Dissociating Normal Aging from Alzheimer's Disease: A View from Cognitive Neuroscience.
Both normal aging and Alzheimer's disease (AD) are associated with changes in cognition, grey and white matter volume, white matter integrity, neural activation, functional connectivity, and neurotransmission. Obviously, all of these changes are more pronounced in AD and proceed faster providing the basis for an AD diagnosis. Since these differences are quantitative, however, it was hypothesized that AD might simply reflect an accelerated aging process. The present article highlights the different neurocognitive changes associated with normal aging and AD and shows that, next to quantitative differences, there are multiple qualitative differences as well. These differences comprise different neurocognitive dissociations as different cognitive deficit profiles, different weights of grey and white matter atrophy, and different gradients of structural decline. These qualitative differences clearly indicate that AD cannot be simply described as accelerated aging process but on the contrary represents a solid entity.


Human urinary and liver conjugates of 17alpha-ethnylestradiol.
Chromatographic profiles of the conjugates of 17alpha-ethynylestradiol (EE2) were obtained from the urine of castrate and normal women given tritium labeled EE2 orally. Five distinct radioactive peaks were observed, with considerable quantitative variation between individuals. Glucosiduronate fractions comprised the dominant excreted radioactivity. In vitro incubation of normal human liver also produced five conjugate types. Simultaneous intravenous/oral (14C/3H) administration of EE2 demonstrated conversion to identical urinary conjugate and free steroid products, with a greater excretion of the intravenous material. Authentic 3-glucuronide of EE2 was synthesized and its position in the chromatographic system relative to the urinary conjugate peaks demonstrated.


Chronobiology of hemostasis and inferences for the chronotherapy of coagulation disorders and thrombosis prevention.
The hemostatic system in its multiple components displays an intricate organization in time which is characterized by circadian (approximately 24-hour), circaseptan (approximately 7-day), menstrual (approximately monthly), and circannual (approximately yearly) bioperiodicities. The interaction of the rhythms of the variables participating in hemostasis determine transient risk states of thromboembolic events, including myocardial infarction and stroke, and of hemorrhage and hemorrhagic events, each with a unique timing. The circadian staging of the rhythms in vascular, cellular, and coagulation factors that favors blood coagulation and thrombosis coincides with the daily minimum in fibrinolytic activity; as a result there is elevated risk in the morning of acute myocardial infarction and stroke. Similar hemostatic rhythms may determine the epidemiology of thromboembolic and hemorrhagic events during the week, month and year. This article focuses on the large-amplitude circadian rhythms operative in the hemostatic system. Their implication for preventive and curative pharmacotherapy of hemostatic disorders is presented, with discussion of related problems.


Implication of endogenous nitric oxide in gastric mucosal protective effect of T-593, a novel anti-ulcer agent, in rats.
The relationship of endogenous nitric oxide (NO) to the gastric mucosal protective effect of the novel anti-ulcer agent T-593, (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3-[2-[[[5-(methylamino) methyl-2-furyl]methyl]thio]ethyl]-2-(methylsulfonyl) guanidine, was investigated in rats. T-593 (3-30 mg/kg, p.o.) dose dependently prevented the formation of gastric mucosal lesions induced by oral administration of aspirin (200 mg/kg) in 0.15 N HCl (HCl-aspirin). Pretreatment with N(G)-nitro-L-arginine methylester (L-NAME), a selective inhibitor of NO synthase (NOS), attenuated the mucosal protective effect of T-593. This effect of L-NAME was antagonized by pretreatment with L-arginine, a substrate of NOS, but not with D-arginine. Activity of total NOS composed of inducible and constitutive NOS in the gastric mucosa was decreased by HCl-aspirin, and T-593 inhibited this decrease. On the other hand, HCl-aspirin and T-593 did not affect inducible NOS activity in the gastric mucosa. Furthermore, we confirmed that T-593 inhibits the decrease in gastric mucosal blood flow (GMBF) induced by HCl-aspirin, and this effect is completely inhibited by pretreatment with L-NAME. These results suggest that the mucosal protective effect of T-593 is partly mediated by endogenous NO via improvement of GMBF and that a possible mechanism for the effect of T-593 is the maintenance of constitutive NOS activity in gastric mucosa.


The influence of naloxone on exercise-induced increase in plasma pituitary hormones and the subjectively experienced level of exhaustion in healthy males.
Opioid peptides seem to play a role as modulators of the pituitary function in man. In the present study, the effect of naloxone on exercise-induced pituitary hormone release and the subjectively experienced level of exhaustion were investigated in nine healthy males. A submaximal work test was performed on two occasions using a bicycle ergometer: 10 min on 50% of maximal working capacity (MWC), immediately followed by 10 min on 80% of MWC. Ten min before exercise, each subject received, in a single-blind randomized order, either a bolus dose of naloxone (100 micrograms/kg) followed by a slow infusion of naloxone (50 micrograms X kg-1 X h-1) or as a control a corresponding volume of the preservatives in the naloxone preparation as a bolus dose followed by an infusion of diluted preservatives. In the control studies, exercise induced a significant increase in GH, PRL, TSH and ACTH. The increase in ACTH was enhanced following naloxone. Naloxone was without effect on exercise-induced changes in GH, PRL and TSH. An increased level of exhaustion was experienced on 80% of MWC during naloxone. It is concluded that opioid receptors with a moderate sensitivity to naloxone are involved in the regulation of the ACTH response to exercise and also influence the subjectively experienced level of exhaustion.


On-chip electroporation, membrane repair dynamics and transient in-cell recordings by arrays of gold mushroom-shaped microelectrodes.
This study demonstrates the use of on-chip gold mushroom-shaped microelectrodes (gMμEs) to generate localized electropores in the plasma membrane of adhering cultured neurons and to electrophysiologically monitor the ensuing membrane repair dynamics. Delivery of an alternating voltage pulse (0.5-1 V, 100 Hz, 300 ms) through an extracellularly positioned micrometer-sized gMμE electroporates the patch of plasma membrane facing the microelectrode. The repair dynamics of the electropores were analyzed by continuous monitoring of the neuron transmembrane potential, input resistance (R(in)) and action potential (AP) amplitude with an intracellular microelectrode and a number of neighbouring extracellular gMμEs. Electroporation by a gMμE is associated with local elevation of the free intracellular calcium concentration ([Ca(2+)](i)) around the gMμE. The membrane repair kinetics proceeds as an exponential process interrupted by abrupt recovery steps. These abrupt events are consistent with the "membrane patch model" of membrane repair in which patches of intracellular membrane fuse with the plasma membrane at the site of injury. Membrane electroporation by a single gMμE generates a neuron-gMμE configuration that permits recordings of attenuated intracellular action potentials. We conclude that the use of on-chip cultured neurons via a gMμE configuration provides a unique neuroelectronic interface that enables the selection of individual cells for electroporation, generates a confined electroporated membrane patch, monitors membrane repair dynamics and records attenuated intracellular action potentials.


Better Accuracy for Better Science . . . Through Random Conclusions.
Conducting research with human subjects can be difficult because of limited sample sizes and small empirical effects. We demonstrate that this problem can yield patterns of results that are practically indistinguishable from flipping a coin to determine the direction of treatment effects. We use this idea of random conclusions to establish a baseline for interpreting effect-size estimates, in turn producing more stringent thresholds for hypothesis testing and for statistical-power calculations. An examination of recent meta-analyses in psychology, neuroscience, and medicine confirms that, even if all considered effects are real, results involving small effects are indeed indistinguishable from random conclusions.


Inorganic-organic hybrid membranes with anhydrous proton conduction prepared from 3-aminopropyltriethoxysilane and sulfuric acid by the sol-gel method.
Inorganic-organic hybrid membranes with anhydrous proton conduction were prepared from 3-aminopropyltriethoxysilane and H2SO4 by the sol-gel method. The membrane has a unique structure: a hexagonal phase formed by the stacking of rodlike polysiloxanes with ion complexes of ammonium groups and HSO4- extruded outside. The membranes showed high conductivity of 2 x 10-3 S cm-1 at 200 degrees C under dry atmosphere. In the membrane, protons probably migrate through the outside of the rodlike polysiloxanes along hydrogen-bond chains formed among HSO4- anions.


Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide.
Although the adhesive and cohesive nature of mussel byssal proteins have long served to inspire the design of materials embodying these properties, their characteristic amino acid compositions suggest that they might also serve to inspire an unrelated material function not yet associated with this class of protein. Herein, it is demonstrated that a peptide derived from mussel foot protein-5, a key protein in mussel adhesion, displays antibacterial properties, a yet unreported activity. This cryptic function serves as inspiration for the design of a new class of peptide-based antibacterial adhesive hydrogels prepared via self-assembly, which are active against drug-resistant Gram-positive bacteria. The gels exert two mechanisms of action, surface-contact membrane disruption and oxidative killing affected by material-produced H2 O2 . Detailed studies relating amino acid composition and sequence to material mechanical adhesion/cohesion and antibacterial activity affords the MIKA2 adhesive gel, a material with a superior activity that is shown to inhibit colonization of titanium implants in mice.


IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques.
Innate lymphoid cells (ILCs) are an emerging subset of lymphocytes involved in surveillance against virally infected cells. Here, we show CD3(-)CD8(high) lymphocytes in macaque blood include major subsets of ILCs including natural killer (NK) cells expressing CD16, NKp46, and NKG2A, but also populations of ILCs in mucosal tissues having different properties. One ILC subset secreted interleukin (IL)-17 (ILC17), but these were restricted to mucosal tissues. Some mucosal ILC17 cells expressed classical NK-cell markers, but little NKG2A or NKG2D. Some ILC17 cells secreted IL-22 and tumor necrosis factor-α, but few produced interferon (IFN)-γ or contained granzyme B. IL-17 production by ILCs was induced by IL-6, transforming growth factor-β, and IL-23. Further, simian immunodeficiency virus (SIV) infection resulted in a significant loss of ILC17 cells, especially in the jejunum, which persisted throughout SIV infection. These findings indicate that ILC17 cells may be involved in innate mucosal immune responses, and their loss may contribute to loss of intestinal mucosal integrity and disease progression in human immunodeficiency virus (HIV)/SIV infection.


[Effect of human silicotic alveolar macrophages on the expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 in human lung fibroblasts].
To study the effect of the cultured supernatant of human silicotic alveolar macrophages (AM) on the expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human lung fibroblasts (FB). Human alveolar macrophages were collected from a silicotic patients by bronchoalveolar lavage and exposed to SiO(2), then the cultured supernatant were incubated with human fetal lung fibroblasts for 6, 12, 18, 24, 36, 48 h. The immunocytochemical method was used to detect the level of expression of MMP-1 and TIMP-1 in lung fibroblasts. The expression of MMP-1 in FB in 24 h incubation was lower in cultured supernatant of silicotic AM unexposed to SiO(2) than in blank control [integrated OD (IOD)]: 0.103 +/- 0.014 vs 0.133 +/- 0.023), while the expression of TIMP-1 was higher (IOD: 0.108 +/- 0.012 vs 0.065 +/- 0.006). The expression of MMP-1 in FB in cultured supernatant of AM exposed to SiO(2) for 24 h was further decreased (IOD: 0.062 +/- 0.008 vs 0.133 +/- 0.023), while that of TIMP-1 was further increased (IOD: 0.143 +/- 0.015 vs 0.065 +/- 0.006). SiO(2) may affect the expression of MMP-1 and TIMP-1 system through AM mediation and participate in the formation of lung fibrosis.


Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features.
The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1) the relative importance of US features as risk factors of malignancy; and 2) a cost-effective management of nonpalpable thyroid nodules. Four hundred ninety-four consecutive patients with nonpalpable thyroid nodules (8-15 mm) were evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology were excluded from the study. All patients with suspicious or malignant cytology underwent surgery, whereas subjects with benign cytology had clinical and US control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). Extracapsular growth (pT(4)) was present in 35.5%, and nodal involvement in 19.4% of neoplastic lesions, with no significant differences between tumors greater or smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87% of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83), intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were independent risk factors of malignancy. FNA performed on hypoechoic nodules with at least one risk factor was able to identify 87% of the cancers at the expence of cytological evaluation of 38.4% of nonpalpable lesions. The majority of nonpalpable thyroid tumors can be identified by cytological evaluation of lesions presenting hypoechoic appearance in conjunction with one independent risk factor. Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis, US-FNA should be performed on all 8-15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions of the thyroid without risk factors should be followed by means of clinical and US evaluation.


Dose escalation of epirubicin in the CEOP-BLEO regimen: a controlled clinical trial comparing standard doses for the treatment of diffuse large cell lymphoma.
One hundred and forty-seven consecutive patients with previously untreated high-intermedium and high clinical risk diffuse large cell lymphoma (DLCL) were included in a prospective clinical trial to evaluate the efficacy and toxicity of escalating doses of epirubicin compared to standard doses in the CEOP-Bleo (cyclophosphamide, epirubicin, vincristine and prednisone and bleomycin) regimen, 55% of the patients were > 60 years old and most patients had adverse prognostic factors at diagnosis. Complete response rates were similar in both groups (68% in the standard dose compared to 73% in the escalating arm, (p = 0.5). However, time to treatment failure (TFF) and overall survival were better after escalating doses. At 3-years TTF at a medial follow-up of 33.6 months was 76% in the patients whose received escalating dose statistical different to 37% of the patients whose received standard doses (p < .01). Overall survival was 81% in the escalated therapy arm which is statistical different to 40% of the patients treated with standard doses (p < .01). Toxicity was mild in both arms. Neutropenia, mucositis and cardiotoxicity were mild in the escalated dose arm and no severe complications were observed. All patients received the planned doses of all drugs. Patients > 60 years old had the same CR rate, TTF and overall survival as younger patients. In conclusion it seems that the dose of epirubicin can be increased in combination chemotherapy regimens with safety and only mild toxicity. The CR rate was not superior compared to the standard dose but the TTF and overall survival were better. Longer follow-up periods are required in order to determine if the cure rate can also be improved. Older patients can also benefit because they also tolerated the increase in epirubicin without severe side effects and also improved their outcome. The use of more aggressive regimens with increase in dose intensity may be the treatment of choice for more patients poor prognosis, with DLCL provided there is no increase in toxicity. In this respect the use of epirubicin in higher doses/appears to be useful.


Rotavirus Strategies Against the Innate Antiviral System.
"Rotaviruses represent the most important etiological agents of acute, severe gastroenteritis in the young of many animal species, including humans." This statement, variations of which are a common beginning in articles about rotaviruses, reflects the fact that these viruses have evolved efficient strategies for evading the innate immune response of the host and for successfully replicating in the population. In this review, we summarize what is known about the defense mechanisms that host cells employ to prevent rotavirus invasion and the countermeasures that these viruses have successfully developed to surpass cellular defenses. Rotaviruses use at least two viral multifunctional proteins to directly interact with, and prevent the activation of, the interferon system, and they use at least one other protein to halt the protein synthesis machinery and prevent the expression of most of the transcriptional antiviral program of the cell. Characterization of the confrontation between rotaviruses and their host cells has allowed us to learn about the virus-host coevolution that prevents the damaging effects of the innate immune response.


When does an intermediate become a transition state? Degenerate isomerization without competing racemization during solvolysis of (S)-1-(3-nitrophenyl)ethyl tosylate.
(S)-1-(3-Nitrophenyl)ethyl tosylate [(S)-2-OTs] was prepared in >99% enantiomeric excess and the change in the chiral purity of this compound was monitored during solvolysis in 50:50 trifluoroethanol/water. The barely detectable formation of 0.5% (R)-2-OTs after two half times for the solvolysis reaction was used to calculate a rate constant of k(rac) approximately equal to 4 x 10-6 s-1. This is 80-fold smaller than kiso = 3.2 x 10-4 s-1 for the isomerization that exchanges oxygen-16 and oxygen-18 of 3-NO2C6H413CH(Me)OS(18O)2Tos during solvolysis and 10-fold smaller than the minimum value of k(rac) = 4.6 x 10-5 s-1 predicted if isomerization and racemization products form by partitioning of a common ion-pair intermediate of a stepwise reaction. It is concluded that the isomerization reaction proceeds mainly by a pathway that avoids formation of this putative intermediate. It is suggested that the solvolysis reaction of 2-OTs may proceed by a stepwise preassociation mechanism where solvent "reorganization" precedes substrate ionization to form an ion-pair intermediate.


A Greek Tragedy: The Growing Complexity of Alzheimer Amyloid Precursor Protein Proteolysis.
Proteolysis of the amyloid precursor protein (APP) liberates various fragments including the proposed initiator of Alzheimer disease-associated dysfunctions, amyloid-β. However, recent evidence suggests that the accepted view of APP proteolysis by the canonical α-, β-, and γ-secretases is simplistic, with the discovery of a number of novel APP secretases (including δ- and η-secretases, alternative β-secretases) and additional metabolites, some of which may also cause synaptic dysfunction. Furthermore, various proteins have been identified that interact with APP and modulate its cleavage by the secretases. Here, we give an overview of the increasingly complex picture of APP proteolysis.


Making spin-crossover crystals by successive polymorphic transformations.
The complex [Fe(tpa)(NCS)(2)] showed successive polymorphic transformations (polymorphs II-IV) that produced crystals with distinct changes in color, crystal structure, and spin-crossover behavior.


[Screening for mild cognitive impairment: usefulness of the 7-Minute Screen Test].
The <<7- Minute Screen>> is a neurocognitive screening test for the detection of Alzheimer's disease (AD) patients in primary care settings. It consists of 4 brief subtests (orientation, memory, visuoconstruction and verbal fluency) and provides a broader neuropsychological profile than other widely used screening tests, The aim of the present study was to study the usefulness of this screening test for the detection of Mild Cognitive Impairment (MCI). Thirty-two patients with probable AD (NINCDS-ADRDA criteria), 25 patients with MCI, and 35 healthy control subjects, matched for age and education, underwent a comprehensive neuropsychological battery and the Rio-de-la-Plata version of the 7-Minute Screen. RESULTS. This test showed 93 % sensitivity and 97% specificity in detecting mild-moderate Alzheimer's disease MMSE<24), but it exhibited a substantially decreased sensitivity (28 %) in its ability to detect MCI in AD (MMSE >2 4 ). The screening batteries do not replace a m o re compre h e n s i ve neuro psychological assessment. Th ey are useful in detecting patients with mild dementia, but caution must be the rule when considering a diagnosis of MCI.


[Surgical management of non-functioning pancreatic neuroendocrine tumors].
To analyze immediate and long-term results of surgical treatment of patients with non-functioning pancreatic neuroendocrine tumors (pNETs). Outcomes in 21 patients with non-functioning pNETs were retrospectively analyzed. Long-term results were followed-up in 18 (85%) cases, median follow-up was 39 months. Postoperative mortality was 4.7%. The incidence of postoperative complications Clavien-Dindo degree IIIA and over was 20.8%, overall 5-year survival - 89%, desease-free 5-year survival - 78%. At present time surgical intervention remains the only radical method of non-functioning pNETs management. Threshold tumor dimension should be 15 mm that determines surgical intervention or active surveillance. From an oncological point of view tumor enucleation is permissible only in case of small dimensions (up to 2 cm) and full confidence in low degree of malignancy. Lymphadenectomy should be performed in all cases in standard fashion because lymph node involvement is reliably poor prognostic sign.


Systems nutrition: an innovation of a scientific system in animal nutrition.
The traditional scientific system of animal nutrition has existed for over 100 years, but substantial changes are yet to take place. With the lapse of time, limitations of this traditional scientific system have been more and more evident and such a system should be dramatically revised with innovations. Beginning in the late 1980s, our group started to use system-science principles and approaches in animal nutrition research. The author published a book entitled "An Introduction to Systems-Nutrition of Animals", which marked the birth of a new scientific system in animal nutrition to stimulate further development of this discipline. System-nutrition is defined as a branch of biological sciences that concerns system-level studies of the integrative picture of flux, metabolism, utilization and regulation of nutrients (e.g., proteins and amino acids) from dietary and endogenous origin in the whole animal system at organism, organs, tissues, cells and molecules levels to achieve such goals as nutritional manipulation and prediction, as well as optimum feeding decision and optimum nutritional engineering programs for animal feeding.


Estimation of cAMP binding in hippocampus CA1 field by a fluorescent probe.
The hippocampus is an allocortex structure involved in many complex processes, from memory formation to spatial navigation. It starts developing during prenatal life but acquires its adult functional properties around the peripubertal age, in both humans and mice. Such prolonged maturation is accompanied by structural changes in microcircuitry and functional changes involving biochemical and electrophysiological events. Moreover, hippocampus undergoes plasticity phenomena throughout life. In murine rodents, the most relevant maturation steps in Cornu Ammonis 1 (CA1) hippocampal subfield occur during the third-fourth weeks of life. During this period, also the expression and localization of cAMP-dependent protein kinases (PKA) refines: many regulatory (R1A) PKA clusters appear, bound to the cytoskeleton. Here the binding characteristics of R1A are determined in CA1 by using confocal microscopy. Apparently, two binding sites are present with no evidence of cooperativity. Equilibrium dissociation constant is estimated around 22.9 nM. This value is lower from that estimated for R1A in soluble form, suggesting a different binding site conformation or accessibility in the tissue. The method described here may be useful to track the developmental changes in binding activity, which affects cAMP availability at selected intracellular microzones. Possible relations with functional consequences are discussed.


selective production and characterization of levan by Bacillus subtilis (Natto) Takahashi.
To meet the industrial need of an efficient microbial method for increased levan production, Bacillus subtilis (natto) Takahashi, a commercial natto starter for preparing fermented soybeans (natto), was used to produce levan. After cultivation for 21 h, 40-50 mg of levan mL(-1) was produced in medium containing 20% (w/w) sucrose, which was approximately 50% yield on available fructose. The product consisted of two fractions with different molecular masses (1794 and 11 kDa), which were easily separated by fractionation using an ethanol gradient. The products were well characterized by GPC, 13C NMR, and 1H NMR. The various sugars and concentrations, initial pH, fermentation temperature, and agitation speed affected the levan production by B. subtilis (natto) Takahashi. Takahashi strain is the most efficient levan-producing strain among all of the B. subtilis strains tested and, as previously reported, it produced the highest yield of levan in the least time (21 h) under the common cultivation condition.


Focal liver masses: differential diagnosis with pulsed Doppler US.
Duplex Doppler ultrasound (US) was used in 68 consecutive patients with focal liver lesions, including 12 hepatocellular carcinomas, one cholangiocarcinoma, 37 metastases, 15 hemangiomas, one hemangioendothelioma, and two focal nodular hyperplasias. Of the hepatocellular carcinomas, six were diffusely hyperechoic, two were hypoechoic, two were single hyperechoic lesions, and two were multifocal and hyperechoic. All ten tumors with Doppler shifts of 5 kHz or above proved to be hepatocellular carcinomas. The other two hepatocellular carcinomas showed Doppler shifts of 3 kHz. In contrast, no hemangioma showed shifts above 0.7 kHz, and ten of the 15 gave no detectable signal. Of the metastases, 20 gave no signal and 17 had signals of up to 4 kHz. Three-kilohertz signals were also obtained from a cholangiocarcinoma, a hemangioendothelioma, and focal nodular hyperplasia. Correlation with angiographic findings suggested that the high-velocity Doppler signals were associated with large pressure gradients due to arteriovenous shunting. Duplex Doppler US can therefore aid in the differential diagnosis of diffuse and focal liver lesions.


Physiologic regulation of heart rate and blood pressure involves connexin 36-containing gap junctions.
Chronically elevated sympathetic nervous activity underlies many cardiovascular diseases. Elucidating the mechanisms contributing to sympathetic nervous system output may reveal new avenues of treatment. The contribution of the gap junctional protein connexin 36 (Cx36) to the regulation of sympathetic activity and thus blood pressure and heart rate was determined using a mouse with specific genetic deletion of Cx36. Ablation of the Cx36 protein was confirmed in sympathetic preganglionic neurons of Cx36-knockout (KO) mice. Telemetric analysis from conscious Cx36 KO mice revealed higher variance in heart rate and blood pressure during rest and activity compared to wild-type (WT) mice, and smaller responses to chemoreceptor activation when anesthetized. In the working heart-brain stem preparation of the Cx36-KO mouse, respiratory-coupled sympathetic nerve discharge was attenuated and responses to chemoreceptor stimulation and noxious stimulation were blunted compared to WT mice. Using whole cell patch recordings, sympathetic preganglionic neurons in spinal cord slices of Cx36-KO mice displayed lower levels of spikelet activity compared to WT mice, indicating reduced gap junction coupling between neurons. Cx36 deletion therefore disrupts normal regulation of sympathetic outflow with effects on cardiovascular parameters.-Lall, V. K., Bruce, G., Voytenko, L., Drinkhill, M., Wellershaus, K., Willecke, K., Deuchars, J., Deuchars, S. A. Physiologic regulation of heart rate and blood pressure involves connexin 36-containing gap junctions.


Disruption of HDX gene in premature ovarian failure.
We present a case of a 19-year-old phenotypically normal girl with premature ovarian failure. Cytogenetic analysis using G banding and fluorescence in situ hybridization (FISH) from cultured peripheral blood lymphocytes of the patient and the family revealed a de novo X;15 translocation and the imbalance to be 46,X,t(X;15)(Xpter → Xq21::15q11 → 15qter;15pter → 15q11::Xq21 → Xqter). ish (CEPX+, wep15+, ISNRPN+, PML+, D15S10+, wcp15-, SNRRN-, PML-)[20]. The X chromosome inactivation (XCI) assay revealed a completely skewed XCI pattern in which selective pressure favors an active maternal allele. The Affymetrix 2.7 M cytogenetics whole-Genome array confirmed the chromosomal imbalance and identified disruption of the HDX gene at Xq21, the translocation breakpoint.


Selenium Biofortification of Crop Food by Beneficial Microorganisms.
Selenium (Se) is essential for human health, however, Se is deficient in soil in many places all around the world, resulting in human diseases, such as notorious Keshan disease and Keshin-Beck disease. Therefore, Se biofortification is a popular approach to improve Se uptake and maintain human health. Beneficial microorganisms, including mycorrhizal and root endophytic fungi, dark septate fungi, and plant growth-promoting rhizobacteria (PGPRs), show multiple functions, especially increased plant nutrition uptake, growth and yield, and resistance to abiotic stresses. Such functions can be used for Se biofortification and increased growth and yield under drought and salt stress. The present review summarizes the use of mycorrhizal fungi and PGPRs in Se biofortification, aiming to improving their practical use.


Upgrading of Low-Grade Colombian Coals via Low-Cost and Sustainable Calcium Nitrate Dense Media Separation.
Wet coal beneficiation in Colombia is prohibitive due to the high cost and scarcity of commonly used dense media. The practical value of this study is that it demonstrates for the first time that a common fertilizer, calcium nitrate, can be used in the beneficiation of low-grade Colombian coals. Three high-ash low-grade Colombian coals (Valle, Cundinamarca, and Antioquia) commonly used in Colombian sugar mill stoker furnaces were tested. Coal mineralogy and prevalence were analyzed before and after washing using mineral liberation analysis. The swelling potential of the coals was assessed using a novel application of thermal mechanical analysis (TMA) and an ash fusion oven (AFO). Calcium nitrate reduced ash levels across all size fractions, even for high-ash coals like Valle (29% to below 7%) to acceptable levels for coke manufacturing or pulverized fuel combustion. The novel use of TMA and AFO to analyze coal swelling demonstrated that swelling varies under constrained and unconstrained conditions and the small sample size allows for rapid testing of coal swelling. This study has demonstrated that the use of common fertilizers can allow beneficiation to become a processing option for low-grade coals in Official Development Assistance countries where conventional dense media is prohibitively expensive.


How to divide the pancreatic parenchyma in patients with a portal annular pancreas: laparoscopic spleen-preserving distal pancreatectomy for serous cystic neoplasms.
Portal annular pancreas (PAP) is a rare pancreatic anomaly in which the uncinate process wraps annularly around the portal vein and fuses to the body of the pancreas. PAP is highly relevant to the development of postoperative pancreatic fistula (POPF) in pancreatic surgery. Here, we describe our experience and surgical technique of laparoscopic spleen-preserving distal pancreatectomy using Warshaw's procedure for patients with the PAP. A 49-year-old woman with PAP was referred to our hospital for a suspicious mucinous cystic neoplasms 1.5 cm in diameter in the pancreatic tail. Laparoscopic spleen-preserving distal pancreatectomy using Warshaw's procedure was performed. Mobilization of the pancreatic tail was first performed, and then, the splenic artery was cut. After dividing the pancreatic tail from the splenic hilum, the ventral pancreatic parenchyma was divided using a stapler. After cutting the splenic vein, complete mobilization of the pancreatic body and tail enabled easy division of the PAP. Finally, the PAP was also divided using the stapler. Although grade B POPF occurred, she was discharged on the 9th postoperative day. Surgeons should understand the anatomical characteristics of PAP and be aware of the possibility of POPF.


Construction of an Integrated mCherry Red Fluorescent Protein Expression System for Labeling and Tracing in Lactiplantibacillus plantarum WCFS1.
Thorough intestinal adhesion and colonization greatly promote the probiotic properties of lactic acid bacteria (LAB). Labeling and tracing with fluorescent proteins are effective and reliable for studying the in vivo physiological activities of LAB including localization, adhesion, and colonization. Lactiplantibacillus plantarum WCFS1 was successfully traced with a red fluorescent protein (RFP), which was expressed by the bacteria-carrying recombinant plasmids. In this study, we aimed to construct a stable RFP mCherry expression system, whose encoding gene was integrated into the bacterial chromosome via double-crossed homologous recombination, and use it for labeling WCFS1 with the goal of avoiding the potential loss of non-chromosomal plasmids along with intestinal growth. First, the constitutive expression of the mCherry protein was improved after adjusting the length of the spacer between the promoter and the gene start codon. Then, the optimized mCherry gene expression cassette was integrated into the chromosome of WCFS1. The resulting strain had normal unimpaired growth and strong fluorescent signals, even after 100 generations, indicating its stability. Furthermore, quantitative polymerase chain reaction (PCR) results revealed a strong positive correlation between the fluorescence intensity of the strain and the number of viable cells, demonstrating its potential usage for the quantification of in vivo WCFS1 cells. Finally, the increased adhesion ability of WCFS1 due to the recombinant expression of the bsh gene was visualized and evaluated using fluorescence intensity, the results of which were consistent with those obtained using the previously established quantification methods. These results suggest that the chromosomal-integrated mCherry labeling system can be extensively used to examine the distribution, colonization, and survival of LAB in vivo in order to determine the mechanism of its probiotic function.


An adjuvanted, low-dose, pandemic influenza A (H5N1) vaccine candidate is safe, immunogenic, and induces cross-reactive immune responses in healthy adults.
To protect a naive global population against pandemic influenza, pandemic vaccines should be effective at low antigen doses, because of limited manufacturing capacity. In a multicenter, randomized, blind-observer phase 1 trial, groups of 50 healthy young adults received 2 doses, 21 days apart, of influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine containing 1.9, 3.8, 7.5 or 15 microg of hemagglutinin with oil-in-water emulsion adjuvant or 7.5 microg of hemagglutinin without adjuvant. Safety was monitored to day 42. Homologous hemagglutination-inhibition (HI) and microneutralization titers were determined after each vaccination. Cross-reactivity against A/Indonesia/05/2005 RG2 was tested after the second vaccination. No vaccine-related significant or serious adverse events occurred. Injection site reactions, but not systemic reactions, were more frequent with adjuvant than without. Even with only 1.9 microg of hemagglutinin plus adjuvant, 72% of subjects had HI titers >or=1:32 after 2 doses. This proportion was 81%-89% with higher adjuvanted doses but was only 34% without adjuvant. Adjuvanted vaccine induced cross-neutralizing antibodies in 39%-65% of samples, versus 7% without adjuvant. The emulsion-adjuvanted pandemic influenza vaccine candidate was safe, immunogenic, and induced cross-reactive antibodies. This adjuvanted 1.9-microg candidate is the lowest effective dose tested to date. This could have a major impact on prepandemic vaccination strategies with stockpiled batches of vaccine. ClinicalTrials.gov identifier: NCT00457509 .


Heavy metal sources identification and sampling uncertainty analysis in a field-scale vegetable soil of Hangzhou, China.
At a field-scale (6.7ha), 100 surface soil samples were collected from a vegetable field to determine total concentrations of Cd, Co, Cu, Hg, Mn, Ni and Zn. To identify possible sources of these metals and characterize their spatial variation, classic statistic and geostatistic techniques were applied. Through correlation and geostatistical analysis, it was found that the primary inputs of Co, Mn and Ni were due to pedogenic sources, whereas the sources of Hg and Cd were mainly due to human activities. Because of their different sources, their variations followed: Hg>Cd approximately Cu>Zn approximately Co approximately Mn approximately Ni. Based on their relationships with other soil properties, co-kriging was used to minimize sampling density. Sampling numbers for Cd, Cu, Zn, Mn, Co and Ni can be reduced from 100 to 90, 80, 70, 60, 60 and 60, respectively, without losing accuracy relative to ordinary kriging.


Dose-dependent nuclear β-catenin response segregates endomesoderm along the sea star primary axis.
In many invertebrates, the nuclearization of β-catenin at one pole of the embryo initiates endomesoderm specification. An intriguing possibility is that a gradient of nuclear β-catenin (nβ-catenin), similar to that operating in vertebrate neural tube patterning, functions to distinguish cell fates in invertebrates. To test this hypothesis, we determined the function of nβ-catenin during the early development of the sea star, which undergoes a basal deuterostomal mode of embryogenesis. We show that low levels of nβ-catenin activity initiate bra, which is expressed in the future posterior endoderm-fated territory; intermediate levels are required for expression of foxa and gata4/5/6, which are later restricted to the endoderm; and activation of ets1 and erg in the mesoderm-fated territory requires the highest nβ-catenin activity. Transcription factors acting downstream of high nβ-catenin segregate the endoderm/mesoderm boundary, which is further reinforced by Delta/Notch signaling. Significantly, therefore, in sea stars, endomesoderm segregation arises through transcriptional responses to levels of nβ-catenin activity. Here, we describe the first empirical evidence of a dose-dependent response to a dynamic spatiotemporal nβ-catenin activity that patterns cell fates along the primary axis in an invertebrate.


Protective effect of eicosapentaenoic acid on insulin resistance in hyperlipidemic patients and on the postoperative course of cardiac surgery patients: the possible involvement of adiponectin.
Accumulated studies have shown that ω-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have protective roles against inflammatory responses such as hyperlipidemia, diabetes mellitus (DM) and cardiovascular diseases. Here we examined the effects of administering EPA to hyperlipidemic patients and other patients undergoing cardiac surgery to determine whether this treatment would increase plasma EPA levels and to clarify the association between EPA treatment and adiponectin production in hyperlipidemic patients. We also assessed the effect of preoperative EPA administration on postoperative adverse events such as postoperative atrial fibrillation (POAF) and postoperative infection in the cardiac surgery patients. The EPA administration significantly increased the serum EPA concentrations in both patient populations (p<0.001). In the hyperlipidemic patients, the EPA administration significantly increased plasma adiponectin levels (p<0.05), accompanied by a decrease in insulin resistance designated by the HOMA-IR (homeostasis model assessment of insulin resistance) score (p<0.05) and Hs-CRP (high sensitivity C-reactive protein) value (p<0.05). In the cardiac surgery patients, no significant effect of EPA on cardiac adverse events such as POAF was observed. However, our results clearly demonstrated that both the neutrophil-to-lymphocyte ratio and the 2nd-line antibiotic requirement in the EPA group were significantly decreased compared to the untreated control group (p<0.05). We suggest that EPA administration may exert anti-inflammatory effects in patients with hyperlipidemia and in those undergoing cardiac surgery, possibly through an increase in plasma adiponectin levels.


Auditory processing deficits are sometimes necessary and sometimes sufficient for language difficulties in children: Evidence from mild to moderate sensorineural hearing loss.
There is a general consensus that many children and adults with dyslexia and/or specific language impairment display deficits in auditory processing. However, how these deficits are related to developmental disorders of language is uncertain, and at least four categories of model have been proposed: single distal cause models, risk factor models, association models, and consequence models. This study used children with mild to moderate sensorineural hearing loss (MMHL) to investigate the link between auditory processing deficits and language disorders. We examined the auditory processing and language skills of 46, 8-16year-old children with MMHL and 44 age-matched typically developing controls. Auditory processing abilities were assessed using child-friendly psychophysical techniques in order to obtain discrimination thresholds. Stimuli incorporated three different timescales (µs, ms, s) and three different levels of complexity (simple nonspeech tones, complex nonspeech sounds, speech sounds), and tasks required discrimination of frequency or amplitude cues. Language abilities were assessed using a battery of standardised assessments of phonological processing, reading, vocabulary, and grammar. We found evidence that three different auditory processing abilities showed different relationships with language: Deficits in a general auditory processing component were necessary but not sufficient for language difficulties, and were consistent with a risk factor model; Deficits in slow-rate amplitude modulation (envelope) detection were sufficient but not necessary for language difficulties, and were consistent with either a single distal cause or a consequence model; And deficits in the discrimination of a single speech contrast (/bɑ/ vs /dɑ/) were neither necessary nor sufficient for language difficulties, and were consistent with an association model. Our findings suggest that different auditory processing deficits may constitute distinct and independent routes to the development of language difficulties in children.


Fundamental Limits to Collective Concentration Sensing in Cell Populations.
The precision of concentration sensing is improved when cells communicate. Here we derive the physical limits to concentration sensing for cells that communicate over short distances by directly exchanging small molecules (juxtacrine signaling), or over longer distances by secreting and sensing a diffusive messenger molecule (autocrine signaling). In the latter case, we find that the optimal cell spacing can be large, due to a trade-off between maintaining communication strength and reducing signal cross-correlations. This leads to the surprising result that sparsely packed communicating cells sense concentrations more precisely than densely packed communicating cells. We compare our results to data from a wide variety of communicating cell types.


An improved cervical radium applicator.
Design improvements have retained the advantages of a previously described afterloading radium system, while facilitating insertion by minimizing the space required for passing the apparatus through the introitus. The mechanical integration of the parts of the apparatus results in smoother insertion, reliability of positioning, and less patient discomfort.


Ultrathin n-type organic nanoribbons with high photoconductivity and application in optoelectronic vapor sensing of explosives.
Well-defined ultrathin nanoribbons have been fabricated from an amphiphilic electron donor-acceptor (D-A) supramolecule comprising perylene tetracarboxylic diimide as the backbone scaffold to enforce the one-dimensional intermolecular assembly via strong pi-stacking. These nanoribbons demonstrated high photoconductivity upon illumination with white light. The high photoconductivity thus obtained is likely due to the optimal molecular design that enables a good kinetic balance between the two competitive processes, the intramolecular charge recombination (between D and A) and the intermolecular charge transport along the nanoribbon. The photoconduction response has also proven to be prompt and reproducible with the light turning on and off. The photogenerated electrons within the nanoribbon can be efficiently trapped by the adsorbed oxygen molecules or other oxidizing species, leading to depletion of the charge carriers (and thus the electrical conductivity) of the nanoribbon, as typically observed for n-type semiconductor materials as applied in chemiresistors. Combination of this sensitive modulation of conductivity with the unique features intrinsic to the nanoribbon morphology (large surface area and continuous nanoporosity when deposited on a substrate to form a fibril film) enables efficient vapor sensing of nitro-based explosives.


Role of Fast and Slow Inhibitors in Oscillatory Rhythm Design.
In biological or abiotic systems, rhythms occur, owing to the coupling between positive and negative feedback loops in a reaction network. Using the Semenov-Whitesides oscillatory network for thioester hydrolysis as a prototype, we experimentally and theoretically analyzed the role of fast and slow inhibitors in oscillatory reaction networks. In the presence of positive feedback, a single fast inhibitor generates a time delay, resulting in two saddle-node bifurcations and bistability in a continuously stirred tank reactor. A slow inhibitor produces a node-focus bifurcation, resulting in damped oscillations. With both fast and slow inhibitors present, the node-focus bifurcation repeatedly modulates the saddle-node bifurcations, producing stable periodic oscillations. These fast and slow inhibitions result in a pair of time delays between steeply ascending and descending dynamics, which originate from the positive and negative feedbacks, respectively. This pattern can be identified in many chemical relaxation oscillators and oscillatory models, e.g., the bromate-sulfite pH oscillatory system, the Belousov-Zhabotinsky reaction, the trypsin oscillatory system, and the Boissonade-De Kepper model. This study provides a novel understanding of chemical and biochemical rhythms and suggests an approach to designing such behavior.


Origins of two hemiclonal hybrids among three Hexagrammos species (Teleostei: Hexagrammidae): genetic diversification through host switching.
Two natural, hemiclonal hybrid strains were discovered in three Hexagrammos species. The natural hybrids, all of which were females that produced haploid eggs containing only the Hexagrammos octogrammus genome (maternal ancestor; hereafter Hoc), generated F1 hybrid-type offspring by fertilization with haploid sperm of Hexagrammos agrammus or Hexagrammos otakii (paternal species; Hag and Hot, respectively). This study was performed to clarify the extent of diversification between the two hybrids and the maternal ancestor. Genealogical analysis using mtDNA revealed that all 38 Hoc/Hot hybrids formed a branch (Branch I) with 18 of the 33 Hoc/Hag hybrids. No haplotype sharing was observed with the maternal ancestor. Further, microsatellite DNA analysis suggested that the members of Branch I shared the same hemiclonal genome set. The results suggested that Hoc/Hot hybrids originated by anomalous hybridization, or "host switching," between Hoc/Hag and Hot, and not from interspecific hybridization between Hoc and Hot. The remaining 9 of 11 Hoc/Hag haplotypes and all of the 27 Hoc haplotypes were mixed within the genealogical tree, as if they had originated from multiple mutations. However, Hoc/Hag could also mate with Hoc. Although offspring from this host switch (Backcross-Hoc) have the same genome as normal Hoc, a part of their genome retains genetic factors capable of producing hemiclones. Consequently, when a descendant of a BC-Hoc hybrid mates with Hag males, a new hemiclone lineage will arise. Multiple haplotype revival through host switching from a single mutation in hybrids is another possible hypothesis for the observed mixing of Hoc/Hag haplotypes within the mtDNA genealogical tree.


Ecoengineering high rate anaerobic digestion systems: analysis of improved syntrophic biomethanation catalysts.
High performance biomethanation granules with operational specific COD removal rates of 7 kg COD removed/kg SS/d were obtained by ecoengineering conventional, granular, UASB digester sludge using a designed protocol of starvation and selection on a defined volatile fatty acid (VFA) based mineral medium. Addition of low (0.15 mM) sulfate levels to this VFA medium increased the maximum shock-load COD removal rate of the ecoengineered biomethanation granules to 9 kg COD/kg SS/d with specific acetate, propionate, and butyrate removal rates of 111, 28, and 64 mol/g SS/d. Addition of moderate (26 mM) calcium levels inhibited growth and altered the structure of granules. The general cellular, growth, stability, and performance features of these ecoengineered granules are described and discussed in relation to their use as improved biomethanation starter cultures.


[Detection of tuberculosis in infants and preschool children].
The paper analyzes 367 case histories of babies, infants and preschool children treated for local tuberculosis at a specialized pediatric unit in 1977-1996. It is ascertained that tuberculosis was detected in 55% of children on their referral for medical aid and in 45% on prophylactic examinations. Prophylactic examinations detected tuberculosis of the intrathoracic lymph nodes more frequently (72.7%) and primary tuberculosis less frequently (26.7%). On referrals, tuberculosis of the intrathoracic lymph nodes, primary tuberculosis, and other forms of pulmonary tuberculosis were diagnosed in 68.8, 25.0, 6.2%, respectively. When tuberculosis was identified on referrals, pulmonary tuberculosis was much more commonly complicated. To form a tuberculosis risk group and to make prophylactic antituberculosis measures are an inherent condition for early detection of tuberculosis.


Kinetic Control over Morphology of Nanoporous Graphene on Surface.
On-surface synthesis of high-quality nanoporous graphene (NPG) for application in nanotechnology and nanodevices remains challenging. Rational design of molecular precursors and proper kinetic control over the reaction process are the two key factors to tune the synthesis. Herein, we report a detailed study of the coupling reactions of a planar halogen-substituted nanographene molecular precursor, hexaiodo-peri-hexabenzocoronene (I6 -HBC), on the Au(111) surface in the synthesis of NPG. The influence of three basic kinetic processes - molecular adsorption, migration, and coupling - on the synthesis was investigated. The results show that the HBC molecules deposited at low temperature predominantly desorb from the Au(111) surface during the annealing process, whereas depositing the precursor molecules onto a hot surface (700 K) can lead to the formation of NPG. However, at such a high surface temperature, simultaneous intermolecular dehydrogenative coupling between HBC monomers can hinder the ordered growth of NPG through Ullmann coupling. Moreover, the deposition rate of the precursors greatly influences the growth morphology of the NPG nanostructures.


Impact of Malaria Diagnostic Technologies on the Disease Burden in the Sub-Saharan Africa.
Worldwide, transmission of emerging and reemerging malaria infections poses a significant threat to human health in the Sub-Saharan Africa, one that can quickly overwhelm public health resources. While the disease burden of malaria in the Sub-Saharan Africa appears to be on a gradual decline, it is characterized by spatial and temporal variability occasioning a sorry state for the Global South Countries. New evidence on long-term complications of malaria heightens our awareness of its public health impact. Given the likelihood of misdiagnosis, and the unknown levels of malaria transmission across different landscapes, many missed opportunities for prevention occur. Africa's population growth, unplanned urbanization, habitat destruction, and trans-border travel are contributing to a rise in the calamitous epidemiology of malaria. Despite empirical statistics demonstrating a downward trend in the malaria disease burden attributable to the scale-up of multiple control strategies, including new diagnostic technologies, malaria remains a global threat to human health in Sub-Sahara Africa. Malaria is a severe public health threat globally, despite several advancements and innovations in its control. Six species of the genus Plasmodium including Plasmodium malariae, Plasmodium falciparum, Plasmodium cynomolgi, Plasmodium knowlesi, Plasmodium ovale, and Plasmodium vivax are known to infect humans. However, greatest disease burden and fatalities are caused by Plasmodium falciparum. Globally, about 3 billion individuals are at risk of contracting malaria disease every year, with over 400,000 fatalities reported in the Sub-Saharan Africa. World Health Organization (WHO) 2018 malaria report indicated that approximately 405,000 mortalities and 228 million cases were reported worldwide, with Africa carrying the highest disease burden. Over the last decade, there has been a significant decline in malaria deaths and infections, which may be related to the availability of effective diagnostic techniques. However, in certain areas, the rate of decline has slowed or even reversed the gains made so far. Accurate diagnosis, adequate treatment, and management of the disease are critical WHO-set goals of eliminating malaria by 2030. Microscopy, rapid diagnostic tests (RDTs), nucleic acid amplification tests (NAATs), and biosensors are all currently accessible diagnostic methods. These technologies have substantial flaws and triumphs that could stymie or accelerate malaria eradication efforts. The cost, ease, accessibility, and availability of skilled persons all influence the use of these technologies. These variables have a direct and indirect ramification on the entire management portfolio of patients. Despite the overall decline in the malaria disease burden driven partly by new diagnostic technologies, a sobering pattern marked by limited number of studies and spatial as well as temporal heterogeneity remains a concern. This review summarizes the principle, performance, gaps, accomplishments, and applicability of numerous malaria diagnostic techniques and their potential role in reducing the malaria disease burden in Sub-Saharan Africa.


Increased 30-day mortality in patients with diabetes undergoing surgery for colorectal cancer.
The primary aim of the study was to determine whether preexisting diabetes is associated with increased 30-day mortality after curative resection of colorectal cancer (CRC). The association between antidiabetic treatment and 30-day mortality was also examined. Patients diagnosed with CRC between 1 January 2003 and 31 December 2012 were identified through the Danish Colorectal Cancer Group National Clinical Database (DCCG). The Danish National Patient Register (NPR) collated all hospital contacts in Denmark and the diagnosis of diabetes was identified by combining NPR data with the use of antidiabetic drugs identified through the Danish National Prescription Registry and DCCG. The 30-day mortality was examined by the Kaplan-Meier method with the log-rank test and the Cox regression model used to test statistical significance. The study included 29 353 patients, of whom 3250 had preexisting diabetes. The 30-day mortality was significantly increased in patients with CRC and preexisting diabetes (adjusted hazard ratio 1.17, 95% CI 1.01-1.35, P = 0.03). The type of antidiabetic medication used was not associated with 30-day mortality. Preexisting diabetes was associated with a higher short-term mortality in patients with CRC. No association between the type of antidiabetic medication and short-term mortality could be shown.


Differential accumulation of leucine and methionine in red and green pea aphids leads to different fecundity in response to nitrogen fertilization.
Nitrogen fertilization affects plants directly and herbivorous insects indirectly. Although insect species and even genotypes are known to differ in their responses to nitrogen fertilization, the physiological and molecular mechanisms remain unclear. This study assessed the fecundity and related regulatory signaling pathways in the green and red morphs of pea aphid (Acyrthosiphon pisum) feeding on Medicago truncatula with and without nitrogen fertilization. Nitrogen fertilization significantly increased foliar amino acid concentrations and consequently increased the concentrations of several individual essential amino acids in body tissue of the green morph. The increased concentration of Leu, Ile, Met and Val was consistent with enhanced biosynthesis of these amino acids in the endosymbiont Buchnera. Under nitrogen fertilization, Leu and Met accumulated in the green morph enhanced the target of rapamycin (TOR) signaling pathway, which consequently increased fecundity by promoting vitellogenin synthesis. In the red morph, however, nitrogen fertilization did not change the concentration of essential amino acids, TOR signaling or fecundity. Specific amino acids accumulation and the nutrient transduction pathway in pea aphids are responsible for genotype-specific fecundity in response to nitrogen fertilization, which could be used as potential target for pest control. © 2018 Society of Chemical Industry.


Cells and cytokines involved in the pathogenesis of sarcoidosis.
Granulomatous inflammation develops under the regulatory influence of cytokines produced by local mononuclear phagocytes, T cells, dendritic cells, fibroblasts, and other local cells. In sarcoidosis, granulomatous inflammation is characterized by dominant expression of T helper 1 (Th1) cytokines such as IFN gamma and interleukin (IL)-2 with low levels of expression of T helper 2 (Th2) cytokines such as IL4 and IL5. Recent studies show that the cytokine IL12, the most important regulator of Th1 immune responses currently known, is upregulated at sites of inflammation in sarcoidosis. In particular, enhanced expression of IL12 is seen in sarcoid lung and lymph node, along with dysregulated production of IL12 by stimulated and unstimulated sarcoid alveolar macrophages. The known dependence of granulomatous inflammation on type 1 cytokines (IFN gamma, IL12) in many experimental models of granulomatous disease makes it likely that these cytokines function in a similar fashion in the initiation and maintenance of granulomatous inflammation in sarcoidosis. Whether these same type 1 cytokines drive granulomatous inflammation in patients with extensive fibrocystic lung disease remains unknown. TGF beta, a known inhibitor of IL12 and IFN gamma production, is produced at higher levels by lung cells from those patients who undergo remission of their disease, suggesting that TGF gamma is important in downregulating granulomatous inflammation in sarcoidosis. These studies offer new insight into the molecular mechanisms of granuloma formation in sarcoidosis and provide a framework for developing new therapeutic strategies for the treatment of this disease.


Self-powered integrated microfluidic point-of-care low-cost enabling (SIMPLE) chip.
Portable, low-cost, and quantitative nucleic acid detection is desirable for point-of-care diagnostics; however, current polymerase chain reaction testing often requires time-consuming multiple steps and costly equipment. We report an integrated microfluidic diagnostic device capable of on-site quantitative nucleic acid detection directly from the blood without separate sample preparation steps. First, we prepatterned the amplification initiator [magnesium acetate (MgOAc)] on the chip to enable digital nucleic acid amplification. Second, a simplified sample preparation step is demonstrated, where the plasma is separated autonomously into 224 microwells (100 nl per well) without any hemolysis. Furthermore, self-powered microfluidic pumping without any external pumps, controllers, or power sources is accomplished by an integrated vacuum battery on the chip. This simple chip allows rapid quantitative digital nucleic acid detection directly from human blood samples (10 to 105 copies of methicillin-resistant Staphylococcus aureus DNA per microliter, ~30 min, via isothermal recombinase polymerase amplification). These autonomous, portable, lab-on-chip technologies provide promising foundations for future low-cost molecular diagnostic assays.


Tissue-Engineered Larynx: Future Applications in Laryngeal Cancer.
This article reviews the latest developments in tissue engineering for the larynx with a specific focus on the treatment of laryngeal cancer. Challenges in tissue engineering a total larynx can be divided into scaffold design, methods of re-mucosalization, and how to restore laryngeal function. The literature described a range of methods to deliver a laryngeal scaffold including examples of synthetic, biomimetic, and biological scaffolds. Methods to regenerate laryngeal mucosa can be divided into examples that use a biological dressing and those that engineer a new mucosal layer de novo. Studies aiming to restore laryngeal function have been reported, but to date, the optimum method for achieving this as part of a total laryngeal transplant is yet to be determined. There is great potential for tissue engineering to improve the treatments available for laryngeal cancer within the next 10 years. A number of challenges exist however and advances in restoring function must keep pace with developments in scaffold design.


Relationship of microbial communities and suppressiveness of Trichoderma fortified composts for pepper seedlings infected by Phytophthora nicotianae.
The understanding of the dynamic of soil-borne diseases is related to the microbial composition of the rhizosphere which is the key to progress in the field of biological control. Trichoderma spp. is commonly used as a biological control agent. The use of next generation sequencing approaches and quantitative PCR are two successful approaches to assess the effect of using compost as substrate fortified with two Trichoderma strains (Trichoderma harzianum or Trichoderma asperellum) on bacterial and fungal communities in pepper rhizosphere infected with Phytophthora nicotianae. The results showed changes in the bacterial rhizosphere community not attributed to the Trichoderma strain, but to the pathogen infection, while, fungi were not affected by pathogen infection and depended on the type of substrate. The Trichoderma asperellum fortified compost was the most effective combination against the pathogen. This could indicate that the effect of fortified composts is greater than compost itself and the biocontrol effect should be attributed to the Trichoderma strains rather than the compost microbiota, although some microorganisms could help with the biocontrol effect.


Current scenario of COVID-19 vaccinations and immune response along with antibody titer in vaccinated inhabitants of different countries.
The COVID-19 pandemic challenges have been only partially addressed so far. The pathogenicity of SARS-CoV-2 is considered the combination of severe and high infectivity. Herdimmunity is attained when a critical proportion of the population is immune, providing the virus with fewer chances to spread locally. To overcome the rising tide of the COVID-19 pandemic, efficacious and safe vaccines providing defensive and long-lasting immunity responses are urgently needed.Vaccines that induce virus-neutralizing antibodies with great affinity can optimally fight against infection. Worldwide, over 120 novel vaccine candidates, including live-attenuated, inactivated, viral-vectored nonreplicating and replicating, peptide- and protein-based, and nucleic acid-based approaches are in the process of preclinical and clinical trials (phase 1-4). In addition to comprehensive safety assessments and immune responses, precise clinical management is also important for trials of vaccines. The recent emergence of different variants of SARS-CoV-2 is becoming a new threat for the world and a challenge for scientists to introduce the most influential vaccine against COVID-19. The possibility of natural and vaccine-induced immunity in variants finds it necessary to establish next-generation vaccines, which generate general neutralization against existing and future variants. Here, we summarize the cellular and humoral responses of SARS-CoV-2, current progress in vaccination development, the antibody titer response of available phase 4 vaccinations in vaccinated populations of different countries worldwide, and the success and challenges ahead of vaccine development.


Oncostatin M signaling in human glioma cell lines.
We have recently found that oncostatin M (OSM) is overexpressed in most human brain tumors. The effects of OSM are unclear with conflicting reports of growth stimulatory or inhibitory effects in various cell types. The aim of this study was to investigate the effects of OSM in 5 glioma cell lines and 7 short-term cultures of human gliomas and in normal cultured human astrocytes. None of the cell lines and short-term cultured tumor cells expressed OSM in vitro. OSM signals through a gp130 containing receptor complex over the JAK/STAT pathway. Immunofluorescence and RT-PCR analysis showed that the tumor cells express gp130 and the other receptor components, LIFRbeta and OSMRbeta. OSM treatment induced phosphorylation of STAT3 and STAT1 indicating presence of a functional JAK/STAT pathway. No OSM effect on proliferation was observed. OSM gave no protective effects against tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced cytotoxicity.


[Effects of peroxisome proliferators-activated receptor-gamma on the function of the vital organs in rats with pancreatitis].
To observe the effects of peroxisome proliferators-activated receptor-gamma (PPARgamma) on the function of the vital organs in rats with pancreatitis. Acute pancreatitis (AP) was induced in 30 male SD rats by ductal injection of 4% sodium taurocholate at 1.0 ml/kg. The rats received subsequent intravenously injection of 0.3 mg/kg of PPARgamma ligand (rosiglitazone, n=10), PPARgamma antagonist (GW9662, n=10) followed 10 min later by rosiglitazone administration at 0.3 mg/kg, or left untreated (AP model group, n=10). Another 10 male SD rats receiving no particular treatment served as the control group. The rats were sacrificed 6 h after the operation, and blood samples were collected for measurement of the biochemical indices of the vital organs. The histological changes of the pancreas and portal vein blood endotoxin content were examined. The rats in AP group and GW9662 group showed significantly higher level of the biochemical indices for the vital organs, pathological scores of the pancreas and portal vein blood endotoxin content were significantly higher in the control group and roglitazone-treated groups (P<0.05). PPARgamma ligand roglitazone can significantly ameliorate multiple organ injuries and effectively protect the functions of the organs in rats with experimental pancreatitis.


Biomechanical rationale for intentionally inclined implants in the posterior mandible using 3D finite element analysis.
Since natural dental arches usually form Monson or Spee occlusal curvatures among the posterior teeth, they tend to incline in mesial and lingual directions. The purpose of this study was to examine the biomechanical rationale for placing implants according to these curvatures in the mandibular posterior region. A 3-dimensional finite element model was created in which 2 implants were placed in the mandibular molar area. Stress distribution in the bone around the implants was analyzed under different distal implant inclinations. Stress in the cervical area of the mesial and distal implants and the surrounding bone was higher when the implants were placed parallel to each other compared to when the distal implant was placed with a mesial or mesiolingual inclination. The slightly smaller effect of a mesiolingual inclination compared to a mesial inclination can be explained by the large cantilever on the buccal side of the superstructure. Within the limitations of this study, it was suggested that there is a biomechanical rationale for placing implants in the posterior mandible area with a mesial inclination similar to that of natural teeth. It was also suggested that too much lingual inclination can put the implant at risk of overload.


[Effect of smoke-free medical school on smoking behavior of medical students].
The purpose of this study was to investigate the effect of designating a medical school environment as smoke-free on the smoking behavior of medical students. The total environment of a medical school in Japan was designated as smoke-free in 2004. Smoking behavior was surveyed among approximately 640 students in each year during the period 2001-2007 (response rate 91.2%). Smoking rates were also monitored among each year's freshmen during their time at the school, before and after 2004. Attitudes to smoking among both current smokers and those who had quit smoking were also investigated. RESULTED: Smoking rates among all students declined after the medical school was declared smoke-free in 2004; the rates were highest in 2002 (41.2%) and lowest in 2007 (22.1%) among men. Smoking rates among each year's freshmen tended to increase as the school year progressed before 2004, but they tended to decrease after 2004. Comparison of smoking rates among identical students showed a decline from 36.0% in 2003 to 25.6% in 2004 (P < 0.05). The rate of smokers wishing to quit smoking increased significantly from 39.1% in 2003 to 60.2% in 2004 (P < 0.01). 20.8% of students who had quit smoking and 50.0% of students who had continued to smoke felt that they would not be confident about educating their patients in smoking cessation (P < 0.01). Making a medical school environment smoke-free could be very effective means to motivating medical students to change their attitudes to smoking and to quit.


An assessment of fatigability following nerve transfer to reinnervate elbow flexor muscles.
Improvements in the evaluation of outcomes following peripheral nerve injury are needed. Recent studies have identified muscle fatigue as an inevitable consequence of muscle reinnervation. This study aimed to quantify and characterize muscle fatigue within a standardized surgical model of muscle reinnervation. This retrospective cohort study included 12 patients who underwent Oberlin nerve transfer in an attempt to restore flexion of the elbow following brachial plexus injury. There were ten men and two women with a mean age of 45.5 years (27 to 69). The mean follow-up was 58 months (28 to 100). Repeated and sustained isometric contractions of the elbow flexors were used to assess fatigability of reinnervated muscle. The strength of elbow flexion was measured using a static dynamometer (KgF) and surface electromyography (sEMG). Recordings were used to quantify and characterize fatigability of the reinnervated elbow flexor muscles compared with the uninjured contralateral side. The mean peak force of elbow flexion was 7.88 KgF (sd 3.80) compared with 20.65 KgF (sd 6.88) on the contralateral side (p < 0.001). Reinnervated elbow flexor muscles (biceps brachialis) showed sEMG evidence of fatigue earlier than normal controls with sustained (60-second) isometric contraction. Reinnervated elbow flexor muscles also showed a trend towards a faster twitch muscle fibre type. The assessment of motor outcomes must involve more than peak force alone. Reinnervated muscle shows a shift towards fast twitch fibres following reinnervation with an earlier onset of fatigue. Our findings suggest that fatigue is a clinically relevant characteristic of reinnervated muscle. Adoption of these metrics into clinical practice and the assessment of outcome could allow a more meaningful comparison to be made between differing forms of treatment and encourage advances in the management of motor recovery following nerve transfer. Cite this article: Bone Joint J 2019;101-B:867-871.


Cortical morphometry in attention deficit/hyperactivity disorder: Contribution of thickness and surface area to volume.
Although lower brain volume is a consistent neuroimaging finding in attention deficit hyperactivity disorder (ADHD), we lack an understanding of whether this effect is driven by changes in cortical thickness or surface area, which are governed by distinct neurodevelopmental processes. This study examined ADHD-control differences in cortical thickness, surface area and volume, and tests whether thickness and surface area mediates any observed volume differences. Magnetic resonance imaging (MRI) data was collected from 35 males with ADHD-combined type and 35 typically developing control participants aged 9-17 years. Morphometric measures were examined for between group differences and the specific contribution of surface area and thickness to group differences in volume tested using mediation analysis. Individuals with ADHD had smaller total cortical volume (7.3%), surface area (4.3%), and mean cortical thickness (2.8%) compared to controls. Differences were pronounced in frontal and parietal lobes. Variance in volume as a function of ADHD diagnosis was accounted for at least in part by the relationship between diagnosis and each of cortical thickness and surface area, with regional variation in the relative contributions of these measures. The surface area of the precuneus was a major driver of volume differences, attesting to the potential relevance of this region for neurodevelopment in ADHD. Both surface area and cortical thickness play a significant mediating role in determining diagnostic differences in volume, with regional variation in the contribution of thickness and surface area to those volume differences, highlighting the importance of examining both cortical thickness and surface area in examining ADHD.


Relay Selection for Dual-Hop Cooperative Ambient Backscatter Communication Systems.
Previous works only focus on the optimization design for the dual-hop cooperative ambient backscatter communication (AmBC) system with single-relay selection. The impact of relay selection on the outage performance of dual-hop cooperative AmBC systems is still missing. Motivated by this, in this paper, we investigate the outage performance of a dual-hop cooperative AmBC system with single-relay selection, where the backscatter link shares the receiver with the cellular link and the harmful direct-link interference (DLI) is mitigated by using successive interference cancellation (SIC). In the system considered, the selected relay has dual functions. One is to forward message for the cellular link, and the other is to act as the radio-frequency (RF) source for the backscatter device (BD). Specifically, after proposing two novel single-relay selection schemes (RSSs), namely reactive RSS and proactive RSS, we derive the closed-form outage probability (OP) expressions for both RSSs, which can be performed in a distributed manner. To gain more insights, the asymptotic OPs at high signal-to-noise ratio (SNR) are explored and the outage performance comparison between the reactive RSS and proactive RSS are also provided. Results show that the proposed reactive RSS is outage-optimal among all possible single-relay selection schemes. The theoretical analysis is validated by Monte Carlo simulations. The results also show that the relay selection scheme, the number of relays, the location of BD, and the reflection coefficient of BD have great impact on the outage performance of cooperative AmBC systems.


["MODERN OVER THE GOOD AND OLD"].
Modern dermatology is a reflection of the advances achieved in the general medical world. Thus, in recent years, dermatology encompasses many different fields and consequently, various subspecialties were created. In addition to dermatopathology and dermatosurgery, which are formal subspecialties, other fields of expertise include: autoimmune diseases, especially bullous diseases, hair and nail disorders, allergic diseases, infectious diseases and pigmented lesion clinics and oncodermatology. This current issue of "Harefuah" incorporates research and review articles from experts of the different subspecialties mentioned. "Do not favor the modern over the good and old" means that alongside innovations one must not forget the traditional approaches. Nowadays, a good medical practice requires a comprehensive and broad vision that includes up-to-date information on diagnostic modalities and advanced treatments in conjunction with the traditional diagnostic tools and therapies (which usually cost less), thus allowing patients to benefit from a broader spectrum of treatment options.


Demographic and clinical predictors of spirituality in advanced cancer patients: a randomized control study.
To study the influence of cancer patients' sociodemographic and clinical characteristics in their spiritual beliefs and attitudes. Patients' sociodemographic and clinical characteristics may have an important role in their spirituality. Failure to control these factors can lead to a false estimation on patients' spiritual beliefs. Previous studies have found that age, gender and health status associate with spiritual attitudes and beliefs.Design. Survey. The Spiritual Involvement and Beliefs Scale was administered to 82 cancer patients. Demographic characteristics, disease status and treatment regimen were recorded. Among the most significant correlations were those between gender and all the subscales, cancer diagnosis, existential/meditative subscale, radiotherapy treatment and external/ritual, internal/fluid and existential meditative. In the prediction of spirituality, the contribution of gender, age, years of education, performance status and radiotherapy is high. Acknowledging the specific patients' demographic and medical characteristics, such as female gender, old age, years of education, performance status and radiotherapy treatment, contributes to the prediction of patients' spiritual beliefs and attitudes. Addressing spiritual needs in palliative care among the dying needs to be a priority and could be a crucial aspect of psychological functioning, especially when considering certain demographic and clinical characteristics.


Pathophysiology of cellulite: Possible involvement of selective endotoxemia.
The most relevant hallmarks of cellulite include a massive protrusion of superficial adipose tissue into the dermis, reduced expression of the extracellular glycoprotein fibulin-3, and an unusually high presence of MUSE cells in gluteofemoral white adipose tissue (gfWAT) that displays cellulite. Also typical for this condition is the hypertrophic nature of the underlying adipose tissue, the interaction of adipocytes with sweat glands, and dysfunctional lymph and blood circulation as well as a low-grade inflammation in the areas of gfWAT affected by cellulite. Here, we propose a new pathophysiology of cellulite, which connects this skin condition with selective accumulation of endogenous lipopolysaccharides (LPS) in gfWAT. The accumulation of LPS within a specific WAT depot has so far not been considered as a possible pathophysiological mechanism triggering localized WAT modifications, but may very well be involved in conditions such as cellulite and, secondary to that, lipedema.


Octahedral {Ta6I12} Clusters.
Ta powder reacts with I2 at 650 °C with the formation of Ta6I14, which belongs to the family of {M6(μ-X)12} clusters. It undergoes aquation with the formation of the intensely colored [Ta6I12(H2O)6]2+. The crystal structure was determined for [Ta6I12(H2O)6](BPh4)2·xH2O (Ta-Ta 2.9322(6) Å, Ta-I 2.8104(7) Å, Ta-O 2.3430(5) Å). With DMF, [Ta6I12(DMF)6]I2·xDMF was isolated (Ta-Ta 2.9500(2) Å, Ta-I 2.8310(4) Å, Ta-O 2.2880(7) Å). Cyclic voltammetry of [Ta6I12(H2O)6]2+ shows two consecutive quasi-reversible one-electron oxidations (E1/2 0.61 and 0.92 V vs Ag/AgCl). Reaction of Ta6I14 with Bu4NCN yields (Bu4N)4[Ta6I12(CN)6]·xCH3CN (Ta-Ta 2.9777(4) Å, Ta-I 2.8165(6) Å, Ta-C 2.2730(7) Å). Quantum chemical calculations reproduce well the experimental geometry of the aqua complex and show the essentially Ta-centered nature of both the HOMO and LUMO. The long-term stability of [Ta6I12(H2O)6]2+ solutions can be greatly enhanced in the presence of polystyrenesulfonate (PSS), which forms nanoparticle associates with the aqua complex in water (ca. 1 cluster per 3 PSS monomeric units).


Transposition of canines.
Eleven cases of canine transposition, in both the maxillary and the mandibular arches, have been reported. Canines were involved in every case. Alignment of the teeth in their transposed position or orthodontic movement to their normal position in the arch are alternatives in treatment. However, should an involved tooth be seriously affected by caries, developmental defects, or trauma, extraction may be the preferred treatment, with alignment of the remaining tooth and closure of the space.


Reassessment of MxiH subunit orientation and fold within native Shigella T3SS needles using surface labelling and solid-state NMR.
T3SSs are essential virulence determinants of many Gram-negative bacteria, used to inject bacterial effectors of virulence into eukaryotic host cells. Their major extracellular portion, a ∼50 nm hollow, needle-like structure, is essential to host cell sensing and the conduit for effector secretion. It is formed of a small, conserved subunit arranged as a helical polymer. The structure of the subunit has been studied by electron cryomicroscopy within native polymers and by solid-state NMR in recombinant polymers, yielding two incompatible atomic models. To resolve this controversy, we re-examined the native polymer used for electron cryomicroscopy via surface labelling and solid-state NMR. Our data show the orientation and overall fold of the subunit within this polymer is as established by solid-state NMR for recombinant polymers.


A comparison of fruit and vegetable intake estimates from three survey question sets to estimates from 24-hour dietary recall interviews.
Fruit and vegetable (F/V) intake surveillance can provide information critical to the design and evaluation of interventions and the assessment of progress toward national intake objectives. The CDC's Youth Risk Behavior Surveillance System (YRBSS) assesses F/V intake among high school students using six questions about the frequency of intake in times per day. It is not known whether F/V intake frequency in times per day can be used as a proxy for intake in servings per day. To compare F/V intake estimates based on responses to three sets of survey questions, including the standard set of six YRBSS questions, with criterion F/V intake in servings per day based on data from 24-hour dietary recall interviews. Study participants were 610 high school students who completed an in-class questionnaire and three telephone-administered 24-hour dietary recall interviews. The questionnaire asked students how many times they consumed 100% fruit juice and ate fruit, carrots, potatoes, green salad, and other vegetables during the "past 7 days" (set 1), the number of times they did so "yesterday" (set 2), and the number of cup-equivalents of fruits and vegetables they consumed per day (set 3). Mean estimated F/V intake either as "times/day" or "servings/day" and the percentage of students whose estimated F/V intake was ≥1, ≥2, and ≥3 times/day or servings/day. t tests and corrected Pearson correlations were used to compare F/V intake estimates based on survey question responses with estimates based on responses to the 24-hour dietary recall interviews. Mean F/V intake estimates (in times/day or servings/day) based on responses to all sets of survey questions were significantly more than servings/day estimates based on responses to the 24-hour dietary recall interviews, and the percentages of students meeting each intake cutpoint were also more. Of the three sets of survey questions, the standard YRBSS questions produced estimates and percentages that were most consistently closest to 24-hour dietary recall interview estimates. For brief self-administered questionnaires of high school students, the current YRBSS questions are recommended for monitoring F/V intake even though mean intake estimates in times/day will likely be higher than, and are not a proxy for, mean intake estimates in servings/day.


[Operational impact of the use of insecticidal products on Aedes aegypti larvae in Havana province].
In spite of the huge efforts of the Aedes aegypti eradication program in Cuba, there are still certain infestation indexes favoring the development of outbreaks or epidemics in some regions of the country. Havana province holds a leading position in this negative indicator, in which the use of insecticides plays an important role. To evaluate the impact of the use of insecticides in the development of drug resistance by this species in Havana. Fifteen Ae. aegypti strains from the fifteen municipalities of the province were used. They were all collected in 2008. The level of susceptibility to insecticides was measured by means of the WHO-recommended bioassays. Sixty percent of the strains were susceptible to chlorpirifos; more resistance to pyrethroid cypermethrin was observed followed by lambdacyalothrin and cifluthrin. The insecticide Chlorpirifos is a good candidate to be used with pyrethroids, on a rotational scheme, to delay the development of resistance to pyrethroids in Ae. aegypti vectors in Havana province.


Prioritization of mental health services in Oregon.
The Oregon Health Plan is an approach to health care reform that increases access to mental health and chemical dependency services. A key feature is the integration of mental and physical health care. The mental health community had to educate policy makers about the importance of mental health and chemical dependency services. They constructed a prioritized list of mental health and chemical dependency services and interdigitated the list with the set of physical health services. The result is a unique attempt to develop a seamless health care system that minimizes discrimination against persons affected by mental illness. The opportunity to achieve parity for mental health must not be delayed or compromised; to do so would worsen the lives of persons already affected by the trauma and stigma associated with mental illness.


Expression and activity of acid-sensing ion channels in the mouse anterior pituitary.
Acid sensing ion channels (ASICs) are proton-gated cation channels that are expressed in the nervous system and play an important role in fear learning and memory. The function of ASICs in the pituitary, an endocrine gland that contributes to emotions, is unknown. We sought to investigate which ASIC subunits were present in the pituitary and found mRNA expression for all ASIC isoforms, including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4. We also observed acid-evoked ASIC-like currents in isolated anterior pituitary cells that were absent in mice lacking ASIC1a. The biophysical properties and the responses to PcTx1, amiloride, Ca2+ and Zn2+ suggested that ASIC currents were mediated predominantly by heteromultimeric channels that contained ASIC1a and ASIC2a or ASIC2b. ASIC currents were also sensitive to FMRFamide (Phe-Met-Arg-Phe amide), suggesting that FMRFamide-like compounds might endogenously regulate pituitary ASICs. To determine whether ASICs might regulate pituitary cell function, we applied low pH and found that it increased the intracellular Ca2+ concentration. These data suggest that ASIC channels are present and functionally active in anterior pituitary cells and may therefore influence their function.


[Sex-dependent differences in sweating of normal probands and atopic patients in cardiovascular stress].
Sweating (perspiratio sensibillis) due to cholinergic sweat gland activity serves predominantly for thermoregulation and is triggered among others by physical stress. Individuals suffering from atopic eczema usually respond to sweating with generalized itching. Different sweat regulation in atopic patients and healthy controls under cholinergic stimulation and heat chamber provocation tests has already been examined in several studies. However, no clinical trial has yet been done on atopic sweat regulation during physical stress. Sex-specific sweat secretion rates have not been evaluated. In our trial we compared sweat amounts of male and female atopics (14 m, 10 f) and healthy controls (14 m, 10 f) during and after physical activity on a bicycle ergometer. We used a special sweat collector system reliable even at intensive body movement. The individual stress limit had been determined by previous endurance training with lactate level and heart rate measurement. We found a highly significant difference in maximum sweat amounts between atopics and controls. On average, healthy individuals (of both sexes) perspired nearly three times as much as atopic patients. Male controls perspired nearly twice as much as corresponding females. Among the atopics, sex-specific differences were found to be not statistically relevant.


Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts.
The existence and importance of tumor-initiating cells (TICs) have been supported by increasing evidence during the past decade. These TICs have been shown to be responsible for tumor initiation, metastasis, and drug resistance. Therefore, it is important to develop specific TIC-targeting therapy in addition to current chemotherapy strategies, which mostly focus on the bulk of non-TICs. In order to further understand the mechanism behind the malignancy of TICs, we describe a method to isolate and to characterize TICs in human sarcomas. Herein, we show a detailed protocol to generate patient-derived xenografts (PDXs) of human sarcomas and to isolate TICs by fluorescence-activated cell sorting (FACS) using human leukocyte antigen class I (HLA-1) as a negative marker. Also, we describe how to functionally characterize these TICs, including a sphere formation assay and a tumor formation assay, and to induce differentiation along mesenchymal pathways. The isolation and characterization of PDX TICs provide clues for the discovery of potential targeting therapy reagents. Moreover, increasing evidence suggests that this protocol may be further extended to isolate and characterize TICs from other types of human cancers.


A two-stage approach to induction and intubation of two infants with Pierre Robin Sequence using a LMA Classic™ and Air-Q®: two cases report.
The laryngeal mask airway (LMA) Classic™ and Air-Q® are supralaryngeal devices used for airway management in routine and difficult pediatric airways. We describe a novel two-stage technique of insertion of the LMA Classic™ awake prior to induction of anesthesia, to assure oxygenation and ventilation, and after induction removal and placement of the Air-Q® for intubation using the flexible fiberoptic bronchoscope. The LMA Classic's™ pliable design and relatively small size allow it to be easily placed in awake infants. In contrast, the Air-Q® is an excellent device for intubation because of its larger internal diameter and removable 9 mm adapter. Our goal was to reduce unpredictability and potentially increase the safety of induction of anesthesia and intubation in infants with Pierre Robin sequence. By using these devices in a two-stage approach we created a technique for consistent oxygenation, ventilation, and intubation in these infants.


A laid-back trip through the Hennigian Forests.
This paper is a comment on the idea of matrix-free Cladistics. Demonstration of this idea's efficiency is a major goal of the study. Within the proposed framework, the ordinary (phenetic) matrix is necessary only as "source" of Hennigian trees, not as a primary subject of the analysis. Switching from the matrix-based thinking to the matrix-free Cladistic approach clearly reveals that optimizations of the character-state changes are related not to the real processes, but to the form of the data representation. We focused our study on the binary data. We wrote the simple ruby-based script FORESTER version 1.0 that helps represent a binary matrix as an array of the rooted trees (as a "Hennigian forest"). The binary representations of the genomic (DNA) data have been made by script 1001. The Average Consensus method as well as the standard Maximum Parsimony (MP) approach has been used to analyze the data. The binary matrix may be easily re-written as a set of rooted trees (maximal relationships). The latter might be analyzed by the Average Consensus method. Paradoxically, this method, if applied to the Hennigian forests, in principle can help to identify clades despite the absence of the direct evidence from the primary data. Our approach may handle the clock- or non clock-like matrices, as well as the hypothetical, molecular or morphological data. Our proposal clearly differs from the numerous phenetic alignment-free techniques of the construction of the phylogenetic trees. Dealing with the relations, not with the actual "data" also distinguishes our approach from all optimization-based methods, if the optimization is defined as a way to reconstruct the sequences of the character-state changes on a tree, either the standard alignment-based techniques or the "direct" alignment-free procedure. We are not viewing our recent framework as an alternative to the three-taxon statement analysis (3TA), but there are two major differences between our recent proposal and the 3TA, as originally designed and implemented: (1) the 3TA deals with the three-taxon statements or minimal relationships. According to the logic of 3TA, the set of the minimal trees must be established as a binary matrix and used as an input for the parsimony program. In this paper, we operate directly with maximal relationships written just as trees, not as binary matrices, while also using the Average Consensus method instead of the MP analysis. The solely 'reversal'-based groups can always be found by our method without the separate scoring of the putative reversals before analyses.


Electrophysiologic and antiarrhythmic effects of nitroglycerin in man.
The electrophysiologic properties and the arrhythmic disposition of the human heart were determined in 16 patients before and after the intravenous administration of nitroglycerin (0.25 and 0.50 micrograms/kg/min). At the higher dose, nitroglycerin significantly shortened the atrial and ventricular effective refractory periods and bundle of His-Purkinje conduction (HV interval). Otherwise, a paucity of general electrophysiologic effects was noted; atrial conduction intervals were not altered, and although a trend toward shortening occurred, the sinus node function studies (conduction and recovery times) and atrioventricular nodal conduction did not change significantly with nitroglycerin. Nitroglycerin demonstrated antiarrhythmic properties; the ventricular echo zone and the number of ventricular echo-repetitive ventricular response beats following ventricular stimulation decreased significantly with nitroglycerin. Nitroglycerin ameliorated the tendency toward sustained repetitive ventricular response in 4 of 5 patients and obliterated the development of this tachyarrhythmia in 1. Although the precise mechanisms were not delineated by this study, it is clear, that nitroglycerin causes some change in the electrophysiologic properties of the human heart and that it appears to have (or elicit) beneficial antiarrhythmic effects.