Optimization of microalgal production in a shallow outdoor flume.
The marine diatom Cyclotella cryptica was grown over a period of 13 months in a 48-m(2) shallow outdoor flume. The use of foil arrays at intervals of 1.2 m to effect systematic vertical mixing in the flume was found to significantly enhance microalgal production (p = 0.006). Average photosynthetic efficiencies (based on visible irradiance) with and without the foil arrays in place were 9.6 +/- 0.8 and 7.5 +/- 0.5% (+/-95% confidence intervals), respectively. A cost-benefit analysis indicated that the foil arrays were cost-effective if the value of the algae exceeded about $2.28 kg(1) of ash-free dry weight (AFDW). Parallel experiments performed in four 9.2-m(2) flumes showed that production was maximized when the cells were grown on a 2-day batch cycle between harvests rather than on a 1- or 3-day batch cycle. The optimum initial concentration (immediately after harvesting) of the algae was negatively correlated with the time interval between harvests and ranged from approximately 39 g AFDW/m(3) on a 3-day cycle to 213 g AFDW/m(3) on a 1-day cycle. The increase in production resulting from growth on a 2-day rather than a 1-day batch cycle was about 19% and was statistically significant at p = 0.0003. Growth of C. cryptica over a total period of 122 days during the 13-month study in the 48-m(2) flume under near-optimal conditions (2-day batch cycle, initial concentration 155 g AFDW/m(3)) resulted in an average production rate (+/-95% confidence interval) of 29.7 +/- 2.7 g AFDW/m(2) d.


Mn2+/Mn4+ co-doped LaM1-xAl11-yO19 (M = Mg, Zn) luminescent materials: electronic structure, energy transfer and optical thermometric properties.
Dual-emitting manganese ion doped LaM1-xAl11-yO19 (M = Mg, Zn) phosphors were prepared by substituting Zn2+/Mg2+ with Mn2+ and replacing Al3+ with Mn4+. The LaM1-xAl11-yO19:xMn2+,yMn4+ phosphors show a narrow green emission band of the Mn2+ ions at 514 nm and a red emission band of the Mn4+ ions at 677 nm. In addition, the thermal stability of luminescence shows that the response of Mn2+ and Mn4+ to the temperature is obviously different in LaMAl11O19, implying the potential of the prepared phosphors as optical thermometers. The decay lifetime of Mn4+ was changed with temperature due to the different fluorescence intensity ratios of Mn2+ and Mn4+, and a dual-mode optical temperature-sensing mechanism was studied in the temperature range of -50-200 °C. The maximum relative sensitivities (Sr) are calculated as 3.22 and 3.13% K-1, respectively. The unique optical thermometric features demonstrate the application potential of LaMAl11O19:Mn2+,Mn4+ in optical thermometry.


Randomized controlled trial of interventions to improve follow-up for latent tuberculosis infection after release from jail.
Adherence to treatment of persons with latent tuberculosis infection after release from jail has been poor. A randomized controlled trial was conducted at the San Francisco City and County Jail, San Francisco, Calif. Subjects undergoing therapy for latent tuberculosis infection who spoke either English or Spanish were randomly allocated to receive education every 2 weeks while in jail; an incentive if they went to the San Francisco County Tuberculosis Clinic within 1 month of release; or usual care. The main outcome measures were completion of a visit to the tuberculosis clinic within 1 month of release and completion of therapy. Of 558 inmates enrolled, 325 were released before completion of therapy. Subjects in either intervention group were significantly more likely to complete a first visit than were control subjects (education group, 37%; incentive group, 37%; and controls, 24%) (adjusted odds ratio based on pooled results for the education and incentive groups, 1.85; 95% confidence interval, 1.04-3.28; P =.02). Those in the education group were twice as likely to complete therapy compared with controls (adjusted odds ratio, 2.2; 95% confidence interval, 1.04-4.72; P =.04). Of those who went to the tuberculosis clinic after release, subjects in the education group were more likely to complete therapy (education group, 65% [24/37]; incentive group, 33% [14/42]; and control group, 48% [12/25]; P =.02). Education or the promise of an incentive improved initial follow-up. Education was superior to an incentive for the completion of therapy. Fairly modest strategies provided in jail can improve adherence. Further links between jail health services and community care should be explored.


Quantification and risk assessment of organic products resulting from non-thermal plasma removal of toluene in nitrogen.
Non-thermal plasma (NTP) has proven to be an effective approach for the removal of volatile organic compounds (VOCs). However, harmful organic by-products, produced during NTP-mediated removal of VOCs, hinder practical applications of this technology. It is necessary to characterize the organic by-products to assess their health risks. A method is proposed for analyzing and evaluating organic by-products for NTP-mediated removal of VOCs in this work. NTP generated by a coaxial dielectric barrier discharge (DBD) reactor was used for the removal of a model VOC, toluene, in nitrogen. Organic products were characterized using a real-time proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) apparatus. The PTR-TOF-MS apparatus has been shown to be effective for real-time high-sensitivity detection of trace VOCs. The main observed organic compounds, with concentrations on the order of ppb/ppm, were hydrogen cyanide, acetonitrile, propanenitrile, benzene, benzonitrile, and benzyl nitrile, etc. A health-related index (HRI) was introduced to assess the health risks associated with these organic products. The HRI was not correlated with the removal efficiency (η), with higher η possibly yielding higher HRI, associated with higher health risks. Specific input energy (SIE) was a key factor affecting the formation of the observed organic products and their HRI values. We conclude that in practical applications, SIE, HRI, and η must be balanced.


Randomized controlled trial of dietary intervention: association between level of urinary phenolics and anti-mutagenicity.
We have undertaken a randomized trial to confirm the ability of a class of phenolics, flavonoids, to increase urinary anti-mutagenicity in smokers. Ninety heavy smokers were recruited and randomly assigned to three groups, who were given three different diets. One diet was rich in flavonoids, but not based on supplementation ('flavonoid'), one was a normal iso-caloric diet with an adequate administration of fruit and vegetables ('normal'), and one was based on supplementation of flavonoids in the form of green tea and soy products ('supplement'). The urinary anti-mutagenicity-as inhibiting effect of the urinary extracts on the mutations induced by MeIQx-was measured in Salmonella typhimurium YG1024 in the presence of liver S9 from male Sprague-Dawley rats treated with Aroclor 1254. The amount of total phenolics in the urinary extracts was measured by use of spectrometric analysis. We found that important dietary modifications can be achieved through special recipes and instructions given by a cook during an intensive course. The intervention was focused on increasing the flavonoid intake, and it was successful in that respect. In fact, differences in flavonoid intake were appreciated mainly between the first group (normal diet) and the other two (flavonoid-rich and supplemented diet), suggesting that dietary modification can be as effective as supplementation. However, both urinary anti-mutagenicity and the amounts of urinary phenolics did not change as a consequence of the trial. These results suggest that only a small fraction of urinary phenolics is influenced by dietary changes in the intake of flavonoids, and that most urinary anti-mutagens and phenolics are metabolites of dietary flavonoids, whose formation is more affected by the activity and diversity of bacterial flora in the colon than by the quantity and type of intake. A strong correlation was found between urinary phenolics and anti-mutagenicity in all the groups involved in the trial. Such correlation was not explained by dietary variables.


Optimization and head-to-head comparison of MISSR-PCR, ERIC-PCR, RAPD and 16S rRNA evolutionary clock for the genotyping of Vibrio cholerae isolated in China.
To establish a new genotyping method for Vibrio cholerae and compare it with other methods. In the current study, a modified inter simple sequence repeat-polymerase chain reaction (MISSR-PCR) system was developed via several rounds of optimisation. Comparison study was then conducted between MISSR-PCR and three other methods, including enterobacterial repetitive intergenic consensus sequences-based PCR (ERIC-PCR), randomly amplified polymorphic DNA (RAPD) and 16S rRNA evolutionary clock, for the detection and genetic tracing of Vibrio cholerae isolated from seafood in China. The results indicated that the MISSR-PCR system could generate the highest polymorphic fingerprinting map in a single round PCR and showed the best discriminatory ability for Vibrio cholerae genotyping by clearly separating toxigenic/nontoxigenic strains, local/foreign strains, and O1/O139/non-O1/non-O139 serogroup strains, comparing to ERIC-PCR, RAPD and 16S rRNA evolutionary clock. Moreover, the MISSR-PCR is superior to previously described traditional simple sequence repeat based PCR method on genotyping by more clearly separating different clusters. To the best of our knowledge, this is the first head-to-head comparison of four detection and genotyping methods for Vibrio cholerae The MISSR-PCR system established here could serve as a simple, quick, reliable and cost-effective tool for the genotyping and epidemiological study.


The association between neuropathic pain and disability grades in leprosy.
To detect neuropathic pain in people who have had leprosy and correlate this association with the WHO Degree of Physical Disability classification (DPD-WHO). Data were collected from medical records, interviews and physical examinations of patients treated in 2013 in a regional referral service that attends 102 municipals. Clinical and general data, the DPD-WHO classification and the Douleur Neuropathique 4 Questionnaire (DN4) were utilised to determine the profile and to diagnose neuropathic pain. Of 84 treated patients, 37 (44.1%) had leprosy-related pain at the time of the interview. The mean age was 53 years, 51.4% were women; 75.7% had multibacillary disease and 72.9% had some kind of reactional episode. Of the 37 patients with pain, 22 (59.5%) had neuropathic pain and 15 (40.5%) had nociceptive pain. The most frequently reported symptoms related to neuropathic pain, apart from numbness (64.9%), were tingling and touch hypoesthesia (56.8%). Of 22 patients with neuropathic pain, 20 had some physical disability; 14 (63.6%) had Grade I disability, six (27.2%) Grade II, and two (9.3%) Grade zero disability. An association was found between neuropathic pain and degree of disability (P-value < 0.05). Of the patients who reported pain related to leprosy, 59.5% had neuropathic pain. The DN4 seems to be suitable for determining the presence of neuropathic pain in leprosy. There is an association between the degree of disability and neuropathic pain, i.e. patients with neuropathic pain tend to have a physical disability too.


Skin and soft tissue infections, active component, U.S. Armed Forces, 2013-2016.
During the 4-year surveillance period, there were 282,571 incident cases of skin and soft tissue infection (SSTI) among active component U.S. military members diagnosed in inpatient or outpatient settings, corresponding to an overall incidence of 558.2 per 10,000 person-years (p-yrs). An additional 10,904 cases occurred in theater of operations (460.0 per 10,000 p-yrs). Approximately half (49.4%) were classified as "other SSTI" (e.g., folliculitis, impetigo); 45.9% were cellulitis/abscess; 4.6% were carbuncles/furuncles; and 0.1% were erysipelas. Annual incidence rates declined by 46.6% over the surveillance period. In general, higher rates of SSTIs were associated with younger age, recruit trainee status, and junior enlisted rank. During the surveillance period, 238,924 service members were treated for SSTIs in outpatient or inpatient settings, which accounted for 395,361 medical encounters and 19,213 hospital bed days. The history of operational significance of skin infections in the military, the high healthcare costs associated with evaluating and treating skin infections, and the risk of infections by antibiotic-resistant organisms highlight the importance of prevention, early diagnosis, and definitive treatment of skin infections, particularly in high-risk settings such as new recruit/basic training populations.


Effect of ligand conformation on melanoma cell alpha3beta1 integrin-mediated signal transduction events: implications for a collagen structural modulation mechanism of tumor cell invasion.
The importance of three-dimensional interactions between receptors with their respective ligands has been extensively explored during the binding process, but considerably less so for postbinding events such as induction of signaling pathways. Tumor cell receptor association with basement membrane proteins is believed to facilitate the metastatic process. Melanoma and ovarian carcinoma cells have been shown to utilize the alpha3beta1 integrin to bind to models of the alpha1(IV)531-543 sequence from basement membrane (type IV) collagen [Miles, A. J., et al. (1994) J. Biol. Chem. 269, 30939-30945; Miles, A. J., et al. (1995) J. Biol. Chem. 270, 29047-29050]. In the present study, the effects of ligand three-dimensional structure on possible signal transduction pathways induced by alpha3beta1 integrin binding have been evaluated. Human melanoma cell binding to type IV collagen resulted in Tyr phosphorylation of p125(FAK), consistent with prior studies correlating beta1 integrin subunit binding to collagen and p125(FAK) Tyr phosphorylation. Cross-linking of an anti-alpha3 integrin subunit monoclonal antibody also induced p125(FAK) Tyr phosphorylation. Incubation of melanoma cells with single-stranded or triple-helical peptide models of alpha1(IV)531-543 induced Tyr phosphorylation of intracellular proteins. Immunoprecipitation analysis identified one of these proteins as pp125(FAK). Induction of p125(FAK) Tyr phosphorylation was enhanced and the time of induction was shortened when the ligand was used in triple-helical conformation. Subsequent clustering of either the single-stranded or the triple-helical ligand also increased the level of p125(FAK) phosphorylation compared to unclustered ligand. The clustered triple-helical peptide ligand induced more rapid paxillin Tyr phosphorylation than the single-stranded ligand. In addition, the induction of activated proteases was found to be more rapid due to ligand triple helicity. Overall, these studies have shown that (i) a model of an isolated sequence from type IV collagen, alpha1(IV)531-543, can induce alpha3beta1 integrin-mediated signal transduction in melanoma cells and (ii) ligand conformation (secondary, tertiary, and/or quaternary structure) can directly influence several alpha3beta1 integrin-mediated signal transduction events. The effects of ligand conformation suggest that a "collagen structural modulation" mechanism may exist for tumor cell invasion, whereby triple-helical collagen promotes cell binding and induction of signal transduction, subsequently leading to collagen dissolution by proteases, decreased signal transduction, and enhanced tumor cell motility.


Production of Lipopeptide Biosurfactant by a Marine Nesterenkonia sp. and Its Application in Food Industry.
Biosurfactants are smart biomolecules which have wide spread application in medicines, processed foods, cosmetics as well as in bioremediation. In food industry, biosurfactants are used as emulsion stabilizing agents, antiadhesives, and antimicrobial/antibiofilm agents. Nowadays biosurfactant demands in industries has increased tremendously and therefore new bacterial strains are being explored for large scale production of biosurfactants. In this study, an actinobacterial strain MSA31 was isolated from a marine sponge Fasciospongia cavernosa which showed high activity in biosurfactant screening assays such as drop collapsing, oil displacement, lipase and emulsification. Lipopeptide produced by MSA31 was found to be thermostable which was evident in differential scanning calorimetry analysis. The spectral data obtained in the Fourier transform infrared spectroscopy showed the presence of aliphatic groups combined with peptide moiety which is a characteristic feature of lipopeptides. The stability index of lipopeptide MSA31 revealed "halo-alkali and thermal tolerant biosurfactant" which can be used in the food industry. Microtiter plate assay showed 125 μg/ml of lipopeptide was effective in reducing the biofilm formation activity of pathogenic multidrug resistant Staphylococcus aureus. The confocal laser scanning microscopic images provided further evidences that lipopeptide MSA31 was an effective antibiofilm agent. The antioxidant activity of lipopeptide MSA31 may be due to the presence of unsaturated fatty acid present in the molecule. The brine shrimp cytotoxicity assay showed lipopeptide MSA31 was non-toxic and can be used as food additives. Incorporation of lipopeptide MSA31 in muffin showed improved organoleptic qualities compared to positive and negative control. This study provides a valuable input for this lipopeptide to be used in food industry as an effective emulsifier, with good antioxidant activity and as a protective agent against S. aureus.


Are sprint accelerations related to groin injuries? A biomechanical analysis of adolescent soccer players.
Groin injuries have one of the highest incidences in soccer and can be career threatening, especially for adolescents, due to their high recurrence rate. Quick accelerations have been connected to groin injuries along with kicking and change of directions. Purpose of this study was to examine the hip joint kinematics, kinetics and the muscle forces of adductor longus and gracilis during first ground contact of a linear sprint acceleration performed by adolescent soccer players. Twenty-two male participants were investigated with 3D motion capture and two force plates. Inverse dynamics were used to calculate the kinematics, kinetics and muscle forces. The kinematics show a constant extension during the stance phase and a quick transition from an abduction to an adduction movement at 90% stance, which coincides with the highest forces in adductor longus and gracilis. This indicates a high load on the adductor muscles due to eccentric contractions combined with high muscle forces in the adductors. Compared to previously investigated inside passing and change of direction movements, adductor muscle forces and angular velocities are higher in this study. Therefore, it is suggested that sprint accelerations are likely to be connected to the development of groin injuries in adolescent soccer players.


Regulatory Plasticity of Earthworm wMT-2 Gene Expression.
Metallothioneins (MTs) are multifunctional proteins occurring throughout the animal kingdom. While the expression and transcriptional regulation of MTs is well-studied in vertebrates, the mechanism of MT activation is still unknown for most invertebrates. Therefore, we examined wMT-2 gene regulation and expression patterns in Lumbricus rubellus and L. terrestris. Transcription levels, the occupation of DNA binding sites, the expression of putative transcriptional regulators, and promotor DNA methylation were determined. We found that wMT-2 expression does not follow a circadian pattern. However, Cd-induced wMT-2 induction was observed, and was, interestingly, suppressed by physical injury. Moreover, the promotor region that is responsible for the wMT-2 gene regulation was elucidated. ATF, a putative transcriptional regulator, showed increased phosphorylation upon Cd exposure, suggesting that it plays a major role in wMT-2 gene activation. The promotor methylation of wMT-2, on the other hand, is probably not involved in transcriptional regulation. Elucidating the regulatory mechanism of the earthworm MT gene activation might provide insights into the molecular coordination of the environmental stress response in invertebrates, and might also reveal a link to wound repair and, in a broader sense, to immunity.


The impact of technological innovation and financial development on environmental pollution in gulf cooperation council - A linear and nonlinear ARDL approach.
Gulf Cooperation Council (GCC) countries are highly vulnerable to climate change, including rising sea levels, extreme weather, and other environmental and social issues. GCC countries showed remarkable economic growth and development. However, this growth and development put severe pressure on the environment, leading to the degradation of the Environment. Therefore, it is essential to investigate essential factors of environmental degradation, such as technological innovation and financial development. However, per capita income and energy consumption are also crucial factors of environmental degradation. Henceforth, the study carried out panel data from 2001 to 2019 to examine the influence of technological innovation, financial development, energy consumption, and per capita income on environmental degradation in GCC. After conducting necessary preliminary tests, the study employed a symmetric and asymmetric ARDL approach to quantify the numerical estimates. Both symmetric and asymmetric models show that technological innovation reduces environmental degradation, while energy consumption, per capita, and financial development expedite the ecological deterioration in GCC. The Wald tests demonstrate the asymmetric relationship between technological innovation, energy consumption, financial development, and environmental degradation. However, the study fails to find a significant asymmetric relationship between per capita and ecological degradation. The recommendations are added in the recommendation part of the paper.


Effects of endurance training on autophagy and apoptotic signaling in visceral adipose tissue of prolonged high fat diet-fed rats.
Autophagy and apoptosis play critical roles in both development and tissue homeostasis in response to (patho)physiological stimuli, such as high-fat diet (HFD) and endurance training (ET). Therefore, we aimed to investigate how ET modulates autophagy and apoptotic-related signaling in visceral adipose tissue of long-standing HFD-fed rats. The study was conducted over a 17-week period on Sprague-Dawley rats, which were divided into four groups (n = 8/group): standard diet sedentary (STD+SED), high-fat diet sedentary (HFD+SED), standard diet ET (STD+ET) and high-fat diet ET (HFD+ET). After 9 weeks of dietary regimens, ET groups were trained for 8 weeks on treadmill (5 days/week at 25 m/min for 60 min/day), while maintaining dietary regimens. Autophagy and apoptotic-signaling markers in epididymal white adipose tissue (eWAT) were determined using RT-qPCR, Western blot and spectrometry techniques. ET reduced body weight, visceral fat mass and HOMA-IR in standard and HF diet-fed animals. Moreover, ET reverted the HFD-induced increases in the percentage of larger adipocytes and also reduced the percentage of smaller adipocytes. The HFD decreased pre-adipocyte factor 1 (DLK1/PREF1) and increased the pro-apoptotic markers (Bax protein and caspase 3-like activity), while having no impact on autophagy markers. However, ET increased DLK1/PREF1 and Bcl-2 in both diet types, while decreasing Bax and caspases 9, 8 and 3-like activities in HFD feeding rats. Additionally, Beclin-1 and p62 protein significantly increased in ET groups of both diet types. Data demonstrate that 8 weeks of ET was effective in attenuating apoptotic-related signaling in long-standing HFD-fed rats. Moreover, HFD and ET had no impact on VAT autophagy markers.


The Importance of Stem Photosynthesis for Two Desert Shrubs Across Different Groundwater Depths.
Water availability could alter multiple ecophysiological processes such as water use strategy, photosynthesis, and respiration, thereby modifying plant water use and carbon gain. However, a lack of field observations hinders our understanding of how water availability affects stem photosynthesis at both organ and plant levels of desert shrubs. In this study, we measured gas exchange and oxygen stable isotopes to quantify water sources, stem recycling photosynthesis, and whole-plant carbon balance in two coexisting Haloxylon species (Haloxylon ammodendron and Haloxylon persicum) at different groundwater depths in the Gurbantonggut Desert. The overall aim of the study was to analyze and quantify the important role of stem recycling photosynthesis for desert shrubs (Haloxylon species) under different groundwater depths. The results showed that (1) regardless of changes in groundwater depth, H. ammodendron consistently used groundwater and H. persicum used deep soil water as their main water source, with greater than 75% of xylem water being derived from groundwater and deep soil water for the two species, respectively; (2) stem recycling photosynthesis refixed 72-81% of the stem dark respiration, and its contribution to whole-plant carbon assimilation was 10-21% for the two species; and (3) deepened groundwater increased stem water use efficiency and its contribution to whole-plant carbon assimilation in H. persicum but not in H. ammodendron. Our study provided observational evidence that deepened groundwater depth induced H. persicum to increase stem recycling photosynthetic capacity and a greater contribution to whole-plant carbon assimilation, but this did not occur on H. ammodendron. Our study indicates that stem recycling photosynthesis may play an important role in the survival of desert shrubs in drought conditions.


Mechanism of N-Methyl-N-Nitroso-Urea-Induced Gastric Precancerous Lesions in Mice.
Early diagnosis and treatment of gastric precancerous lesions (GPL) are key factors for reducing the incidence and morbidity of gastric cancer. The study is aimed at examining GPL in mice induced by N-methyl-N-nitroso-urea (MNU) and to illustrate the underlying mechanisms of tumorigenesis. In this study, we utilized an in vivo MNU-induced GPL mouse model, and histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (H&E-stain) and alcian blue (AB-PAS-stain). The level of miR-194-5p in the gastric mucosa was determined by real-time polymerase chain reaction. We used transmission electron microscopy to observe the effects of MNU on gastric chief cells and parietal cells. We performed immunohistochemical detection of HIF-1α, vWF, Ki-67, and P53, while the changes in the protein expression of key genes in LKB1-AMPK and AKT-FoxO3 signaling pathways were detected by western blot analysis. We demonstrated that the miR-194-5p expression was upregulated under hypoxia in GPL gastric tissues, and that a high miR-194-5p expression level closely related with tumorigenesis. Mechanistically, miR-194-5p exerted the acceleration of activities related to metabolic reprogramming through LKB1-AMPK and AKT-FoxO3 pathways. Furthermore, similar to miR-194-5p, high expression levels of AMPK and AKT were also related to the metabolic reprogramming of GPL. Moreover, we revealed the correlation between the expression levels of miR-194-5p, p-AMPKα, p-AKT, and FoxO3a. These findings suggest that miR-194-5p/FoxO3 pathway is important for the reversal of metabolic reprogramming in GPL. Thus, exploring strategies to regulate the miR-194-5p/FoxO3a pathway may provide an efficient strategy for the prevention and treatment of GPL.


Complete pathologic response after chemoradiotherapy in a patient with rectal squamous cell carcinoma: a case report.
Squamous cell carcinoma (SCC) of the rectum is a rare disease. A 59-year-old man presented with SCC of the middle rectum located 10 cm from the anus. The stage of the tumor was revealed to be T3N+M0. The patient received a combined treatment with cisplatin and fluorouracil in concomitance with external radiation therapy. He then underwent an anterior resection of the rectum. The postoperative histopathological findings classified the tumor as ypT0N0 with cancer-free margins and lymph nodes. Treatment of SCC remains very challenging, and the acquisition of more consistent data is needed.


Adjusted calcium concentration as a predictor of ionized hypocalcemia in hypoalbuminemic dogs.
Ionized calcium (iCa) is the biologically active fraction of total calcium (tCa) with clinical relevance to evaluate calcium homeostasis, but not all primary veterinarians have access to serum iCa. Formulas that adjust tCa to correct for variability in serum protein concentrations were not designed to predict iCa and are considered unreliable surrogates for iCa. To determine whether adjusted calcium concentration (aCa) can predict ionized hypocalcemia in hypoalbuminemic dogs without hyperphosphatemia. A total of 262 hypoalbuminemic dogs without hyperphosphatemia. Retrospective review of paired tCa and iCa. Patients were included if serum albumin concentration was ≤2.5 g/L and serum phosphorus concentration was ≤5 mg/dL. The aCa was calculated using tCa (mg/dL) - serum albumin concentration (g/dL) + 3.5 (g/dL). Sensitivity, specificity, positive (PPVs) and negative (NPVs) predictive values, and accuracy were determined for tCa and aCa at predicting any (<1.13 mmol/L) and moderate (<1.02 mmol/L) ionized hypocalcemia. Patients also were stratified into mild-to-moderate (2.0-2.5 g/dL) and severe hypoalbuminemia (<2.0 g/dL). A total of 4296 dogs had paired results of which 262 met the inclusion criteria. Of these, 35 (13.4%) dogs had iCa < 1.13 mmol/L and 13 dogs (5.0%) had concentrations <1.02 mmol/L. The sensitivity, specificity, NPVs and PPVs of a decreased tCa and aCa for detecting moderate ionized hypocalcemia were 100% and 92.3%, 57.8% and 94.8%, 100% and 99.6%, and 11.0% and 48.2%, respectively, and accuracy was 60.0% and 94.7%, respectively. A low aCa was useful to detect ionized hypocalcemia in hypoalbuminemic nonhyperphosphatemic dogs. A normal aCa indicated that moderate ionized hypocalcemia was unlikely.


Pharmacologic induction of CD8+ T cell memory: better living through chemistry.
The generation of a robust population of memory T cells is critical for effective vaccine and cell-based therapies to prevent and treat infectious diseases and cancer. A series of recent papers have established a new, cell-intrinsic approach in which small molecules target key metabolic and developmental pathways to enhance the formation and maintenance of highly functional CD8(+) memory T cells. These findings raise the exciting new possibility of using small molecules, many of which are already approved for human use, for the pharmacologic induction of immunologic memory.


The flowering integrator FT regulates SEPALLATA3 and FRUITFULL accumulation in Arabidopsis leaves.
The transition to flowering involves major changes in the shoot apical meristem and in the fate of existing leaf primordia. Transcripts of the Arabidopsis thaliana flowering-promoting gene FLOWERING LOCUS T (FT) are present in leaf tissue but can also promote flowering when artificially introduced into the meristem. FT may normally act in the leaf and/or the meristem, initiating or constituting a mobile flower-promoting signal. We studied FT-dependent events in the rosette leaf, some of which might precede or mimic events in the meristem and its primordia. We show FT-dependent transcript accumulation of the MADS box transcription factors FRUITFULL (FUL) and SEPALLATA3 (SEP3) in leaves. Abnormally high levels of FT further increase the expression of these genes, leading to morphological changes in the leaves. Loss of the flowering-time gene FD, as well as environmental conditions that delay flowering, reduce FT's effect on leaves via reduced activation of its targets. FUL, SEP3, and APETALA1 accumulation in the meristem is associated with and contributes to the transition to flowering. We propose that FT functions through partner-dependent transcriptional activation of these and as-yet-unknown genes and that this occurs at several sites. Organ fate may depend on both degree of activation and the developmental stage reached by the organ before activation occurs.


Hedgehog signaling controls Soma-Germen interactions during Drosophila ovarian morphogenesis.
The genetic analysis of Drosophila adult oogenesis has provided insights into the molecular mechanisms that control cell proliferation, differentiation, migration, and intercellular signaling. However, little is known about the larval and pupal cellular events leading to the formation of the highly organized adult ovary, which is composed of ovarioles each containing germline cells enveloped by specialized somatic cells. We describe here the presence of ovarioles devoid of any germ cells in adult females mutant for fused, which encodes a Hedgehog signal transducing serine/threonine kinase. We show that this phenotype corresponds to a requirement for fused function for the organization of germ cells with respect to ovarian somatic cells during ovariole formation specifically during pupal stages and provide some evidence by means of clonal analysis suggesting that fused function may be necessary in the germline. hedgehog is expressed specifically in somatic terminal filament cells in pupal ovaries, and females bearing hedgehog strong loss-of-function mutations also exhibit aberrant germ cell distribution and formation of agametic ovarioles. These results indicate a positive role for Fused in the transduction of somatic Hedgehog signaling instructing ovariole morphogenesis. We also provide evidence for the use of noncanonical Hedgehog signal transducer(s) within germline cells.


[Total cholesterol findings in Austria--an overview of epidemiologic studies].
Hyperlipoproteinaemia is the most important public health risk factor for ischaemic heart disease. This publication gives a review of six Austrian epidemiological studies covering more than 87,000 people in all. The results are not representative for Austria, but give a picture of the epidemiology in Austria. Mean values were calculated age-standardized (age-adjusted when ten-year age groups are registered) to the Austrian population of 1985, for the age group 20 to 79 years. This age range covers 99.77% of the adult male population aged 20 or more, and 95.70% of the women. Mean total cholesterol level for the six studies is 224.2 mg/dl in men and 227.3 mg/dl in women. These results are similar to those of a representative study in the province of Vorarlberg in western Austria (220.0 mg/dl, and 227.4 mg/dl respectively). Variation range is 20.4 mg/dl in men, and 22.5 mg/dl in women; the coefficient of variation is 3.9% in both, men and women.


Rapid diagnosis of mycobacterial infections and quantitation of Mycobacterium tuberculosis load by two real-time calibrated PCR assays.
Sensitive and specific techniques to detect and identify Mycobacterium tuberculosis directly in clinical specimens are important for the diagnosis and management of patients with tuberculosis (TB). We developed two real-time PCR assays, based on the IS6110 multicopy element and on the senX3-regX3 intergenic region, which provide a rapid method for the diagnosis of mycobacterial infections. The sensitivity and specificity of both assays were established by using purified DNA from 71 clinical isolates and 121 clinical samples collected from 83 patients, 20 of whom were affected by TB. Both assays are accurate, sensitive, and specific, showing a complementary pattern of Mycobacterium recognition: broader for the IS6110-based assay and restricted to the M. tuberculosis complex for the senX3-regX3-based assay. Moreover, the addition of a synthetic DNA calibrator prior to DNA extraction allowed us to measure the efficiency of DNA recovery and to control for the presence of PCR inhibitors. The mycobacterial burden of the clinical samples, as assessed by direct microscopy, correlates with the M. tuberculosis DNA load measured by the senX3-regX3-based assay. In addition, reduced levels of M. tuberculosis DNA load are present in those patients subjected to successful therapy, suggesting a potential use of this assay for monitoring treatment efficacy. Therefore, these assays represent a fully controlled high-throughput system for the evaluation of mycobacterial burden in clinical specimens.


Conjugation of synthetic cannabinoids JWH-018 and JWH-073, metabolites by human UDP-glucuronosyltransferases.
K2, a synthetic cannabinoid (SC), is an emerging drug of abuse touted as "legal marijuana" and marketed to young teens and first-time drug users. Symptoms associated with K2 use include extreme agitation, syncope, tachycardia, and visual and auditory hallucinations. One major challenge to clinicians is the lack of clinical, pharmacological, and metabolic information for the detection and characterization of K2 and its metabolites in human samples. Information on the metabolic pathway of SCs is very limited. However, previous reports have shown the metabolites of these compounds are excreted primarily as glucuronic acid conjugates. Based on this information, this study evaluates nine human recombinant uridine diphosphate-glucuronosyltransferase (UGT) isoforms and human liver and intestinal microsomes for their ability to glucuronidate hydroxylated metabolites of 1-naphthalenyl-1(1-pentyl-1H-indol-3-yl)-methanone (JWH-018) and (1-butyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-073), the two most common SCs found in K2 products. Conjugates were identified and characterized using liquid chromatography/tandem mass spectrometry, whereas kinetic parameters were quantified using high-performance liquid chromatography-UV-visible methods. UGT1A1, UGT1A3, UGT1A9, UGT1A10, and UGT2B7 were shown to be the major enzymes involved, showing relatively high affinity with K(m) ranging from 12 to 18 μM for some hydroxylated K2s. These UGTs also exhibited a high metabolic capacity for these compounds, which indicates that K2 metabolites may be rapidly glucuronidated and eliminated from the body. Studies of K2 metabolites will help future development and validation of a specific assay for K2 and its metabolites and will allow researchers to fully explore their pharmacological actions.


Encapsulated insular carcinoma of the thyroid arising in graves' disease: report of a case and review of the literature.
Insular carcinoma represents a rather rare form of thyroid cancer. Total encapsulation and history of hyperthyroidism are even extremely rarer events with only a few cases reported in the literature. This article reports an insular carcinoma of the thyroid in a 51-year-old woman, displaying these features and pulmonary metastasis with no cervical lymph node involvement.


Bilateral quadriceps tendon rupture: a rare finding in a healthy man after minimal trauma.
Quadriceps tendon rupture is an uncommon injury; the incidence of simultaneous bilateral quadriceps tendon rupture is extremely rare. Two distinct categories-individuals older than 50 years and between 27 and 54 years-have been described. Bilateral quadriceps tendon rupture is more common in patients older than 50 years and is thought to be the result of tendon weakening due to obesity and arteriosclerosis-induced fibrotic changes, or previous injury.In younger individuals, bilateral simultaneous quadriceps rupture is less frequent and has been associated with anabolic steroid use, but more frequently with underlying comorbid medical conditions such as chronic renal failure, hyperparathyroidism, endocrine disorder, gout, diabetes and obesity, which predispose the patients to tendon rupture. Our case report is unique because we report the simultaneous bilateral quadriceps tendon rupture following minor trauma in an otherwise healthy 43-year-old man with no predisposing comorbidity.


[Studies on susceptibility of isolated organisms from pediatric infections against various antimicrobial agents].
Twelve oral antimicrobial agents were tested for their antimicrobial activities against causative organisms isolated from pediatric infections. Activities of these antimicrobial agents against Streptococcus pyogenes were also examined in relation to T-antigen typing of the species. The results of the investigation are summarized as follows. 1. Against Staphylococcus aureus, rokitamycin (RKM), josamycin, ofloxacin, minocycline exhibited strong antimicrobial activities, and few strains of S. aureus showed resistance to these antimicrobial agents. More strains exhibited resistance to erythromycin (EM) than to other macrolide antibiotics (MLs) examined. Amoxicillin (AMPC)-resistance was often observed also. 2. Against S. pyogenes, beta-lactam antibiotics (beta-lactams) and RKM had MIC80 of 0.20 microgram/ml or below, and no resistant strains of this organism were observed against these antibiotics. Only 2 resistant strains (2.0%) of S. pyogenes to MLs were detected, but resistance to tetracyclines (TCs) was observed at a high frequency, with 71.4% or more strains among T-4, T-6, T-12 and T-28 antigen types exhibited resistance to TCs. Among the 21 strains of T-12 antigen type examined, only one strain (4.8%) was found resistant to MLs. These observations suggested that the reduction in the frequency of ML-resistant strains was not due to the reduction in the number of T-12 antigen type strains but due to losses of resistance factors against MLs of plasmids. 3. Antibacterial activities of beta-lactams and MLs against Streptococcus pneumoniae strains were good, similarly to activities against S. pyogenes. But many strains of S. pneumoniae were resistant to TCs. 4. New quinolone antimicrobial agents (quinolones) showed excellent activities against Branhamella catarrhalis strains with EM and RKM showing the next best activities. The number of resistant strains against quinolones, however, seemed to be on an increase. 5. Quinolones had strong antimicrobial activities against Haemophilus influenzae, few strains of which showed resistance to quinolones. AMPC had the next best activity, but approximately 10% of H. influenzae exhibited resistance to this antibiotic. 6. Against Campylobacter spp., quinolones and MLs showed the best activities with MIC80 values at or below 0.25 microgram/ml, and no resistant strains of the species against these antimicrobial agents were observed. Fosfomycin and TCs showed somewhat inferior activities to quinolones and MLs, with beta-lactams showing still lower activities. 7. Only few strains of Mycoplasma pneumoniae and Chlamydia trachomatis were examined, but MLs and TCs appeared to be effective against these organisms.(ABSTRACT TRUNCATED AT 400 WORDS)


Rapid, specific assay for plasma cortisol by competitive protein binding.
We describe a modified competitive protein-binding method for assay of plasma cortisol. Plasma samples are deproteinized by dilution with an ethanol/phosphate buffer, followed by heating at 100 degrees C for 2 min. Horse serum is used as the source of transcortin. Free radioactivity is separated from the protein-bound component by partition into liquid scintillation counting within 60 min. The assay has better specificity and precision than a competitive protein-binding assay in which ethanol extraction and Florisil adsorbent are used, and results correlate well with those of a specific radioimmunoassay method.


[The gastric anatomico-functional aspects (parietal cell mass, stimulated acid secretion and gastrinemia) in pernicious anemia].
We present here a study of parietal cell mass, stimulated acid secretion and basal gastrinemia both in the course of isolated chronic atrophic gastritis of the body-fundus and in chronic atrophic gastritis of the body-fundus associated with pernicious anemia. Analysis of our results evidences an overlapping cyto-secretory profile characterized by hypoparietalism with hypo-achlorhydria. The higher basal gastrinemia levels in pernicious anemia depend on the histological status of the antral mucosa--which was always normal in the patients with pernicious anemia--rather than any substantial morpho-functional differences of the body-fundus. We thus conclude that the term "atrophic gastritis" should be abolished, and that the term "chronic atrophic gastritis" be used to describe both conditions.


[Liver injuries].
The analyses of literature data on the results of the treatment of patients with mechanical injuries of the liver have been done. Analyses of 458 cases of open and closed liver traumas made it possible to determine 2 clinical forms of liver injuries: hemorrhagic and peritoneal. The separate subforms of traumatic liver disease in isolated multiple and combined injuries are determined. A diagnostic role of various methods was evaluated. Use of laparoscopy in 17 patients has exposed a superficial character of liver injuries and allowed not to perform surgery. Use of low-frequency ultrasound and polymeric adhesive sulfacrilat for the treatment of liver wounds in 63 patients has decreased the rate of postoperative complications to 18%, and the rate of mortality in mechanical liver injuries to 11.4% (in patients with mechanical liver injuries operated on with the use of ligature-free suture).


High-field magnetic resonance imaging of brain iron in Alzheimer disease.
Increased iron deposition in the brain may occur in several neurodegenerative diseases, including Alzheimer disease (AD). Iron deposits shorten T2 relaxation times on T2-weighted magnetic resonance (MR) images. Iron-dependent contrast increases with magnetic field strength. We hypothesized that T2 mapping using 3 T MR imaging (MRI) can disclose differences between normal controls and AD subjects. High-resolution brain imaging protocols were developed and applied to 24 AD patients and 20 age-matched controls using 3 T MRI. Eight anatomical regions of interest were manually segmented, and T2 histograms were computed. A visual analysis technique, the heat map, was modified and applied to the large image data sets generated by these protocols. A large number (163) of features from these histograms were examined, and 38 of these were significantly different (P < 0.05) between the groups. In the hippocampus, evidence was found for AD-related increases in iron deposition (shortened T2) and in the concentration of free tissue water (lengthened T2). Imaging of a section of postmortem brain before and after chemically extracting the iron established the presence of MRI-detectable iron in the hippocampus, cortex, and white matter in addition to brain regions traditionally viewed as containing high iron concentrations.


Catalase is a determinant of the colonization and transovarial transmission of Rickettsia parkeri in the Gulf Coast tick Amblyomma maculatum.
The Gulf Coast tick (Amblyomma maculatum) has evolved as a competent vector of the spotted-fever group rickettsia, Rickettsia parkeri. In this study, the functional role of catalase, an enzyme responsible for the degradation of toxic hydrogen peroxide, in the colonization of the tick vector by R. parkeri and transovarial transmission of this pathogen to the next tick generation, was investigated. Catalase gene (CAT) expression in midgut, salivary glands and ovarian tissues exhibited a 2-11-fold increase in transcription level upon R. parkeri infection. Depletion of CAT transcripts using an RNA-interference approach significantly reduced R. parkeri infection levels in midgut and salivary gland tissues by 53-63%. The role of CAT in transovarial transmission of R. parkeri was confirmed by simultaneously blocking the transcript and the enzyme by injecting double-stranded RNA for CAT and a catalase inhibitor (3-amino-1,2,4-triazole) into gravid females. Simultaneous inhibition of the CAT transcript and the enzyme significantly reduced the egg conversion ratio with a 44% reduction of R. parkeri transovarial transmission. These data suggest that catalase is required for rickettsial colonization of the tick vector and transovarial transmission to the next generation.


No differences in objective dynamic instability during acceleration of the knee with or without subjective instability post-total knee arthroplasty.
Instability after total knee arthroplasty is a critical problem. The purpose of this study was to clarify the stability of implanted knees during walking by comparing differences in dynamic instability during knee acceleration between individuals with or without previously experienced subjective instability, as measured by self-reported questionnaire. We examined 92 knees with medial pivot implants. Mean patient age and follow-up duration were 78.4 years and 32.8 months, respectively. An accelerometer was used to investigate the accelerations along three axes; that is, vertical (VT), mediolateral (ML), and anteroposterior (AP) directions in 3-dimensional (3D) space. The analysis in the stance phase and gait cycle was performed by: (1) root mean square (RMS) values of acceleration and (2) frequency domain analysis using fast Fourier transformation (FFT). A self-reported knee instability score was used for the subjective feeling of instability. A total of 76 knees did not feel unstable (group 0), but 16 knees felt unstable (group 1) in patients during activities of daily living. Regarding the RMS, there were no differences in each direction between the groups. For FFT, the cumulative amplitude in the frequency < 30 Hz also showed no significant differences in all directions between the groups during the stance phase (VT, p = 0.335; ML, p = 0.219; AP, p = 0.523) or gait cycle (VT, p = 0.077; ML, p = 0.082; AP, p = 0.499). Gait analysis based on the acceleration data showed that there were no between-group differences in objective dynamic instability during acceleration of the knee, with or without reports of previously experienced subjective instability, as assessed by the self-reported questionnaire.


Using Inertial Fusion Implosions to Measure the T+^{3}He Fusion Cross Section at Nucleosynthesis-Relevant Energies.
Light nuclei were created during big-bang nucleosynthesis (BBN). Standard BBN theory, using rates inferred from accelerator-beam data, cannot explain high levels of ^{6}Li in low-metallicity stars. Using high-energy-density plasmas we measure the T(^{3}He,γ)^{6}Li reaction rate, a candidate for anomalously high ^{6}Li production; we find that the rate is too low to explain the observations, and different than values used in common BBN models. This is the first data directly relevant to BBN, and also the first use of laboratory plasmas, at comparable conditions to astrophysical systems, to address a problem in nuclear astrophysics.


[Historical vignettes. History of vasculitis].
This article gives a summary of the history of vasculitis through early and past descriptions. Known, reported and depicted since time immemorial those diseases are quite polymorphous, depending on type and localization of the affected vessels. Clear classification criteria were finally laid down at the end of the XXth century giving a new impulse as well to the detection and the identification of specific biological markers as to the way to treat effectively those severe diseases.


Differences in Characteristics and Clinical Outcomes Among Hispanic/Latino Men and Women Receiving HIV Medical Care - United States, 2013-2014.
The prevalence of diagnosed human immunodeficiency virus (HIV) infection among Hispanics/Latinos in the United States is approximately twice that of non-Hispanic whites (1). Barriers to, and experiences with, medical care have been found to vary by sex (2). Describing characteristics of Hispanics/Latinos in care by sex can help identify disparities and inform delivery of tailored services to this underserved population. Data from the 2013 and 2014 cycles of the Medical Monitoring Project (MMP) were analyzed to describe demographic, behavioral, and clinical characteristics among Hispanics/Latinos by sex. MMP is an annual cross-sectional, nationally representative surveillance system that, during 2013-2014, collected information about behaviors, medical care, and clinical outcomes among adults receiving outpatient HIV care. Hispanic/Latina women were significantly more likely than were men to live in poverty (78% versus 54%), report not speaking English well (38% versus 21%), and receive interpreter (27% versus 16%), transportation (35% versus 21%), and meal (44% versus 26%) services. There were no significant differences between Hispanic/Latino women and men in prescription of antiretroviral therapy (ART) (95% versus 96%) or sustained viral suppression (68% versus 73%). Although women faced greater socioeconomic and language-related challenges, the clinical outcomes among Hispanic/Latina women were similar to those among men, perhaps reflecting their higher use of ancillary services. Levels of viral suppression for Hispanics/Latinos are lower than those found among non-Hispanic whites (3) and lower than the national prevention goal of at least 80% of persons with diagnosed HIV infection. Providers should be cognizant of the challenges faced by Hispanics/Latinos with HIV infection in care and provide referrals to needed ancillary services.


Effect of bismuth subcitrate on amphibian gastroduodenal bicarbonate secretion.
The ulcer healing and cytoprotective properties of colloidal bismuth (De-Nol) are well established although its mode of action is unclear. We have examined the action of bismuth subcitrate, the active ingredient of De-Nol, on gastroduodenal bicarbonate secretion by isolated amphibian mucosa. Addition of bismuth subcitrate (10(-6) to 10(-4) M) to the luminal solution produced a dose dependent increase in bicarbonate secretion from both gastric and duodenal mucosae without a change in transmucosal potential difference. The magnitude of this stimulation was greater for gastric than duodenal mucosae at all dose ranges. A second bismuth salt, bismuth oxynitrate, produced similar increases in bicarbonate secretion from gastric mucosae. Pretreatment of gastric mucosa with the cyclooxygenase inhibitor, indomethacin (10(-5) and 10(-4) M), did not abolish the secretory response to bismuth subcitrate. Similar treatment with the chloride transport inhibitor, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) (10(-3) M) prevented the secretory response to bismuth subcitrate.


Doctor-pharmacist communication in hospitals: strategies, perceptions, limitations and opportunities.
Background Effective communication between health professionals contributes to safe and efficient patient care, whereas communication breakdown can lead to adverse patient outcomes and increased healthcare expenditure. Information on how pharmacists and doctors communicate with each other in hospitals is limited. Objective To explore usage and perceptions of communication methods by doctors and pharmacists in hospital settings. Setting Four public hospitals in Australia. Method A mixed method study utilising a pilot questionnaire, semi-structured interviews, and electronic survey was designed. Frequentist statistics and logistic regression were used to analyse survey data. Thematic analysis was conducted to evaluate semi-structured interview data and free-text survey comments. Frequency of use of communication methods, perceptions of the convenience, time taken to use, accuracy and effectiveness of each method. Results More than 95% of doctors and pharmacists combined used face-to-face and phone calls to communicate with each other, 70% used a medication management plan, and 62% used progress notes. A preference for oral communication was confirmed with the expressed need for building professional rapport and receiving responses. Perceptions regarding effectiveness of oral communication methods were related to perceptions of their convenience and accuracy. Professional groups described differences in perceived ownership of various modes of communication. Conclusions Preferences for oral communication create potential issues with recall and comprehension. Integrating oral communication features into written communication methods, e.g. creating responses, conversations, building rapport, may change doctors' and pharmacists' perceptions of effectiveness. Communication receipt and response functionality in electronic medication and record management systems may improve communication.


Simple and novel method for measuring conduction velocity of A delta fibers in humans.
We report a simple new method for measuring the conduction velocity (CV) of A delta fibers in normal subjects. A large positive component of somatosensory evoked potential (SEP) whose peak latency was approximately 250 ms was clearly recorded only when strong electrical stimulation causing a definite painful feeling was applied to the skin. The CV of the peripheral nerve was calculated by measuring the latency difference of this component between the distal-stimulated SEP and proximal-stimulated SEP and the distance between two stimulus sites. The CV was approximately 11.4 m/s, (range 8.8-15.9 m/s), in the range of A delta fibers. The sleep effect on pain-related SEP was also observed in 3 subjects. The amplitude of pain-related SEP decreased with the progress of sleep stage. This simple and novel method is available in most clinics and should be very useful in investigating the physiologic functions of peripheral nerves in patients as well as normal subjects.


Giant cell arteritis in Jerusalem: a 12-year epidemiological study.
The prevoting conception of the incidence of giant cell arteritis (GCA) among population underscores the very low incidence of this disease among Jews. We studied the epidemiology, ethnic background, and seasonality of GCA among the Jewish population of Jerusalem. Eighty-four patients with biopsy-proven GCA were identified in a period of 12 yr, from 1980-1991. The age, sex and period-adjusted incidence of GCA was 10.2 per 100,000 population aged > or = 50 yr, approximately 20-fold higher than that reported for the Jewish population in Israel for the years 1960-1978. The female:male ratio was 1.6. A declining trend in the annual incidence was observed for men but not for women. The incidence rate was similar among non-western and western Jews. The onset of GCA was more common during the early summer months (May-June).


Detrimental Effects of Induced Soil Compaction on Morphological Adaptation and Physiological Plasticity of Selected Multipurpose Tree Species.
Soil compaction has become a global problem affecting soil worldwide. With an increased population, more demands for food and wood have resulted in intensive cultivation and increased mechanization of our farmlands and irrigated plantations. The use of heavy machinery results in soil compaction, which affects the entire soil ecosystem. This study was conducted to analyze the impact of compacted soil on germination and initial growth stages of four major agro-forest trees of central Punjab, Pakistan. Morpho-physiological traits of all selected species (Eucalyptus camaldulensis, Albizia lebbeck, Vachellia nilotica, and Zyziphus mauritiana) were measured against soil compaction. Results indicated that the root and shoot length, biomass, root-shoot ratio, diameter at root collar, no. of leaves and branches, leaf area, germination, and survival %, and physiological traits (i.e., photosynthetic rate, transpiration rate, stomatal conductance, internal CO2 concentration, and photosynthetic water use efficiency) were significantly affected by the induced soil compaction. Eucalyptus camaldulensis Dehnh. performed better and exhibited 96% germination percentage under (1.40 mg m-3) compaction level and gradually decreased by 11% with the increase of compaction level (1.80 mg m-3). It shows that the shorter roots developed due to soil compaction decreased water use efficiency, photosynthesis, and whole-plant physiological performance. The findings concluded that judicious use of machinery is highly desired for sustainable and good-quality wood production from farm trees.


Mass spectrometry-based immunoassays for the next phase of clinical applications.
Recent applications of affinity mass spectrometry into clinical laboratories brought a renewed interest in immunoaffinity mass spectrometry as a more specific affinity method capable of selectively targeting and studying protein biomarkers. In mass spectrometry-based immunoassays, proteins are affinity retrieved from biological samples via surface-immobilized antibodies, and are then detected via mass spectrometric analysis. The assays benefit from dual specificity, which is brought about by the affinity of the antibody and the protein mass readout. The mass spectrometry aspect of the assays enables single-step detection of protein isoforms and their individual quantification. This review offers a comprehensive review of mass spectrometry-based immunoassays, from historical perspectives in the development of the immunoaffinity mass spectrometry, to current applications of the assays in clinical and population proteomic endeavors. Described in more detail are two types of mass spectrometry-based immunoassays, one of which incorporates surface plasmon resonance detection for protein quantification. All mass spectrometry-based immunoassays offer high-throughput targeted protein investigation, with clear implications in clinical research, encompassing biomarker discovery and validation, and in diagnostic settings as the next-generation immunoassays.


Assessing the environmental benefit of palladium-based single-atom heterogeneous catalysts for Sonogashira coupling.
The Pd-Cu catalysed Sonogashira coupling of terminal alkynes and aryl halides is a cornerstone synthetic strategy for C-C bond formation. Homogeneous organometallic systems conventionally applied are typically not reusable and require efficient downstream Pd removal steps for product purification, making it challenging to fully recover the precious metal. A holistic cradle-to-gate life cycle assessment (LCA) unveils that process footprint can be improved up to two orders of magnitude from repeated catalyst reuse. New classes of heterogeneous catalysts based on isolated metal atoms (single-atom catalysts, SACs) demonstrate promising potential to synergise the benefits of solid and molecular catalysts for efficient Pd utilisation. Here we show that using Pd atoms anchored on nitrogen-doped carbon permits full recovery of the metal and reuse of the catalyst over multiple cycles. A hybrid process using the Pd-SAC with a homogeneous CuI cocatalyst is more effective than a fully heterogeneous analogue based on a bimetallic Pd-Cu SAC, which deactivates severely due to copper leaching. In some scenarios, the LCA-based metrics demonstrate the footprint of the hybrid homogeneous-heterogeneous catalytic process is leaner than the purely homogeneous counterpart already upon single reuse. Combining LCA with experimental evaluation will be a useful guide to the implementation of solid, reusable catalysts for sustainable organic transformations.


Intensities of Incident and Transmitted Ultraviolet-A Rays through Gafchromic Films.
Gafchromic films have been applied to X-ray dosimetry in diagnostic radiology. To correct nonuniformity errors in Gafchromic films, X-rays in the double-exposure technique can be replaced with ultraviolet (UV)-A rays. Intensities of the incident and transmitted UV-A rays were measured. However, it is unclear whether the chemical color change of Gafchromic films affects the UV-A transmission intensity. Gafchromic EBT3 films were suitable to be used in this study because non-UV protection layers are present on both sides of the film. The film is placed between UV-A ray light-emitting diodes and a probe of a UV meter. Gafchromic EBT3 films were irradiated by UV-A rays for up to 60 min. Data for analysis were obtained in the subsequent 60 min. Images from before and after UV-A irradiation were subtracted. When using 375 nm UV-A, the mean ± standard deviation (SD) of the pixel values in the subtracted image was remarkably high (11,194.15 ± 586.63). However, the UV-A transmissivity remained constant throughout the 60 min irradiation period. The mean ± SD UV-A transmission intensity was 184.48 ± 0.50 μm/cm2. Our findings demonstrate that color density changes in Gafchromic EBT3 films do not affect their UV-A transmission. Therefore, Gafchromic films were irradiated by UV-A rays as a preexposure.


Ecological data of Travassosnema travassosi travassosi (Dracunculoidea: Guyanemidae) from the humour of the eyes of Acestrorhynchus lacustris from Tibagi River, Paraná, Brazil.
Data obtained between 1990 and 1995 provide, for the first time, ecological information of the parasitic nematode Travassosnema travassosi travassosi Costa, Moreira & Oliveira, 1991 from Acestrorhynchus lacustris (Characiformes: Acestrorhynchidae) collected in the Tibagi River, Sertanópolis, Paraná, Brazil. These nematode occurred with low prevalences (7.7% to 28.6%) and intensities (1 to 3) during almost the whole year. The observation of mature females throughout the year indicate that liberation of larvae can occur during all the year around. This is the first report on the occurrence of T. travassosi travassosi inside the eyes. These nematodes were mostly located in humour of the eyes (87% of cases), being less frequently detected in tissues behind the eyes (13% of cases).


Molecular mimicry in translational regulation: the case of ribosomal protein S15.
Ribosomal protein S15 is highly conserved among prokaryotes. It plays a pivotal role in the assembly of the central domain of the small ribosomal subunit and regulates its own expression by a feedback mechanism at the translational level. The protein recognizes two RNA targets (rRNA and mRNA) that share only partial similarity. Its interaction with 16S rRNA has been fully characterized, while mRNA interactions and regulatory mechanisms have been extensively studied in E. coli and in T. thermophilus. Recently, we have characterized which aminoacids are involved in E. coli mRNA recognition, using an in vivo assay allowing to identify S15 mutations affecting the S15-mRNA interactions without altering 30S subunit assembly. Here, we address the following questions: Are common determinants used by S15 to recognize its rRNA and mRNA targets? What is the extent of molecular mimicry? Is the regulatory mechanism conserved? Our results indicate that specific recognition of mRNA and rRNA relies on both mimicry and site differentiation. They also highlight the high plasticity of RNA to adapt to evolutionary constraints.


Traditional Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Xanthium strumarium L.: A Review.
Xanthium strumarium L. (Asteraceae) is a common and well-known traditional Chinese herbal medicine usually named Cang-Er-Zi, and has been used for thousands of years in China. The purpose of this paper is to summarize the progress of modern research, and provide a systematic review on the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics, and toxicology of the X. strumarium. Moreover, an in-depth discussion of some valuable issues and possible development for future research on this plant is also given. X. strumarium, as a traditional herbal medicine, has been extensively applied to treat many diseases, such as rhinitis, nasal sinusitis, headache, gastric ulcer, urticaria, rheumatism bacterial, fungal infections and arthritis. Up to now, more than 170 chemical constituents have been isolated and identified from X. strumarium, including sesquiterpenoids, phenylpropenoids, lignanoids, coumarins, steroids, glycosides, flavonoids, thiazides, anthraquinones, naphthoquinones and other compounds. Modern research shows that the extracts and compounds from X. strumarium possess wide-ranging pharmacological effects, including anti- allergic rhinitis (AR) effects, anti-tumor effects, anti-inflammatory and analgesic effects, insecticide and antiparasitic effects, antioxidant effects, antibacterial and antifungal effects, antidiabetic effects, antilipidemic effects and antiviral effects. However, further research should focus on investigating bioactive compounds and demonstrate the mechanism of its detoxification, and more reasonable quality control standards for X. strumarium should also be established.


Biorecovery of gold.
Recovery of ionic and metallic gold (Au) from a wide variety of solutions by selected species of bacteria, yeasts, fungi, algae, and higher plants is documented. Gold accumulations were up to 7.0 g/kg dry weight (DW) in various species of bacteria, 25.0 g/kg DW in freshwater algae, 84.0 g/kg DW in peat, and 100.0 g/kg DW in dried fungus mixed with keratinous material. Mechanisms of accumulation include oxidation, dissolution, reduction, leaching, and sorption. Uptake patterns are significantly modified by the physicochemical milieu. Crab exoskeletons accumulate up to 4.9 g Au/kg DW; however, gold accumulations in various tissues of living teleosts, decapod crustaceans, and bivalve molluscs are negligible.


ERK and p38 MAP kinase pathways are mediators of intestinal epithelial wound-induced signal transduction.
Repair of gastrointestinal epithelial injury involves cell migration, proliferation, and specific gene expression. The pathways responsible for epithelial wound signal transduction are poorly understood. Mechanical wounding of IEC-6 cell monolayers resulted in rapid activation of the extracellular signal-regulated kinase (ERK) and p38 MAP kinase pathways, while c-Jun amino-terminal protein kinases were not significantly activated. Two minutes after wounding cells at the wound edge strongly expressed cytoplasmic phospho-ERK. By five minutes, immunostaining was concentrated within the nucleus. Consistent with activated MAP kinase signaling cascades (which phosphorylate transcription factors implicated in immediate-early gene induction), monolayer wounding resulted in greater than 30- and 8-fold increases in c-Fos and early growth response-1 mRNA by Northern blot analysis, peaking at 20 minutes. Only slight increases in c-Jun mRNA were detected. Thus, intestinal epithelial wound signal transduction is, at least in part, mediated by activation of ERK and p38 MAP kinase signaling cascades. ERK and p38 pathways may regulate pathophysiologically relevant genes in wound repair by the induction of transcription factors.


[Partial endoprosthetic reconstruction of the pelvis in malignant tumors].
Twenty-five patients underwent an internal hemipelvectomy with endoprosthetic reconstruction of the pelvis for primary bone tumor (n = 17) or bone metastasis in the pelvis (n = 8). According to the Enneking tumor classification system, there were 9 stage II B tumors and 16 stage III. Conventional metal or polyacetal prostheses were used in 5 cases, and in 20 anatomically adaptable modular prostheses with intramedullary anchorage were implanted. In the last 11 cases a 3D CT-controlled manufactured model of the pelvis was used. The functional results according to Enneking were good in 5 cases, fair in 11, and poor in 7. The last endoprosthetic system showed better results, because it is easier to implant and the possibility failure is reduced. The learning curve of the surgeon is important, too.


The role of miR-145 in microvasculature.
Increasing evidence suggests that microRNAs(miRs) play a crucial role in the cardiovascular system, and recent studies have revealed a significant role of miRs in vascular biology and disease, miR-145 is one of the most-studied miRs, and especially in the vascular smooth muscle cell (VSMCs) proliferation, differentiation, and phenotypic switching. In cardiovascular system, miR-145 is not only important for heart and vascular development but also plays an essential role in cardiac pathological factors, such as hypertrophy, and ischemia. However, its potential role in microvasculature has not been systematically evaluated yet. We are just beginning to understand the regulation of miR in vascular biology. In particular, the miR biogenesis and regulatory pathways in the vascular system have not yet been well characterized, This review focuses on the basic biology and mechanism of action of miR-145 specifically pertaining to microvascular development, pericyte and disease, In addition it addresses the potential for miR-145 to be used therapeutically in the treatment of microvascular disease.


Separation of plastics by froth flotation. The role of size, shape and density of the particles.
Over the last few years, new methods for plastic separation in mining have been developed. Froth flotation is one of these techniques, which is based on hydrophobicity differences between particles. Unlike minerals, most of the plastics are naturally hydrophobic, thus requiring the addition of chemicals that promote the selective wettability of one of its components, for a flotation separation. The floatability of six granulated post-consumer plastic - Polystyrene (PS), Polymethyl methacrylate (PMMA), Polyethylene Terephthalate (PET-S, PET-D) and Polyvinyl Chloride (PVC-M, PVC-D) - in the presence of tannic acid (wetting agent), and the performance of the flotation separation of five bi-component plastic mixtures - PS/PMMA, PS/PET-S, PS/PET-D, PS/PVC-M and PS/PVC-D - were evaluated. Moreover, the effect of the contact angle, density, size and shape of the particles was also analysed. Results showed that all plastics were naturally hydrophobic, with PS exhibiting the highest floatability. The contact angle and the flotation recovery of six plastics decreased with increasing tannic acid concentration, occurring depression of plastics at very low concentrations. Floatability differed also with the size and shape of plastic particles. For regular-shaped plastics (PS, PMMA and PVC-D) floatability decreased with the increase of particle size, while for lamellar-shaped particles (PET-D) floatability was slightly greater for coarser particles. Thus, plastic particles with small size, lamellar shape and low density present a greater floatability. The quality of separation varied with the mixture type, depending not only on the plastics hydrophobicity, but also on the size, density and shape of the particles, i.e. the particle weight. Flotation separation of plastics can be enhanced by differences in hydrophobicity. In addition, flotation separation improves if the most hydrophobic plastic, that floats, has a lamellar shape and lower density and if the most hydrophilic plastic, that sinks, has a regular shape and higher density. The results obtained show that froth flotation is a potential method for plastics separation, in particular for plastics with particle size greater than 2.0mm.


Pharmacognostic Profile and Screening of Anti-Proliferative Potential of Methanolic Extract of Tripterygium wilfordii Plant on WRL-68 Cell Line and Function of Polycystin-1.
Tripterygium wilfordii is a medicinal plant that plays a crucial role in health care programs, especially in developing countries, and had anti-tumor, anti-inflammatory, anti-fertility, anti-bacterial, and other therapeutic effects. This study was designed to determine the anti-proliferative effects of methanolic extract of T. wilfordii on the WRL-68 cell line and the function of polycystin-1 (PC-1). The half-maximal inhibitory concentration (IC50) values were recorded in WRL-68 and AsPC-1 cell lines as 193 µg/ml and 149.2 µg/ml, respectively, at 2-2.55 and 2-2.2 µg/ml methanolic plant concentrations. The maximum cytotoxic activities of the extract on the growth inhibition of WRL-68 and AsPC-1 were generally observed at 97.64% and 95.94% at extract concentrations of 50 µg/ml and 25 µg/ml, respectively. The pharmacognostic profile of T. wilfordii extract was found to be alkaloids, tannins, terpenoides, flavonoids, glycosides, and phenols. The extracts of T. wilfordii were tested through gas chromatography-mass spectrometry showing four peaks representing mostly of 3-Oxobutanol; ethyl acetate; acetic acid ethyl ester; chlorbromuron; 1-(methylthio)-, (E)-; n-Hexadecanoic acid; tetradecanoic acid; and 9-Octadecenoic acid. Therefore, the results of this study revealed that the methanolic extract of T. wilfordii was more potential in inducing anti-proliferative activity of WRL-68 and AsPC-1 human cell lines than the control. In addition, the current study was the first study that reported the anti-proliferative potential of T. wilfordii in the treatment of human embryonic liver WRL-68 cancer cells.


Stable Isotope Ratios of Mercury in Commercially Available Thermometers and Fluorescent Tubes.
Five stable isotope ratios of mercury (199Hg/198Hg, 200Hg/198Hg, 201Hg/198Hg, 202Hg/198Hg, and 204Hg/198Hg) in commercially available thermometers and fluorescent tubes were analyzed to characterize their potential anthropogenic emission source to landfills, manufacturing factories, and our daily lives. The results for the liquid metal mercury yielded from the thermometers showed similar mass-independent fractionation values to those in the literature. The analysis of fluorescent tubes resulted in that more than 96% of mercury in the fluorescent tubes was found in the adsorbed state, and up to 3.5% of mercury was in the gas-phase. Unique mass-independent isotope fractionation values were found in the gaseous and adsorbed mercury in the fluorescent tubes. This fractionation is distinct from other emission sources and systematic; therefore, it can potentially be used to fingerprint mercury in fluorescent tubes in environmental samples.


Degenerative spondylolysis: a concise report of scintigraphic observations.
Spondylolysis is traditionally thought to be a diagnosis of adolescence and childhood, and is ascribed to mechanical stress through the immature pars interarticularis. Over the last 4 yr we have noted a presentation of spondylolysis in association with hypertrophic zygapophyseal joint disease in the lumbar spine in an older age group. Records of 94 patients presenting with low back pain were examined. A pattern of intense zygapophyseal joint uptake in association with extended uptake in the pars interarticularis was ascribed as degenerative spondylolysis. The ages of the 94 cases ranged from 33 to 80 yr (mean 64 yr). There were 53 males and 41 females. In the group with degenerative spondylolysis the mean age was 72 yr, with four females and two males. None of these six patients gave a history of childhood spinal disease or back pain and all were relatively inactive in terms of current participation in sport. All cases of spondylolysis were confirmed by computed tomography scanning. The finding of hypertrophic zygapophyseal joint disease in association with spondylolysis is easily recognized by scintigraphic tomographic imaging.


The utility of a medical admissions pharmacist in a hospital in Australia.
Background Medication-related hospital admissions in Australia have previously been estimated to account for approximately 3% of all hospital admissions, with hospital entry points being a point of vulnerability. The timely medication review and reconciliation by a pharmacist at the early stage of an admission for patients admitted to the Acute Medical Unit (AMU) would be beneficial. Setting The Emergency Department (ED) and AMU in a 300 bed tertiary teaching hospital, in South Australia. Objective To investigate the impact of a Medical Admissions (MA) pharmacist on the proportion of AMU patients who receive a complete and accurate medication history by a pharmacist prior to admission and within 4 h of presentation. Method This prospective observational study with a non-concurrent parallel study design examined a standard clinical pharmacist service within the AMU and ED to a Medical Admissions (MA) Pharmacist, in addition to the standard AMU and ED pharmacist service. Continuous variables were analysed using a two sample t test, whilst categorical data were analysed using Fisher's exact test. Risk ratios were also calculated for categorical data, with p < 0.05 taken as statistically significant. Main outcome measures Rates of completion of a complete medication history prior to admission and proportion of patients seen within 4 h of presentation by a pharmacist. Results The intervention resulted in more patients receiving a complete medication history prior to admission (2.7% in the control group vs 18.5%, p < 0.01) and being seen by the pharmacist within 4 h of presentation (1.6% in the control group vs 7.5%, p < 0.01). Conclusion Implementation of an extended hours clinical pharmacy service in the form of a medical admissions pharmacist based in the ED significantly increased the number of complete medication histories and clinical reviews completed for patients being admitted to an AMU. These were also completed earlier in the patients' admission. There was also a small trend toward increasing the proportion of patients discharged by 11 am in the intervention group.


The Combined Use of Tea Polyphenols and Lactobacillus Plantarum ST8SH Bacteriocin in a Rabbit Model of Infection Following Femoral Fracture with Internal Fixation.
BACKGROUND Worldwide, the increasing use of antibiotics has resulted in antimicrobial resistance, leading to studies to find alternative antimicrobial treatments. Tea polyphenols have antibacterial properties. Bacteriocins produced by probiotic lactobacilli can inhibit Gram-positive bacteria. This study used a rabbit model of infection, following femoral fracture with internal fixation, to evaluate the efficacy of the combined use of tea polyphenols and Lactobacillus plantarum ST8SH bacteriocin. MATERIAL AND METHODS Twenty-four New Zealand White rabbits underwent femoral fracture, internal fixation, and insertion of a mini-titanium implant, and were inoculated intravenously with suspensions of Staphylococcal bacteria. Four treatment groups included group A, injected with tea polyphenols and bacteriocins (N=6); group B, injected with cefradine and bacteriocins (N=6); group C, injected with tea polyphenols and cefradine (N=6); and group D (controls), injected with saline (N=6). Blood samples were collected at 1, 6, 12, 24, and 48 hours after the injection of bacteriocins. Biofilms that formed on the mini-titanium implant were studied by fluorescence microscopy. Serum levels of level of interleukin (IL)-8, IL-6, and tumor necrosis factor-α (TNF-α) were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS The combination of tea polyphenols and bacteriocins (group A) had a significant inhibitory effect on Staphylococcus aureus (P<0.05) and significant differences in serum levels of IL-8, TNF-α, and IL-6 levels in serum (P<0.05) when compared with groups, B, C, and D. CONCLUSIONS In a rabbit model of femoral fracture with internal fixation, the combined use of tea polyphenols and Lactobacillus plantarum ST8SH bacteriocin effectively controlled Staphylococcus aureus infection.


First-principles evaluation of dopant impact on structural deformability and processability of Li7La3Zr2O12.
Li7La3Zr2O12 (LLZO) and related ceramic solid electrolytes feature excellent stability and reasonable ionic conductivity, but processing remains challenging. High-temperature co-sintering is required for successful integration with the electrode, which is energetically costly and can lead to unacceptable cathode degradation. The introduction of dopants can promote lower-temperature processing by improving deformability and disrupting lattice integrity; however, an unbiased, systematic study correlating these properties to the dopant chemistry and composition is lacking. Here, we rely on a set of static and dynamic metrics derived from first-principles simulations to estimate the impact of doping on LLZO processability by quantifying LLZO structural deformability. We considered three distinct dopants (Al, Ba, and Ta) as representatives of substitutional incorporation on Li, La, and Zr sites. Our descriptors indicate that doping in general positively impacts lattice deformability, although significant sensitivities to dopant identity and concentration are observed. Amongst the tested dopants, Al doping (on the Li site) appears to have the greatest impact, as signaled across nearly the entire set of computed features. We suggest that these proxy descriptors, once properly calibrated against well-controlled experiments, could enable the use of first-principles simulations to computationally screen new ceramic electrolyte compositions with improved processability.


Primary stability of cementless threaded acetabular cups at first implantation and in the case of revision regarding micromotions as indicators.
The primary stability of cementless total hip endoprosthesis is of vital importance for proximate, long-term osteointegration. The extent of micromotions between implant and acetabulum is an indicator of primary stability. Based on this hypothesis, different cementless hip joint endoprosthesis were studied with regard to their micromotions. The primary stability of nine different cementless threaded acetabular cups was studied in an experimental setup with blocks of rigid foam. The micromotions between implant and implant bearing were therefore evaluated under cyclic, sinusoidal exposure. The blocks of polymer foam were prepared according to the Paprosky defect classifications. The micromotions increased with the increasing degree of the defect with all acetabuli tested. Occasionally coefficients of over 200 μm were measured. From a defect degree of 3b according to Paprosky, the implants could no longer be appropriately placed. The exterior form of the spherical implants tended to exhibit better coefficients than the conical/parabolic implants.


The loci of insect phenotypic evolution.
Insects are important elements of terrestrial ecosystems because they pollinate plants, destroy crops, transmit diseases to livestock and humans, and are important components of food chains. Here, I used Gephebase, a manually curated database of genetic variants associated with natural and domesticated trait variation, to explore current knowledge about the genes and the mutations known to contribute to natural phenotypic variation in insects. Analysis of over 600 mutations reveals that data are concentrated toward certain species and traits and that experimental approaches have changed over time. The distribution of coding and cis-regulatory changes varies with traits, experimental approaches, and identified gene loci. Recent studies highlight the important role of standing variation, repeated mutations in hotspot genes, recombination, inversions, and introgression.


Sphingosine kinase 1 as a potential therapeutic target in epithelial ovarian cancer.
Sphingosine kinase 1 (SK1) is over-expressed in multiple types of human cancer. SK1 has growth-promoting effects and has been proposed as a potential therapeutic target. We investigated the therapeutic effects of SK1 inhibition in epithelial ovarian carcinoma (EOC). SK1 siRNA or inhibitors were tested in EOC cell lines, including A2780, SKOV3ip1, A2780-CP20, SKOV3-TR, ES2 and RMG2. Cells were treated with SK inhibitor or FTY720, and cell proliferation, apoptosis, angiogenesis and invasion were examined by MTT, FACS, ELISA and wound-healing assays, respectively. In vivo experiments were performed to test the effects of FTY720 on tumor growth in orthotopic mouse xenografts of EOC cell lines A2780 or SKOV3ip1 and a patient-derived xenograft (PDX) model of clear cell ovarian carcinoma (CCC). Blocking SK1 with siRNA or inhibitors significantly reduced proliferation, angiogenesis and invasion, and increased apoptosis in chemosensitive (A2780 and SKOV3ip1) and chemoresistant (A2780-CP20, SKOV3-TR, ES2 and RMG2) EOC cells. SK1 inhibitors also decreased the intracellular enzymatic activity of SK1. Furthermore, FTY720 treatment significantly decreased the in vivo tumor weight in xenograft models of established cell lines (A2780 and SKOV3ip1) and a PDX model for CCC compared to control (p < 0.05). These results support therapeutic targeting of SK1 as a potential new strategy for EOC.


Multigene Phylogeny and Morphology Reveal Three Novel Species and a Novel Record of Agaricus From Northern Thailand.
Agaricus is a saprophytic mushroom genus widely distributed throughout the world. In this study, a survey of the Agaricus species carried out around Chiang Mai University in northern Thailand from 2018 to 2019 yielded 12 collections. Morphological characteristics and phylogenic analyses based on the internal transcribed spacers (ITS) and a fragment of the large subunit (LSU) of the nuclear ribosomal DNA (rDNA), and a fragment of the translation elongation factor 1-alpha (tef1) genes were investigated. The results revealed that these collections belong to six species including Agaricus erectosquamosus, Agaricus pallidobrunneus, Agaricus subrufescens, and three new species. Agaricus thailandensis sp. nov. was found to belong to Agaricus sect. Minores, which is placed in Agaricus subg. Minores. Aagricus pseudoerectosquamosus sp. nov. was placed in Agaricus sect. Brunneopicti within Agaricus subg. Pseudochitonia. Furthermore, Agaricus lannaensis remains an incertae sedis in Agaricus subg. Pseudochitonia. Additionally, this study was proposed that A. pallidobrunneus was discovered in Thailand for the first time. Full descriptions, color photographs, illustrations, and phylogenetic trees are provided.


YtxR, a conserved LysR-like regulator that induces expression of genes encoding a putative ADP-ribosyltransferase toxin homologue in Yersinia enterocolitica.
Yersinia enterocolitica causes human gastroenteritis, and many isolates have been classified as either "American" or "non-American" strains based on their geographic prevalence and virulence properties. In this study we describe identification of a transcriptional regulator that controls expression of the Y. enterocolitica ytxAB genes. The ytxAB genes have the potential to encode an ADP-ribosylating toxin with similarity to pertussis toxin. However, a ytxAB null mutation did not affect virulence in mice. Nevertheless, the ytxAB genes are conserved in many Y. enterocolitica strains. Interestingly, American and non-American strains have different ytxAB alleles encoding proteins that are only 50 to 60% identical. To obtain further insight into the ytxAB locus, we investigated whether it is regulated as part of a known or novel regulon. Transposon mutagenesis identified a LysR-like regulator, which we designated YtxR. Expression of ytxR from a nonnative promoter increased Phi(ytxA-lacZ) operon fusion expression up to 35-fold. YtxR also activated expression of its own promoter. DNase I footprinting showed that a His(6)-YtxR fusion protein directly interacted with the ytxA and ytxR control regions at similar distances upstream of their probable transcription initiation sites, identified by primer extension. Deletion analysis demonstrated that removal of the regions protected by His(6)-YtxR in vitro eliminated YtxR-dependent induction in vivo. The ytxAB locus is not present in most Yersinia species. In contrast, ytxR is conserved in multiple Yersinia species, as well as in the closely related organisms Photorhabdus luminescens and Photorhabdus asymbiotica. These observations suggest that YtxR may play a conserved role involving regulation of other genes besides ytxAB.


Tumor neocapillary density in hepatocellular carcinoma cells implanted nude mice model.
Tumor angiogenesis is an important process for several kinds of tumor, especially, during its angiogenic switch. The present study was aimed to investigate the dynamical process of tumor neocapillarization in Hepatocellular carcinoma cells implanted nude mice model. Male BALB/c nude mice (20-25 g) were used. After the implantation of a dorsal skin-fold chamber, the Hepatocellular carcinoma cells (HepG2) (30 microl of 2 x 10(6) cells) were inoculated into the upper layer of the skin within the chamber (HepG2-group), while the shammed control group (Sham-group) was received a normal saline. Intravital fluorescence videomicroscopy was performed to monitor the tumor neocapillary on days 7 and 14 post-inoculation by intravenous injection of 0.1 ml rhodamine B isothiocyanate-labeled dextran (0.5%). Based on the recorded videoimages, the tumor microvascular networks were measured using a digital image analysis. The neovascular density and configuration were represented in terms of microvascular density index (MVDI) and neovascular bifurcation ratio (BR). The MVDI levels of HepG2-group were significantly increased on day 7 and 14 compared to the age-matched Sham-group. The increase in MVDI agreed with the increase in the BR. In conclusion, our dorsal skin-fold chamber technique with intravital fluorescence videomicroscopy and digital image analysis was most useful to monitor the neovascular network for quantitatively evaluating the progression of tumor angiogenesis in terms of MVDI and BR values.


In vivo and in vitro anti-inflammatory effects of ethanol fraction from Periploca forrestii Schltr.
To determine the anti-inflflammatory effects of an ethanol fraction of Periploca forrestii Schltr. (EFPF) and to investigate the potential mechanisms underlying in vivo and in vitro models. The antiinflflammatory effects of EFPF were evaluated using the xylene-induced mouse ear edema and carrageenan-induced rat paw edema models in vivo. In vitro, RAW264.7 cells were exposed to 0-800 μg/mL EFPF and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then cells were treated with different concentrations of EFPF (100-400 μg/mL) and stimulated with lipopolysaccharide (LPS, 1 μg/mL) for 24 h. The supernatant was analyzed for nitric oxide (NO) using the Griess reagent, and the levels of inflflammatory mediators and cytokines were determined using enzyme-linked immunosorbent assays for prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin (IL) 6, and IL-10. The protein expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor κB (NF-κB), and mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK were examined by Western blot. Compared with the control group, EFPF signifificantly reduced mouse ear edema and rat paw edema rate (P<0.05 or P<0.01). Compared with the LPS group, EFPF signifificantly inhibited the LPS-stimulated production of NO, PGE2, TNF-α and IL-6 (P<0.05 or P<0.01), and increased the IL-10 production (P<0.05). EFPF also signifificantly inhibited LPS-induced protein expressions of iNOS and COX-2, suppressed the phosphorylation and degradation of inhibitor of NF-κB-α, decreased p65 level, and inhibited the phosphorylation of p38, ERK1/2 and JNK P<0.05 or P<0.01). EFPF exerted anti-inflflammatory effect by reducing protein expressions of iNOS and COX-2 and the production of the inflflammation factors, including TNF-α, IL-6, NO and PGE2, mainly through inhibition of LPS-mediated stimulation of NF-κB and MAPK signaling pathways.


Elderly caring for the elderly: spirituality as tensions relief.
To investigate the forms of coping used to relieve tensions by elderly caregivers of elderly relatives and to know the type of support they receive from the Primary Health Care service at home. A qualitative study with a theoretical-methodological contribution of Grounded Theory, carried out with 10 elderly caregivers interviewed between August 2014 and January 2015. Participants use primarily religious coping to deal with adverse situations that arise in their lives; they attribute to the sacred the strength to continue to age and care for another elderly person at home. Religiousness was the main coping strategy used by the participants, but little recognized by the health service. It is recommended that the Primary Health Care service provide greater support to these caregivers and be attentive to the spiritual dimension as an auxiliary element in the process of comprehensive and inclusive health care of these elderly caregivers.


Growth inhibition effect of peptide P110 plus cisplatin on various cancer cells and xenotransplanted tumors in mice.
The combined use of currently used anticancer genotoxins with other drugs is a therapeutic tool for potentially increasing the efficacy of the genotoxins. In the present study, the effects of a RasGAP-derived peptide, P110 (RasGAP301-316), designed to target Ras-GTPase activating protein SH3 domain-binding proteins (G3BPs), on the chemotherapeutic agent, cisplatin (DDP), were examined. P110 was demonstrated to enhance the effect of DPP in vitro and in vivo. The results indicate that P110 significantly increased the DDP-induced apoptosis in SGC-7901, HCT-116, HeLa and A-549 cells. Furthermore, P110 combined with DDP significantly suppressed the growth of C26 xenograft tumors in a dose-dependent manner. This synergistic effect may be associated with DDP-induced apoptosis, involving the downregulation of Bcl-2 and the upregulation of Bax, cytochrome c and caspase-3. The results of the present study indicate that P110, in combination with chemotherapeutics, is likely to represent a potential therapeutic strategy for cancer.


[Metabolic syndrome in postmenopausal breast cancer survivors].
To assess the occurrence of metabolic syndrome (MetS) in postmenopausal breast cancer survivors. A total of 158 breast cancer survivors were included in this cross-sectional study. Eligibility criteria were: women with amenorrhea >12 months and age ≥45 years, treated for breast cancer and no metastasis for at least five years. Clinical history and anthropometric indicator data (body mass index (BMI), and waist circumference, (WC) were collected. Biochemical parameters, including total cholesterol, HDL, LDL, triglycerides (TG), glucose and C-reactive protein (CRP), were measured. MetS was diagnosed as the presence of at least three of the following diagnostic criteria: WC>88 cm, blood pressure≥130/85 mmHg, triglycerides≥150 mg/dl, HDL <50 mg/dL,and glucose≥100 mg/dL. The Student's t-test and χ2 test were used for statistical analysis. The mean age of breast cancer survivors was 63.1±8.6 years, with a mean follow-up of 9.1±4.0 years. MetS was diagnosed in 48.1% (76/158) and the most prevalent diagnostic criterion was abdominal obesity (WC>88 cm), affecting 54.4% (86/158) of the women. The patients without MetS had a longer follow-up compared those with MetS (p<0.05). Regarding the current BMI, PN average, those without MetS were overweight, and those with MetS were obese (p<0.05). Among the latter, comparison of BMI at the time of cancer diagnosis and current BMI (27.8±5.4 versus 33.4±5.4 kg/m²) showed a significant weight gain (p<0.05). Mean CRP values were higher in women with MetS (p<0.05). In the comparison of tumor characteristics and cancer treatments there was no difference between groups (p>0.05). Postmenopausal breast cancer survivors had a higher risk of developing metabolic syndrome and central obesity.