Regulatory properties of an inducible aliphatic amidase in a thermophilic bacillus.
A thermophilic bacillus growing on acetamide as both carbon and nitrogen sources produces an inducible amidase. This amidase hydrolysed the following amides in decreasing order or activity, in comparison with acetamide (1.00): propionamide (0.97), fluoroacetamide (0.84), formamide (0.35) and glycinamide (0.12). Cyanoacetamide, dimethylacetamide, dimethylformamide and urea also induced the synthesis of the amidase, but were not substrates of the enzyme. Studies with protoplasts suggest that the amidase is located in the cytoplasm. Glucose strongly inhibited amidase synthesis; and limiting nitrogen did not release this inhibition. Urea strongly inhibited amidase activity in a competitive manner; but the inhibition caused by iodoacetamide and cyanoacetamide was non-competitive. Both thioacetamide and thiourea were effective inhibitors of enzyme induction. Bacteria grown on a succinate-minimal medium exhibited a lag in amidase synthesis, which could be eliminated by decreasing the concentration of succinate. Acetate- or pyruvate-grown cultures behaved similarly, while those grown on alanine or glutamate exhibited no lag in enzyme induction. In the mutant strain E21, repression of amidase synthesis by glucose was much less evident and no lag for induction was apparent with any of the other carbon sources mentioned.


Erythrocyte sedimentation rate as an independent prognostic marker for mortality: a prospective population-based cohort study.
A very high erythrocyte sedimentation rate (ESR) is usually an indication of underlying pathology. Additionally, a moderately elevated ESR may also be attributable to biological ageing. Whether the ESR is a prognostic factor for mortality, regardless of age, has been scarcely investigated. Therefore, the objective was to analyse the association between elevated ESR levels and the risk of mortality in a prospective cohort of the general population. We studied data from the Rotterdam Study (1990-2014). ESR levels were measured at baseline and individuals were followed until death or end of study. Associations between moderately (20-50 mm h-1 ) and markedly (>50 mm h-1 ) elevated ESR levels and all-cause mortality were assessed using multivariate Cox proportional hazard models. In total, 5226 participants were included, and the mean age was 70.3 years. During a median follow-up time of 14.9 years, 3749 participants died (71.7%). After adjustment, both a moderately elevated ESR and a markedly elevated ESR were associated with a significantly higher risk of overall mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.12-1.35 and HR 1.89, 95% CI 1.38-2.60, respectively]. Although the ESR becomes higher with age, in a group aged above 75 years, without any comorbidities, an ESR > 20 mm h-1 remained associated with a significantly increased risk of mortality (HR 1.29, 95%CI 1.01-1.64). An elevated ESR is an independent prognostic factor for mortality. Despite the fact that ESR increases with age, it remains associated with an increased risk of mortality and warrants close follow-up.


[Sequential pattern of the propagation of excitation in the heart of the sheep Ovis brachyurae].
With the aid of intramural multipolar technique, the earliest focus of the depolarization is revealed in the myocard thickness of the cranioventral region of the right atrium of the sheep. From there the depolarization wave with a saw-edged front is spread along the thickness of the atria. The chronotopography of the intramural activation wave front shows a more complicated picture of the atrial excitation than a smiply radial one. Apparently it is connected with the presence of the atrial conduction system. The main mass of myocardium of free ventricle walls and the lower two thirds of the septum are activated by means of multifocal depolarization. The base third of the septum is the last to be activated. These features of excitation of the ovine ventricle myocardium can be explained by special character of distribution of the Purkinje fibers in myocardium ventricles.


Effect of hypoxic acclimation on anoxia tolerance in Vitis roots: response of metabolic activity and K+ fluxes.
The effect of a hypoxic pre-treatment (HPT) on improving tolerance to prolonged anoxia conditions in two contrasting Vitis species (V. riparia, anoxia tolerant; V. rupestris, anoxia sensitive) was evaluated. The energy economy of root cells was studied by measuring heat production, the activity of pyruvate decarboxylase (PDC) and alcohol dehdrogenase (ADH), ethanol and ATP production, and K(+) fluxes. The results showed that HPT is an effective tool in order to maintain a sustainable metabolic performance in both the species under anoxia conditions, especially in sensitive species such as V. rupestris. Our results showed that the improved tolerance was mainly driven by: (i) an enhanced activity of key enzymes in alcohol fermentation (ADC and PDC); (ii) the capability to maintain a higher level of respiration, evidenced by a lesser decrease in heat development and ATP production; and (iii) the maintenance of a better ion homeostasis (highlighted by measurement of K(+) fluxes) and K(+) channel functionality.


Adverse Effects of Coumestrol and Genistein on Mammary Morphogenesis and Future Milk Production Ability of Mammary Epithelial Cells.
Isoflavones are a class of flavonoids present in legumes and are called phytoestrogens because of their estrogen-like activity. Endogenous estrogen is well known to regulate mammary gland morphogenesis during pregnancy. Each isoflavone also has different physiological activities. However, it is difficult to investigate the direct effect of each isoflavone in mammary morphogenesis in vivo because isoflavones are metabolized into different isoflavones by enteric bacteria. In this study, investigated are the direct influences of coumestrol, daidzein, and genistein on mammary structure development and future milk production ability of mammary epithelial cells (MECs) using in vitro culture models. Mouse MECs are cultured in Matrigel with basic fibroblast growth factor and epidermal growth factor to induce ductal branching and alveolar formation, respectively. Coumestrol and genistein inhibit ductal branching and alveolar formation by affecting the proliferation and migration of MECs with the induction of apoptosis. Daidzein hardly influences mammary structure development. Furthermore, pretreatment with coumestrol adversely affects the induction of milk production ability of MECs. These results suggest that each isoflavone differentially influences mammary morphogenesis and future milk production by affecting MEC behaviors. These results also suggest that the culture models are effective to study mammary epithelial morphogenesis in vitro.


Development and validation of a discriminative dissolution method for atorvastatin calcium tablets using in vivo data by LC and UV methods.
A dissolution method to analyze atorvastatin tablets using in vivo data for RP and test pilot (PB) was developed and validated. The appropriate conditions were determined after solubility tests using different media, and sink conditions were established. The conditions used were equipment paddle at 50 rpm and 900 mL of potassium phosphate buffer pH 6.0 as dissolution medium. In vivo release profiles were obtained from the bioequivalence study of RP and the generic candidate PB. The fraction of dose absorbed was calculated using the Loo-Riegelman method. It was necessary to use a scale factor of time similar to 6.0, to associate the values of absorbed fraction and dissolved fraction, obtaining an in vivo-in vitro correlation level A. The dissolution method to quantify the amount of drug dissolved was validated using high-performance liquid chromatography and ultraviolet spectrophotometry, and validated according to the USP protocol. The discriminative power of dissolution conditions was assessed using two different pilot batches of atorvastatin tablets (PA and PB) and RP. The dissolution test was validated and may be used as a discriminating method in quality control and in the development of the new formulations.


Relationships between integumental characteristics and thermoregulation in South American camelids.
Hair fibre is regarded as a unique mammalian feature with an important role for endothermy. Artificial selection for hair characteristics resulted in marked changes with regard to follicle number, type, distribution, growth and natural shedding. This review focuses on the fine fibre-producing South American camelids (SACs) and the relationship between their hair coat and thermoregulation. SACs have developed several special integumental characteristics. While the hair coat of the wild lamoids vicuña (Vicugna vicugna) and guanaco (Lama guanicoe) is formed by two types of hair (the coarse outer guard hairs and a finer undercoat), the domesticated llamas (Lama glama) and alpaca (Lama pacos) exhibit variably double coat and predominantly single coat, respectively. The distribution of the hair coat across the body is not homogenous. Thermal windows with shorter hair or thinner skin can be identified at the ventral abdomen, axillary space and inside of the thighs (about 20% of the skin), thus allowing to modulate heat dissipation. In contrast to sheep wool, lamoid fibres are mainly medullated. The thermal conductance of summer pelage was higher than that of the winter fleece and highest for the axillar and lower flanks. Lamoids have developed behavioural strategies to modify heat loss by adopting specific postures according to ambient conditions by closing or opening the thermal windows. Energy savings of 67% attributed to posture were calculated. SACs have shown to be able to adapt to a broad range of different climatic conditions. The specific integumental characteristics of SACs indicate that they have developed adaptation mechanisms particularly suited for cooler climates. Accordingly, hyperthermia might become a problem in hot, humid areas outside of their original habitat. Several studies showed the beneficial effect of shearing against heat stress. In particular, fertility in males exposed to heat stress may be improved by shearing. Infrared thermography reveals that in shorn animals the heat is radiated across the entire body surface and is not restricted to the thermal windows. However, shearing also changes the conditions of the protective layer, resulting in a loss of thermal conductance that may result in adverse effects when animals are kept under cold temperatures. The length of residual fibre appears to be crucial in avoiding excessive heat loss in a cold environment, as demonstrated by shearing experiments with different shearing machines. There is, therefore, potential for welfare considerations to conflict with industrial demands for fibre length or homogenous quality.


Performance and aging of a high power 2-D laser diode array.
The effects of shot life on the output power, spectrum, near field, and far field patterns of a high power laser diode array have been measured and are reported, along with a description of the apparatus used to perform the measurements. The array operated for a total of 5.9 x 10(7) shots at a power output equivalent to 1 kW/cm(2). A 23% degradation in output power was observed, accompanied by a 3-nm red shift of the emission maximum. The effects of the measured drop in performance are particularly relevant to the application of these devices for pumping solid state lasers.


Mediterranean spotted fever in Portugal: risk factors for fatal outcome in 105 hospitalized patients.
Mediterranean spotted fever (MSF) is the most important tick-borne disease in Portugal. It is a notifiable disease and during 1989-2000 the annual incidence rate in Portugal was 9.8/10(5) inhabitants. Although recognized as a benign acute disease and treated mainly with ambulatory procedures, some cases are severe and fatalities have increased in the last few years. In 1997, MSF mortality became more evident in Beja, a Portuguese southern district, with a case fatality rate of 32.3% in hospitalized patients. Analysis of 55 variables regarding epidemiologic, clinical, laboratory, and therapeutic data of fatal and nonfatal MSF cases were compared to identify risk factors in 105 patients hospitalized in Beja District Hospital, between 1994 and 1998. It was statistically significant that the patients dying in 1997 were younger than those in other years. The risk of dying is statistically significant in those who presented with diabetes, vomiting, dehydration, and uremia. The interval between the onset of symptoms to administration of anti-rickettsial therapy was the same for all patients. Therapy delay, reported by some authors to be associated with mortality of MSF, was not a risk factor in our study. The patients who died in 1997 died faster than those in other years. The variables studied could not explain the higher mortality rates observed in our study. Although one may speculate that the pathogenic strain of Israeli tick typhus, isolated in 1997, could be responsible for this increase of fatality rate, inherited patient factors might also be strongly associated with mortality.


Novel reference gene, High-mobility-group protein I/Y, used in qualitative and real-time quantitative polymerase chain reaction detection of transgenic rapeseed cultivars.
With the development of transgenic crops, regulations to label the genetically modified organisms (GMOs) and their derived products have been issued in many countries. Polymerase chain reaction (PCR) methods are thought to be reliable and useful techniques for qualitative and quantitative detection of GMOs. These methods are generally needed to amplify the transgene and compare the amplified results with that of a corresponding reference gene to get the reliable results. Specific primers were developed for the rapeseed (Brassica napus), high-mobility-group protein I/Y(HMG-I/Y) single-copy gene and PCR cycling conditions suitable for the use of this sequence as an endogenous reference gene in both qualitative and quantitative PCR assays. Both methods were assayed with 15 different rapeseed varieties, and identical amplified products were obtained with all of them. No amplification was observed when templates were the DNA samples from the other species of Brassica genus or other species, such as broccoli, stem mustard, cauliflower, Chinese cabbage, cabbage, sprouts, Arabidopsis thaliana, carrot, tobacco, soybean, mung bean, tomato, pepper, eggplant, plum, wheat, maize, barley, rice, lupine, and sunflower. This system was specific for rapeseed. Limits of detection and quantitation in qualitative and quantitative PCR systems were about 13 pg DNA (about 10 haploid genomes) and about 1.3 pg DNA (about 1 haploid genome), respectively. To further test the feasibility of this HMG-I/Y gene as an endogenous reference gene, samples containing transgenic rapeseed GT73 with the inserted glyphosate oxidoreductase (GOX) gene were quantitated. These demonstrated that the endogenous PCR detection systems were applicable to the qualitative and quantitative detection of transgenic rapeseed.


Atherogenic risk factors and hearing thresholds.
The objective of this study was to evaluate the influence of atherogenic risk factors on hearing thresholds. In a cross-sectional study we analyzed data from a Danish survey in 2009-2010 on physical and psychological working conditions. The study included 576 white- and blue-collar workers from children's day care units, financial services and 10 manufacturing trades. Associations between atherogenic risk factors (blood lipids, glycosylated hemoglobin, smoking habits, body mass index (BMI), and ambulatory blood pressure) and hearing thresholds were analyzed using multiple linear regression models. Adjusted results suggested associations between smoking, high BMI and triglyceride level and low high-density lipoprotein level and increased low-frequency hearing thresholds (average of pure-tone hearing thresholds at 0.25, 0.5 and 1 kHz). Furthermore, an increasing load of atherogenic risk factors seemed associated with increased low-frequency hearing thresholds, but only at a borderline level of statistical significance. Associations were generally strongest with hearing levels of the worst hearing ear. We found no statistically significant associations between atherogenic risk factors and high-frequency hearing thresholds (average of pure-tone hearing thresholds at 4, 6 and 8 kHz).


A semi-supervised learning approach for RNA secondary structure prediction.
RNA secondary structure prediction is a key technology in RNA bioinformatics. Most algorithms for RNA secondary structure prediction use probabilistic models, in which the model parameters are trained with reliable RNA secondary structures. Because of the difficulty of determining RNA secondary structures by experimental procedures, such as NMR or X-ray crystal structural analyses, there are still many RNA sequences that could be useful for training whose secondary structures have not been experimentally determined. In this paper, we introduce a novel semi-supervised learning approach for training parameters in a probabilistic model of RNA secondary structures in which we employ not only RNA sequences with annotated secondary structures but also ones with unknown secondary structures. Our model is based on a hybrid of generative (stochastic context-free grammars) and discriminative models (conditional random fields) that has been successfully applied to natural language processing. Computational experiments indicate that the accuracy of secondary structure prediction is improved by incorporating RNA sequences with unknown secondary structures into training. To our knowledge, this is the first study of a semi-supervised learning approach for RNA secondary structure prediction. This technique will be useful when the number of reliable structures is limited.


The changing picture of patients with pulmonary arterial hypertension in the United States: how REVEAL differs from historic and non-US Contemporary Registries.
REVEAL (The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) provides current demographics of patients with group 1 pulmonary arterial hypertension (PAH) in the United States. A total of 2,967 patients with PAH diagnosed based on right-sided heart catheterization were enrolled in REVEAL between March 2006 and September 2007. Demographics from the REVEAL patient cohort and REVEAL subpopulations (matched by inclusion criteria to other registries) were compared with historic US registry data and other contemporary US and non-US national PAH registries by inclusion criteria, including the National Institutes of Health (NIH) PAH registry and the French PAH registry. REVEAL patients matched to NIH registry patients were older at diagnosis (mean ± SE, 44.9 ± 0.6 years vs 36.4 ± 1.1 years; difference, 8.5 ± 1.4; P < .001) and more likely to be women (78.7 ± 1.2% vs 63.1 ± 3.5%; P < .001). REVEAL patients matched to French registry patients had similar age and severity at diagnosis, but REVEAL patients were more likely to be women (79.8 ± 0.8% vs 65.3 ± 1.8%; P < .001) and obese (BMI, ≥ 30 kg/m(2), 32.5 ± 1.0% vs 14.8 ± 1.4%; P < .001), whereas French patients were more likely to have HIV-associated PAH (6.2% vs 2.3%). The female preponderance is similar to that in other US-based contemporary registries. At diagnosis, REVEAL patients were older than NIH registry patients and similar in age to patients enrolled in contemporary registries. Compared with NIH and contemporary European and UK registries, there was a striking preponderance of women, and REVEAL patients were more likely to be obese. These observations and the difference in HIV-associated PAH between REVEAL and other non-US contemporary registries warrant further investigation. ClinicalTrials.gov; No.: NCT00370214; URL: clinicaltrials.gov.


Lambda Gam protein inhibits the helicase and chi-stimulated recombination activities of Escherichia coli RecBCD enzyme.
The lambda Gam protein was isolated from cells containing a Gam-producing plasmid. The purified Gam protein was found to bind to RecBCD without displacing any of its subunits. Gam was shown to inhibit all known enzymatic activities of RecBCD: ATP-dependent single- and double-stranded DNA exonucleases, ATP-independent single-stranded endonuclease, and the ATP-dependent helicase. When produced in vivo, Gam inhibited chi-activated recombination in lambda red gam crosses but had little effect on the host's ability to act as a recipient in conjugational recombination. These experiments suggest that RecBCD possesses an additional "unknown" activity that is resistant to or induced by Gam. Additionally, the expression of Gam in recD mutants sensitizes the host to UV irradiation, indicating that Gam alters one or more of the in vivo activities of RecBC(D-).


Dynamic variation of the microbial community structure during the long-time mono-fermentation of maize and sugar beet silage.
This study investigated the development of the microbial community during a long-term (337 days) anaerobic digestion of maize and sugar beet silage, two feedstocks that significantly differ in their chemical composition. For the characterization of the microbial dynamics, the community profiling method terminal restriction fragment length polymorphism (TRFLP) in combination with a cloning-sequencing approach was applied. Our results revealed a specific adaptation of the microbial community to the supplied feedstocks. Based on the high amount of complex compounds, the anaerobic conversion rate of maize silage was slightly lower compared with the sugar beet silage. It was demonstrated that members from the phylum Bacteroidetes are mainly involved in the degradation of low molecular weight substances such as sugar, ethanol and acetate, the main compounds of the sugar beet silage. It was further shown that species of the genus Methanosaeta are highly sensitive against sudden stress situations such as a strong decrease in the ammonium nitrogen (NH₄(+)-N) concentration or a drop of the pH value. In both cases, a functional compensation by members of the genera Methanoculleus and/or Methanosarcina was detected. However, the overall biomass conversion of both feedstocks proceeded efficiently as a steady state between acid production and consumption was recorded, which further resulted in an equal biogas yield.


Troxerutin and Cerebroprotein Hydrolysate Injection Protects Neurovascular Units from Oxygen-Glucose Deprivation and Reoxygenation-Induced Injury In Vitro.
Cerebral ischemia/reperfusion (I/R) injury involves complex events of cellular and molecular processes. Previous studies suggest that a neurovascular unit (NVU) acts as an intricate network to maintain the neuronal homeostatic microenvironment. The present study established an NVU model for oxygen-glucose deprivation and reoxygenation (OGD/R) damage, trying to target the major components of the NVU using a coculture of rat neurons, astrocytes, and rat brain microvascular endothelial cells (rBMECs) to investigate the therapeutic effects of troxerutin and cerebroprotein hydrolysate injections (TCHis). The study observed that OGD/R downregulated the expressions of GAP-43, Claudin-5, and AQP-4 obviously detected by Western blotting and immunocytochemical analysis, respectively, while TCHi ameliorated the effect of OGD/R significantly. Meanwhile, TCHi alleviated the abnormalities of ultrastructure of neurons and rBMECs induced by OGD/R. Furthermore, both levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and cell adhesion molecules (VCAM-1 and ICAM-1) detected by ELISA in NVU supernatant were found elevated significantly through OGD/R, but TCHi ameliorated the trend. In addition, TCHi also mitigated the increase of proapoptotic factors (Bax, p53, and caspase-3) induced by OGD/R in NVU model statistically. All these findings demonstrated that TCHis played a protective role, which was reflected in anti-inflammation, antiapoptosis, and blood-brain barrier maintenance. The results of the study concluded that the NVU is an ideal target and TCHi acts as a neuroprotective agent against cerebral I/R injuries.


Palliative surgery for rare cases of anterior urethral metastasis in prostate cancer.
Penis metastasis from prostate cancer is very rare, and its management varies from case to case as there are very few cases reported in the literature. We describe a patient with prostate cancer treated with radiotherapy and androgen deprivation therapy who presented with urethral bleeding as a symptom of anterior urethral metastasis during followup. We propose a way to manage this and review the literature.


The epithelial integrin alphavbeta6 is a receptor for foot-and-mouth disease virus.
Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use the RGD-dependent integrin alphavbeta3 as a cellular receptor on cultured cells. However, several other RGD-dependent integrins may have the potential to act as receptors for FMDV in vivo. Of these, alphavbeta6 is a likely candidate for use as a receptor by FMDV as it is expressed on epithelial cells, which correlates with the tissue tropism of the virus. In this report, we show that human colon carcinoma cells (SW480) that are normally nonpermissive for FMDV become susceptible to infection as a result of transfection with the integrin beta6 subunit and expression of alphavbeta6 at the cell surface. Integrin alphavbeta6 is the major site for virus attachment on the beta6-transfected cells, and binding to alphavbeta6 serves to increase the rate of virus entry into these cells. In addition, we show that virus binding and infection of the beta6-transfected cells is mediated through an RGD-dependent interaction that is specifically inhibited by a monoclonal antibody (10D5) that recognizes alphavbeta6. These studies establish a role for alphavbeta6 as a cellular receptor for FMDV.


Preclinical evaluation of sunitinib as a single agent in the prophylactic setting in a mouse model of bone metastases.
A substantial number of breast cancer patients are identified as being at high risk of developing metastatic disease. With increasing number of targeted therapeutics entering clinical trials, chronic administration of these agents may be a feasible approach for the prevention of metastases within this subgroup of patients. In this preclinical study we examined whether sunitinib, a multi-tyrosine kinase inhibitor which has anti-angiogenic and anti-resorptive activity, is effective in the prevention of bone metastases. Sunitinib was administered daily with the first dose commencing prior to tumor cell inoculation. Intracardiac injection was performed with MDA-MB23 bone-seeking cells, which were stably transfected with DsRed2. In vivo plain radiography and fluorescent imaging (Berthold NightOwl) was used in the analysis of bone metastases. Histomorphometry was used for the quantification of TRAP+ cells from bone sections and immunohistochemistry was performed using an antibody reactive to CD34 for quantification of microvessel density. Preventive dosing administration of sunitinib does not inhibit colonization of tumor cells to bone or reduce the size of osteolytic lesions. There was a decrease in the number of TRAP+ cells with sunitinib treatment but this did not reach significance. Sunitinib inhibited tumor growth as determined by imaging of fluorescent tumor area. Immunohistochemical analyses of microvessel density revealed a concomitant decrease in the number of tumor blood vessels. The findings suggest that sunitinib can be used as a therapeutic agent for the treatment of bone metastases but as a single agent it is not effective in terms of prevention. Therefore a combination approach with other cytostatic drugs should be pursued.


The Reproductive Toxicity of Monosodium Glutamate by Damaging GnRH Neurons Cannot Be Relieved Spontaneously Over Time.
The present study aims to evaluate the effect of monosodium glutamate on testicular spermatogenesis in mice from the perspective of the hypothalamic-pituitary-testicular axis and whether this destructive effect is alleviated with time. Neonatal mice were randomly divided into a monosodium glutamate (MSG) group and a control group, just below the interscapular region after birth with 10 µL MSG to deliver 4 mg/g (body mass), or with equivalent volumes of 0.9% saline. Samples which involved blood, brains and testicles of mice were collected and measured at puberty at 60 days and adulthood at 90 days. The results show that the fluorescence intensity of GnRH nerve fibers, the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) hormones in the reproductive system, the number of spermatocytes and spermatozoa in testicular sections, the body length, body weight, testicular weight, and testicular index in the 60-day-old mice in monosodium glutamate group (MSG60 group) and the MSG90 group were lower than those in the 60-day-old mice in normal control group (NC60 group) (p < 0.05), but the number of apoptotic cells in the testicular section was higher than in the NC60 group (p < 0.05). When the 90-day-old mice in monosodium glutamate group (MSG90 group) was compared with the MSG60 group, except for body weight and testicular weight increase (p < 0.05), there is no significant difference in the other parameters mentioned above (p > 0.05). Monosodium glutamate can cause reproductive toxicity to male mice by damaging GnRH neurons, and this reproductive toxicity cannot be relieved spontaneously over time. These findings are supported by observed histological changes.


Spatially targeted screening to reduce tuberculosis transmission in high-incidence settings.
As the leading infectious cause of death worldwide and the primary proximal cause of death in individuals living with HIV, tuberculosis remains a global concern. Existing tuberculosis control strategies that rely on passive case-finding appear insufficient to achieve targets for reductions in tuberculosis incidence and mortality. Active case-finding strategies aim to detect infectious individuals earlier in their infectious period to reduce onward transmission and improve treatment outcomes. Empirical studies of active case-finding have produced mixed results and determining how to direct active screening to those most at risk remains a topic of intense research. Our systematic review of literature evaluating the effects of geographically targeted tuberculosis screening interventions found three studies in low tuberculosis incidence settings, but none conducted in high tuberculosis incidence countries. We discuss open questions related to the use of spatially targeted approaches for active screening in countries where tuberculosis incidence is highest.


Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status.
Abuse of Δ⁹-THC by females during adolescence may produce long-term deficits in complex behavioral processes such as learning, and these deficits may be affected by the presence of ovarian hormones. To assess this possibility, 40 injections of saline or 5.6 mg/kg of Δ⁹-THC were administered i.p. daily during adolescence to gonadally intact or ovariectomized (OVX) female rats, yielding four treatment groups (intact/saline, intact/THC, OVX/saline, and OVX/ THC). Δ⁹-THC (0.56-10 mg/kg) was then re-administered to each of the four groups during adulthood to examine their sensitivity to its disruptive effects. The behavioral task required adult subjects to both learn (acquisition component) different response sequences and repeat a known response sequence (performance component) daily. During baseline (no injection) and control (saline injection) sessions, OVX subjects had significantly higher response rates and lower percentages of error in both behavioral components than the intact groups irrespective of saline or Δ⁹-THC administration during adolescence; the intact group that received Δ⁹-THC had the lowest response rates in each component. Upon re-administration of Δ⁹-THC, the groups that received adolescent ovariectomy alone, adolescent Δ⁹-THC administration alone, or both treatments were found to be less sensitive to the rate-decreasing effects, and more sensitive to the error-increasing effects of Δ⁹-THC than the control group (i.e. intact subjects that received saline during adolescence). Neurochemical analyses of the brains from each adolescent-treated group indicated that there were also persistent effects on cannabinoid type-1 (CB-1) receptor levels in the hippocampus and striatum that depended on the brain region and the presence of ovarian hormones. In addition, autoradiographic analyses of the brains from adolescent-treated, but behaviorally naïve, subjects indicated that ovariectomy and Δ⁹-THC administration produced effects on receptor coupling in some of the same brain regions. In summary, chronic administration of Δ⁹-THC during adolescence in female rats produced long-term effects on operant learning and performance tasks and on the cannabinoid system that were mediated by the presence of ovarian hormones, and that altered their sensitivity to Δ⁹-THC as adults.


Computational prediction models for assessing endocrine disrupting potential of chemicals.
Endocrine disrupting chemicals (EDCs) mimic natural hormones and disrupt endocrine function. Humans and wildlife are exposed to EDCs might alter endocrine functions through various mechanisms and lead to an adverse effects. Hence, EDCs identification is important to protect the ecosystem and to promote the public health. Leveraging in-vitro and in-vivo experiments to identify potential EDCs is time consuming and expensive. Hence, quantitative structure-activity relationship is applied to screen the potential EDCs. Here, we summarize the predictive models developed using various algorithms to forecast the binding activity of chemicals to the estrogen and androgen receptors, alpha-fetoprotein, and sex hormone binding globulin.


Exploring genetic risk for catatonia in a genome wide association study and polygenic risk score analysis.
Catatonia is an under-recognized disorder characterized by psychomotor (increased, decreased, or abnormal) changes, affective symptoms, and disturbance of volition, which may arise in the setting of decompensated psychiatric or non-psychiatric medical disorders. Genetic studies of catatonia are limited, and to the best of our knowledge no prior genome wide association studies of catatonia have been performed to date. First we performed a genome wide association study of catatonia regardless of etiology (psychiatric or non-psychiatric). Secondarily we evaluated whether there was an elevated genetic risk profile for predisposing psychiatric disorders (schizophrenia spectrum disorder, bipolar affective disorder, etc.) in patients with catatonia. We used a matched case control design and applied polygenic risk scores to evaluate for a shared polygenetic contribution to catatonia from common psychiatric phenotypes that show a high prevalence of catatonia in their decompensated states. Anxiety, bipolar affective disorder, schizophrenia spectrum disorder and cross disorder polygenic risk scores were significantly associated with catatonia case status in both unadjusted and adjusted logistic regression models for the European Ancestry set even after correcting for multiple comparisons. Depression, Alzheimer's, Autism Spectrum Disorder and Obsessive Disorder polygenic risk scores were not significantly associated with catatonia status in participants of European Ancestry. In the African Ancestry set, no psychiatric polygenic risk scores were significantly associated with catatonia status in either the unadjusted or adjusted regression models. Even after controlling for relevant covariates, anxiety, bipolar affective disorder, schizophrenia spectrum disorder and cross disorders were significantly associated with catatonia status suggesting that there might be a shared genetic risk for those disorders amongst patients with catatonia.


A model for differential leg joint function during human running.
Locomotion requires coordination of leg joints to maintain stability and to maneuver. We studied leg joint function during constant-average-velocity running and the sagittal-plane maneuvers of step ascent and descent. We tested two hypotheses: (1) that leg joints perform distinct functions during locomotion; and (2) that humans select functional parameters to maximize intrinsic dynamic stability. We recorded whole-body kinematics and forces when participants stepped up or down a single vertical step, and found that leg joints show functional differences during both constant-average-velocity locomotion and maneuvers. The hip, knee and ankle function as a motor, damper, and spring, respectively. We therefore constructed a simplified computational model of a human leg with a motor, damper, and spring in series (MDS). The intrinsic dynamics of the model resulted in sustained locomotion on level ground within narrow parameter ranges. However, using parameters experimentally derived from humans, the model showed only short-term stability. Humans may not optimize intrinsic dynamic stability alone, but may instead choose mechanical and behavioral parameters appropriate for both constant-average-velocity locomotion and maneuvers. Understanding joint-level mechanical function during unsteady locomotion helps to understand how differential joint function contributes to whole-body performance, and could lead to improvements in rehabilitation, prosthetic and robotic design.


Fifty years of tobacco carcinogenesis research: from mechanisms to early detection and prevention of lung cancer.
The recognition of the link between cigarette smoking and lung cancer in the 1964 Surgeon General's Report initiated definitive and comprehensive research on the identification of carcinogens in tobacco products and the relevant mechanisms of carcinogenesis. The resultant comprehensive data clearly illustrate established pathways of cancer induction involving carcinogen exposure, metabolic activation, DNA adduct formation, and consequent mutation of critical genes along with the exacerbating influences of inflammation, cocarcinogenesis, and tumor promotion. This mechanistic understanding has provided a framework for the regulation of tobacco products and for the development of relevant tobacco carcinogen and toxicant biomarkers that can be applied in cancer prevention. Simultaneously, the recognition of the link between smoking and lung cancer paved the way for two additional critical approaches to cancer prevention that are discussed here: detection of lung cancer at an early, curable stage, and chemoprevention of lung cancer. Recent successes in more precisely identifying at-risk populations and in decreasing lung cancer mortality with helical computed tomography screening are notable, and progress in chemoprevention continues, although challenges with respect to bringing these approaches to the general population exist. Collectively, research performed since the 1964 Report demonstrates unequivocally that the majority of deaths from lung cancer are preventable.


Community health assessment. The first step in community health planning.
Hospitals face a paradigm shift: from planning service delivery to population-based community health planning. Comprehensive community health planning is a two-step process: assessment and action, in that order. Assessment identifies community problems and resources; action follows planning, which determines which of those problems should be addressed with which resources. This paper provides an overview of the community assessment process. The first challenge in launching a community health initiative is to identify and recruit partners drawn from the ranks of prominent community organizations, such as school boards, public health agencies, and elected officials. The best enlistment strategies are those that empower persons outside the hospital to take visible control. Defining the community is the first step in analyzing the community. It is important that everyone involved in the assessment process agree on the definition, which should take in those characteristics that make the community unique, including its social systems, environmental factors, and demographics. The next step in the process is developing a community health profile, a set of key community indicators or measures that will help you set priorities, document successes and failures, and monitor trends. There are a number of models available to consult in developing indicators, whether traditional, medically oriented determinants of health or broader parameters, such as housing and public safety. Criteria for selecting indicators include validity, stability and reliability, and responsiveness. Most indicators will be developed using secondary, or already existing, sources of data, such as census data, Medicare and Medicaid files, police records, and hospital admission and exit records. Conducting the community assessment involves putting together a list of problems to be solved and a list of available resources, both of which can be compiled using the same four-step process of gathering and analyzing data: obtaining community input, identifying problems already being addressed, consulting with professional experts, and analyzing existing data. Demographics are one way of analyzing data; another is using a "community scoreboard" that groups causal factors into four categories: lifestyle, environment, human biology, and health services. Once the community assessment is complete, planning and implementation of programs can begin. At the same time, it is essential to mobilize the community to support your initiative. Again, you must look beyond the hospital walls to build a constituency for change, to community leaders in education, employment, transportation and recreation, housing, and the physical environment, as well as health education and preventive services.(ABSTRACT TRUNCATED AT 400 WORDS)


Squamous cell carcinoma of the lacrimal sac.
The clinical and histopathological findings in a 40-year-old man with a lacrimal sac tumor are reported. Although the clinical history indicated a lacrimal sac obstruction and recurrent dacryocystitis, the lesion was diagnosed by light microscopy as a squamous cell carcinoma.


Resource utilization and outcome at a university versus a community teaching hospital in tPA treated stroke patients: a retrospective cohort study.
Comparing patterns of resource utilization between hospitals is often complicated by biases in community and patient populations. Stroke patients treated with tissue plasminogen activator (tPA) provide a particularly homogenous population for comparison because of strict eligibility criteria for treatment. We tested whether resource utilization would be similar in this homogenous population between two hospitals located in a single Midwestern US community by comparing use of diagnostic testing and associated outcomes following treatment with t-PA. Medical records from 206 consecutive intravenous t-PA-treated stroke patients from two teaching hospitals (one university, one community-based) were reviewed. Patient demographics, clinical characteristics and outcome were analyzed, as were the frequency of use of CT, MRI, MRA, echocardiography, angiography, and EEG. Seventy-nine and 127 stroke patients received t-PA at the university and community hospitals, respectively. The two patient populations were demographically similar. There were no differences in stroke severity. All outcomes were similar at both hospitals. Utilization of CT scans, and non-invasive carotid and cardiac imaging studies were similar at both hospitals; however, brain MR, TEE, and catheter angiography were used more frequently at the university hospital. EEG was obtained more often at the community hospital. Utilization of advanced brain imaging and invasive diagnostic testing was greater at the university hospital, but was not associated with improved clinical outcomes. This could not be explained on the basis of stroke severity or patient characteristics. This variation of practice suggests substantial opportunities exist to reduce costs and improve efficiency of diagnostic resource use as well as reduce patient exposure to risk from diagnostic procedures.


Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism.
Iatrogenic hypothyroidism can occur after treatment of hyperthyroidism, and is correlated with a reduced glomerular filtration rate in humans and dogs. Cats with iatrogenic hypothyroidism after treatment for hyperthyroidism will have a greater incidence of azotemia than euthyroid cats. Eighty client owned cats with hyperthyroidism. Two retrospective studies. (1) Longitudinal study of 12 hyperthyroid cats treated with radioiodine (documented as euthyroid after treatment), to assess changes in plasma thyroid stimulating hormone (TSH) concentration over a 6-month follow-up period, (2) Cross-sectional study of 75 hyperthyroid cats (documented as euthyroid) 6 months after commencement of treatment for hyperthyroidism to identify the relationship between thyroid status and the development of azotemia. Kaplan-Meier survival analysis was performed to identify relationships between thyroid and renal status and survival. Plasma TSH concentrations were not suppressed in 7 of 8 cats with hypothyroidism 3 months after radioiodine treatment. The proportion of cats with azotemia was significantly (P= .028) greater in the hypothyroid (16 of 28) than the euthyroid group (14 of 47). Twenty-eight of 41 cats (68%) with plasma TT4 concentration below the laboratory reference range had an increased plasma TSH concentration. Hypothyroid cats that developed azotemia within the follow-up period had significantly (P= .018) shorter survival times (median survival time 456 days, range 231-1589 days) than those that remained nonazotemic (median survival time 905 days, range 316-1869 days). Iatrogenic hypothyroidism appears to contribute to the development of azotemia after treatment of hyperthyroidism, and reduced survival time in azotemic cats.


An in situ approach to detect tree root ecology: linking ground-penetrating radar imaging to isotope-derived water acquisition zones.
Tree root distribution and activity are determinants of belowground competition. However, studying root response to environmental and management conditions remains logistically challenging. Methodologically, nondestructive in situ tree root ecology analysis has lagged. In this study, we tested a nondestructive approach to determine tree coarse root architecture and function of a perennial tree crop, Theobroma cacao L., at two edaphically contrasting sites (sandstone and phyllite-granite derived soils) in Ghana, West Africa. We detected coarse root vertical distribution using ground-penetrating radar and root activity via soil water acquisition using isotopic matching of δ(18)O plant and soil signatures. Coarse roots were detected to a depth of 50 cm, however, intraspecifc coarse root vertical distribution was modified by edaphic conditions. Soil δ(18)O isotopic signature declined with depth, providing conditions for plant-soil δ(18)O isotopic matching. This pattern held only under sandstone conditions where water acquisition zones were identifiably narrow in the 10-20 cm depth but broader under phyllite-granite conditions, presumably due to resource patchiness. Detected coarse root count by depth and measured fine root density were strongly correlated as were detected coarse root count and identified water acquisition zones, thus validating root detection capability of ground-penetrating radar, but exclusively on sandstone soils. This approach was able to characterize trends between intraspecific root architecture and edaphic-dependent resource availability, however, limited by site conditions. This study successfully demonstrates a new approach for in situ root studies that moves beyond invasive point sampling to nondestructive detection of root architecture and function. We discuss the transfer of such an approach to answer root ecology questions in various tree-based landscapes.


Flexible computation of shape symmetries within the maximal disk paradigm.
Shape symmetries, like medial axes , contain a wealth of information useful in engineering and many different models for symmetry computation have been proposed. We present the hybrid symmetry transform (HST) as a compactly reformulated version of the maximal disk methods. HST is inspired by shunting inhibition networks and general concepts in wave dynamics. Through adjusting a shunting coefficient, the strength of adherence to the maximal disk paradigm becomes tunable. Each image location is scanned with a set of concentric rings which are then combined via weighted (shunting) summation, as opposed to the winner-takes-all approach in strict maximal disk methods. The new model is simple yet operates flexibly to compute maximal disk symmetries in a variety of conditions, interpreted as different wave propagation modes.


Influences on physical activity and screen time amongst postpartum women with heightened depressive symptoms: a qualitative study.
Postpartum women are at higher risk of depression compared to the general population. Despite the mental health benefits an active lifestyle can provide, postpartum women engage in low physical activity and high screen time. Very little research has investigated the social ecological (i.e. individual, social and physical environmental) influences on physical activity and screen time amongst postpartum women, particularly amongst those with depressive symptoms. Therefore, this study sought to examine the influences on physical activity and screen time amongst postpartum women with heightened depressive symptoms. 20 mothers (3-9 months postpartum) participating in the Mums on the Move pilot randomised controlled trial who reported being insufficiently active and experiencing heightened depressive symptoms participated in semi-structured telephone interviews exploring their perceptions of the key influences on their physical activity and screen time across various levels of the social ecological model. Strategies for promoting physical activity and reducing screen time were explored with participants. Thematic analyses were undertaken to construct key themes from the qualitative data. Findings showed that postpartum women with depressive symptoms reported individual (i.e. sleep quality, being housebound, single income), social (i.e. childcare, social support from partner and friends) and physical environmental (i.e. weather, safety in the local neighbourhood) influences on physical activity. Postpartum women reported individual (i.e. screen use out of habit and addiction, enjoyment) and social (i.e. positive role modelling, social isolation) influences on screen-time, but no key themes targeting the physical environmental influences were identified for screen time. Strategies suggested by women to increase physical activity included mother's physical activity groups, home-based physical activity programs and awareness-raising. Strategies to reduce screen time included the use of screen time tracker apps, increasing social connections and awareness-raising. Amongst postpartum women with heightened depressive symptoms, influences on physical activity encompassed all constructs of the social ecological model. However, screen time was only perceived to be influenced by individual and social factors. Intervention strategies targeting predominantly individual and social factors may be particularly important for this high-risk group. These findings could assist in developing targeted physical activity and screen time interventions for this cohort.


Dopamine release in the nucleus accumbens during heroin self-administration is modulated by kappa opioid receptors: an in vivo fast-cyclic voltammetry study.
Mu and kappa opioid agonists are known to produce different, and sometimes opposite, effects on several pharmacological and behavioral measures. However, whether kappa agonists can be used to antagonize the reinforcing and putative dopamine (DA)-releasing properties of a mu agonist such as heroin is unclear. With the use of the high temporal and spatial resolution of in vivo fast-cyclic voltammetry to measure changes in extracellular DA in the nucleus accumbens (NAcc), we observed (1) dose-dependent increases in DA in the NAcc during heroin self-administration (SA), (2) that coadministration of the kappa agonist U50,488H with heroin or intracerebroventricular dynorphin A pretreatment significantly depressed the heroin-stimulated DA release during SA, where U50,488H alone inhibited the basal DA release in the NAcc, (3) that coadministration of low-dose U50,488H or dynorphin A significantly increased heroin SA behavior, whereas high-dose U50,488H, which alone did not support SA behavior, reduced or completely blocked heroin SA and (4) that nor-binaltorphimine dihydrochloride (a selective kappa receptor antagonist) potentiated DA release in the NAcc and modestly decreased heroin SA. Taken together, these data suggest that endogenous kappa receptor activation can inhibit mu agonist-induced activation of the mesolimbic DA pathway, which may in turn depress heroin-induced reinforcement.


Comments on "A new look at low-energy nuclear reaction research".
Cold fusion researchers have accumulated a large body of anomalous results over the last 20 years that they claim proves a new, mysterious nuclear reaction is active in systems they study. Krivit and Marwan (J. Environ. Monit., 2009, 11, 1731) give a brief and wholly positive view of this body of research. Unfortunately, cold fusion researchers routinely ignore conventional explanations of their observations, and claim much greater than the real accuracy and precision for their techniques. This paper attempts to equally briefly address those aspects of the field with the intent of providing a balanced view of the field, and to establish some criteria for subsequent publications in this arena.


Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of nonvertebral fractures among patients with COPD in the UK General Practice Research Database.
There has been inconsistent evidence on the association between use of inhaled corticosteroids (ICS) and increased risk of nonvertebral fractures in patients with asthma or chronic obstructive pulmonary disease (COPD). In a large population-based study in the United Kingdom, we estimated the association between fluticasone propionate/salmeterol fixed-dose combination (FSC) and other ICS use and nonvertebral fracture incidence among patients with COPD. We identified a cohort of patients aged ≥ 45 years with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. We used a nested case-control design to estimate the odds of incident nonvertebral fractures associated with prior prescriptions of FSC and other ICS, applying conditional logistic regression and controlling for potential confounders. Exposure to FSC and other ICS was assessed by recency, duration, and number of prescriptions. Average daily dose was defined as low, medium, high, or very high using fluticasone propionate equivalents. We identified 1523 nonvertebral fracture cases among 53 191 patients with COPD at risk in the cohort. Use of FSC in the year prior to the index date was associated with a statistically significant increase in the odds of nonvertebral fractures (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.07-1.47); however, there was no increase in the odds of nonvertebral fractures for other ICS use (OR, 1.12; 95% CI, 0.97-1.30). When examining results by the recent use of prescriptions, an exposure that occurred farther from the index date was associated with a significant increase in nonvertebral fracture (26-52 days prior OR, 1.36; 95% CI, 1.04-1.77; 53-365 days prior OR, 1.39; 95% CI, 1.07-1.78), whereas categories of more recent use (0-12 days prior or 13-25 days prior) were not associated with nonvertebral fractures relative to no FSC use. No pattern of association between increasing levels of FSC or other ICS average daily dose and increased odds of nonvertebral fracture was observed. We did not observe a consistent association between prescriptions of FSC or other ICS in terms of recent use or average daily dose in the prior year and increases in the odds of nonvertebral fractures in patients with COPD, although ever use of FSC was associated with a slight elevation in the odds.


Inhibitory effect of mouse neocortex layer I on the underlying cellular network.
The mammalian cortical layer I is a convergence site for axons of sub- and intracortical origin, and the apical dendritic tufts of pyramidal neurons. A prominent feature of layer I is an extensive plexus of inhibitory axons, which originate from stellate cells in all cortical laminae. The role of this inhibitory projection in the activity of cortical networks has yet to be determined. We investigated the degree to which inhibitory inputs within layer I affect the activity of the underlying cellular network. Field potentials (FPs) were recorded in layer II/III. Focal application of the GABAA blocker picrotoxin in layer I above the recording pipette or the removal of layer I resulted in larger FP amplitudes for stimulations at control-equal intensities. When inhibition was partially blocked, the removal of layer I caused a significant reduction in the threshold stimulus intensity required for generating epileptiform events, and a rise in the propagation velocity of these events. Immunocytochemistry for chemical markers of interneurons proved that the inhibitory input to layer I is predominantly somatostatin immunoreactive (SM-ir), such that layer I contains approximately one-third of all SM-ir axons in the cortex. Calretinin-immunoreactive axons were also present in layer I at a lower density. We conclude that the impact of layer I on the cortical cellular network includes a significant inhibitory component. This inhibition confers a moderate restraining influence, and its removal increases the excitability of cortical circuits, but not sufficiently to induce epileptic phenomena.


Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).
Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.


Probiotics and mechanisms of their curative action.
Information about probiotics used for the correction of resident normal colon microflora and mechanism of their positive therapeutic actions are presented. Probiotics are drugs containing live microbes or substances of microbial origin that, when introduced by natural methods, are expected to confer beneficial physiologic, biochemical and immune effects to the host through the stabilization and optimization of functions of normal microflora. Probiotics containing the Bifidobacterium, Lactobacillus, Escherichia, Enterococcus, Asporogenic aerobe Bacillus and Saccharomyces boulardii microorganisms are characterized.


Glial cells drive preconditioning-induced blood-brain barrier protection.
The cerebrovascular contribution to ischemic preconditioning (IPC) has been scarcely explored. Using in vivo and in vitro approaches, we investigated the involvement of the blood-brain barrier and the role of its cellular components. Seven-minute occlusion of the right middle cerebral artery, used as in vivo IPC stimulus 4 days before permanent occlusion of the right middle cerebral artery, significantly reduced brain infarct size (8.45±0.7 versus 13.61±0.08 mm3 measured 7 days after injury) and preserved blood-brain barrier function (Evans blue leakage, 0.54±0.1 versus 0.89±0.1 ng/mg). Assessment of neuronal, endothelial, and glial gene expression revealed that IPC specifically increased glial fibrillary acidic protein mRNA, thus showing selective astrocyte activation in IPC-protected mice. The blood-brain barrier was modeled by coculturing murine primary brain microvessel endothelial and astroglial cells. One-hour oxygen-glucose deprivation (OGD), delivered 24 hours before a 5-hour OGD, acted as an IPC stimulus, significantly attenuating the reduction in transendothelial electric resistance (199.17±11.7 versus 97.72±3.4 Ωcm2) and the increase in permeability coefficients for sodium fluorescein (0.98±0.11×10(-3) versus 1.8±0.36×10(-3) cm/min) and albumin (0.12±0.01×10(-3) versus 0.29±0.07×10(-3) cm/min) induced by severe OGD. IPC also prevented the 5-hour OGD-induced disorganization of the tight junction proteins ZO-1 and claudin-5. IPC on glial (but not endothelial) cells alone preserved transendothelial electric resistance, permeability coefficients, and ZO-1 localization after 5 hours of OGD. Astrocyte metabolic inhibition by fluorocitrate abolished IPC protection, confirming the critical role of astrocytes. IPC significantly increased glial fibrillary acidic protein, interleukin-6, vascular endothelial growth factor-a, and ciliary neurotrophic factor gene expression after OGD in glial cells, indicating that multiple pathways mediate the glial contribution to IPC. Our data show that the blood-brain barrier can be directly preconditioned and that astrocytes are major mediators of IPC protection.


High genetic diversity of Enterococcus faecium and Enterococcus faecalis clinical isolates by pulsed-field gel electrophoresis and multilocus sequence typing from a hospital in Malaysia.
Little is known on the genetic relatedness and potential dissemination of particular enterococcal clones in Malaysia. We studied the antibiotic susceptibility profiles of Enterococcus faecium and Enterococcus faecalis and subjected them to pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). E. faecium and E. faecalis displayed 27 and 30 pulsotypes, respectively, and 10 representative E. faecium and E. faecalis isolates (five each) yielded few different sequence types (STs): ST17 (2 isolates), ST78, ST203, and ST601 for E. faecium, and ST6, ST16, ST28, ST179, and ST399 for E. faecalis. Resistance to tazobactam-piperacillin and ampicillin amongst E. faecium isolates was highly observed as compared to E. faecalis isolates. All of the isolates were sensitive to vancomycin and teicoplanin. The presence of epidemic and nosocomial strains of selected E. faecium STs: 17, 78, and 203 and E. faecalis ST6 as well as high rates of resistance to multiple antibiotics amongst E. faecium isolates is of a particular concern.


Studies on sex-organ development. Changes in chromatin structure during spermatogenesis in maturing rooster testis as demonstrated by the initiation pattern of ribonucleic acid synthesis in vitro.
To probe the structural change in the genome of the differentiating germ cell of the maturing rooster testis, the chromatin from nuclei at various stages of differentiation were transcribed with prokaryotic RNA polymerase from Escherichia coli or with eukaryotic RNA polymerase II from wheat germ. The transcription was performed under conditions of blockage of RNA chain reinitiation in vitro with rifampicin or rifampicin AF/013. With the E. coli enzyme, the changes in (1) the titration curve for the enzyme-chromatin interaction, (2) the number of initiation sites, (3) the rate of elongation of RNA chains, and (4) the kinetics of the formation of stable initiation complexes revealed the unmasking of DNA in elongated spermatids and the masking of DNA in spermatozoa. In both cases the stability of the DNA duplex in the initiation region for RNA synthesis greatly increased. In contrast with the E. coli enzyme, the wheat-germ RNA polymerase II was relatively inefficient at transcribing chromatin of elongated spermatids. Such behaviour can be predicted if unmasked double-stranded DNA is present in elongated spermatids.


Fetal cardiovascular alterations in twin-to-twin transfusion syndrome.
Twin-to-twin transfusion syndrome (TTTS) is the consequence of vascular anastomoses of the shared placenta of monochorionic twin pregnancies. Both circulating inter-twin blood flow and vasoactive mediators imbalance cause hypovolemia in the donor and hypervolemia in the recipient fetus. If left untreated, TTTS has a high perinatal mortality rate and adverse long-term outcomes mainly cardiovascular and neurological. The recipient has cardiovascular changes including atrioventricular valve regurgitation, diastolic dysfunction and pulmonary stenosis/atresia. The maladaptive response to vascular changes determines a constant decreased blood flow in the donor that permanently modifies the arterial structure leading to postnatal alterations in the vascular system. Fetoscopic LASER surgery of placental vascular anastomoses may disrupt the underlying pathophysiology and improves cardiovascular function with normalization of systolic and diastolic function within weeks after treatment. The impact of cardiovascular changes is relevant for the safety of the management of a TTTS case. The improvement of the perinatal survival after intrauterine surgery leads to viable infants with the longer-term sequelae. Therefore accurate quantification of cardiovascular involvement is essential for clinicians for pregnancy management but also for patient counseling about the potential treatment options the outcome.


T-RFLP-based differences in oral microbial communities as risk factor for development of oral diseases under stress.
The human oral microbiome is comprised of approximately 800 different bacterial species many of which are as yet uncultivated. Their dynamics and variability in relation to health and disease are still poorly understood. Here we tested the hypothesis that the emergence of stress-induced periodontal diseases is predictable based on the composition of the initial microbiota. As a model, we analysed 58 individuals performing a challenging expedition (exposure to various stress-factors due to changes in diet, hygiene, temperature, physical and mental stress) in remote regions of the Himalayans (Annapurna Himal). Plaque samples were taken at start (Bhulbule) and destination (3000 meter difference in altitude) seven days later (Manang). Twenty-eight individuals remained symptom-free (Group I) while 30 participants developed periodontal problems, mostly gingivitis (Group II). The microbiota was monitored via T-RFLP-analysis of amplified 16S rRNA genes directly from the plaque samples. Based on the Additive-Main-Effects-Multiplicative-Interactions-model (AMMI) using the T-Rex software variation from T-RF main effects was at least 95%, indicating that most variation was due to inherent differences in microbial communities among individuals. However, an interaction signal up to 3% was consistently observed between groups I and II but not between the two time points of sampling regardless of selected analytical parameters. The data, supported by heterogeneity, diversity and similarity indices indicated marked differences between groups I and II already prior the onset of clinical symptoms. These differences may provide the basis for using ecological parameters of oral microbial communities as early diagnostic marker for the onset of oral disorders and infections.


Spinal Tumors: Diagnosis and Treatment.
Tumors that present in or around the spine can be challenging to diagnose and treat. A proper workup involves a complete history and physical examination, appropriate staging studies, appropriate imaging of the entire spine, and a tissue biopsy. The biopsy defines the lesion and guides treatment, but in some rare instances, rapid neurological decline may lead to urgent or emergent surgery before it can be analyzed. "Enneking-appropriate" margins should remain the goal for primary tumors while adequate debulking/separation/stabilization are often the goals in metastatic disease. Primary tumors of the spine are rare and often complex tumors to operate on-achieving Enneking-appropriate margins provides the greatest chance of survival while decreasing the chance of local recurrence. Metastatic tumors of the spine are increasingly more common, and timing of surgery must be considered within the greater framework of the patient and the patient's disease, deficits, stability, and other treatments available. The specific tumor type will dictate what other multidisciplinary approaches are available, allowing for chemotherapy and radiation as needed.


Competencies for occupational therapy practice in homelessness: A Delphi study.
Homelessness is growing internationally, and resources to guide occupational therapy practice in this area are needed. To identify competencies needed for occupational therapists to support individuals during and following homelessness. We conducted a three-round Delphi study with occupational therapy practitioners and researchers with expertise in homelessness. Of 35 potential participants, n = 16 participated in Round I, n = 20 participated in Round II, and n = 18 participated in Round III. Participants included occupational therapists and researchers in Canada, United States, Brazil, UK, Ireland and New Zealand. Consensus was achieved on a total of 93 competencies in 10 categories after 15 were eliminated in Rounds II and III. The categories with the greatest number of competencies included occupational knowledge (n = 18), followed by psychosocial competencies (n = 16). This study represents the first to identify the competencies needed for occupational therapists working in the area of homelessness. Practitioners and educators are encouraged to view the identified competencies as a guide for the professional development of occupational therapists in this context. Stakeholders consulted for this study were able to communicate in English and situated in middle to high-income countries. As such, the competencies identified in this study only apply to these sociocultural contexts.


Role of EUS in the preoperative staging of pancreatic cancer: a large single-center experience.
Current methods for staging pancreatic cancer can be inaccurate, invasive, and expensive. Endoscopic ultrasound (EUS) is reported to be highly accurate for local staging of gastrointestinal tumors including pancreatic cancer. The aim of this study was to assess the utility of EUS and CT for staging pancreatic cancer by comparing staging accuracies in surgical patients and evaluating the potential impact of EUS staging and training. This was a preoperative comparison of the diagnostic operating characteristics of these procedures in a referral-based academic medical center. Data were collected on 151 consecutive patients referred with confirmed pancreatic cancer between April 1990 and November 1996. All patients had preoperative CT and EUS performed for staging. In patients undergoing surgery, the surgical staging and/or findings were used to confirm EUS and CT staging. Eighty-one (60%) of 151 patients underwent surgery and made up the study subset. In these 81 patients, surgical exploration provided a final T staging in 93% (75 of 81), N staging in 88% (71 of 81) and data on vascular invasion in 93% (75 of 81). In the surgical patient group, with surgical correlation, EUS accuracy for T staging was as follows: T1 92%, T2 85%, T3 93%, and for N staging was: N0 72%, and N1 72%. CT accuracy for T staging was as follows: T1 65%, T2 67%, T3 38%, and for N staging was as follows: N0 52% and N1 100%. CT failed to detect a mass in 26% of patients with a confirmed tumor at surgery. Overall accuracy for T and N staging was 85% and 72% for EUS and 30% and 55% for CT, respectively. The ability to accurately predict vascular invasion was 93% for EUS and 62% for CT (p < 0.001). EUS was 93% accurate for predicting local resectability versus 60% for CT (p < 0.001). Last, the data were divided into two groups for the senior endosonographer's experience: procedures performed between 1990 and 1992 (98 cases) and 1993 and 1994 (53 cases). This analysis revealed that 7 of 9 instances of mis-staging (78%) occurred in the earlier group, during the learning phase for EUS. EUS is more accurate than CT for staging pancreatic malignancies, including predicting vascular invasion and local resectability. EUS staging was significantly better than CT for T1, T2, and T3 tumors. EUS staging accuracy improved after 100 cases, thus suggesting a correlation between the accuracy of EUS staging and the number of procedures performed.


Fatty acid elongase 7 catalyzes lipidome remodeling essential for human cytomegalovirus replication.
Human cytomegalovirus (HCMV) infection rewires host-cell metabolism, upregulating flux from glucose into acetyl-CoA to feed fatty acid metabolism, with saturated very-long-chain fatty acids (VLFCAs) required for production of infectious virion progeny. The human genome encodes seven elongase enzymes (ELOVL) that extend long-chain fatty acids into VLCFA. Here, we identify ELOVL7 as pivotal for HCMV infection. HCMV induces ELOVL7 by more than 150-fold. This induction is dependent on mTOR and SREBP-1. ELOVL7 knockdown or mTOR inhibition impairs HCMV-induced fatty acid elongation, HCMV particle release, and infectivity per particle. ELOVL7 overexpression enhances HCMV replication. During HCMV infection, mTOR activity is maintained by the viral protein pUL38. Expression of pUL38 is sufficient to induce ELOVL7, and pUL38-deficient virus is partially defective in ELOVL7 induction and fatty acid elongation. Thus, through its ability to modulate mTOR and SREBP-1, HCMV induces ELOVL7 to synthesize the saturated VLCFA required for efficient virus replication.


A survey of the attitudes and beliefs about the use of TENS for pain management by physiotherapists working in two cities in Sri Lanka.
Transcutaneous electrical nerve stimulation (TENS) is a noninvasive, inexpensive, self-administered technique used throughout the world to relieve pain. In Sri Lanka, physiotherapists may use TENS for their patients as they receive a small amount of education about the principles and practice of TENS in their undergraduate training. To date, there have been no data gathered about the use of TENS by physiotherapists in Sri Lanka. The aim of this study was to assess attitudes and beliefs of physiotherapists working in Sri Lanka about their use of TENS for pain management. A postal survey was undertaken using a 12-item questionnaire developed by the investigators to gather information about attitudes, beliefs and use of TENS in clinical practice. The questionnaire was distributed to 100 physiotherapists working in three government hospitals and six private hospitals in the cities of Kandy and Colombo. A descriptive analysis of data was performed. Sixty-seven completed questionnaires were returned (67% response rate). Over half of the respondents (58.2%) reported that they used TENS to treat pain "often" or "very often", with use for musculoskeletal/orthopedic (61.3%) and neuropathic/neuralgic (79.1%) pain being most common. TENS was used less for postsurgical pain and rarely for cancer pain. Most (95.5%) respondents reported that their patients benefitted "considerably" from TENS. 76.1% of the respondents reported that they did not recommend and/or prescribe TENS for patients to use at home. Physiotherapists value TENS as a treatment option to manage musculoskeletal and neuropathic pain. However, there is a need for systems and resources to enable to patients to self-administer TENS rather than having to visit clinics.


Genetic structure and the search for genotype-phenotype relationships: an example from disequilibrium in the Apo B gene region.
We analyzed allelic associations (disequilibria) for four restriction fragment length polymorphisms (RFLPs) in the region of the 43-kb Apo B gene in a sample of 233 unrelated individuals from Montreal, Canada, sampled for health. This total sample (T) included 160 individuals of known French Canadian (FC) ancestry. We present a rigorous application of current methodology to these samples, including estimation of type II error probabilities and correlations between markers for estimates of disequilibria. We then consider the utility of these estimates of allelic disequilibria for the interpretation of genotype-phenotype relations. Significant deviations from Hardy-Weinberg equilibrium were not predicted by proximity to other markers in disequilibrium. We found significant quadri-allelic disequilibrium for two marker pairs despite absence of significant deviations from Hardy-Weinberg equilibrium for either marker or tri-allelic disequilibrium, respectively. Altogether these results underscore the complexity of the genotypic structure of the data. A combination of nonevolutionary factors, including sampling for health, small sample size and data exclusion due to methodological constraints of not successfully typing all members of the sample for every RFLP, is a likely explanation for this complexity. These types of factors are common to many RFLP studies. Patterns of composite di-allelic disequilibrium indicated that some RFLP allele pairs may have a longer shared evolutionary history than others and that disequilibrium is not predicted by distance between RFLPs. Type II error probabilities were generally much higher than those for type I errors. Correlations between marker pairs for disequilibria were generally not high. We show from a review of 14 published studies of association between the XbaI RFLP and variation in a total of 15 lipid traits that deviations from Hardy-Weinberg equilibrium can cause substantial differences in the estimation of variability associated with phenotypic differences among marker genotypes relative to Hardy-Weinberg conditions.


Exploring Critical Factors Associated with Completion of Childhood Immunisation in the Eastern Province of Saudi Arabia.
(1) Background: surveillance data from the Saudi Ministry of Health shows that the Kingdom's large-scale immunisation programme has significantly reduced the mortality and morbidity of the target diseases among children. In this study, we review relevant literature and test a number of hypotheses related to the association between demographic, socio-economic, clinic-related, and parents-related variables and completion of childhood immunisation. In doing so, this study identifies critical factors associated with completion of childhood immunisation and presents important implications to healthcare practitioners, particularly in Saudi Arabia; (2) Literature review: a systematic literature review was conducted to understand what is currently published concerning parents' immunisation compliance in Saudi Arabia and the factors associated with immunisation compliance. (3) Methods: from March to May 2022, an online survey was administered to parents attending one of the 27 primary health care (PHC) centres in Qatif. Data from parents (n = 353) were analysed using exploratory factor analysis, correlation, and a series of OLS and logistic regression models; (4) Results: parental (child) age was negatively (positively) associated with the completion status of childhood immunisation (both p < 0.05). Parents with positive attitudes, social norms, perceptions towards immunisation, and those working in private companies were more likely to immunise their children (all p < 0.05). Conversely, living in an apartment building, walking to PHCs, waiting longer at PHCs, and having higher knowledge of immunisation were negatively associated with the completion of childhood immunisation (all p < 0.05); (5) Conclusions: several factors that positively or negatively influence the completion of childhood immunisation have been identified. Future studies may investigate the causal link between these factors and parental decision-making regarding childhood immunisation.


Electrification-Enhanced Low-Temperature NOx Storage-Reduction on Pt and K Co-Supported Antimony-Doped Tin Oxides.
NOx storage-reduction (NSR), a promising approach for removing NOx pollutants from diesel vehicles, remains elusive to cope with the increasingly lower exhaust temperatures (especially below 250 °C). Here, we develop a conceptual electrified NSR strategy, where electricity with a low input power (0.5-4 W) is applied to conductive Pt and K co-supported antimony-doped tin oxides (Pt-K/ATO), with C3H6 as a reductant. The ignition temperature for 10% NOx conversion is nearly 100 °C lower than that of the traditional thermal counterpart. Furthermore, reducing the power in the fuel-lean period relative to that in the fuel-rich period increases the maximum energy efficiency by 23%. Electrically driven release of lattice oxygen is revealed to play vital roles in multiple steps in NSR, including NO adsorption, desorption, and reduction, for improved NSR activity. This work provides an electrification strategy for developing high-activity NSR catalysis utilizing electricity onboard hybrid vehicles.


Experience-dependent changes in NMDAR1 expression in the visual cortex of an animal model for amblyopia.
When normal binocular visual experience is disrupted during postnatal development, it affects the maturation of cortical circuits and often results in the development of poor visual acuity known as amblyopia. Two main factors contribute to the development of amblyopia: visual deprivation and reduced binocular competition. We investigated the affect of these two amblyogenic factors on the expression of the NMDAR1 subunit in the visual cortex because activation of the NMDA receptor is a key mechanism of developmental neural plasticity. We found that disruption of binocular correlations by monocular deprivation promoted a topographic loss of NMDAR1 expression within the cortical representations of the central visual field and the vertical and horizontal meridians. In contrast, binocular deprivation, which primarily affects visual deprivation, promoted an increase in NMDAR1 expression throughout the visual cortex. These different changes in NMDAR1 expression can be described as topographic and homeostatic plasticity of NMDA expression, respectively. In addition, the changes in NMDA expression in the visual cortex provide a greater understanding of the neural mechanisms that underlie the development of amblyopia and the potential for visual recovery.


Inhibition of Autophagy is Involved in the Protective Effects of Ginsenoside Rb1 on Spinal Cord Injury.
Spinal cord injury (SCI) is a devastating neurological disorder. Autophagy is induced and plays a crucial role in SCI. Ginsenoside Rb1 (Rb1), one of the major active components extracted from Panax Ginseng CA Meyer, has exhibited neuroprotective effects in various neurodegenerative diseases. However, it remains unknown whether autophagy is involved in the neuroprotection of Rb1 on SCI. In this study, we examined the regulation of autophagy following Rb1 treatment and its involvement in the Rb1-induced neuroprotection in SCI and in vitro injury model. Firstly, we found that Rb1 treatment decreased the loss of motor neurons and promoted function recovery in the SCI model. Furthermore, we found that Rb1 treatment inhibited autophagy in neurons, and suppressed neuronal apoptosis and autophagic cell death in the SCI model. Finally, in the in vitro injury model, Rb1 treatment increased the viability of PC12 cells and suppressed apoptosis by inhibiting excessive autophagy, whereas stimulation of autophagy by rapamycin abolished the anti-apoptosis effect of Rb1. Taken together, these findings suggest that the inhibition of autophagy is involved in the neuroprotective effects of Rb1 on SCI.


A comprehensive factorial design study of variables affecting protein extraction from formalin-fixed kidney tissue samples.
Formalin-fixed tissues are an important source of biological samples for biomedical research. However, proteomics analysis of formalin-fixed tissues has been set aside by formalin-induced protein modifications, which reduce protein extraction efficiency. In this study, a two level full factorial experimental design (2(4)) was used to determine the effects of the extracting conditions in the efficiency of protein recovery from formalin-fixed kidney samples. The following variables were assessed: temperature of extraction, pH of extraction, composition of the extracting buffer and the use ultrasonic energy applied with probe. It is clearly demonstrated that when hating and ultrasonic energy are used in conjunction, a 7-fold increase (p < 0.05) in protein extraction is obtained if compared to extracting conditions for which neither heating nor ultrasonic energy are used. The optimization study was done following the amount of protein extracted by UV (Nanodrop(®) technology, protein ABS at 280 nm) and by 1D SDS-PAGE. Extracts obtained with the optimized conditions were subjected to LC-MALDI MS/MS. A total of 112 proteins were identified.


Accelerated Evolution of Tissue-Specific Genes Mediates Divergence Amidst Gene Flow in European Green Lizards.
The European green lizards of the Lacerta viridis complex consist of two closely related species, L. viridis and Lacerta bilineata that split less than 7 million years ago in the presence of gene flow. Recently, a third lineage, referred to as the "Adriatic" was described within the L. viridis complex distributed from Slovenia to Greece. However, whether gene flow between the Adriatic lineage and L. viridis or L. bilineata has occurred and the evolutionary processes involved in their diversification are currently unknown. We hypothesized that divergence occurred in the presence of gene flow between multiple lineages and involved tissue-specific gene evolution. In this study, we sequenced the whole genome of an individual of the Adriatic lineage and tested for the presence of gene flow amongst L. viridis, L. bilineata, and Adriatic. Additionally, we sequenced transcriptomes from multiple tissues to understand tissue-specific effects. The species tree supports that the Adriatic lineage is a sister taxon to L. bilineata. We detected gene flow between the Adriatic lineage and L. viridis suggesting that the evolutionary history of the L. viridis complex is likely shaped by gene flow. Interestingly, we observed topological differences between the autosomal and Z-chromosome phylogenies with a few fast evolving genes on the Z-chromosome. Genes highly expressed in the ovaries and strongly co-expressed in the brain experienced accelerated evolution presumably contributing to establishing reproductive isolation in the L. viridis complex.


Factors Influencing Functional Exercise Capacity After Lung Resection for Non-Small Cell Lung Cancer.
Purpose: We investigated, in patients who underwent lung resection for non-small cell lung cancer (NSCLC), the magnitude of early limitation in functional exercise capacity and the associations with pre- and postoperative factors. Methods: Consecutive patients with preoperative clinical stage I to IIIA NSCLC who underwent lung resection were prospectively enrolled. We measured functional exercise capacity (6-minute walk distance [6MWD]) and skeletal muscle strength (handgrip [HF] and quadriceps force [QF]) within 2 days prior to surgery and on day 7 postoperatively. Results: Two hundred eighteen participants were recruited (median age 69 years) of whom 49 developed postoperative complications (POCs). 6MWD was markedly decreased (514 m vs 469 m, P < .001); HF and QF were slightly decreased following surgery. Multiple linear regression showed that preoperative vital capacity (P < .01), QF (P < .05), the duration of chest tube drainage (P < .001), and presence of POCs (P < .05) were significant predictors. However, intraoperative factors were not significantly associated with the decline in 6MWD. Conclusions: These results suggest that patients with preoperative impairments in pulmonary function and muscle strength, and those who require prolonged chest tube drainage or develop POCs are likely to have impaired exercise capacity. Therefore, individual assessment and follow-up of patients with such factors is indicated.


Oral steroid therapy in chronic rhinosinusitis with and without nasal polyposis.
Chronic rhinosinusitis (CRS) is a heterogeneous group of disorders characterized by inflammation of the sinonasal mucosa. CRS can be divided into two subtypes: CRS without polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). Corticosteroids are frequently employed to treat CRS due to their potent anti-inflammatory effects. Treatment of CRS with oral steroids must be carefully balanced against potential adverse effects. This article reviews the current literature on management of CRS with systemic corticosteroids. We discuss the available evidence in CRSsNP, CRSwNP, and allergic fungal sinusitis (AFS). Studies are evaluated for level of evidence and graded to provide evidence-based recommendations. Our review finds a lack of high-quality evidence supporting oral corticosteroid therapy in CRSsNP. In comparison, randomized controlled trails support the use of oral corticosteroids for CRSwNP. Similarly, systemic steroids for AFS treatment are supported by quality studies demonstrating efficacy. Utilization of steroids is also recommended in the perioperative setting for CRSwNP.


Changes in hippocampal volume and shape across time distinguish dementia of the Alzheimer type from healthy aging.
Rates of hippocampal volume loss have been shown to distinguish subjects with dementia of the Alzheimer type (DAT) from nondemented controls. In this study, we obtained magnetic resonance scans in 18 subjects with very mild DAT (CDR 0.5) and 26 age-matched nondemented controls (CDR 0) 2 years apart. Large-deformation high-dimensional brain mapping was used to quantify and compare changes in hippocampal shape as well as volume in the two groups of subjects. Hippocampal volume loss over time was significantly greater in the CDR 0.5 subjects (left = 8.3%, right = 10.2%) than in the CDR 0 subjects (left = 4.0%, right = 5.5%) (ANOVA, F = 7.81, P = 0.0078). We used singular-value decomposition and logistic regression models to quantify hippocampal shape change across time within individuals, and this shape change in the CDR 0.5 and CDR 0 subjects was found to be significantly different (Wilks's lambda, P = 0.014). Further, at baseline, CDR 0.5 subjects, in comparison to CDR 0 subjects, showed inward deformation over 38% of the hippocampal surface; after 2 years this difference grew to 47%. Also, within the CDR 0 subjects, shape change between baseline and follow-up was largely confined to the head of the hippocampus and subiculum, while in the CDR 0.5 subjects, shape change involved the lateral body of the hippocampus as well as the head region and subiculum. These results suggest that different patterns of hippocampal shape change in time as well as different rates of hippocampal volume loss distinguish very mild DAT from healthy aging.


Naoxintong Capsule Inhibits the Development of Cardiovascular Pathological Changes in Bama Minipig Through Improving Gut Microbiota.
Naoxintong capsule (NXT), a Chinese medicine, has performed excellent effects on the prevention and treatment against cardiovascular diseases. NXT is a fine powder mixture without any herb extraction, and there must be lots of ingredients hard to be absorbed. However, little is known about the correlation between the NXT's cardioprotective effects and gut microbiota. Herein, we report the effect of NXT on the development of cardiovascular diseases and clarify the correlation between NXT's cardioprotective effects and gut microbiota. In the current study, minipigs were selected and fed with high-fat diet and NXT daily for successive 8 months. During the process, up to 18 biomedical parameters were monthly determined to observe the dynamic changes after NXT treatment. At the end of experimental process, pathological examinations of heart, coronary artery, carotid artery, thoracic aorta, and abdominal aorta were conducted by HE staining and 16SrDNA sequencing, and analyzing of gut microbiota were conducted. Our results showed that NXT's effects against cardiovascular diseases were through regulating blood lipid profiles, inhibiting vascular inflammation, enhancing antioxidant capacity, and alleviating myocardial injury, without damages on liver and kidney particularly. Concurrently, we also found that long-term administration of NXT increased the diversity of gut microbiota, influenced the microbiome structure and composition stably, and revered the increase of the ratio of the Firmicutes to Bacteroidetes (F/B ratio) in relative abundance. Specifically, our results revealed some key bacterium of Caproiciproducens (enhanced), Sutterella (enhanced), Erysipelotrichaceae (enhanced), and Romboutsia (decreased) that were closely involved in NXT's effects. Taken together, our study demonstrates that NXT can inhibit the development of cardiovascular diseases by ameliorating high-fat diet-induced metabolic disorders and partly through improving gut microbiota.


Necrotizing fasciitis associated with porphyria cutanea tarda.
A case is presented of a 31-year-old white woman with necrotizing fasciitis. She had had a previous diagnosis of porphyria cutanea tarda that was manifested in part by bullous lesions on her forearms and hands. A soft tissue infection developed in her left hand and forearm in an area of bullous disease. After a delay of 8 days the diagnosis of necrotizing fasciitis was made. She recovered following surgical debridement, extensive fasciotomy, broad-spectrum antibiotic coverage, and hyperbaric oxygen therapy.


[Prevalence of anxiety in the presurgical area].
Anxiety is a complex personal reaction against situations and stimuli that is potentially dangerous or at least perceived as such by the sufferer. Surgery is an important stressing agent, which may cause problems not only for the patient and their family but also for the healthcare system and therefore addressing the anxiety prior to surgery must be a priority. This research is centered on the prevalence of anxiety in the pre-surgical area of the Royo Villanova Hospital located in Zaragoza, Spain, and the risk factors. The present study is a transverse descriptive observational study of 100 patients aged between 50 and 95 years. Data collection was carried out in the pre-surgical area by means of a personal interview and a STAI-STADO test. Out of 100 patients, 45% showed light anxiety, while 34% of the sample showed high or acute anxiety. Statistically significant differences were determined in the levels of anxiety reported between married and non-married patients as well as in the levels of those patients that had not undertaken a previous surgical procedure versus those that had. Both of these groups experienced lower levels of anxiety. The lack of a partner (widowed or single patients) has been identified as a risk factor for experiencing higher pre-surgical anxiety. Not having experienced any prior surgical procedure has been identified as a protective factor with these patients reporting lower pre-surgical anxiety than those with prior surgical procedures.


The art of fluorescence imaging with chemical sensors.
Fluorescence imaging techniques involving chemical sensors are essential tools in many fields of science and technology because they enable the visualization of parameters which exhibit no intrinsic color or fluorescence, for example, oxygen, pH value, CO(2), H(2)O(2), Ca(2+), or temperature, to name just a few. This Review aims to highlight the state of the art of fluorescence sensing and imaging, starting from a comprehensive overview of the basic functional principles of fluorescent probes (or indicators) and the design of sensor materials. The focus is directed towards the progress made in the development of multiple sensors and methods for their signal read out. Imaging methods involving optical sensors are applied in quite diverse scientific areas, such as medical research, aerodynamics, and marine research.