone to less active metabolites, which might be the basis for the association between CYP3A polymorphisms and prostate cancer. However, it is unknown whether the CYP3A enzymes are expressed at relevant levels in the prostate and which polymorphisms could affect this tissue-specific CYP3A activity. Thus, we measured CYP3A4, CYP3A5, CYP3A7, and CYP3A43 mRNA in 14 benign prostatic hyperplasias and ten matched non-tumoral/tumoral prostate samples. We found that CYP3A5 mRNA in non-tumoral prostate tissue was 10% of the average amount of liver samples, whereas the expression of the other CYP3A genes was much lower. Similarly to liver, CYP3A5*3 polymorphism decreased CYP3A5 mRNA content 13-fold. CYP3A5 protein was detected in non-tumoral prostate microsomes by western blot, and immunohistochemistry (IHC) localized CYP3A5 exclusively in the basolateral prostate cells. In contrast to the normal tissue, IHC and RT-PCR showed that tumoral tissue lacked CYP3A5 expression. In conclusion, prostate basolateral cells express high levels of CYP3A5 which dramatically decrease in tumoral tissue. This finding supports an endogenous function of CYP3A5 related to the metabolism of intra-prostatic androgens and cell growth, and that polymorphisms affecting CYP3A5 activity may result in altered prostate cancer risk and aggressiveness.


CoronaVac vaccine does not affect ovarian reserve.
In this study, our aim is to investigate the effect of CoronaVac vaccine on ovarian reserve in female patients followed up for infertility. Our study is a retrospective study. Forty-six infertile patients who received two doses of CoronaVac vaccine one month apart and had not had a previous Covid 19 infection were included in the study. Anti-müllerian hormone (AMH) and folliculometry of 46 patients one month before CoronaVac vaccine and one month after the second dose of vaccine were compared. There was no statistically significant difference in the change of AMH level and follicle number before and after vaccination (respectively p = 0.366; 0.610). Considering that having a COVID-19 infection has a negative effect on female fertility and causing ovarian damage in recent studies, vaccination is a rational and cost-effective approach to protect ovarian reserve. Knowing that the vaccine does not have a negative effect on fertility may increase the application of the vaccine in women of reproductive age.


Modeling and detection of respiratory-related outbreak signatures.
Time series methods are commonly used to detect disease outbreak signatures (e.g., signals due to influenza outbreaks and anthrax attacks) from varying respiratory-related diagnostic or syndromic data sources. Typically this involves two components: (i) Using time series methods to model the baseline background distribution (the time series process that is assumed to contain no outbreak signatures), (ii) Detecting outbreak signatures using filter-based time series methods. We consider time series models for chest radiograph data obtained from Midwest children's emergency departments. These models incorporate available covariate information such as patient visit counts and smoothed ambient temperature series, as well as time series dependencies on daily and weekly seasonal scales. Respiratory-related outbreak signature detection is based on filtering the one-step-ahead prediction errors obtained from the time series models for the respiratory-complaint background. Using simulation experiments based on a stochastic model for an anthrax attack, we illustrate the effect of the choice of filter and the statistical models upon radiograph-attributed outbreak signature detection. We demonstrate the importance of using seasonal autoregressive integrated average time series models (SARIMA) with covariates in the modeling of respiratory-related time series data. We find some homogeneity in the time series models for the respiratory-complaint backgrounds across the Midwest emergency departments studied. Our simulations show that the balance between specificity, sensitivity, and timeliness to detect an outbreak signature differs by the emergency department and the choice of filter. The linear and exponential filters provide a good balance.


The robustness of persistent homology of brain networks to data acquisition-related non-neural variability in resting state fMRI.
There is increasing interest in investigating brain function based on functional connectivity networks (FCN) obtained from resting-state functional magnetic resonance imaging (fMRI). FCNs, typically obtained using measures of time series association such as Pearson's correlation, are sensitive to data acquisition parameters such as sampling period. This introduces non-neural variability in data pooled from different acquisition protocols and MRI scanners, negating the advantages of larger sample sizes in pooled data. To address this, we hypothesize that the topology or shape of brain networks must be preserved irrespective of how densely it is sampled, and metrics which capture this topology may be statistically similar across sampling periods, thereby alleviating this source of non-neural variability. Accordingly, we present an end-to-end pipeline that uses persistent homology (PH), a branch of topological data analysis, to demonstrate similarity across FCNs acquired at different temporal sampling periods. PH, as a technique, extracts topological features by capturing the network organization across all continuous threshold values, as opposed to graph theoretic methods, which fix a discrete network topology by thresholding the connectivity matrix. The extracted topological features are encoded in the form of persistent diagrams that can be compared against one another using the earth-moving metric, also popularly known as the Wasserstein distance. We extract topological features from three data cohorts, each acquired at different temporal sampling periods and demonstrate that these features are statistically the same, hence, empirically showing that PH may be robust to changes in data acquisition parameters such as sampling period.


The effect of asymptomatic nocturnal hypoglycemia on glycemic control in diabetes mellitus.
To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (+/- SE) plasma glucose level reached a nadir of 4.5 +/- 0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9 +/- 0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6 +/- 0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4 +/- 0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3 +/- 0.2 mmol per liter) and postbreakfast (12.5 +/- 0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2 +/- 0.2 mmol per liter and 8.7 +/- 0.4 mmol per liter, respectively; P less than 0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P less than 0.001), growth hormone (r = 0.57, P less than 0.009), and cortisol (r = 0.52, P less than 0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P less than 0.005). We conclude that asymptomatic nocturnal hypoglycemia can cause clinically important deterioration in glycemic control (the Somogyi phenomenon) in patients receiving intensive insulin therapy, and should therefore be considered in the differential diagnosis of unexplained morning hyperglycemia.


Prediction of canned black bean texture (Phaseolus vulgaris L.) from intact dry seeds using visible/near infrared spectroscopy and hyperspectral imaging data.
Texture is a major quality parameter for the acceptability of canned whole beans. Prior knowledge of this quality trait before processing would be useful to guide variety development by bean breeders and optimize handling protocols by processors. The objective of this study was to evaluate and compare the predictive power of visible and near infrared reflectance spectroscopy (visible/NIRS, 400-2498 nm) and hyperspectral imaging (HYPERS, 400-1000 nm) techniques for predicting texture of canned black beans from intact dry seeds. Black beans were grown in Michigan (USA) over three field seasons. The samples exhibited phenotypic variability for canned bean texture due to genetic variability and processing practice. Spectral preprocessing methods (i.e. smoothing, first and second derivatives, continuous wavelet transform, and two-band ratios), coupled with a feature selection method, were tested for optimizing the prediction accuracy in both techniques based on partial least squares regression (PLSR) models. Visible/NIRS and HYPERS were effective in predicting texture of canned beans using intact dry seeds, as indicated by their correlation coefficients for prediction (Rpred ) and standard errors of prediction (SEP). Visible/NIRS was superior (Rpred = 0.546-0.923, SEP = 7.5-1.9 kg 100 g-1 ) to HYPERS (Rpred = 0.401-0.883, SEP = 7.6-2.4 kg 100 g-1 ), which is likely due to the wider wavelength range collected in visible/NIRS. However, a significant improvement was reached in both techniques when the two-band ratios preprocessing method was applied to the data, reducing SEP by at least 10.4% and 16.2% for visible/NIRS and HYPERS, respectively. Moreover, results from using the combination of the three-season data sets based on the two-band ratios showed that visible/NIRS (Rpred = 0.886, SEP = 4.0 kg 100 g-1 ) and HYPERS (Rpred = 0.844, SEP = 4.6 kg 100 g-1 ) models were consistently successful in predicting texture over a wide range of measurements. Visible/NIRS and HYPERS have great potential for predicting the texture of canned beans; the robustness of the models is impacted by genotypic diversity, planting year and phenotypic variability for canned bean texture used for model building, and hence, robust models can be built based on data sets with high phenotypic diversity in textural properties, and periodically maintained and updated with new data. © 2017 Society of Chemical Industry.


Water: a neglected nutrient in the young child? A South African perspective.
Water is considered an essential nutrient because the body cannot produce enough water itself, by metabolism of food, to fulfil its need. When the quantity or quality of water is inadequate, health problems result, most notably dehydration and diarrhoea. As a result of contaminated water and poor hygiene, related infections are still a serious problem. Indeed, in the South African setting water availability and sanitation are critical issues because of the prevalence of childhood diarrhoea and also the HIV/AIDS crisis. Though considerable efforts have been made to improve the water and sanitation problems in South Africa - especially with regard to water supply infrastructure - there is still room for much improvement. Water is a healthy alternative to calorie-dense, non-nutritive beverages, such as artificial fruit drinks and soda. The latter should be avoided as they contribute little other than energy and may contribute to overweight and obesity. Also, they displace more nutritious foods from the child's diet. Consumption of fruit juice should also be limited. These issues highlight the need for a specific guideline relating to water intake in the paediatric food-based dietary guidelines.


Endovascular repair for retrograde type A intramural hematoma with focal intimal disruption in descending aorta.
This study aims to report the experience of a single center using thoracic endovascular aortic repair (TEVAR) to treat retrograde type A intramural hematoma (IMH) with focal intimal disruption (FID) in descending aorta. A total of 24 consecutive patients with retrograde type A IMH and complicated with FID in descending aorta underwent TEVAR in our center from 2015 to 2020. Their clinical data, imaging manifestation and follow-up results were retrospectively reviewed and analyzed. The median age of patients was 57.9 years (range, 42-80 years) and 18 were men (75%). As the preoperative CT angiography showed, the 24 patients developed IMH complicated with different kinds of FIDs in descending aorta [5 had intramural blood pool (IBP), 15 had ulcer-like projection (ULP), 2 had penetrating atherosclerotic ulcer (PAU), and 5 had localized dissection]. Successful deployment of aortic stent graft was achieved in all patients. There was no endoleak, stent graft migration, spinal cord ischemia, stroke, or 30-day mortality observed after TEVAR. The median duration of follow-up was 30.0 months (range, 3-60 months). As the last follow-up CT angiography showed, most of the patients (23 in 24, 96%) had favorable aortic remodeling. The maximum hematoma thicknesses and maximum diameters of both ascending and descending aorta were significantly decreased. During follow-up, 1 patient developed retrograde type A aortic dissection (RAAD) and underwent open surgery 3 months after TEVAR. 1 patient died of lung cancer 2 years later. There was no aorta-related death observed. TEVAR provides a safe and effective treatment strategy for selected patients with retrograde type A IMH, and FID developed in descending aorta could be the possible treatment target. However, RAAD remains one of the most serious postoperative complications of concern.


Enzyme recycle and fed-batch addition for high-productivity soybean flour processing to produce enriched soy protein and concentrated hydrolysate of fermentable sugars.
Despite having high protein and carbohydrate, soybean flour utilization is limited to partial replacement of animal feed to date. Enzymatic process can be exploited to increase its value by enriching protein content and separating carbohydrate for utilization as fermentation feedstock. Enzyme hydrolysis with fed-batch and recycle designs were evaluated here for achieving this goal with high productivities. Fed-batch process improved carbohydrate conversion, particularly at high substrate loadings of 250-375g/L. In recycle process, hydrolysate retained a significant portion of the limiting enzyme α-galactosidase to accelerate carbohydrate monomerization rate. At single-pass retention time of 6h and recycle rate of 62.5%, reducing sugar concentration reached up to 120g/L using 4ml/g enzyme. When compared with batch and fed-batch processes, the recycle process increased the volumetric productivity of reducing sugar by 36% (vs. fed-batch) to 57% (vs. batch) and that of protein product by 280% (vs. fed-batch) to 300% (vs. batch).


Psychometric evaluation of the Chinese version of the Toronto Hospital Alertness Test.
Alertness is an important part of attention which is different from the opposite of sleepiness. This study aimed to translate and assess the measurement properties of the Toronto Hospital Alertness Test (THAT) in Hong Kong Chinese population. The standard forward-backward translation procedure and cognitive debriefing were conducted to obtain the Chinese THAT. One hundred Chinese adults completed the Chinese THAT, the Center for Epidemiological Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Athens Insomnia Scale (AIS) by telephone interviews. The factorial validity was assessed by confirmatory factor analysis, and the internal reliability was examined by coefficient omega. The two negatively worded items of the THAT had low factor loadings and were removed. One more item was removed based on the modification indices of the eight-item model. The remaining seven-item THAT showed satisfactory unidimensionality with root mean square error of approximation (RMSEA) = 0.06, standardized root mean square residual (SRMR) = 0.08, and comparative fit index (CFI) = 1.00. The coefficient omega of the seven-item Chinese THAT was 0.80 (95% CI: 0.74-0.86). Convergent validity was demonstrated with THAT moderately associated with CES-D (r = - 0.45, P < 0.01), PSQI (r = - 0.40, P < 0.01), and AIS (r = - 0.45, P < 0.01). The Chinese version of THAT demonstrated acceptable reliability and validity in a Chinese population.


[Normal ultrastructure of the small bronchi and bronchioli in man].
Ultrastructural topographic and morphological analysis of the small bronchi and bronchioli was carried out on selected biopsy specimens obtained from 6 operative specimens. The small bronchi had a ciliated cylindrical epithelium identical to that in the large bronchi, apart from a smaller number of goblet cells. Their reticulin layer was thin (1 to 3 microns). The glands in the submucosa were rare whereas there was a rich submucosal vascular network. The lobular bronchioli had a ciliated cylindrical epithelium without goblet cells but possessing rare Clara cells. The epithelium of the terminal bromchioli was characterized by: 1 - The presence of numerous Clara cells, generally grouped in groups of 2 or 3. 2 - The appearance on the opposite side of a satellite artery (this side shows alveoli first) of cells which we interpreted as pre-ciliated cells. These cells possess a range of basal corpuscles under the luminal membrane but do not have cilia. 3 - The appearance of small membranous pneumocytes in islets. The epithelium covering the smooth wall of the respiratory bronchioles still have a gutter of ciliated cells and Clara cells which become thinner towards the periphery. After the secondary respiratory bronchioli, there appears in this gutter a new cell type, the cubical cells. These cells which have poorly differentiated cytoplasmic characteristics, seem to us to be immature bronchial cells, precursors of the Clara cells rather than of the ciliated cells. The remainder of the smooth wall of the respiratory bronchioli is covered with membranous pneumocytes and, in the case of the 3rd order of bronchioli, also by granular pneumocytes. The sub-basal reticulin layer is lacking in the terminal and respiratory bronchioli. The total thickness of the wall becomes considerably thinner, the muscular layer becoming proportionally very thick.


Serum cytokine and soluble interleukin-2 receptors in patients with panic disorder.
There has been very little research investigating the interface between panic disorder and the immune system. This preliminary study explores the relationship between panic disorder and serum levels of cytokines, which have potent immune and central nervous system activity, and soluble interleukin-2 receptors, a well-known marker of T-cell activation. Fifteen women with panic disorder and 19 healthy female subjects had serum levels of interleukin-1, interleukin-2, and soluble interleukin-2 receptors (SIL-2Rs) measured by enzyme-linked immunoassay. Women with panic disorder had slightly increased serum levels of interleukin-2 but did not differ from age-comparable and gender-matched controls in serum interleukin-1 alpha, or interleukin-1 beta. And although the mean SIL-2R levels were not different for the two groups, the SIL-2R levels were present across a wider range of values in the women with panic disorder. Our data suggest that more extensive investigation of circulating levels of interleukin-2 and the soluble interleukin-2 receptor in patients with panic disorder may be warranted.


Peptide coated quantum dots for biological applications.
Quantum dots (QDOTs) have been widely recognized by the scientific community and the biotechnology industry, as witnessed by the exponential growth of this field in the past several years. We describe the synthesis and characterization of visible and near infrared QDots--a critical step for engineering organic molecules like proteins and peptides for building nanocomposite materials with multifunctional properties suitable for biological applications.


Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors.
Left-right asymmetry of the brain has been studied mostly through psychological examination and functional imaging in primates, leaving its molecular and synaptic aspects largely unaddressed. Here, we show that hippocampal CA1 pyramidal cell synapses differ in size, shape, and glutamate receptor expression depending on the laterality of presynaptic origin. CA1 synapses receiving neuronal input from the right CA3 pyramidal cells are larger and have more perforated PSD and a GluR1 expression level twice as high as those receiving input from the left CA3. The synaptic density of GluR1 increases as the size of a synapse increases, whereas that of NR2B decreases because of the relatively constant NR2B expression in CA1 regardless of synapse size. Densities of other major glutamate receptor subunits show no correlation with synapse size, thus resulting in higher net expression in synapses having right input. Our study demonstrates universal left-right asymmetry of hippocampal synapses with a fundamental relationship between synaptic area and the expression of glutamate receptor subunits.


[Spinal hemangioblastoma in infants with dysraphic malformation of the CNS].
Spinal hemangioblastoma in early infancy is an extreme rarity. In the case presented here such a hamartomatous tumor is combined with dysraphic malformation of the CNS in a male infant aged seven months. The morphological, epidemiological and clinical aspects are discussed with special reference to the possibility of congenital occurrence.


A new species of Naxia Latreille, 1825 (Brachyura: Majidae) from deep water off Brazil.
A new species of spider crab, Naxia atlantica n. sp., is described and illustrated from deep waters off São Paulo (southeastern Brazil). The new species can be separated from its congeners by a suite of characters including shapes of the propodi of the walking legs, rostrum and basal antennal article. This is the first record of the genus outside southern Australia and New Zealand.


Induction of hypoferremia and modulation of macrophage iron metabolism by tumor necrosis factor.
The effects of recombinant tumor necrosis factor (TNF), tumor necrosis serum (TNS), recombinant interleukin 1 (IL-1), and prostaglandin E2 on serum iron parameters and iron handling by macrophages in mice have been investigated. Recombinant TNF caused a significant decrease in serum iron levels after 6 hours, but none of the mediators caused significant changes in total iron binding capacity at this time, although TNS caused a significant increase in total iron binding capacity after 24 hours. Peritoneal macrophages taken from mice 6 hours after inoculation of the mediators were pulsed with 59Fe, 125I-transferrin-antitransferrin immune complexes, and subsequent degradation of the complexes and release of iron were investigated. Both recombinant TNF and TNS caused significant increases in uptake and degradation of the complexes, but with recombinant TNF this was not accompanied by a corresponding increase in iron release. IL-1 and prostaglandin E2 also caused increased degradation of the immune complexes, but uptake of the complexes and iron release were unaffected. When peritoneal macrophages from normal mice were treated with the mediators in vitro and then pulsed with labeled immune complexes, recombinant TNF caused a significant decrease in iron release, but none of the other mediators had any effect. None of the mediators affected uptake or degradation of the immune complexes. These results suggest that TNF, rather than IL-1, mediates the hypoferremia of inflammatory disease and that alterations in the ability of macrophages to handle iron may be responsible.


Total Corneal Melt in Patient with Porphyria Cutanea Tarda in Presence of Another Risk Factor.
Purpose: To report a case of two siblings affected by porphyria cutanea tarda (PCT) presenting with varying severity of ocular disease and evaluation of difference in the presence of risk factors. Methods: Case report Result: A 42-year-old Indian male diagnosed with PCT and history of daily intake of alcohol, presented with sudden decrease in vision of right eye. Examination showed perforated cornea surrounded by rim of 360-degree avascular necrotic sclera, with no evidence of infection. Similar systemic history was present in his elder brother. He did not consume alcohol and presented with mere localized scleral thinning. Since the patient's sibling acted as a natural control for the evaluation of alcohol as an independent risk factor, the difference in severity of disease can be explained on the basis of difference in alcohol intake. Conclusion: In the presence of progression of the disease, other risk factors like intake of alcohol should be evaluated.


Pancreatic cystadenoma and cystadenocarcinoma.
Cystadenomas and cystadenocarcinomas are rare but not exceptional tumours of the pancreas. In this report six cases are added to the more than 300 cystadenomas and over 100 cystadenocarcinomas reported in the literature. We present here the case histories of four cystadenomas and two cystadenocarcinomas with complete follow-up. There is no evidence of recurrence after a maximum of 22 years in cystadenoma and 4 years in cystadenocarcinoma following resection. We have the impression that cystic lesions of the pancreas are nowadays more often detected than in former years. This might be due to abdominal investigation by computerized tomography and ultrasound on a large scale. Pathological features of proliferative cystic lesions of the pancreas permit distinction of three different tumours: serous cystadenoma, mucinous cystadenoma and cystadenocarcinoma. The serous cystadenoma is benign. The mucinous cystadenoma has to be considered as potentially malignant. The cystadenocarcinoma is malignant by definition. As benign and malignant elements can be found in the same cyst biopsy cannot exclude cystadenocarcinoma. Therefore all cystadenomas and cystadenocarcinomas should be totally excised, especially as prognosis after resection of cystadenocarcinoma is much better than after resection of adenocarcinoma of the pancreas.


Illusory Body Ownership Affects the Cortical Response to Vicarious Somatosensation.
Fundamental human feelings such as body ownership ("this" body is "my" body) and vicariousness (first-person-like experience of events occurring to others) are based on multisensory integration. Behavioral links between body ownership and vicariousness have been shown, but the neural underpinnings remain largely unexplored. To fill this gap, we investigated the neural effects of altered body ownership on vicarious somatosensation. While recording functional brain imaging data, first, we altered participants' body ownership by robotically delivering tactile stimulations ("tactile" stroking) in synchrony or not with videos of a virtual hand being brushed ("visual" stroking). Then, we manipulated vicarious somatosensation by showing videos of the virtual hand being touched by a syringe's plunger (touch) or needle (pain). Only after the alteration of body ownership (synchronous visuo-tactile stroking) and specifically during late epochs of vicarious somatosensation, vicarious pain was associated with lower activation in premotor and anterior cingulate cortices with respect to vicarious touch. At the methodological level, the present study highlights the importance of the neural response's temporal evolution. At the theoretical level, it shows that the higher-level (cognitive) impact of a lower-level (sensory) body-related processing (visuo-tactile) is not limited to body ownership but also extends to other psychological body-related domains, such as vicarious somatosensation.


Case report: Multidrug-resistant Streptococcus pseudoporcinus isolated from an infected surgical wound of a 9-year-old spayed female Great Dane dog.
Streptococcus pseudoporcinus (S. pseudoporcinus) is a β-hemolytic, Gram-positive novel bacterium first identified in 2006. It is a catalase-negative, non-motile coccus arranged in short chains. Furthermore, it has a broad beta-hemolytic reaction on sheep blood agar and cross-reacts with Lancefield group B antigen agglutination reagent. In this study, we report a case of S. pseudoporcinus infection of a surgical wound on the left metatarsus of a dog. The patient is a 9-year-old spayed female Great Dane dog with a brief history of multiple cutaneous masses being removed. Post-surgery, the post-surgical site on the left metatarsus became infected and discharged purulent material with a fetid odor. Upon preliminary diagnostic testing, we detected catalase-negative Gram-positive cocci exhibiting beta-hemolytic growth on sheep blood agar. A VITEK® 2 Compact machine from bioMérieux identified the bacterium as S. pseudoporcinus. Furthermore, antibiotic testing revealed multidrug resistance. Therefore, we document a multidrug-resistant S. pseudoporcinus isolate as a cause of canine post-surgical wound infection. Furthermore, it was the only isolate detected from the sample; hence, it is the cause of the infection. To our knowledge, this case is the first report of S. pseudoporcinus in a dog.


Correlates of change in adolescent alcohol consumption in Ireland: implications for understanding influences and enhancing interventions.
Studies of two similar cohorts of students in Ireland in 1984 and 1992 showed a dramatic increase in the consumption of alcohol, especially in the frequency with which students reported being drunk. A comparison of measures obtained at both times showed that there were major changes with regard to beliefs about consequences of alcohol consumption in a direction favorable to consumption as well as increases in the perceived social support for drinking. However, there were no strong indications that changes in problem behavior were associated with the observed increases in drinking patterns. These results are supportive of some explanatory models of initiation to substance use and have associated implications for programs designed to reduce consumption.


Use of docetaxel in low- and high-burden metastatic hormone-sensitive prostate cancer: A systematic review and assessment of subgroup analyses.
Use of docetaxel in low- and high-burden metastatic hormone-sensitive prostate cancer presents considerable controversy. There is literature suggesting lack of benefit for low-volume of metastases. The study aims to develop a systematic review and methodological assessment of subset analysis about use of docetaxel in metastatic hormone-sensitive prostate cancer regarding volume of metastatic disease. A systematic review in the Pubmed® database was conducted up to 25 September 2020. A reference tracking was also developed. Randomised clinical trials with subgroup analysis according volume of metastatic disease for overall survival were selected. Two methodologies were used. One of them considered statistical interaction of subsets (p(i) < 0.1), pre-specification, biological plausibility and consistency among subset results of similar randomised clinical trials. The second methodology was a two-part validated tool: preliminary questions to discard subset analysis without minimal relevance and a checklist The checklist provides recommendations for applicability of subgroup analysis in clinical practice. A total of 31 results were found in systematic reviews in the Pubmed® database. One result was identified in the reference tracking. Of the total of 32 results, four randomised clinical trials were included in the study. About first methodology, statistical interaction among subgroups was obtained in one randomised clinical trial. Subgroup analysis was pre-specified in two randomised clinical trials. Biological plausibility was reasonable. No external consistency among results of subgroup analyses in randomised clinical trials was observed. Preliminary questions of second methodology rejected applicability of subgroup analysis in three randomised clinical trials. A 'null' recommendation for applicability of subset results was obtained in the remaining randomised clinical trial. Patients with low- and high-burden metastatic hormone-sensitive prostate cancer would benefit from docetaxel therapy. No consistent differences for overall survival were observed in subgroup analyses regarding volume of metastatic disease.


Identification of delphinidin 3-O-(6''-O-malonyl)-beta-glucoside-3'-O-beta-glucoside, a postulated intermediate in the biosynthesis of ternatin C5 in the blue petals of Clitoria ternatea (butterfly pea).
Ternatins are blue anthocyanins found in the petals of Clitoria ternata (butterfly pea). Among them, ternatin C5 (delphinidin 3-O-(6''-O-malonyl)-beta-glucoside-3',5'-di-O-beta-glucoside; 2) has the structure common to all the ternatins, which is characterized by its glucosylation pattern: a 3,3',5'-triglucosylated anthocyanidin. In the course of studying biosynthetic pathways of ternatins, the key enzymatic activities to produce ternatin C5 were discovered in a crude enzyme preparation from the petals of a blue petal line of C. ternatea. When this preparation was tested for activity against several delphinidin glycosides, delphinidin 3-O-(6''-O-malonyl)-beta-glucoside-3'-O-beta-glucoside (6), a postulated intermediate, was found in the reaction mixture, together with three known anthocyanins, which were spectroscopically structurally identified. As a result of structural identification, the following enzymatic activities were identified: UDP-glucose :delphinidin 3-O-(6''-O-malonyl)-beta-glucoside-3'-O-beta-glucoside 5'-O-glucosyltransferase (5'GT), UDP-glucose :delphinidin 3-O-(6''-O-malonyl)-beta-glucoside 3'-O-glucosyltransferase (3'GT), UDP-glucose :delphinidin 3-O-glucosyltransferase, and malonyl-CoA :delphinidin 3-O-beta-glucoside 6''-malonyltransferase. In a mauve petal line, which did not accumulate ternatins but delphinidin 3-O-(6''-O-malonyl)-beta-glucoside in its petal, there were neither 5'GT nor 3'GT activities. Thus, the early biosynthetic pathway of ternatins may be characterized by the stepwise transfer of two glucose residues to 3'- and 5'-position of delphinidin 3-O-(6''-O-malonyl)-beta-glucoside (1; Scheme) from UDP-glucose.


Influence of needle bevel design on injection pain and needle deformation in dental local infiltration anaesthesia - randomized clinical trial.
The aims of this in vivo study were to evaluate the impact of needle bevel design on patients' pain perception and the mechanical deformation of the needle tip after the injection. In a prospective single-blinded trial, 150 patients received conventional infiltration anaesthesia for dental treatment by one examiner. Patients were randomized for one out of three different needle bevel types (scalpel-designed bevel needle (SB), n=50; triple bevel needle (TB), n=50; regular bevel needle (RB), n=50). Subjects' self-reported injection pain perception was evaluated using a numeric rating scale (NRS). For each needle tip, deformations after single use were measured using SEM. A significant lower injection pain level was found in SB (mean 2.1±1.2) than in TB (mean 3.5±1.6;) and RB (mean 3.4±1.0; all P<0.001). A needle deformation was detected in about 97.3% of all needles (SB 50/50, TB 50/50, and RB: 46/50). A higher number of barbs were found in SB (29/50) versus TB (17/50) and RB (19/50). For dental local infiltration anaesthesia, injection needles with a scalpel-designed bevel demonstrated significantly less injection pain. Needle tip deflections after anaesthetic agent infiltration, especially barbed hooks on the non-cutting edge may result in greater soft tissue trauma.


Quinone reductase 2 is a catechol quinone reductase.
The functions of quinone reductase 2 have eluded researchers for decades even though a genetic polymorphism is associated with various neurological disorders. Employing enzymatic studies using adrenochrome as a substrate, we show that quinone reductase 2 is specific for the reduction of adrenochrome, whereas quinone reductase 1 shows no activity. We also solved the crystal structure of quinone reductase 2 in complexes with dopamine and adrenochrome, two compounds that are structurally related to catecholamine quinones. Detailed structural analyses delineate the mechanism of quinone reductase 2 specificity toward catechol quinones in comparison with quinone reductase 1; a side-chain rotational difference between quinone reductase 1 and quinone reductase 2 of a single residue, phenylalanine 106, determines the specificity of enzymatic activities. These results infer functional differences between two homologous enzymes and indicate that quinone reductase 2 could play important roles in the regulation of catecholamine oxidation processes that may be involved in the etiology of Parkinson disease.


[Molecular epidemiological markers of Legionella pneumophila in the Valencian Community (II). Restriction enzyme profiles of chromosomal DNA].
Restriction enzyme profiles of chromosomal DNA obtained from 96 Legionella pneumophila strains isolated from environmental and clinical isolates and digested with Hind III have been analyzed. A method to obtain chromosomal DNA to be use in restriction studies and its electrophoretic analysis have been developed. Studying the fragments showing higher differences when comparing the profiles obtained, 5 subtypes are defined and correlated with the isolation areas. There are similar restriction profiles independent of the plasmid contents.


Long-term quality of life after definitive treatment for prostate cancer: patient-reported outcomes in the second posttreatment decade.
Definitive treatment for prostate cancer includes radical prostatectomy (RP), external beam radiation therapy (EBRT), and brachytherapy (BT). The different side effect profiles of these options are crucial factors for patients and clinicians when deciding between treatments. This study reports long-term health-related quality of life (HRQOL) for patients in their second decade after treatment for prostate cancer. We used a validated survey to assess urinary, bowel, and sexual function and HRQOL in a prospective cohort of patients diagnosed with localized prostate cancer 14-18 years previously. We report and compare the outcomes of patients who were initially treated with RP, EBRT, or BT. Of 230 eligible patients, the response rate was 92% (n = 211) and median follow-up was 14.6 years. Compared to baseline, RP patients had significantly worse urinary incontinence and sexual function, EBRT patients had worse scores in all domains, and BT patients had worse urinary incontinence, urinary irritation/obstruction, and sexual function. When comparing treatment groups, RP patients underwent larger declines in urinary continence than did BT patients, and EBRT and BT patients experienced larger changes in urinary irritation/obstruction. Baseline functional status was significantly associated with long-term function for urinary obstruction and bowel function domains. This is one of the few prospective reports on quality of life for prostate cancer patients beyond 10 years, and adds information about the late consequences of treatment choices. These data may help patients make informed decisions regarding treatment choice based on symptoms they may experience in the decades ahead.


The single-dose pharmacokinetics of the novel CCK1 receptor antagonist, dexloxiglumide, are not influenced by age and gender.
The effects of age and gender on the single-dose pharmacokinetics of dexloxiglumide, a selective cholecystokinin (CCK1-subtype) receptor antagonist, were assessed in healthy young and elderly male and female subjects. In total, 24 males and 24 females (12 young and 12 elderly subjects per gender group) received a single oral dose of 200 mg dexloxiglumide under fasted conditions. Mean (range) ages were 23.8 (18 - 32) and 71.3 (66 - 88) years for young and elderly subjects, respectively. Analysis of covariance (ANCOVA) with age group and gender as factors and body weight as a covariate was performed on the dexloxiglumide pharmacokinetic parameters of peak plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC). The p values obtained from ANCOVA were considered for the assessment of age and gender effects. A small (approximately 18%) but statistically significant (p < or = 0.036) increase in the area under the plasma concentration-time curve from 0 to time of last quantifiable concentration (AUC(0-t) and the area under the plasma concentration-time curve from 0 to infinity (AUC(0-infinity)) in elderly compared to young subjects was noted. Given the lack of age effects on the other pharmacokinetic parameters of dexloxiglumide, this limited difference is unlikely to be clinically relevant. Without the adjustment for body weights, female subjects exhibited mean C(max) and AUC values approximately 26% and 36% higher than male subjects; however, these exposure differences did not reach statistical significance (p > 0.05) following ANCOVA analysis with body weight as a covariate. Likewise, there were no statistically significant differences (p > 0.05) observed for any other pharmacokinetic parameters between young and elderly and between male and female groups. Dose adjustments based on age and gender are not necessary. Dexloxiglumide administration was safe and well tolerated in these subjects.


Factors influencing community nursing roles and health service provision in rural areas: a review of literature.
This review sought to better understand the issues and challenges experienced by community nurses working in rural areas and how these factors shape their role. Databases were searched to identify relevant studies, published between 1990 and 2015, that focussed on issues and challenges experienced by rural community nurses. Generic and grey literature relating to the subject was also searched. The search was systematically conducted multiple times to assure accuracy. A total of 14 articles met the inclusion criteria. This critical review identified common issues impacting community nursing and included role definition, organisational change, human resource, workplace and geographic challenges. Community nurses are flexible, autonomous, able to adapt care to the service delivery setting, and have a diversity of knowledge and skills. Considerably more research is essential to identify factors that impact rural community nursing practice. In addition, greater advocacy is required to develop the role.


Pleiotropic protective effects of phytochemicals in Alzheimer's disease.
Alzheimer's disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD.


[Anopheles cruzii parity in dense rain forest in Southern Brazil].
To determine the parity and ovarian development of Anopheles cruzii species during the seasons. Collections were carried out fortnightly in the morning in the Palmito State Park in the municipality of Paranaguá, Southern Brazil, between April 2004 and April 2005. Adult mosquitoes were captured using human landing rate. Dissections were performed using Detinova's and Polovodova's methods and follicular development was assessed following Christophers and Mer's criteria. A total of 208 specimens of Anopheles cruzii were dissected. Most females dissected were nulliparous in the seasons; 14.4% of them were found to be nulliparous above Christophers and Mer's stage II, which shows previous blood meal prior to the first oviposition. It was observed that Anopheles cruzii populations comprised young mosquitoes, probably due to high mortality among parous females. The likely gonotrophic discordance is epidemiologically relevant because female mosquitoes can search for more than one host to complete the maturation of their eggs.


Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes.
Coding synonymous single nucleotide polymorphisms (SNPs) have attracted little attention until recently. However, such SNPs located in epigenetic, CpG sites modifying exonic splicing enhancers (ESEs) can be informative with regards to the recently verified association of intragenic methylation and splicing. The present study describes the association of type 2 diabetes (T2D) with the exonic, synonymous, epigenetic SNPs, rs3749166 in calpain 10 (CAPN10) glucose transporter (GLUT4) translocator and rs5404 in solute carrier family 2, member 2 (SLC2A2), also termed GLUT2, which, according to prior bioinformatic analysis, strongly modify the splicing potential of glucose transport-associated genes. Previous association studies reveal that only rs5404 exhibits a strong negative T2D association, while data on the CAPN10 polymorphism are contradictory. In the present study DNA from blood samples of 99 Greek non-diabetic control subjects and 71 T2D patients was analyzed. In addition, relevant publicly available cases (40) resulting from examination of 110 Personal Genome Project data files were analyzed. The frequency of the rs3749166 A allele, was similar in the patients and non-diabetic control subjects. However, AG heterozygotes were more frequent among patients (73.24% for Greek patients and 54.55% for corresponding non-diabetic control subjects; P=0.0262; total cases, 52.99 and 75.00%, respectively; P=0.0039). The rs5404 T allele was only observed in CT heterozygotes (Greek non-diabetic control subjects, 39.39% and Greek patients, 22.54%; P=0.0205; total cases, 34.69 and 21.28%, respectively; P=0.0258). Notably, only one genotype, heterozygous AG/CC, was T2D-associated (Greek non-diabetic control subjects, 29.29% and Greek patients, 56.33%; P=0.004; total cases, 32.84 and 56.58%, respectively; P=0.0008). Furthermore, AG/CC was strongly associated with very high (≥8.5%) glycosylated plasma hemoglobin levels among patients (P=0.0002 for all cases). These results reveal the complex heterozygotic SNP association with T2D, and indicate possible synergies of these epigenetic, splicing-regulatory, synonymous SNPs, which modify the splicing potential of two alternative glucose transport-associated genes.


Effect of Systematic Control of Pd Thickness and Annealing Temperature on the Fabrication and Evolution of Palladium Nanostructures on Si (111) via the Solid State Dewetting.
Si-based optoelectronic devices embedded with metallic nanoparticles (NPs) have demonstrated the NP shape, size, spacing, and crystallinity dependent on light absorption and emission induced by the localized surface plasmon resonance. In this work, we demonstrate various sizes and configurations of palladium (Pd) nanostructures on Si (111) by the systematic thermal annealing with the variation of Pd thickness and annealing temperature. The evolution of Pd nanostructures are systematically controlled by the dewetting of thin film by means of the surface diffusion in conjunction with the surface and interface energy minimization and Volmer-Weber growth model. Depending on the control of deposition amount ranging between 0.5 and 100 nm at various annealing temperatures, four distinctive regimes of Pd nanostructures are demonstrated: (i) small pits and grain formation, (ii) nucleation and growth of NPs, (iii) lateral evolution of NPs, and (iv) merged nanostructures. In addition, by the control of annealing between 300 and 800 °C, the Pd nanostructures show the evolution of small pits and grains, isolated NPs, and finally, Pd NP-assisted nanohole formation along with the Si decomposition and Pd-Si inter-diffusion. The Raman analysis showed the discrepancies on phonon modes of Si (111) such that the decreased peak intensity with left shift after the fabrication of Pd nanostructures. Furthermore, the UV-VIS-NIR reflectance spectra revealed the existence of surface morphology dependent on absorption, scattering, and reflectance properties.


High-temperature quantum oscillations caused by recurring Bloch states in graphene superlattices.
Cyclotron motion of charge carriers in metals and semiconductors leads to Landau quantization and magneto-oscillatory behavior in their properties. Cryogenic temperatures are usually required to observe these oscillations. We show that graphene superlattices support a different type of quantum oscillation that does not rely on Landau quantization. The oscillations are extremely robust and persist well above room temperature in magnetic fields of only a few tesla. We attribute this phenomenon to repetitive changes in the electronic structure of superlattices such that charge carriers experience effectively no magnetic field at simple fractions of the flux quantum per superlattice unit cell. Our work hints at unexplored physics in Hofstadter butterfly systems at high temperatures.


Prostaglandin endoperoxide H synthase (PGHS) activity and PGHS-1 and -2 messenger ribonucleic acid abundance in human chorion throughout gestation and with preterm labor.
Term and preterm parturition is associated with elevated intrauterine PG production. Although an increase of PG synthesis by the fetal membranes during term labor is well documented, there is little data available regarding the prostanoid production of these tissues at term, before the spontaneous onset of labor. In the present study, we determined the expression of PG H2 synthase (PGHS), the committing and rate-limiting enzyme of prostanoid biosynthesis, in the chorion laeve during gestation. Tissues were collected from 18 patients at term (37-41 weeks of gestation) and from 13 patients between 17 and 35 weeks of pregnancy. None of the patients were in labor. PGHS-specific activity and the abundance of messenger RNAs (mRNAs) encoding the two PGHS isoenzymes (the constitutive PGHS-1 and the inducible PGHS-2) were measured by a cell-free enzyme assay and specific ribonuclease protection assays, respectively. PGHS-specific activity as well as PGHS-1 and -2 mRNA levels were significantly (P < 0.01) higher at term before labor than earlier during gestation. Furthermore, PGHS activity at term exhibited significant positive correlation with PGHS-2 mRNA levels, but not with PGHS-1 mRNA levels. In situ hybridization indicated that the expression of both PGHS mRNAs increased in the epithelial and the mesenchymal cells of the amnion and the chorion laeve at term. Additionally, PGHS activity and mRNA levels were determined in the chorion laeve of a group of patients who gave birth spontaneously before term (30.6 +/- 1 weeks, mean +/- SEM, n = 5), and the values were compared with a group who delivered by cesarean section before labor at a similar gestational age (31.9 +/- 1.4 weeks, n = 5, P > 0.05 vs. the preterm labor group). None of the patients exhibited signs of genital tract infection. PGHS-specific activity and PGHS-1 and -2 mRNA levels were significantly higher in the preterm labor group than in the group who delivered preterm without labor. In situ hybridization suggested that the enhanced PGHS-1 and -2 mRNA expression occurred predominantly in the mesenchymal cells of the fetal membranes at preterm labor. Thus, PGHS-1 and -2 expression increases in the chorion laeve at term before labor, with PGHS-2 as the functionally prevalent isoform. This supports the possibility that PGs originating in the fetal membranes promote the onset of normal labor. Furthermore, preterm labor is associated with the elevated expression of the two PGHS isoenzymes in the chorion laeve. The maturation of the fetal membranes in preparation for term labor involves both the epithelial and the mesenchymal cells, whereas preterm labor is accompanied by the maturation of the mesenchymal tissue components, as reflected by PGHS expression. This difference may have implications in the early recognition of preterm labor.


Importance of the 5 S rRNA-binding ribosomal proteins for cell viability and translation in Escherichia coli.
A specific complex of 5 S rRNA and several ribosomal proteins is an integral part of ribosomes in all living organisms. Here we studied the importance of Escherichia coli genes rplE, rplR and rplY, encoding 5 S rRNA-binding ribosomal proteins L5, L18 and L25, respectively, for cell growth, viability and translation. Using recombineering to create gene replacements in the E. coli chromosome, it was shown that rplE and rplR are essential for cell viability, whereas cells deleted for rplY are viable, but grow noticeably slower than the parental strain. The slow growth of these L25-defective cells can be stimulated by a plasmid expressing the rplY gene and also by a plasmid bearing the gene for homologous to L25 general stress protein CTC from Bacillus subtilis. The rplY mutant ribosomes are physically normal and contain all ribosomal proteins except L25. The ribosomes from L25-defective and parental cells translate in vitro at the same rate either poly(U) or natural mRNA. The difference observed was that the mutant ribosomes synthesized less natural polypeptide, compared to wild-type ribosomes both in vivo and in vitro. We speculate that the defect is at the ribosome recycling step.


Peroxiredoxin V Reduces β-Lapachone-induced Apoptosis of Colon Cancer Cells.
Peroxiredoxin (Prx) V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS). Also, Prx V has been shown to mediate cell apoptosis in various cancers. However, the mechanism of Prx V-induced apoptosis in colon cancer cells remains unknown. Thus, in this study we analyzed the effects of Prx V in β-lapachone-induced apoptosis in SW480 human colon cancer cells. β-lapachone-induced apoptosis was analyzed by the MTT assay, western blotting, fluorescence microscopy, Annexin V staining and flow cytometry. Overexpression of Prx V, significantly decreased β-lapachone-induced cellular apoptosis and Prx V silencing increased β-lapachone-induced cellular apoptosis via modulating ROS scavenging activity compared to mock SW480 cells. In addition, to further explore the mechanism of Prx V regulated β-lapachone-induced SW480 cells apoptosis, the Wnt/β-catenin signaling was studied. The Wnt/ β-catenin signaling pathway was found to be induced by β-lapachone. Prx V regulates SW480 cell apoptosis via scavenging ROS cellular levels and mediating the Wnt/β-catenin signaling pathway, which was induced by β-lapachone.


Development and evaluation of an augmented reality education program for pediatric research.
Children often have limited understanding of clinical research and what they might expect from participating in a clinical study. Studies, however, suggest that multimedia delivery of medical and research information may promote greater understanding and engagement compared with standard written approaches. This study was designed to examine the effects of a novel interactive augmented reality (AR) program on children's understanding of clinical research. Children (ages 7-13 years) were randomized to receive the basic information about clinical research using either a printed storybook (control) or the same storybook enhanced using a video see-through AR iPad program (AR) with embedded interactive quizzes. Children were interviewed to assess their understanding of the material before (pre-test) and after (post-test) receiving either of the randomized interventions. Both parents and children completed short surveys to measure their perceptions of the information delivery. Ninety-one parent/child dyads were included in the analysis. There were no differences between the control and AR children's pre-test understanding of the research information. However, both groups demonstrated significant and similar improvements in post-test understanding. Parents of children in the AR group found the information to be of higher quality and greater clarity compared with the control group, and 91.7% of children in the AR group found the inclusion of interactive quizzes to be helpful. Both parents and children found the AR program very easy to use and 85.0 % and 71.2%, respectively, indicated that if recruited for a future study that they would prefer information delivered using some type of iPad AR program together with a discussion with the researcher. Results demonstrated the importance of providing children and parents with information in an easy to read and visually compelling manner. Although both groups demonstrated improved understanding, children and their parents preferred the AR program and reported a preference for receiving information using computer-based technology. Given the seemingly insurmountable challenge of keeping children and families engaged in health research related information exchange, the use of AR would appear to provide a novel and effective vehicle for enhancing children's and parents assimilation and understanding of research (and medical) information and as a potential tool to optimize the informed consent and assent processes. This study reinforces the importance in providing information to research participants and patients in an easy-to-read and visually salient manner. Although the AR program used in this study did not result in an increased level of understanding, AR was deemed the preferred method of information delivery. It is hoped that the results of this study will serve as a platform for future studies.


Directing the differentiation of embryonic stem cells to neural stem cells.
Embryonic stem cells (ESCs) are a potential source of neural derivatives that can be used in stem cell-based therapies designed to treat neurological disorders. The derivation of specific neuronal or glial cell types from ESCs invariably includes the production of neural stem cells (NSCs). We describe the basic mechanisms of neural induction during vertebrate embryogenesis and how this information helped formulate several protocols used to generate NSCs from ESCs. We highlight the advantages and disadvantages of each approach and review what has been learned about the intermediate stages in the transition from ESC to NSC. Recent data describing how specific growth factors and signaling molecules regulate production of NSCs are described and a model synthesizing this information is presented.


Note-taking in the employment interview: effects on recall and judgments.
Although note-taking in the employment interview is highly recommended, little research has examined its effects. This study investigated the effects of note-taking styles, review of the notes, and content of the notes on participants' cued recall of information and decisions made from videotaped employment interviews. Note-taking increased recall accuracy but not judgment accuracy. Being able to review notes resulted in increased judgment accuracy for those taking conventional-style notes. The content of the notes also had important implications for conventional note-takers, suggesting some benefits of recording notes using the key-points style. The findings suggest that the act of note-taking may be more important for memory and legal reasons than for improving the decisions made by interviewers.


Incidence, risk factors and prognostic impact of acute kidney injury after coronary angiography and intervention in kidney transplant recipients: a single-center retrospective analysis.
Kidney transplant recipients (KTR) represent a high-risk population for cardiovascular disease. Coronary artery disease (CAD) is the most common cause of morbidity and mortality in this population. In KTR, coronary angiography and intervention (CI) can be associated with the risk of acute kidney injury (AKI). Data about the incidence and impact of AKI after CI in this population are rare. The aim of the present study is to describe the incidence and risk factors of AKI, periprocedural bleeding and the prognostic impact on 1-year mortality in KTR undergoing CI. This retrospective single-center study includes all KTR undergoing CI at University Hospital Frankfurt between 2005 and 2015. A total of 135 CIs in KTR were analyzed. AKI occurred in 31 of 135 CIs (23%, AKI group). Patients of the AKI group were older; other baseline characteristics did not show significant differences. The amount of contrast dye used was higher in the AKI group (p = NS). Periprocedural bleeding defined by BARC criteria occurred more often in the AKI group (23% vs. 5%, p < 0.01) and persisted as a risk factor of AKI in multivariate analysis (odds ratio = 6.43, 95% CI: 1.78-23.20, p = 0.01). In-hospital mortality was 3% in the AKI group; no patient of the non-AKI group died during hospitalization (p = 0.2). One-year-survival was significantly higher in the non-AKI group (94% vs. 81%, p = 0.02). AKI is an important prognostic determinant in KTR undergoing coronary angiography and percutaneous coronary intervention (PCI). Periprocedural bleeding events were associated with AKI. Well-known risk factors for AKI such as contrast agent and diabetes were of minor impact.


Correlation of steroid receptors in synchronous tissues with survival in breast cancer patients.
Estrogen and progesterone receptors (ER and PR) were estimated in 129 synchronous (primary and metastatic lymph node) breast cancer tissues, of which 40% were premenopausal and 60% were postmenopausal. ER and PR accordance was seen in 68% and 70% patients, and ER and PR discordance was seen in 32% and 30%, respectively. The mean level of ER in patients having ER accordance was higher in responders than in nonresponders. In patients having steroid receptors in accordance, there was a trend towards gain of receptors (type II) in responders, and loss of receptors (type I) in nonresponders. In ER discordant cases 48% were of type I while in PR discordant cases 46% were of type I. In postmenopausal patients, survival was lower in patients showing accordance than in those showing discordance. In nonresponders showing loss of receptors in lymph node, the survival was shorter than in those who showed gain of receptors in lymph node. No such trend was seen in premenopausal patients. Our study suggests that in postmenopausal patients, survival was better related to ER accordance than ER discordance and PR accordance or discordance. However, a larger patient series is needed for confirmation.


Involvement of nurses in caring for patients requesting euthanasia in Flanders (Belgium): a qualitative study.
Although nurses worldwide are confronted with euthanasia requests, how nurses experience their involvement in euthanasia remains unclear. To explore nurses' involvement in the care for patients requesting euthanasia. A qualitative grounded theory strategy. Two general hospitals (A, B) and a palliative care setting in Flanders (Belgium). Nurses who fulfilled the following inclusion criteria: (a) Dutch-speaking; (b) working for at least one year in hospital A or B; (c) working at least part-time (50%); and (d) ever received a euthanasia request. We collected data using purposeful sampling, superseded by theoretical sampling in a palliative care setting. The sample included one intensive care nurse, one oncology nurse, eight palliative care nurses, and five internal medicine nurses. All but five were women. Their age ranged from 24 to 49 years. We conducted one-on-one semi-structured interviews between November 2001 and September 2002. Grounded theory was applied for guiding data collection and analysis. The trustworthiness of data was ensured by several strategies. Although euthanasia was still illegal, the nurses unanimously stated that they had an important role in caring for patients requesting euthanasia. Their personal and intense involvement caused them to experience a spectrum of emotions, chief among them being a sense of powerlessness. Several elements contributed to the nurses' conflicted involvement. Nurses became frustrated if the context (e.g., lack of time) hindered their efforts to provide compassionate care. The palliative care setting and its associated culture (group mentality, care philosophy) created the opportunity for nurses to take time to holistically support patients and their relatives. Hospital nurses are confronted with patients' euthanasia requests. Each stage of this process requires that the nurses possess specific competencies. Their willingness to personally care for these patients, in addition to their specific care expertise, allows them to be skilled companions.


Nanostructured hybrid silicon/carbon nanotube heterostructures: reversible high-capacity lithium-ion anodes.
Lithium-ion batteries have witnessed meteoric advancement the last two decades. The anode area has seen unprecedented research activity on Si and Sn, the two anode alternatives to currently used carbon following the initial seminal work by Fuji on tin oxide nanocomposites. Recent reports on silicon nanowires, porous Si, and amorphous Si coatings on graphite nanofibers (GNF) have been very encouraging. High capacity and long cycle life anodes are still, however, elusive and much needed to meet the ever increasing energy storage demands of modern society. Herein, we report for the first time the synthesis of novel 1D heterostructures comprising vertically aligned multiwall CNTs (VACNTs) containing nanoscale amorphous/nanocrystalline Si droplets deposited directly on VACNTs with clearly defined spacing using a simple two-step liquid injection CVD process. A hallmark of these single reactor derived heterostructures is an interfacial amorphous carbon layer anchoring the nanoscale Si clusters directly to the VACNTs. The defined spacing of nanoscale Si combined with their tethered CNT architecture allow for the silicon to undergo reversible electrochemical alloying and dealloying with Li with minimal loss of contact with the underlying CNTs. The novel heterostructures thus exhibit impressive reversible stable capacities approximately 2050 mAh/g with very good rate capability and an acceptable first cycle irreversible loss approximately 20% comparable to graphitic anodes indicating their promise as high capacity Li-ion anodes. Although warranting further research, particularly with regard to long-term cycling, it can be envisaged that optimization of this simple approach could lead to reversible high capacity next generation Li-ion anodes.


Acupuncture for systemic lupus erythematosus: a pilot RCT feasibility and safety study.
The objective of this study was to determine the feasibility of studying acupuncture in patients with systemic lupus erythematosus (SLE), and to pilot test the safety and explore benefits of a standardized acupuncture protocol designed to reduce pain and fatigue. Twenty-four patients with SLE were randomly assigned to receive 10 sessions of either acupuncture, minimal needling or usual care. Pain, fatigue and SLE disease activity were assessed at baseline and following the last sessions. Safety was assessed at each session. Fifty-two patients were screened to enroll 24 eligible and interested persons. Although transient side effects, such as brief needling pain and lightheadedness, were reported, no serious adverse events were associated with either the acupuncture or minimal needling procedures. Twenty-two participants completed the study, and the majority (85%) of acupuncture and minimal needling participants were able to complete their sessions within the specified time period of 5-6 weeks. 40% of patients who received acupuncture or minimal needling had >/=30% improvement on standard measures of pain, but no usual care patients showed improvement in pain. A ten-session course of acupuncture appears feasible and safe for patients with SLE. Benefits were similar for acupuncture and minimal needling.


The mannitol cycle in Pleurotus ostreatus (Florida).
In mushroom, presence of the mannitol cycle has not been reported so far although the polyol is supposed to be generated by the reduction of fructose by mannitol dehydrogenase. This study submits evidence for the presence of the mannitol cycle in Pleurotus ostreatus. The key enzyme of the cycle, mannitol-1-phosphate dehydrogenase (M1PDH), was present appreciably in all the developmental stages of the mushroom. However, the enzyme level dropped significantly at the onset of sporulation. The presence of M1DPH was confirmed by isozyme analysis and RT-PCR mediated amplification of a approximately 400 bp DNA fragment.


São Paulo city health information system--a case report.
São Paulo is the largest city in Brazil and one of the largest in the world. In 2004, São Paulo City Department of Health decided to implement a Healthcare Information System that would support managing healthcare services and provide an ambulatory health record. The system was designed to build on from national standards that identify healthcare workers, organizations and the relationships among them and reuse as much as possible existing concepts and software. At the same time, the system should reduce fragmentation, not only by integrating existing redundant or competing systems but also by providing a framework in which new modules would be naturally integrated to each other. Today, the web-based system, known as SIGA Saúde, runs in more than 370 healthcare units, processes some 8 thousand appointment scheduling daily and more than 10 thousand high-cost procedure authorizations monthly. This paper profiles the São Paulo City and its needs and describes the project, obstacles and results so far.


A new approach to amplified telomerase detection with polyvalent oligonucleotide nanoparticle conjugates.
We report a new assay for human telomerase activity that relies on polyvalent oligonucleotide nanoparticle conjugates as diagnostic probes and amplification units. Gold nanoparticles functionalized with specific oligonucleotide sequences can efficiently capture telomerase enzymes and subsequently be elongated. Both the elongated and unmodified oligonucleotide sequences are simultaneously measured. The two strands not only serve as internal positive controls for each other but also provide a way of amplifying signal. At high concentrations, both elongated and unmodified strands exhibit measurable responses. At low telomerase concentrations (e.g., from 10 HeLa cells), elongated strands cannot be detected, but the unmodified sequences, which come from the same probe particles, can be detected because their concentration is higher, providing a novel form of amplification. This new assay rivals the sensitivity of the conventional PCR-based method of telomerase detection.


Characterization and physical mapping of the genome of bacteriophage phi Aa from Actinobacillus actinomycetemcomitans.
The size, configuration and restriction map of Actinobacillus actinomycetemcomitans bacteriophage phi Aa DNA was determined by means of restriction endonuclease analysis. Digestion of the phi Aa DNA with restriction enzymes Hind III, Eco RI and Sal I produced 6, 5, and 4 fragments, respectively. Based upon the sum of the sizes of the restriction fragments of these enzymes, the DNA was estimated to be 47.2 kilobase pairs in length. A restriction map was constructed using Hind III and Sal I. Incubation with exonuclease Bal 31 for increasing lengths of time resulted in progressive hydrolysis of the DNA, as expected for a linear molecule. No sub-molar fragments or diffuse bands were observed in the agarose gels of the restriction endonuclease digests of the phi Aa DNA. Attempts at ligating the ends of the DNA were consistently unsuccessful. Therefore, we found no evidence for cohesive ends, a circular permutation of the genome or for headful packaging mechanism from a concatameric DNA precursor.


Cardiac ISL1-Interacting Protein, a Cardioprotective Factor, Inhibits the Transition From Cardiac Hypertrophy to Heart Failure.
Heart failure is characterized by the inability of the heart to pump effectively and generate proper blood circulation to meet the body's needs; it is a devastating condition that affects more than 100 million people globally. In spite of this, little is known about the mechanisms regulating the transition from cardiac hypertrophy to heart failure. Previously, we identified a cardiomyocyte-enriched gene, CIP, which regulates cardiac homeostasis under pathological stimulation. Here, we show that the cardiac transcriptional factor GATA4 binds the promotor of CIP gene and regulates its expression. We further determined that both CIP mRNA and protein decrease in diseased human hearts. In a mouse model, induced cardiac-specific overexpression of CIP after the establishment of cardiac hypertrophy protects the heart by inhibiting disease progression toward heart failure. Transcriptome analyses revealed that the IGF, mTORC2 and TGFβ signaling pathways mediate the inhibitory function of CIP on pathologic cardiac remodeling. Our study demonstrates GATA4 as an upstream regulator of CIP gene expression in cardiomyocytes, as well as the clinical significance of CIP expression in human heart disease. More importantly, our investigation suggests CIP is a key regulator of the transition from cardiac hypertrophy to heart failure. The ability of CIP to intervene in the onset of heart failure suggests a novel therapeutic avenue of investigation for the prevention of heart disease progression.


[Histological observation and vascularization evaluation of porcine acellular dermal matrix processed with matrix metalloproteinase 7 after implanted into rats].
To investigate the histological changes and vascularization of the porcine acellular dermal matrix (P-ADM) processed with matrix metalloproteinase 7 (MMP-7) (P-ADM-pm) after implanted into rats. Sixty-two pieces of porcine reticular layer dermis which were from the pig abdominal skin and obtained by using a mechanical method, were randomly divided into group A (n = 31) and group B (n = 31). The porcine reticular layer dermis in 2 groups were treated with decellularization (P-ADM), then the P-ADM in group B were treated with processing by MMP-7 (P-ADM-pm). Thirty adult male Wistar rats were selected. P-ADM (group A) and P-ADM-pm (group B) were subcutaneously transplanted into the left and right fascia lacuna, respectively. The implants were harvested from 6 rats at 3, 7, 14, 21, and 28 days after implantation, respectively. Gross, histochemical, and immunohistochemical observations, and scanning electron microscopy (SEM) examination were performed to observe host cells, microvessels infiltration and histological changes in the implants. No rat died in the experiment, incision healed well and no obvious inflammatory reaction was seen in all rats. Gross observation suggested that the implants of 2 groups were encapsulated by a thin layer of connective tissue at 7 days after implantation. With the time of implantation, the microvessels increased and coarsened, and the changes of group B were more obvious than those of group A. At 21 days, the microvessels of 2 groups decreased, and the implants of group B showed complete vascularization. The histochemical and immunohistochemical observations showed that group A had more severe inflammatory response than group B. Fibroblasts and microvessels in group B appeared in the superficial zone of implant at 3 and 7 days after implantation and they could be observed in the center zone of implant at 14 and21 days. However, fibroblasts and microvessels in group A appeared in the superficial zone of implant at 3 and 14 days and they could not be observed in the center zone of implant at 28 days. Fibroblasts and microvessels of group B were significantly more than those of group A (P < 0.05). SEM examination showed that more fibroblasts and new collagen fibrils were observed in group B at 14 days. The host response to P-ADM-pm is similar to normal wound healing, and P-ADM-pm as implantable scaffold material plays a good template conduction role.


IgE binding proteins in honey: discussion on their origin.
Pollen proteins, most frequently from Compositae plants, and glandular enzymes from Hymenoptera insects are the only honey allergens involved in every case of honey sensitization reported so far. Surprisingly, we found three patients, all showing the same pattern of honey sensitization with clinical history, cutaneous test and specific IgE clearly positive to honey crude extract but not to the aforementioned components. IgE binding bands, mainly at 54, 46, 17 and 16 kDa, were recognized by the sera of the three patients on blots following electrophoretic separation of a local honey extract under dissociating conditions. Attempts to identify these proteins with the most common honey allergens by means of SDS-PAGE immunoblotting failed, leaving open the question on the origin of protein allergens in cases of honey allergy. Thus, if bee-derived components are not proven to be involved in honey sensitization, other protein sources, such as nectar, should not be disregarded.


Attenuation of lead-induced oxidative stress in rat brain, liver, kidney and blood of male Wistar rats by Moringa oleifera seed powder.
Moringa oleifera is a tree belonging to Moringaceae family and its leaves and seeds are reported to have ameliorative effects against metal toxicity. In the present investigation, M. oleifera seed powder was tested against lead-induced oxidative stress and compared against meso-2, 3-dimercaptosuccinic acid (DMSA) treatment. Male Wistar rats (100-120 g) were divided into four groups: control (2000 ppm of sodium acetate for 2 weeks), exposed (2000 ppm of lead acetate for 2 weeks), Moringa treated (500 mg/kg for 7 days after lead exposure), and DMSA treated (90 mg/kg for 7 days after lead exposure). After exposure and treatment periods, rats were sacrificed and the brain was separated into cerebellum, hippocampus, frontal cortex, and brain stem; liver, kidney, and blood were also collected. The data indicated a significant (p<0.05) increase in reactive oxygen species (ROS), lipid perioxidation products (LPP), total protein carbonyl content (TPCC), and metal content of brain regions, liver, and kidney in the exposed group compared with their respective controls. In the blood, delta-amino levulinic acid dehydratase (ALAD) activity, RBC, WBC, hemoglobin, and hematocrit showed significant (p<0.05) decrease on lead exposure. However, administration of M. oleifera restored all the parameters back to control, tissue-specifically, and also showed improvement in restoration better than DMSA treatment, indicating reduction of the negative effects of lead-induced oxidative stress.