Structure-activity study in the class of 6-(3'-hydroxyphenyl)naphthalenes leading to an optimization of a pharmacophore model for 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) inhibitors.
17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyzes the transformation of estrone (E1) into the most potent estrogen, estradiol (E2), which stimulates cell proliferation and decreases apoptosis. 17beta-HSD1 is often strongly overexpressed in estrogen-dependent diseases (like breast cancer and endometriosis). Thus, this over expressed enzyme is a promising novel target for the development of selective inhibitors, which could be used as drugs for the treatment of these diseases. Using a structure- and ligand-based approach, a pharmacophore model was proposed and a new class of non-steroidal inhibitors of 17beta-HSD1 was designed. Enzyme inhibition was evaluated in vitro using the human enzyme. After identification of the 6-(3'-hydroxyphenyl)-2-naphthol scaffold 1, the potency of this class of inhibitors was further improved by substitution of the 1-position of the naphthalene ring by a phenyl group (compound 18, IC(50)=20nM). Compound 18 also showed a good selectivity toward 17beta-HSD2 and the estrogen receptors alpha and beta.


Evaluation of NK-to-target cell binding and evidence for T cell conjugates by flow cytometry.
A flow cytometric methodology was set up to assess the binding capability of peripheral blood NK and T cells to the K562 tumor cell line. Differential side scatter characteristics between effectors and targets were used to analyze conjugated and unconjugated cells. The previous labeling of NK and T cells with anti-Leu 11c and anti-Leu 4 monoclonal antibodies, allowed the distinction between unconjugated non-fluorescent and conjugated fluorescent targets and the percentual evaluation of bound anti-Leu 11c(+) and anti-Leu 4(+) cells.


Appearance of circulating DNA during hemodialysis.
The appearance of circulating DNA during hemodialysis was investigated by use of a modified counterimmunoelectrophoresis assay capable of detecting as little as 0.02 to 0.05 microng of native DNA per milliliter of plasma. It was found that free DNA was regularly released during procedure in widely varying amounts which ranged as high as 5 microng/ml. Both the amount of plasma DNA and its rate of appearance increased progressively throughout the procedure and had no temporal correlation with the transitory early leukopenia that was previously described. Circulation in vitro of fresh blood through a dialysis coil also resulted in the appearance of plasma DNA suggesting that passage of blood through the coil itself can account, at least in part, for circulating DNA, presumably by release from leukocytes. Neither the presence (nor reversal) of the uremic state per se nor removal of inhibitors of the assay during hemodialysis are able to account for the findings. Whether free circulating DNA is of clinical importance is, as yet, unknown. A hypothesis is proposed linking chronic exposure to circulating intracellular materials, including DNA, to the accelerated atherosclerosis recently described as a late complication of hemodialysis. Currently, hemodialysis is the only clinical state known to be characterized by the presence of circulating DNA over long periods of time. Since this phenomenon is iatrogenically induced, further exploration of possible pathogenetic implications seems particularly important.


Response of the airways and autonomic nervous system to acid perfusion of the esophagus in patients with asthma: a laboratory study.
Gastro-esophageal reflux disease (GERD) predisposes to airway disease through a vagally-mediated esophago-bronchial reflex. This study investigates this vagal response to esophageal acid perfusion. 40 asthmatics with mild stable asthma participated. Each subject underwent spirometry and autonomic function testing (valsalva maneuver, heart rate response to deep breathing and to standing from supine position) four times: a) before intubation, b) after intubation, and then immediately after perfusion with, in random order, c) concentrated lime juice solution (pH 2-3) and d) 0.9% saline. Subjects were blinded to the solution perfused. Asthmatics were of mean (SD) age 34.3 years (1.3), and 67.5% of them were females. pH monitoring demonstrated that 20 subjects had abnormal reflux and 20 did not. In each group 10 subjects had a positive GERD symptom score. Following perfusion with acid compared to saline, all subjects showed significant decreases in FEV1 and PEFR and significant increases in the mean valsalva ratio and heart rate difference on deep breathing from baseline values, but no changes in FVC or heart rate ratio on standing. There were no significant differences in any of the parameters between subjects with and without reflux. Acid stimulation of the distal esophagus results in increased parasympathetic activity and concomitant broncho-constriction in asthmatics irrespective of their reflux state. This strengthens the hypothesis that GER triggers asthma-like symptoms through a vagally mediated esophago-bronchial reflex and encourages a possible role for anti-cholinergic drugs in the treatment of reflux-associated asthma.


One-step thoracotomy approach for atrial-esophageal fistula repair without cardiopulmonary bypass.
Atrial-esophageal fistula is an extremely rare disease and a life-threatening complication after catheter ablation for atrial fibrillation. There is no consensus on the management or repair for atrial-esophageal fistula which has a high mortality rate. Here, we describe a lateral thoracotomy approach focused on simplifying the repair procedure for atrial-esophageal fistula in two patients.


Lipase-producing microorganisms from a Kenyan alkaline soda lake.
Lipolytic enzyme production of 150 isolated strains from samples of Lake Bogoria (Kenya) was examined. Among these, fifteen isolates were selected on the basis of their lipolytic activities and subjected to morphological and 16S rRNA gene sequencing analyses for their identification. All the microorganisms have been selected under culture conditions with pH ranges between 7-10 and temperatures of 37-55 degrees C. Most of them showed optimal growth at 37 degrees C and tolerated salinity up to 10% (w/v). Ten of the isolates were Gram-negative, nine of which were closely related to the Pseudomonas cluster and one to the Halomonas cluster sharing high similarity profile with Halomonas desiderata. The remaining Gram-positive isolates were closely related to the Bacillus cluster, and were grouped with Bacillus halodurans, Bacillus alcalophilus and Bacillus licheniformis. Four members of the Bacillus cluster and the Halomonas sp. produced lipolytic activity under alkaline conditions, while others did so at neutral pH values.


Hypothermia and adverse outcomes during the transfer of extremely low birth weight infants.
We aimed to explore whether hypothermia during the transfer of extremely low birth weight (ELBW) infants was associated with increased morbidity and mortality. Retrospective cohort study of transfers of ELBW infants by the London Neonatal Transfer Service between April 2015 and January 2017. Hypothermia was defined as an axillary temperature below 36.5°C. Hypothermia was recorded in 36-47% of the 146 transfers depending on the time point of measurement from admission at the referring unit to admission at the receiving unit. Infants with hypothermia had a lower gestational age [25.1 (24.1-26.6) versus 26.0 (25.3-27.0) weeks, p < 0.001], birth weight [750 (600-830) versus 800 (730-885) gr, p = 0.004) and age at referral [1 (0.8-3) versus 1.5 (1-4) hours, p = 0.049] compared to infants without hypothermia. Infants with hypothermia had a longer median (IQR) duration of invasive ventilation [22(6-44) days] compared to infants without hypothermia [10 (4-21) days, p = 0.002]. Infants with hypothermia had a higher incidence of a patent ductus arteriosus and mortality before discharge from neonatal care compared to infants without hypothermia (79% vs. 27%, p = 0.043 and 29% vs. 13%, p = 0.025, respectively). Among ELBW infants, hypothermia during transfer was common, particularly in infants of lower gestational age. Hypothermia was associated with a longer duration of ventilation and increased mortality before discharge from neonatal care.


Evaluation of the immunogenicity of replication-competent V-knocked-out and replication-defective F-deleted Sendai virus vector-based vaccines in macaques.
Viral vectors are promising vaccine tools for eliciting antigen-specific T-cell responses. We previously showed the potential of recombinant Sendai virus (SeV) vectors to induce virus-specific T-cell responses in macaque AIDS models. Here, we have evaluated the immunogenicity of replication-competent V-knocked-out and replication-defective F-deleted SeV vectors in macaques. Intranasal replication-competent and replication-defective SeV immunizations both elicited robust systemic antigen-specific T-cell responses, whereas the responses induced by the former were more durable than those by the latter. However, even the latter-induced T-cell responses remained detectable in a local, retropharyngeal lymph node two months after the immunization. These findings are useful for establishment of a vaccine protocol using SeV vectors.


A dopamine mechanism is implied in the acquisition and expression of amphetamine and stress-induced effects observed in the lymphocyte subpopulations.
Drugs of abuse and stress are associated with changes in circulating cell populations and reductions in cell-mediated immune responses. The main goal of this study was to determine the influence of repeated and acute d-amphetamine treatments on the foot-shock stress-induced effects on the peripheral lymphocyte subpopulations, and the involvement of a dopamine mechanism in the development and expression of this phenomenon. Wistar rats received an acute (5 mg/kg/day i.p.) or a repeated (2 mg/kg/day i.p. during 9 days) amphetamine treatment, and were exposed to a foot-shock stress (1 mA, 3 s) 4 days after the last amphetamine injection. Another group was administered with haloperidol (1 mg/kg/day i.p.) 15 min previous to each daily amphetamine injection or previous to the foot-shock stress session. Then, blood cells stained with monoclonal antibodies against CD3-FITC, CD8-PE and CD4-Cy-Chrome, and against CD161a-FITC, CD3-PE, and CD45RA-Cy-Crhome, were analyzed by multiparameter flow cytometry. The exposure to a foot-shock stress induced a decrease in the absolute number of peripheral lymphocytes, as well as in CD4+ and CD8+ T-cells and B-cells in acute and repeatedly amphetamine-treated rats, whereas the NK-cell population remained unchanged. Haloperidol administration previous to each drug administration or the foot-shock stress session reversed these effects. This study provides strong evidence that dopamine can play a more general role in the influence of amphetamine on the stress-induced effects on the lymphocyte subsets.


Utility of Two Surgical Techniques Using a Lateral Intercostal Artery Perforator Flap after Breast-Conserving Surgery: A Single-Center Retrospective Study.
Immediate partial breast reconstruction after breast-conserving surgery has become a new paradigm in treating breast cancer. Among the volume replacement techniques used for small to moderate-sized breasts, the perforator flap method has many advantages. The authors present anatomical studies and two surgical techniques using lateral intercostal artery perforator flaps. Data from 40 patients who underwent breast reconstruction using the lateral intercostal artery perforator flap between January of 2011 and June of 2016 were included. The authors conducted comparative analyses of the propeller flap and the turnover flap. They used three-dimensional computed tomography in lateral intercostal artery perforator flap anatomical studies, analyzing the distribution probability of the dominant perforator, the vertical distance from the axillary fold, and the horizontal distance from the anterior border of the latissimus dorsi. The most dominant perforator used for lateral intercostal artery perforator flaps was the sixth lateral intercostal artery perforator (43.6 percent of cases), followed by the seventh lateral intercostal artery perforator (39.1 percent of cases); their mean distances from the latissimus dorsi and the axillary folds were determined and reported. Complications included three cases requiring additional treatment for fat necrosis (propeller method, two cases; turnover method, one case) and venous congestion in only two cases that used the propeller method. Cosmetic satisfaction was 90 percent or greater for both techniques, indicating that results were rated as either excellent or good. The authors believe that their study results can broaden the application of partial breast reconstruction by using the lateral intercostal artery perforator flap after breast-conserving surgery, with three-dimensional computed tomography for anatomical studies, and using one of the authors' two described surgical techniques. Therapeutic, III.


Quantifying CBM-Carbohydrate Interactions Using Microscale Thermophoresis.
Microscale thermophoresis (MST) is an emerging technology for studying a broad range of biomolecular interactions with a high sensitivity. The affinity constant can be obtained for a wide range of molecules within minutes based on reactions in microliters. Here we describe the application of MST in quantifying protein-carbohydrate interactions. A CBM3a and a CBM4 are titrated with insoluble substrate (cellulose nanocrystal) and soluble oligosaccharide (xylohexaose), respectively.


Differentiation of HaCaT cell and melanocyte from their malignant counterparts using micro-Raman spectroscopy guided by confocal imaging.
Skin cancer is the most common type of cancer in humans. Current techniques for identifying normal and neoplastic tissues are either destructive or not sensitive and specific enough. Raman spectroscopy and confocal imaging may obviate many limitations of existing methods by providing noninvasive, high-resolution, and real-time morphological and biochemical analysis of living tissues and cells. We conducted micro-Raman spectroscopy studies on HaCaT cells, melanocytes (MC) and their malignant counterparts squamous cell carcinoma (SCC) and melanoma (MM) cells, respectively. Reflectance confocal imaging is used as guidance for the spectral measurements. Significant differences were found between the spectra of HaCaT cells and SCC cells, MC cells and MM cells, as well as all normal cells (HaCaT and MC) and all tumor cells (SCC and MM). Approximately 90% sensitivity and specificity was achieved for all the separations that we performed. Our results demonstrated the robust capability of confocal Raman spectroscopy in separating different cell lines. The acquired Raman spectra of major types of skin cells and their malignant counterparts will be useful for the interpretation of Raman spectra from in vivo skin. We believe it will eventually help diagnosis of skin cancer and other skin disease in clinical dermatology.


A microporous indium-organic framework with high capacity and selectivity for CO2 or organosulfurs.
Presented here is a multifunctional microporous indium-organic framework material with doubly linked MIL-88D structure, which exhibits high surface area, excellent CO(2)/N(2) adsorption selectivity, good hydrogen storage ability and notable desulfurization behavior.


Recurrent life-threatening hyperkalemia without typical electrocardiographic changes.
Hyperkalemia is generally associated with electrocardiographic (ECG) changes and these changes have been used to follow the effects of high serum potassium (K+) levels on the heart. It is known that chronic renal impairment may diminish the toxic effects of hyperkalemia on ECG abnormality formation. (1-3) Here, we report a case of recurrent severe hyperkalemia without any significant ECG changes in a patient with normal baseline renal function.


Anesthetic management of the pregnant patient for endovascular coiling of an unruptured intracranial aneurysm.
Diagnosis of an intracranial aneurysm during pregnancy is a rare event requiring multidisciplinary care for successful management. The knowledge base for the anesthesiologist involves principles of both obstetric and neuroanesthesia, as well as critical care. This article reports such a case and discusses the relevant pathophysiology, along with details of the perioperative management by the anesthesiology team.


Behavioural plasticity and the transition to order in jackdaw flocks.
Collective behaviour is typically thought to arise from individuals following fixed interaction rules. The possibility that interaction rules may change under different circumstances has thus only rarely been investigated. Here we show that local interactions in flocks of wild jackdaws (Corvus monedula) vary drastically in different contexts, leading to distinct group-level properties. Jackdaws interact with a fixed number of neighbours (topological interactions) when traveling to roosts, but coordinate with neighbours based on spatial distance (metric interactions) during collective anti-predator mobbing events. Consequently, mobbing flocks exhibit a dramatic transition from disordered aggregations to ordered motion as group density increases, unlike transit flocks where order is independent of density. The relationship between group density and group order during this transition agrees well with a generic self-propelled particle model. Our results demonstrate plasticity in local interaction rules and have implications for both natural and artificial collective systems.


Baker yeast-induced fever in young rats: characterization and validation of an animal model for antipyretics screening.
In this study we describe a low-cost and reliable method for inducing fever in young male rats (28-30 days of age, 75-90 g), which seems suitable for the screening of new antipyretics. The effects of temperature measuring procedure-induced stress on the basal rectal temperature and on Baker yeast-induced hyperthermia was assessed. Rectal temperature (T) was recorded every hour for 12 h (07:00-19:00 h) with a lubricated thermistor probe. The animals were injected intraperitoneally with baker yeast (0.25, 0.135, 0.05 g/kg) or the equivalent volume of saline at 7:00 h. The administration of 0.135 g/kg baker yeast induced a sustained increase in rectal temperature for 4 h. Classical (dipyrone and acetaminophen) and novel (MPCA and FPCA) antipyretics, at doses that had no effect per se, reverted baker yeast-induced fever. The method presented induces a clear-cut fever, which is reverted by antipyretics commonly used in human beings and selected novel antipyretics in small animals. The method also allows antipyretic evaluation with low amount of drugs, due to the use of small animals and to the small variability of the pyretic response, which ultimately causes a significant reduction in the number of animals necessary for antipyretic evaluation. Therefore, this study describes an animal model of fever that is not only advantageous from the economical and technical point of view, but that also bears ethical concerns.


Finite element analysis for ternary hybrid nanoparticles on thermal enhancement in pseudo-plastic liquid through porous stretching sheet.
Thermal performance can be enhanced due to the mixing of nanoparticles in base fluid. This research discusses the involvement of ternary hybrid nanoparticles in the mixture of pseudo-plastic fluid model past over a two dimensional porous stretching sheet. Modelling of energy equation is carried out in the presence of external heat source or sink and viscous dissipation. The flow presenting equations and derived in Cartesian coordinate system under usual boundary layer theory in the form of complex coupled partial differential equations (PDEs). The derived PDEs have been converted into corresponding ordinary differential equations (ODEs) with the engagement of suitable transformation. The engineers, scientists and mathematicians have great interest in the solution of differential equations because to understand the real physics of the problem. Here, finite element scheme has been used to approximate the solution of the converted problem. The contribution of several emerging parameters on solution have been displayed through graphs and discussed. It is recommended that the finite element method can be engaged to approximate the solution of nonlinear problems arising in modelling the problem in mathematical physics.


Cephalosporin Prodrug Inhibitors Overcome Metallo-β-Lactamase Driven Antibiotic Resistance.
The increasing prevalence of metallo-β-lactamase (MBL)-expressing bacteria presents a worrying trend in antibiotic resistance. MBLs rely on active site zinc ions for their hydrolytic activity and the pursuit of MBL-inhibitors has therefore involved the investigation of zinc chelators. To ensure that such chelators specifically target MBLs, a series of cephalosporin prodrugs of two potent zinc-binders: dipicolinic acid (DPA) and 8-thioquinoline (8-TQ) was prepared. Although both DPA and 8-TQ bind free zinc very tightly (Kd values in the low nm range), the corresponding cephalosporin conjugates do not. The cephalosporin conjugates are efficiently hydrolyzed by MBLs to release DPA or 8-TQ, as confirmed by using both NMR and LC-MS studies. Notably, the cephalosporin prodrugs of DPA and 8-TQ show potent inhibitory activity against NDM, VIM, and IMP classes of MBLs and display potent synergy with meropenem against MBL-expressing clinical isolates of K. pneumoniae and E. coli.


[Clinico-experimental research on the use of collagen in periodontal disease].
Clinico-experimental studies of a new collagen derivative are presented. Experimental investigation in 30 rats showed the substance to promote wound healing. It also proved efficient in the five-years clinical follow-up of 254 patients after 441 surgical interventions (generalized periodontitis).


Importance of ultrasound examination: A case of peritoneal catheter tunnel infection.
Some peritoneal dialysis catheter infections cannot be detected via a physical examination. Ultrasound of the PD catheter tunnel should be performed in cases of suspected infection or clinical abnormality at the catheter tunnel site.


Low-dose total skin electron beam therapy as a debulking agent for cutaneous T-cell lymphoma: an open-label prospective phase II study.
Total skin electron beam therapy (TSEBT) is a powerful treatment for cutaneous T-cell lymphoma (CTCL). Based on the occurrence of relapses with low radiation doses, doses of 30-36Gy are commonly used but most patients still eventually relapse and repeat treatment courses are limited due to the cumulative toxicity. Complete response (CR) rates are about 60-90% for T2-4 stages with a 5-year relapse-free survival of 10-25% for stages IB-III. To evaluate prospectively the efficacy of low-dose TSEBT (10Gy) in terms of complete cutaneous response rate, overall response rate and response duration in CTCL. Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an open-label manner with four fractions of TSEBT 1Gy weekly to a total skin dose of 10Gy. Treatment responses were assessed at 1 and 3months after treatment and subsequently at least every 6months for a total period of 2years or to disease relapse or progression. Patients achieved an overall response rate of 90%. The rate of CR or very good partial response (VGPR; <1% skin affected with patches/plaques) was 70%. The median response duration was 5·2months (range 83-469days) for CR and VGPR. Adverse effects were generally mild to moderate in severity. Low-dose TSEBT (10Gy) gave a satisfactory response rate and was well tolerated in patients with MF stage IB-IV. Future studies should determine if the combination of low-dose TSEBT with other agents could increase the rate of CR and response duration.


N-(Phenoxyalkyl)amides as MT(1) and MT(2) ligands: antioxidant properties and inhibition of Ca(2+)/CaM-dependent kinase II.
Recently a series of chiral N-(phenoxyalkyl)amides have been reported as potent MT(1) and MT(2) melatonergic ligands. Some of these compounds were selected and tested for their antioxidant properties by measuring their reducing effect against oxidation of 2',7'-dichlorodihydrofluorescein (DCFH) in the DCFH-diacetate (DCFH-DA) assay. Among the tested compounds, N-[2-(3-methoxyphenoxy)propyl]butanamide displayed potent antioxidant activity that was stereoselective, the (R)-enantiomer performing as the eutomer. This compound displayed strong cytoprotective activity against H(2)O(2)-induced cytotoxicity resulting slightly more active than melatonin, and performed as Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibitor, too.


Design, synthesis, and evaluation of trifluoromethyl ketones as inhibitors of SARS-CoV 3CL protease.
A series of trifluoromethyl ketones as SARS-CoV 3CL protease inhibitors was developed. The inhibitors were synthesized in four steps from commercially available compounds. Three different amino acids were explored in the P1-position and in the P2-P4 positions varying amino acids and long alkyl chain were incorporated. All inhibitors were evaluated in an in vitro assay using purified enzyme and fluorogenic substrate peptide. One of the inhibitors showed a time-dependent inhibition, with a K(i) value of 0.3 microM after 4h incubation.


Expression of Bcl-2 family members and presence of Epstein-Barr virus in the regulation of cell growth and death in classical Hodgkin's lymphoma.
To examine the expression of the Bcl-2 family of proteins (Bcl-2, Bcl-x, Bcl-xL and Bax) in classical Hodgkin's lymphoma (cHL) and to correlate the expression of these proteins with proliferation, apoptosis and the presence of Epstein-Barr virus (EBV). Expression of the Bcl-2 family of proteins was detected by immunohistochemistry, proliferation was determined by Ki67 labelling and apoptosis by TUNEL in-situ hybridization. EBV was detected by Epstein-Barr virus early RNA (EBER) in-situ hybridization. Expression of Bcl-2, Bcl-x, Bcl-xL and Bax was detected in the Hodgkin/Reed-Sternberg (H/RS) cells in 43.7% (27/62), 87.5% (56/64), 67.2% (41/61) and 74.6% (47/63) of the cHL cases, respectively. EBER was detected in 53% (35/66) of the cases, whereas Ki67 was observed in 86.7% (52/60) of the cases. Apoptotic H/RS cells were observed infrequently, and only 43.2% (11/26) of the cases showed an apoptotic index of > or = 10% in the H/RS cells. A statistically significant inverse relationship was observed between the expression of Bcl-2 and the presence of EBV (P = 0.003). Bcl-xL showed an inverse correlation with apoptosis in the H/RS cells (P = 0.004). The higher Bcl-xL expression (67.2%) compared with Bcl-2 expression (43.5%) observed in cHL as well as the statistically significant inverse relationship between Bcl-xL and apoptosis suggests that Bcl-xL plays an important role in the survival of H/RS cells. Expression of Bax may be neutralized by other anti-apoptotic members of the family such as Bcl-2 and/or Bcl-xL.


Encapsulated membrane proteins: A simplified system for molecular simulation.
Over the past 50years there has been considerable progress in our understanding of biomolecular interactions at an atomic level. This in turn has allowed molecular simulation methods employing full atomistic modelling at ever larger scales to develop. However, some challenging areas still remain where there is either a lack of atomic resolution structures or where the simulation system is inherently complex. An area where both challenges are present is that of membranes containing membrane proteins. In this review we analyse a new practical approach to membrane protein study that offers a potential new route to high resolution structures and the possibility to simplify simulations. These new approaches collectively recognise that preservation of the interaction between the membrane protein and the lipid bilayer is often essential to maintain structure and function. The new methods preserve these interactions by producing nano-scale disc shaped particles that include bilayer and the chosen protein. Currently two approaches lead in this area: the MSP system that relies on peptides to stabilise the discs, and SMALPs where an amphipathic styrene maleic acid copolymer is used. Both methods greatly enable protein production and hence have the potential to accelerate atomic resolution structure determination as well as providing a simplified format for simulations of membrane protein dynamics. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.


Anticipatory postural adjustments associated with rotational perturbations while standing on fixed and free-rotating supports.
The role of anticipatory postural adjustments (APAs) has been commonly hypothesized to stabilize the body's center of mass (COM) from reaction forces and torques induced by voluntary movements in a feed-forward manner. This hypothesis was developed from studies which investigated movements that induced anterior-posterior or medial-lateral perturbation to body posture. However, the role of APAs in tasks that induce perturbations about the vertical axis, which are associated with minimal COM displacements, is unclear. The purpose of this study was to examine APAs associated with upper arm movements that induce perturbation about the body's vertical axis. Eight healthy subjects performed bilateral or unilateral shoulder movements in the sagittal or frontal plane that induced rotational perturbation about the body's vertical axis, while standing on a support which was either fixed or free to rotate about the body's vertical axis. Changes in the background activity of trunk and leg muscles on both sides of the body, as well as reaction moment about the vertical axis were quantified within the time interval typical of APAs. On the fixed support, clear asymmetry between right and left muscle activity was observed in biceps femoris and soleus during APAs across all tasks. These asymmetries were specific to the movement direction. When the same tasks were performed on a free-rotating support, the asymmetry that was observed on fixed support decreased. We suggest that the CNS uses asymmetric activity of right and left muscles during APAs to rotate the body segments in the direction opposite to the perturbation. When ground reaction moments did not aid in counteracting the forthcoming perturbation while standing on a free-rotating support, the asymmetric muscle activity decreased to minimize further inter-segmental rotations.


6-Substituted amiloride derivatives as inhibitors of the urokinase-type plasminogen activator for use in metastatic disease.
The oral K+-sparing diuretic amiloride shows anti-cancer side-activities in multiple rodent models. These effects appear to arise, at least in part, through moderate inhibition of the urokinase-type plasminogen activator (uPA, Ki = 2.4 µM), a pro-metastatic trypsin-like serine protease that is upregulated in many aggressive solid malignancies. In applying the selective optimization of side-activity (SOSA) approach, a focused library of twenty two 6-substituted amiloride derivatives were prepared, with multiple examples displaying uPA inhibitory potencies in the nM range. X-ray co-crystal structures revealed that the potency increases relative to amiloride arise from increased occupancy of uPA's S1β subsite by the appended 6-substituents. Leading compounds were shown to have high selectivity over related trypsin-like serine proteases and no diuretic or anti-kaliuretic effects in rats. Compound 15 showed anti-metastatic effects in a xenografted mouse model of late-stage lung metastasis.


Cognitive behavioral therapy for depression.
CBT is a valuable treatment for mild, moderate, and severe forms of major depression. It is equally effective and more durable than medication alone, and the combination of medication and CBT may increase the response rate and extend durability when CBT is employed after pharmacotherapy is successful. Therapist competence has been shown to influence outcomes in CBT for depression. Practitioners who wish to learn more about CBT may access a wide variety of educational materials: basic texts, course offerings at major scientific meetings, and local and national training centers are available. The Academy of Cognitive Therapy website (www.academyofct.org) provides detailed information about obtaining training and certification in CBT.


Radioiodinated 2'-iodospiperone: a new radioligand for in vivo dopamine receptor study.
In vivo dopamine receptor binding of the newly synthesized ligand, 125I-2'-iodospiperone (125I-2'-ISP), was studied in mouse brain. The highest accumulation was found in the striatum. Analysis of the striatal homogenate showed the 125I-2'-ISP to be metabolically stable. Furthermore, this striatal binding was saturable and displaced only by dopaminergic drugs. On the other hand, the accumulation in the cortex was as low as that of the cerebellum and uneffected by the administration of serotoninergic drugs and dopaminergic drugs; results assessed by macroautoradiographic studies. Thus, the newly synthesized 125I-2'-ISP presented high affinity for dopamine receptors in vivo and therefore, holds great potential for the in vivo dopamine receptor studies, provided 123I becomes readily available.


Effect of cynomorium flavonoids on morphology of perimenopausal depression mice model.
In this report, the effects of cynomorium flavonoids on mouse model of perimenopausal depression were investigated. 60 ovariectomized female mice were randomly divided into 6 groups evenly: high, medium and low doses of cynomorium flavonoids groups (400 mg kg(-1), 200 mg kg(-1), 100 mg kg(-1)), Gengnian'an capsule group (675 mg kg(-1)), soy isoflavones soft capsule group (250 mg kg(-1)), and model group. Give the corresponding drug five days after surgery once a day, consecutive thirty days. The model group and control group were given the water of same volume. The model related groups were applied with different stress for consecutive eighteen days. Kill the mice and remove the thymus, spleen, uterus and one hand of brain when it is 2 h after the last administration in mice of each group. Observe the histological changes of each group under light microscope. By observing the pathological section, compared with model group, the pathological changes of the uterus and hypothalamus of mice were significantly improved. The thymic cortex markedly thickened, volume of splenic nodule also significantly increased, and the number of lymphocytes significantly increased (p < 0.01). Simulation results show that the high dose of cynomorium flavonoids group has the best effective. Cynomorium flavonoids on mouse uterus, hypothalamus, thymus and spleen lesions have a significant role in the improvement. Cynomorium flavonoids have a good therapeutic effect on mice with perimenopausal depression.


Identifying Suicide Risk Factors in Lesbian, Gay, Bisexual, Transgender, and Queer Veterans.
The purpose of this article is to provide an overview of risk and protective factors for suicide in the lesbian (L), gay (G), bisexual (B), transgender (T), and queer (Q) veteran population, identify the tools and resources necessary to address their mental health needs and outline an evidence-based approach for community health care professionals to use as a guide for treatment and suicide prevention in this unique population. The importance of applying an intersectional lens to the multidimensional identity of LGTQ veterans is emphasized. Recommendations are provided for safety planning, follow-up, and treatment.


Fulleretic Well-Defined Scaffolds: Donor-Fullerene Alignment Through Metal Coordination and Its Effect on Photophysics.
Herein, we report the first example of a crystalline metal-donor-fullerene framework, in which control of the donor-fullerene mutual orientation was achieved through chemical bond formation, in particular, by metal coordination. The (13) C cross-polarization magic-angle spinning NMR spectroscopy, X-ray diffraction, and time-resolved fluorescence spectroscopy were performed for comprehensive structural analysis and energy-transfer (ET) studies of the fulleretic donor-acceptor scaffold. Furthermore, in combination with photoluminescence measurements, the theoretical calculations of the spectral overlap function, Förster radius, excitation energies, and band structure were employed to elucidate the photophysical and ET processes in the prepared fulleretic material. We envision that the well-defined fulleretic donor-acceptor materials could contribute not only to the basic science of fullerene chemistry but would also be used towards effective development of organic photovoltaics and molecular electronics.


Localization and quantitation of hsp84 in mammalian cells.
In order to investigate the function of heat shock protein 84 (hsp84) we have isolated the protein from mouse neuroblastoma cells and raised a polyclonal antiserum which was affinity-purified. The specificity of the antibody was established by immunoprecipitation and immunoblotting. Immunofluorescence studies revealed both a cytoplasmic and a nuclear localization of hsp84 in five different mammalian cell lines (mouse neuroblastoma cells and fibroblasts, rat hepatoma cells, and HeLa cells). In none of the five cell lines were found significant differences in the total cellular levels of hsp84 before and immediately after a heat shock (4 h, 42 degrees C) by immunoblot quantification. Furthermore after heat shock the fluorescence of anti-hsp84-labeled nuclei was increased relative to that of the surrounding cytoplasm. The increased fluorescence disappeared upon reincubation at 37 degrees C. The heat-induced increase in contrast between cytoplasmic and nuclear fluorescence could be explained by a combination of three factors: (a) decrease in nuclear projection area, (b) increase in cytoplasmic projection area, and (c) translocation of hsp84. The contribution of these factors to the increase after heat treatment was different for the cell lines.


Polyamine regulation of the synthesis of thymidine kinase in bovine lymphocytes.
Concanavalin A-activated lymphocytes were made polyamine deficient by treatment with alpha-difluoromethylornithine and ethylglyoxal bis(guanylhydrazone). Thymidine kinase activity in polyamine-deficient cells was 17% of the level in normal cells. Thymidine kinase mRNA increased with time after concanavalin A activation and reached a maximum at 36 h after concanavalin A addition. The amount of thymidine kinase mRNA in polyamine-deficient cells was approximately 75% of that in normal cells. The transcription of thymidine kinase gene in isolated nuclei of polyamine-deficient cells was also 75% of that from normal cells. The turnover rate of thymidine kinase mRNA in both normal and polyamine-deficient cells was nearly equal. In normal cells, 95% of thymidine kinase mRNA was polysome associated, while in polyamine-deficient cells, 60% of the mRNA was polysome associated. In addition, the size of polysomes associated with thymidine kinase mRNA in polyamine-deficient cells was smaller than that in normal cells. Synthesis of thymidine kinase was stimulated approximately seven-fold by 0.3 mM spermidine in a rabbit reticulocyte polyamine-free protein synthetic system. The half-life of thymidine kinase activity in both normal and polyamine-deficient cells was nearly equal. Thymidine kinase activity was not influenced significantly by 0.3 mM spermidine. These combined results suggested that the synthesis of thymidine kinase was mainly regulated by polyamines at the level of translation.


Complexity analysis of stride interval time series by threshold dependent symbolic entropy.
The stride interval of human gait fluctuates in complex fashion. It reflects the rhythm of the locomotor system. The temporal fluctuations in the stride interval provide us a non-invasive technique to evaluate the effects of neurological impairments on gait and its changes with age and disease. In this paper, we have used threshold dependent symbolic entropy, which is based on symbolic nonlinear time series analysis to study complexity of gait of control and neurodegenerative disease subjects. Symbolic entropy characterizes quantitatively the complexity even in time series having relatively few data points. We have calculated normalized corrected Shannon entropy (NCSE) of symbolic sequences extracted from stride interval time series. This measure of complexity showed significant difference between control and neurodegenerative disease subjects for a certain range of thresholds. We have also investigated complexity of physiological signal and randomized noisy data. In the study, we have found that the complexity of physiological signal was higher than that of random signals at short threshold values.


Endotoxin-like activity associated with Lyme disease Borrelia.
The newly recognized spirochete, Borrelia burgdorferi, the causative agent of Lyme Disease, has been examined for endotoxin-like activities as measured by the standard Farmacopea Ufficiale della Republica Italiana rabbit fever test and the Limulus amoebocyte lysate assay. The suspension of heat-killed microorganism caused a febrile response at a dose of 1 X 10(8) bacteria pro kilo. Similar results were obtained in the Limulus assay where the heat-killed spirochetes stimulated formation of solid clot until the concentration of 1 X 10(5) per ml. Both in pyrogen test and in Limulus assay heat-killed Escherichia coli exhibited a higher degree of potency. These results show that LD-Borrelia possess endotoxin-like activities which could help in understanding the pathogenesis of the clinical symptomatology of the disease.


Chronic myelogenous leukaemia: a model for human cancers.
In this chapter I reviewed the biological and molecular abnormalities associated with CML and related disorders. Much is known about this disease and it is probably not an overstatement to say that there are more data regarding the molecular and biological events underlying CML than any other human cancer. Nevertheless, this review emphasizes how inadequate these data are in explaining most of the important aspects of this disorder. Thus, if CML is to be used as a model of other cancers, much work remains to be done.


Clozapine resistance: augmentation strategies.
Clozapine (CLZ) is not effective in more than 50% of treatment-resistant schizophrenic patients. In these cases, several pharmacological strategies are used in clinical practice, with different levels of evidence for both safety and efficacy. In the present paper we critically reviewed literature data regarding the efficacy and safety of adjunctive agents in CLZ-resistant schizophrenics. The following classes of agents were considered: 1) antipsychotics, 2) antidepressants, 3) mood stabilizers, 4) other agents (e.g. fatty acid supplement and glutamatergic agents), 5) electroconvulsive therapy (ECT). For lamotrigine and risperidone sufficient data were available to perform a meta-analysis. A Medline literature search covering a 20-year period was performed. For the meta-analysis, data were entered and analyzed with the Cochrane Collaboration Review Manager Software (RevMan version 5). 62 pertinent studies were identified, including 1556 schizophrenic or schizoaffective patients. Among treatments investigated, there is evidence for CLZ augmentation with 1) amisulpride and aripiprazole, 2) mirtazapine and 3) ethyl eicosapentaenoic acid (E-EPA). Although promising, ECT augmentation needs further validation. The meta-analyses did not support either the use of risperidone or lamotrigine as CLZ adjunct. Overall, there is scarce evidence of efficacy and safety as regards adjunctive strategies for CLZ-resistant patients. However, several limitations do not allow to draw any definitive conclusion; among these we underline the small sample size of clinical trials, the variable definitions of CLZ resistance, the heterogeneity of outcome measures and methodological designs.


[Transnasal-sphenoided endosurgical and microsurgical technique of pituitary adenometomies].
To evaluate the surgical technique of pituitary adenomas by naso-sphenoid way and the prevention of complication. The pituitary adenomas in 19 cases were removed under endoscope and microscope by the transnasosphenoided way. Sphenoid-saddle base was restructed with lip-tendon-membrane and the nasal separate bone. Seventeen cases had entire resection in the 19 patients. Two cases had subtotal resection. The symptoms were improved with no sever complications in 19 cases during the period of 3-36 months follow-up and no recovery in 17 cases. lt is a effective surgical technique that the pituitary neoplasms are removed by nasosphenoidal way under the endoscope and microscope with the alcohol for preventing the tumor recovery and with the lip-tendon-membrane and nasal separate bone for restructing the saddle base.


Pseudoaneurysm: a review.
Pseudoaneurysms may arise from any artery in the human body. Most commonly found to involve the femoral artery after angiography, the presentation may vary from being clinically silent to a life-threatening emergency scenario. Recognition of this condition and treatment largely depend on the hemodynamic stability and anatomy of the pseudoaneurysm. Advances in treatment have enabled nonsurgical therapy in a significant number of cases. Ultrasound-guided thrombin injection is a fairly easy and effective treatment option. Other endovascular approaches, such as stent graft repair and coil embolization, are also available. Endovascular techniques play an important role in treating pseudoaneurysms arising from the aorta as a result of blunt trauma or previous aortic surgery. It is important to recognize the indications for surgery to avoid delay in the management of this potentially limb- or life-threatening condition.


Pseudomonas aeruginosa infections in the podiatric patient.
Pseudomonal infections of the skin, soft tissue, bone, and toe web may often be very difficult to treat. This article reviews the microbiology, pathogenesis, and treatment of pseudomonal infections that are related to podiatric medicine and surgery.


Ecological quality assessment of small estuaries from the Portuguese coast based on benthic macroinvertebrate assemblages indices.
Benthic macroinvertebrates communities are the most consistently emphasized biotic component of aquatic ecosystems and are one of the biological indicators required for assessment by the European Water Framework Directive. In this context, several indices based on these communities have been developed in order to assess ecological quality of estuarine systems. In the present work we used AMBI, M-AMBI, BENTIX and BAT to distinguish ecological status of five small estuarine systems of the Portuguese south and southwest coasts. Although indices outputs did not differ between systems and sampling seasons, results indicated that the metrics in which these indices are based could differentiate community structures as a result of two main gradients that force these communities: the natural variability, and the anthropogenic impact.


Diffractive optics and micro-optics: introduction to the feature issue.
This issue of Applied Optics features 16 papers related to the fabrication, design, and application of diffractive and micro-optical elements. A companion feature in the Journal of the Optical Society of America A [J. Opt. Soc. Am. A 16(5), 1091 (1999)] includes papers on the modeling of diffractive elements.


Building hospital management capacity to improve patient flow for cardiac catheterization at a cardiovascular hospital in Egypt.
Quality improvement (QI) has been shown to be effective in improving hospital care in high-income countries, but evidence of its use in low- and middle-income countries has been limited to date. The impact of a QI intervention to reduce patient waiting time and overcrowding for cardiac catheterization-the subset of procedures associated with the most severe bottlenecks in patient flow at the National Heart Institute in Cairo-was investigated. A pre-post intervention study was conducted to examine the impact of a new scheduling system on patient waiting time and overcrowdedness for cardiac catheterization. The sample consisted of 628 consecutive patients in the pre-intervention period (July-August 2009) and 1,607 in the postintervention period (September-November 2010). The intervention was associated with significant reductions in waiting time and patient crowdedness. On average, total patient waiting time from arrival to beginning the catheterization procedure decreased from 208 minutes to 180 minutes (13% decrease, p < .001). Time between arrival at registration and admission to inpatient ward unit decreased from 33 minutes to 24 minutes (27% decrease, p < .001). Patient waiting time immediately prior to the catheterization laboratory procedure decreased from 79 minutes to 58 minutes (27% decrease, p < .001). The percentage of patients arriving between 7:00 A.M. and 9:00 A.M. decreased from 88% to 44% (50% decrease, p < .001), reducing patient crowding. With little financial investment, the patient scheduling system significantly reduced waiting time and crowdedness in a resource-limited setting. The capacity-building effort enabled the hospital to sustain the scheduling system and data collection after the Egyptian revolution and departure of the mentoring team in January 2011.


Epididymitis in infancy.
The occurrence of epididymitis in infants suggests the presence of urinary infection and the likelihood of an associated structural genitourinary abnormality, requiring complete urologic investigation. The advent of testicular scanning and the ultrasonic stethoscope, coupled with an increased index of suspicion, makes possible the non-operative diagnosis and management of a condition usually made by surgical exploration.


Calcium- and integrin-binding protein-1 and calcineurin are upregulated in the right atrial myocardium of patients with atrial fibrillation.
The aim of this study was to determine whether altered expression and distribution of calcium- and integrin-binding protein-1 (CIB1) is involved in the pathogenesis of different types of patients with atrial fibrillation (AF) associated with valvular heart disease (VHD). Right atrial specimens obtained from 65 patients undergoing valve replacement surgery were divided into three groups: sinus rhythm group (n= 24), paroxysmal atrial fibrillation group (PaAF; n= 10), and persistent atrial fibrillation group (PeAF; AF lasting >6 month; n= 31). The expression levels of mRNA and protein content for CIB1, calcineurin B, calcineurin A, and Na(+)-Ca(2+) exchanger-1 (NCX1) were measured. We also measured the combination of CIB1 with calcineurin B, L-type Ca(2+) channel, and NCX1 using immunoprecipitation. Expression of mRNA and protein content of CIB1, calcineurin B, calcineurin A, and NCX1 was increased in the AF group. Calcium- and integrin-binding protein-1 interacted with calcineurin B and L-type Ca(2+) channel. Surprisingly, CIB1 also combined with NCX1. The CIB1 and calcineurin expression was increased in AF atrial tissue and was related to the type of AF. This finding suggests that CIB1 may be involved in the pathogenesis of AF in VHD patients.


Change in symptom clusters perioperatively in patients with lung cancer.
To describe the trajectory, number, and types of symptom clusters at three time points (i.e., day of admission [T1], 2-4 days postoperatively [T2], and 1 month postoperatively [T3]) using ratings of symptom occurrence and severity and to identify the changes in these symptom clusters over time in patients with lung cancer. We analysed the data of 217 lung cancer patients who received surgical treatment at a tertiary hospital affiliated to Anhui Medical University, in Hefei City, China. The occurrence and severity of 19 symptoms at all points of measurement were measured using the general and lung cancer modules of the M.D. Anderson Symptom Inventory. Exploratory factor analysis was performed to extract the symptom clusters. Seven symptom clusters were identified across symptom dimensions. However, only three of them (i.e., lung cancer specific, sleep disturbance, and nervous system) were relatively stable across dimensions and time. Two symptom clusters varied over time but not with dimensions (nutritional and gastrointestinal). The other two symptom clusters (psychological and respiratory) differed in terms of time and dimensions. Findings may provide insights into the seven identified clusters and overall stability of three symptom clusters in lung cancer patients perioperatively.


Blood fibrinogen level as a biomarker of adverse outcomes in patients with coronary artery disease: A systematic review and meta-analysis.
The association between elevated fibrinogen level and adverse outcomes in patients with coronary artery disease (CAD) remains conflicting. This systematic review and meta-analysis aims to evaluate the association between fibrinogen level and adverse outcomes in CAD patients. Relevant studies were identified by searching PubMed, Web of Science, and Embase databases from their inception to September 30, 2021. Observational studies that investigated the association of blood fibrinogen level with cardiovascular death, all-cause mortality, and major adverse cardiovascular events were eligible. A total of 20,395 CAD patients from 15 articles (13 studies) were included. Comparison with the highest and the lowest fibrinogen level indicated that elevated fibrinogen level was associated with higher risk of cardiovascular death (risk ratio [RR] 2.24; 95% confidence interval [CI] 1.69-2.98), all-cause mortality (RR 1.88; 95% CI 1.50-2.36), and major adverse cardiovascular events (RR 1.46; 95% CI 1.18-1.81). Elevated fibrinogen level is significantly associated with an increased risk of cardiovascular and all-cause mortality in patients with CAD. Baseline fibrinogen level can serve as a promising biomarker for risk stratification of CAD.


miRNAs link metabolic reprogramming to oncogenesis.
The most profound biochemical phenotype of cancer cells is their ability to metabolize glucose to lactate, even under aerobic conditions. This alternative metabolic circuitry is sufficient to support the biosynthetic and energy requirements for cancer cell proliferation and metastasis. Alterations in oncogenes and tumor-suppressor genes are involved in the metabolic switch of cancer cells to aerobic glycolysis, increased glutaminolysis, and fatty acid biosynthesis. miRNAs mediate fine-tuning of genes involved directly or indirectly in cancer metabolism. In this review we discuss the regulatory role of miRNAs on enzymes, signaling pathways, and transcription factors involved in glucose and lipid metabolism. We further consider the therapeutic potential of metabolism-related miRNAs in cancer.


Urticaria after breakthrough Omicron BA.5.1 severe acute respiratory syndrome coronavirus 2 infection in a triple-vaccinated (Pfizer) patient: a case report.
Severe acute respiratory syndrome coronavirus 2 continues to threaten public health. The virus is causing breakthrough infections in vaccinated individuals. Also, scarce information is available about cutaneous manifestations after severe acute respiratory syndrome coronavirus 2 infection. A case of a triple-vaccinated (Pfizer) 37-year-old Hispanic American (Colombian) male who developed urticaria after Omicron BA.5.1 severe acute respiratory syndrome coronavirus 2 breakthrough infection is described. Virus isolation and whole genome sequencing along with immune and molecular assays were performed. Dermatological manifestations (skin rash and urticaria) after Omicron BA.5.1 infection were observed. Sequence analysis of the Omicron BA.5.1 isolate also revealed several important mutations. Hemogram analysis revealed leukocytosis and neutrophilia. Serology testing revealed anti-spike immunoglobulin G serum titers but negative detection of immunoglobulin M at 10 days after symptom onset. Anti-nucleocapsid, anti-spike 1 immunoglobulin G, anti-spike trimer, and anti-receptor-binding-domain immunoglobulin G and immunoglobulin E sera were detected at different titers 10 days after symptom onset. Several serum levels of chemokines/cytokines (Interferon-α, interferon-γ, interleukin-12/interleukin-23p40, interleukin-18, interferon gamma-induced protein-10, monocyte chemoattractant protein-1, monokine induced by gamma, macrophage inflammatory protein-1α, chemokine (C-C motif) ligand-5 , tumor necrosis factor-β1, Tumor necrosis factor-α) were detected, but interleukin-2, interleukin-4, interleukin-6, interleukin-8, and interleukin-17A were below the limit of detection. To our knowledge, this is the first study describing skin effects of a severe acute respiratory syndrome coronavirus 2 Omicron BA.5 variant breakthrough infection in a triple-vaccinated patient in Colombia. Several important mutations were found in the spike glycoprotein of the virus isolated; these mutations are associated with immune evasion and changes in antigenic properties of the virus. Physicians overseeing coronavirus disease 2019 cases should be aware of the potential skin effects of the infection. Pathogenesis of severe acute respiratory syndrome coronavirus 2 infection and its association with proinflammatory cytokines and chemokines may enhance the development of urticaria and other skin manifestations in immunized individuals. However, further studies are needed to better understand the complexity of coronavirus disease in such situations.


Stability of single sheet GNNQQNY aggregates analyzed by replica exchange molecular dynamics: antiparallel versus parallel association.
Protein and peptide aggregation into amyloid plaques is associated with a large variety of neurodegenerative diseases. The definition of the molecular bases of these pathologies is hampered by the transient nature of pre-fibrillar small-oligomers that are considered the toxic species. The ability of the peptide GNNQQNY to form amyloid-like structures makes it a good model to investigate the complex processes involved into amyloid fiber formation. By employing full atomistic replica exchange molecular dynamics simulations, we constructed the free energy surface of small assemblies of GNNQQNY to gain novel insights into the fiber formation process. The calculations suggest that the peptide exhibits a remarkable tendency to form both parallel and antiparallel beta-sheets. The data show that GNNQQNY preference for parallel or antiparallel beta-sheets is governed by a subtle balance of factors including assemblies' size, sidechain-sidechain interactions and pH. The samplings analysis provides a rationale to the observed trends.


Heligmosomoides polygyrus infection reduces severity of type 1 diabetes induced by multiple low-dose streptozotocin in mice via STAT6- and IL-10-independent mechanisms.
Some parasitic helminths are known to protect their hosts from allergic and autoimmune disorders. Here, we tested the effects of a gastrointestinal nematode, Heligmosomoides polygyrus (Hp), on streptozotocin (STZ)-induced type 1 diabetes (T1D) in mice. Hp infection significantly suppressed hyperglycemia induced by multiple low-dose administration of STZ, but did not affect hyperglycemia induced by single high-dose administration of STZ. In the multiple low dose model, Hp infection prevented a decrease in pancreatic islet size. The augmentation of TNF-α and IL-1β expression in the pancreas was abrogated by Hp infection. The genetic absence of IL-10 or STAT6 did not abrogate the anti-hyperglycemic effect of Hp. Hp has a suppressive effect on immune mechanism-mediated experimental T1D via Th2 polarization-independent mechanisms.


On the fracture behavior of cortical bone microstructure: The effects of morphology and material characteristics of bone structural components.
Bone encompasses a complex arrangement of materials at different length scales, which endows it with a range of mechanical, chemical, and biological capabilities. Changes in the microstructure and characteristics of the material, as well as the accumulation of microcracks, affect the bone fracture properties. In this study, two-dimensional finite element models of the microstructure of cortical bone were considered. The eXtended Finite Element Method (XFEM) developed by Abaqus software was used for the analysis of the microcrack propagation in the model as well as for local sensitivity analysis. The stress-strain behavior obtained for the different introduced models was substantially different, confirming the importance of bone tissue microstructure for its failure behavior. Considering the role of interfaces, the results highlighted the effect of cement lines on the crack deflection path and global fracture behavior of the bone microstructure. Furthermore, bone micromorphology and areal fraction of cortical bone tissue components such as osteons, cement lines, and pores affected the bone fracture behavior; specifically, pores altered the crack propagation path since increasing porosity reduced the maximum stress needed to start crack propagation. Therefore, cement line structure, mineralization, and areal fraction are important parameters in bone fracture. The parameter-wise sensitivity analysis demonstrated that areal fraction and strain energy release rate had the greatest and the lowest effect on ultimate strength, respectively. Furthermore, the component-wise sensitivity analysis revealed that for the areal fraction parameter, pores had the greatest effect on ultimate strength, whereas for the other parameters such as elastic modulus and strain energy release rate, cement lines had the most important effect on the ultimate strength. In conclusion, the finding of the current study can help to predict the fracture mechanisms in bone by taking the morphological and material properties of its microstructure into account.


Variability over time in the mutagenicity of ashes from municipal solid-waste incinerators.
Incineration of municipal solid waste as an alternative to its disposal in landfills has advantages such as volume reduction and generation of energy. However, both air emissions and the residual ash may pose environmental and human health hazards. The Ames mutagenicity assay was used to determine the mutagenicity of fly and bottom ash from two incinerators over time. This assay is an alternative to costly and time-consuming chemical analyses and is more realistic for the assessment of the best disposition of the ash i.e. whether it could pose a risk to handlers of the ash, whether it can be used in cement or as a fertilizer or whether it should be relegated to a landfill. The mutagenic potency of fly and bottom ash on a per g weight basis of material is similar. Furthermore, the variability over time in mutagenicity indicates that constant monitoring of incineration products and byproducts is essential.


Descriptive review of acute cholecystitis: Japan-Taiwan collaborative epidemiological study.
Since the publication of the Tokyo Guidelines (TG13) for the management of acute cholecystitis (AC), multidirectional studies have been published. However, epidemiological research about AC with big data was not projected. The aim of this study was to reveal the actual clinical conditions of AC. The study was designed as an international multicenter retrospective study of AC in Japan and Taiwan from 2011 to 2013. The factors investigated comprised data related to demographic, history, physical examinations, laboratory and imaging findings. Based on these data, we investigated the various values of AC, and real situation with respect to severity and treatment. A total of 5,459 patients with AC were reviewed. Thirty-day mortality rate was 1.1%. Based on the diagnostic criteria, 4,088 patients had a definite diagnosis and 291 had a suspected diagnosis. According to the severity grading, 939 patients were classified as Grade III, 2,308 as Grade II, and 2,130 as Grade I. Cholecystectomy was performed in total of 4,266 patients and 2,765 patients had laparoscopic cholecystectomy. The main etiologies were gallbladder stones in 4,623 cases. This epidemiological study with large population will undoubtedly contribute to establish the best practice for managing AC worldwide.


Reliability of the transepicondylar line as a parameter of femoral axial alignment.
The purpose of this research was to determine the significance of the transepicondylar line as a parameter of femoral axial alignment. Standing full-length X-ray films of 124 knees of 91 patients (63 women, 28 men) with osteoarthritis, rheumatoid arthritis, or osteonecrosis were used in this study, in which the lateral angles formed by the femoral anatomical axis intersecting with the transepicondylar line (angle a'), horizontal line (angle b'), and femoral condylar line (angle r') were measured. The mean value of angle b' in knees with neutral alignment was significantly smaller than that in knees with varus alignment, and significantly larger than that in knees with valgus alignment; no significant difference was found in angle a'. Also, there was no significant difference in angle a' among the patients with osteoarthritis, rheumatoid arthritis, and osteonecrosis. These findings suggest that the transepicondylar line, which is a stable reference of femoral rotation, is also a very reliable parameter of axial alignment of the femur. In the future design of extramedullary guiding for total knee arthroplasty, the transepicondylar line may play an important role as a parameter for proper and accurate implant setting.


Acute hypothyroidism in a severely ill surgical patient.
A case of acute postoperative hypothyroidism in a 62-year old woman is presented. One month before emergency admission because of a perforated gastric ulcer the patient had normal thyroid function, despite removal of a thyroid adenoma 20 years earlier. Following surgery the patient developed circulatory instability, renal insufficiency, hypothermia and immeasurable concentrations of thyroxine (T4) and triiodothyronine (T3). Treatment with triiodothyronine was commenced but the patient died following an episode of severe hypotension.


Modulating effect of a selective endothelin A receptor antagonist on pulmonary endothelin system protein expression in experimental diaphragmatic hernia.
Previously, we reported that perinatal administration of atrasentan, a selective endothelin A receptor (ETA) antagonist, provided a beneficial effect on the cardiopulmonary profile under short-term conditions in newborn lambs with surgically induced congenital diaphragmatic hernia (CDH). We hypothesized that changes in the hemodynamic profile that we observed at birth in treated animals could be influenced by pulmonary modulation of the endothelin (ET) system. The effect of atrasentan on protein expression levels of ETs and ET receptors (ETA and ETB receptor) was investigated by immunohistochemistry in lung tissues of untreated control (n = 3), treated control (n = 6), untreated CDH (n = 6), and treated CDH newborn lambs (n = 8). Right lung tissue of treated control lambs showed significantly higher ETA protein expression levels in both vascular adventitia and airway epithelia when compared with that of untreated control lambs (P < .05). In contrast, protein expression levels of ETA and ETB receptor were significantly lower in the vascular smooth muscle cells among other tissue subcompartments of the right lung of treated CDH newborn lambs vs CDH lambs (P < .02 and P = .005, respectively). We speculate that rapid pulmonary modulation of ET system protein expression levels by atrasentan results from an indirect effect possibly dependent on ventilation and/or perfusion. In CDH groups, this could contribute to the beneficial effect of the treatment.


Symptoms and Engagement in Anti-social Behavior 10 years After Mild Traumatic Brain Injury Within a Community Civilian Sample: A Prospective Cohort Study With Age-Sex Matched Control Group.
To determine if there are longer-term effects on symptoms, health status, mood, and behavior 10 years after a mild traumatic brain injury (mTBI). Prospective cohort study. Community-based, civilian sample. Adults aged ≥16 years at follow-up who experienced an mTBI 10 years ago, and an age and sex-matched non-injured control group. Not applicable. mTBI cases and controls were asked to complete self-report assessments of functioning (WHO Disability Assessment Schedule Version 2), symptoms (Rivermead Post-Concussion Symptom Questionnaire), health status (100-point scale), alcohol (Alcohol Use Disorders Identification Test) and substance use (Alcohol, Smoking and Substance Involvement Screening Test), and whether they had engaged in any anti-social behaviors over the past 12 months. Data were analyzed for 368 participants (184 mTBI cases and 184 age-sex matched controls). Just over a third of mTBI cases (64, 34.8%) reported that they were still affected by their index mTBI 10 years later. After adjusting for education and ethnicity, the mTBI group had statistically higher overall symptom burden (F=22.32, P<.001, ηp2=0.07) compared with controls. This difference remained after excluding those who experienced a recurrent TBI. The mTBI group were more than 3 times as likely to have engaged in anti-social behavior during the previous 12 months (F=5.89, P=.02). There were no group differences in health status, functioning, or problematic alcohol or substance use 10 years post-injury. This study provides evidence of potential longer-term associations between mTBI, post-concussion symptoms, and anti-social behavior which warrants further evaluation. Future research should also examine if longer-term effects may be preventable with access to early rehabilitation post-injury.


Selective thyroid hormone receptor-beta activation: a strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability.
Few treatments for obesity exist and, whereas efficacious therapeutics for hyperlipidemia are available, further improvements are desirable. Thyroid hormone receptors (TRs) regulate both body weight and cholesterol levels. However, thyroid hormones also have deleterious effects, particularly on the heart. The TR beta subtype is involved in cholesterol lowering and possibly elevating metabolic rate, whereas TR alpha appears to be more important for control of heart rate (HR). In the current studies, we examined the effect of TR beta activation on metabolic rate and HR with either TR alpha 1-/- mice or the selective TR beta agonist KB-141 in mice, rats, and monkeys. 3,5,3'-triiodi-l-thyronine (T3) had a greater effect on increasing HR in WT than in TR alpha-/- mice (ED15 values of 34 and 469 nmol/kg/day, respectively). T3 increased metabolic rate [whole body oxygen consumption (MVO2)] in both WT and TR alpha-/- mice, but the effect in the TR alpha 1-/- mice at the highest dose was half that of the WT mice. Thus, stimulation of MVO2 is likely due to both TR alpha and -beta. T3 had equivalent potency for cholesterol reduction in WT and TR alpha-/- mice. KB-141 increased MVO2 with selectivities of 16.5- and 11.2-fold vs. HR in WT and TR alpha 1-/- mice, respectively. KB-141 also increased MVO2 with a 10-fold selectivity and lowered cholesterol with a 27-fold selectivity vs. HR in rats. In primates, KB-141 caused significant cholesterol, lipoprotein (a), and body-weight reduction (up to 7% after 1 wk) with no effect on HR. TR beta-selective agonists may constitute a previously uncharacterized class of drugs to treat obesity, hypercholesterolemia, and elevated lipoprotein (a).


Magnetic solid-phase extraction based on diphenyl functionalization of Fe3O4 magnetic nanoparticles for the determination of polycyclic aromatic hydrocarbons in urine samples.
Superparamagnetic Fe(3)O(4) diphenyl nanoparticles were prepared according to a solvothernal procedure and characterized by X-ray diffraction, infrared spectroscopy, surface area measurements, scanning electron microscopy, X-ray photoelectron spectroscopy and transmission electron microscopy. The magnetic phases present in the nanoparticle samples were analyzed by thermomagnetic analysis and the samples' magnetic properties were studied by vibrating sample magnetometry. The resulting nanoparticles having an average diameter of 200 nm were then used as solid-phase extraction sorbent for the determination of polycyclic aromatic hydrocarbons in urine samples. Method validation proved the feasibility of the developed beads for the quantitation of the investigated analytes at trace levels obtaining lower limit of quantitation values in the ng/l range. A good precision with coefficients of variations always lower than 15% was obtained. Finally, the superior extraction performance of the synthesized nanoparticles with respect to commercially available beads was proved.


Worrisome trends in rising minimum inhibitory concentration values of antibiotics against methicillin resistant Staphylococcus aureus - Insights from a tertiary care center, South India.
Appearance of isolated reports of resistance to anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs is worrisome underscoring the need to continuously monitor the susceptibility of clinical MRSA isolates to these drugs. Hence, the present study is conducted to determine the susceptibility of MRSA isolates to various classes of anti-MRSA drugs such as vancomycin (glycopeptide), daptomycin (lipopeptide), tigecycline (glycylcycline), and linezolid (oxazolidinone) to determine the MIC50 and MIC90 values, and to observe MIC creep over a three year period, if any, with respect to these drugs. A total of 200 isolates of MRSA obtained from clinical specimens were included. MIC was determined by E-test for anti-MRSA antibiotics vancomycin, linezolid, daptomycin, and tigecycline. Non-parametric methods (Kruskal-Wallis and Chi-square test) were used to assess MIC trends over time. In addition, MIC50 and MIC90 values were also calculated. No isolate was found resistant to vancomycin, daptomycin, or linezolid; five isolates were resistant to tigecycline. Seven VISA isolates were encountered with the MIC value for vancomycin of 4μg/mL. MIC values for vancomycin, tigecycline, linezolid showed a definite increase over a 3-year period which was statistically significant with p-values <0.0001, 0.0032, 0.0242, respectively. When the percentage of isolates with a median MIC value less than or equal to that of the index year was calculated, the change was most striking with vancomycin. The proportion of isolates with higher MIC values was greater in 2014 than 2012 and 2013. MIC creep was notably observed with vancomycin, and to some extent with tigecycline and linezolid. Selection pressure may result in creeping MICs, which may herald the emergence of resistant organisms.


Visualisation and analysis of hepatitis C virus non-structural proteins using super-resolution microscopy.
Hepatitis C virus (HCV) RNA replication occurs in the cytosol of infected cells within a specialised membranous compartment. How the viral non-structural (NS) proteins are associated and organised within these structures remains poorly defined. We employed a super-resolution microscopy approach to visualise NS3 and NS5A in HCV infected cells. Using single molecule localisation microscopy, both NS proteins were resolved as clusters of localisations smaller than the diffraction-limited volume observed by wide-field. Analysis of the protein clusters identified a significant difference in size between the NS proteins. We also observed a reduction in NS5A cluster size following inhibition of RNA replication using daclatasvir, a phenotype which was maintained in the presence of the Y93H resistance associated substitution and not observed for NS3 clusters. These results provide insight into the NS protein organisation within hepatitis C virus RNA replication complexes and the mode of action of NS5A inhibitors.


Artificial intelligence-driven malware detection framework for internet of things environment.
The Internet of Things (IoT) environment demands a malware detection (MD) framework for protecting sensitive data from unauthorized access. The study intends to develop an image-based MD framework. The authors apply image conversion and enhancement techniques to convert malware binaries into RGB images. You only look once (Yolo V7) is employed for extracting the key features from the malware images. Harris Hawks optimization is used to optimize the DenseNet161 model to classify images into malware and benign. IoT malware and Virusshare datasets are utilized to evaluate the proposed framework's performance. The outcome reveals that the proposed framework outperforms the current MD framework. The framework generates the outcome at an accuracy and F1-score of 98.65 and 98.5 and 97.3 and 96.63 for IoT malware and Virusshare datasets, respectively. In addition, it achieves an area under the receiver operating characteristics and the precision-recall curve of 0.98 and 0.85 and 0.97 and 0.84 for IoT malware and Virusshare datasets, accordingly. The study's outcome reveals that the proposed framework can be deployed in the IoT environment to protect the resources.


Muscle p62 stimulates the expression of antioxidant proteins alleviating cancer cachexia.
Oxidative stress plays an important role in skeletal muscle atrophy during cancer cachexia, and more glycolytic muscles are preferentially affected. Sequestosome1/SQSTM1 (i.e., p62), particularly when phosphorylated at Ser 349 (Ser 351 in mice), competitively binds to the Kelch-like ECH-associated protein 1 (Keap1) activating Nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 then stimulates the transcription of antioxidant/electrophile-responsive elements in target genes. However, a potential role for p62 in the protection of muscle wasting in cachexia remains to be determined. Here, using the well-established cachexia-inducing model of Lewis Lung Carcinoma (LLC) in mice we demonstrate higher expression of antioxidant proteins (i.e., NQO1, HO-1, GSTM1, CuZnSOD, MnSOD, and EcSOD) in the more oxidative and cachexia resistant soleus muscle than in the more glycolytic and cachexia prone extensor digitorum longus muscle. This was accompanied by higher p62 (total and phosphorylated) and nuclear Nrf2 levels in the soleus, which were paralleled by higher expression of proteins known to either phosphorylate or promote p62 phosphorylation (i.e., NBR1, CK1, PKCδ, and TAK1). Muscle-specific p62 gain-of-function (i.e., in p62 mTg mice) activated Nrf2 nuclear translocation and increased the expression of multiple antioxidant proteins (i.e., CuZnSOD, MnSOD, EcSOD, NQO1, and GSTM1) in glycolytic muscles. Interestingly, skeletal muscle Nrf2 haplodeficiency blunted the increases of most of these proteins (i.e., CuZnSOD, EcSOD, and NQO1) suggesting that muscle p62 stimulates antioxidant protein expression also via additional, yet to be determined mechanisms. Of note, p62 gain-of-function mitigated glycolytic muscle wasting in LLC-affected mice. Collectively, our findings identify skeletal muscle p62 as a potential therapeutic target for cancer cachexia.


Biosynthesized iron sulfide nanoparticles by mixed consortia for enhanced extracellular electron transfer in a microbial fuel cell.
The bioanode of mixed consortia was for the first time used to in-situ synthesize iron sulfide nanoparticles in a microbial fuel cell (MFC) over a long-term period (46 days). These poorly crystalline nanoparticles with an average size of 29.97 ± 7.1 nm, comprising of FeS and FeS2, significantly promoted extracellular electron transfer and thus the electricity generation of the MFC. A maximum power density of 519.00 mW/m2 was obtained from the MFC, which was 1.92 times as high as that of the control. The cell viability was promoted by a small amount of iron sulfide nanoparticles but inhibited by the thick nanoparticle "shell" covered on the bacterial cells. Some electroactive and sulfur reducing bacteria (eg. Enterobacteriaceae, Desulfovibrio, and Geobacter) were specifically enriched on the anode. This study provides a novel insight for improving the performance of bioelectrochemical systems through in-situ sustainable nanomaterials biofabrication by mixed consortia.


Genetic studies in varicocele infertility: I: pedigree, nuclear sex and seminal nucleic acids.
The hereditary predisposition of varicocele men to develop infertility was investigated in a controlled study involving 30 infertile varicocele patients. Analysis of the pedigree charts, determination of sex chromatin constitution, and biochemical measurement of seminal nucleic acid (DNA/RNA) were undertaken. Sibs and Kins of infertile varicocele patients showed various developmental anomalies particularly of the genito-crural area. cocele formation while the gonads develop in the normal line. Such condition may be represented in fertile men with clinically detectable varicocele. In addition, the postulated defective gene in VI patients may interfere as well with the normal development of the mesenchyme-derived interstitial cells of Leydig. Defective testicular steroid hormone biosynthesis thus obtained may explain the reported decrease in androgen level in peripheral blood, sexual impotentia and accessory genital gland dysfunction (Raboch and Starka - 1971; Comhaire and Vermeulen - 1975). Moreover, being androgen dependent (Lacy - 1973), spermatogenesis may display abnormal patterns due to lowered intratesticular androgen concentration (Rodriguez-Rigau et al. - 1978). The outcome and severity of spermatogenic derangement may depend partially on the severity of disordered androgen biosynthesis. The present work showed significant decrease in sperm count, motility, normal forms and nucleic acid content (DNA and RNA) of the seminal fluid in VI patients. The decrease in the amount of DNA per millilitre of seminal fluid in VI patients may be explained by the decrease in sperm population (oligozoospermia). The decrease in the amount of RNA per millilitre of seminal fluid in VI patients may be due to the total decrease in cellular content of the seminal fluid.(ABSTRACT TRUNCATED AT 250 WORDS)


Intratympanic Injection of Steroid for Treatment of Tinnitus.
Tinnitus has become one of the most challenging tasks faced by the medical field. It has a moderately negative impact on patient's quality of life. Different methods had been developed in medical science for managing tinnitus but none of these offered a permanent cure. In our study we used a simple procedure of intratympanic injection of dexamethasone in managing our tinnitus patients. Total number of patients involved in this study were 40, 26 females and 14 males with age spanned from 15 to 65 years. Out of 40 patients, 22 of them complained of tinnitus only while the other 18 of them complained of tinnitus with impaired hearing which was confirmed further by pure tone audiometry. Injection was given under otologic microscopic vision through posteroinferior quadrant of tympanic membrane in weekly interval. After receiving several number of injections, 24 patients (60%) reported complete disappearance of tinnitus, 10 of them (25%) still had residual tinnitus but comparatively less severe and 6 (15%) of them reported no improvement.


Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation.
Constitutive androstane receptor (CAR) is a transcription factor to regulate the expression of several genes related to drug-metabolism. Here, we demonstrate that CAR protein accumulates during G1 in human SW480 and HepG2 cells. After the G1/S phase transition, CAR protein levels decreased, and CAR was hardly detected in cells by the late M phase. CAR expression in both cell lines was suppressed by RNA interference-mediated suppression of CDK4. Depletion of CAR by RNA interference in both cells and by hepatocyte growth factor treatment in HepG2 cells resulted in decreased MDM2 expression that led to p21 upregulation and repression of HepG2 cell growth. Thus, our results demonstrate that CAR expression is an early G1 event regulated by CDK4 that contributes to MDM2 expression; these findings suggest that CAR may influence the expression of genes involved in not only the metabolism of endogenous and exogenous substances but also in the cell proliferation.


ADAM28 participates in the regulation of tooth development.
Disintegrin and metalloprotease (ADAM) proteins are a family of membrane-anchored glycoproteins with diverse functions in fertilisation, development, neurogenesis and protein ectodomain shedding. ADAM28 is a newly discovered member of the ADAM family in humans and murine with autocatalytic activity. Recently, the authors screened ADAM28 genes from patients with congenital hypoplasia of tooth root, and studied the relationship between ADAM28 and tooth development. A polyclonal antibody (pAb) against ADAM28 was preparared, and the expression and localisation of ADAM28 were detected in tooth germ and dental mesenchymal cells. The results indicated that the prokaryotic expression vector pGEX-4T-ADAM28 was constructed successfully. Glutathione S-transferase-ADAM28 fusion protein was generated after inducement by isopropylthio-beta-d-galactoside and isolated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The purified fusion protein was used as an antigen for production of antibody. Western blot and enzyme-linked immunosorbent assay analyses verified that the antibody had a high specificity and titre. Immunohistochemistry and reverse transcriptase-polymerase chain reaction showed that ADAM28 was expressed at each stage of tooth germ development at different levels. Moreover, it was expressed in human dental follicle cells, human dental papilla cells, human dental pulp stem cells, human periodontal ligament cells and human dental cervical loop epithelial cells at transcription level. In conclusion, it is reasonable to suggest that ADAM28 may participate in tooth development and the regulation of odontogenic mesenchymal cells through progressive reciprocal inductive interactions between the epithelium and the mesenchyme.


Movento effects on learning and hippocampal brain-derived neurotrophic factor protein of adult male rats.
Spirotetramat is a toxic commercially known as Movento used to control pistachio psylla pests. In the present study, the effects of Movento on passive avoidance learning of rats and their ability to explore the novel object in the novel object recognition test were investigated. The changes in the concentration of hippocampal brain-derived neurotrophic factor (BDNF) proteins were evaluated, too. Male Wistar rats were gavaged at different dosages of the Movento (50, 100, 250, 500, 1000, 1250, and 1500 mg/kg) or saline for 7 days (administered every 2 days). We showed that Movento caused 50 and 100% mortality at the dose of 1250 and 1500 mg/kg, respectively. At the dose of 1000 mg/kg, Movento significantly decreased locomotor activity (P < 0.05). These rats also displayed a significant decrease in the number of training trials in the shuttle box and the ability to recognize a novel object compared with the control group (P < 0.01). The BDNF protein level of hippocampus also showed a significant decrease in the Movento (1000 mg/kg) compared with the control group (P < 0.01) while the number of pancellular necrosis pyramidal CA1 cells increased significantly in the Movento group (P < 0.001). We concluded that exposure to Movento can decline sensory, motor, and learning in rats.


Expectations Attenuate the Negative Influence of Neural Adaptation on the Processing of Novel Stimuli: ERP Evidence.
When processing repeated stimuli, the neural response is attenuated (i.e., neural adaptation) and performance seems to be facilitated; however, this neural adaptation negatively influences the subsequent processing of novel stimuli. The present study was designed to test whether and how temporal expectations reduce neural adaptation and attenuate the negative influence of neural adaptation on subsequent novel problem solving. Temporal expectations were experimentally manipulated by asking participants to solve a novel problem following three to five repeated problems, generating the expectation of repeated events in the first three serial positions as well as that of novel events in the fourth to sixth serial positions. Compared to the first occurrence, repeated problems evoked more negative deflections, including greater N1, lower P2 and greater LNC amplitudes, regardless of whether participants expected a repeated or novel event; however, the mean amplitudes of the P2 and LNC were smaller in the latter condition. These results show neural adaptation during processing of repeated stimuli and demonstrate that neural adaptation is reduced when a novel event is expected. Regarding the novel events, the conflict monitoring- and resolution-related N400, P600 and LNC amplitudes decreased with decreased neural adaptation. These results indicate that the expectation of novel events attenuate the negative influence of neural adaptation on the subsequent processing of novel events. This study provides new insight into alleviating the constraints imposed by frequently used knowledge on the processing of novel stimuli.


Factors that affect recurrence after incisional herniorrhaphy with prosthetic material.
To evaluate the risk factors for recurrence after prosthetic incisional herniorrhaphy. Retrospective study. Tertiary referral centre, Spain. 246 patients who had incisional herniorrhaphy with a prosthetic material (polypropylene) between 1990 and 1997 A reinforcement mesh was inserted when the hernia was more than 5 cm. In incisional hernias less than 5 cm the reinforcement mesh was inserted when the repair was under tension or when tissues were noted to be weak during the operation. Age, sex, obesity, the presence of bronchial disease, previous repair of the incisional hernia, type of surgery, size and site of hernia and presence of local complications during the immediate postoperative period. Mean (SD) follow-up was 77 (6) months (minimum follow up two years). The hernia recurred in 43 cases (17%) (mean time of recurrence 10 (8) months). Age over 60 years, previous herniorrhaphy, size of hernia, and postoperative local complications were significant risk factors (p < 0.01) in both the univariate and multivariate analyses. Patients at the greater risk of recurrence are those aged over 60 years, with large, recurrent hernias and who develop local complications during the postoperative period.


The effects of synthetic prostaglandin analogs on canine hepatic bile flow.
The synthetic prostaglandin analogs 16, 16-dimethyl PGF2 alpha and 16, 16-dimethyl PGE2 were administered to dogs with chronic biliary and gastric fistulas. The effects of 16, 16 diMePGF2 alpha and 16, 16 diMePGE2 were evaluated on bile flow and composition and bile adenosine 3', 5' monophosphate (cyclic AMP) secretion. 16, 16 diMePGF2 alpha in doses of 0.125 and 0.25 microgram-kg-min significantly increased hepatic bile flow. The choleresis was characterized by increased chloride and bicarbonate secretion. Measurement by radioimmunoassay of bile cyclic AMP concentration demonstrated no evident increase in bile cyclic AMP secretion associated with the choleresis produced by 16, 16 diMePGF2 alpha. The administration of 16, 16 diMePGE2 in a dose range 0.01 to 1.0 microgram-kg-min did not significantly alter bile flow rates or composition. Bile erythritol-14C clearance, a measure of canalicular bile flow, was significantly increased by PGF2 alpha but not by 16, 16-dimethyl PGF2 alpha, suggesting that the mechanism of action of PGF2 alpha in stimulating hepatic bile flow may be different from that involved in 16, 16-dimethyl PGF2 alpha choleresis. The results of this study indicate that the synthetic PGF2 alpha analog produces a choleretic response not mediated by adenylate cyclase and associated with increased chloride and bicarbonate secretion.


Tobacco use among low-income housing residents: does hardship motivate quit attempts?
The purpose of this study was to examine material hardship among smokers to determine whether such hardship was positively associated with current attempts to quit tobacco use. We analyzed cross-sectional data from the Health in Common (HIC) study, an observational study to investigate social and physical determinants of cancer risk-related behaviors among residents of low-income housing in three cities in the Boston metropolitan area. In this study, three indicators of hardship were used: food hardship, financial hardship, and material hardship (food and financial hardship combined). Logistic regression models were used to obtain the odds of currently trying to quit among current smokers in the HIC (n = 170) across hardship types experienced, adjusting for sociodemographic and psychosocial factors. Fully adjusted models revealed no statistically significant association between trying to quit tobacco use and indicators of material hardship: food hardship and financial hardship present (OR 1.33 (0.42-4.2); food hardship and no financial hardship OR 3.83 (0.97-15.13); and financial hardship but no food hardship OR 0.5 (0.1-2.39). These findings suggest that even in the presence of material hardship, low-income housing resident tobacco users are not more likely to quit tobacco use; therefore, cessation efforts focused on the financial benefits of quitting may be insufficient to motivate quit attempts among low-income smokers.


Radial keratotomy increases the effects of disability glare: initial results.
Attempts to correct myopia by surgical intervention (radial keratotomy) are increasing, and disability glare is emerging as a common subjective postsurgical complaint. To date, efforts to quantify this complaint have failed. By measuring increment thresholds in the presence of a point-glare source, we have been able to measure large glare effects (up to six times normal) at low background luminance levels.


Subnuclear associations of the v-myb oncogene product and actin are dependent on ionic strength during nuclear isolation.
The method used to isolate nuclei has a direct effect on the subnuclear association of the v-myb product, p48v-myb, and nuclear actin. Analysis of nuclei subjected to various isolation procedures showed that disruption of native nuclear structure during hypotonic treatment resulted in dissociation of p48v-myb from the nuclear matrix.


The effect of experimental pleurodesis caused by aluminum hydroxide on lung and chest wall mechanics.
The aim of this study was to evaluate the effect of a chemical sclerosing agent, aluminum hydroxide, on pleural remodeling and on respiratory mechanics in rats. Saline (2 mL) or aluminum hydroxide [2 mL (0.15 g/mL)] was instilled intrapleurally in anesthetized male rats. The animals were studied 7 or 30 days after the instillation. Respiratory system, lung, and chest wall elastic, resistive, and viscoelastic/inhomogeneous pressures were measured by the end-inflation occlusion method. We studied the pleural remodeling process by means of semiquantitative analysis of the induced inflammation and quantitative analysis of the collagen extracellular matrix component. The effects on the underlying lung were analyzed morphometrically. Chest wall elastic and viscoelastic pressures increased after aluminum hydroxide instillation independent of time after instillation. Pleural inflammation was observed 7 days after instillation, while pleural adherence with a marked increase in the type I/type III collagen ratio was present 30 days after instillation. Histological examination demonstrated no differences in lung parenchyma among the groups. In conclusion, the present model describes the establishment of pleurodesis by aluminum hydroxide, which thwarts the normal chest wall mechanical profile without inducing any changes in the underlying lungs. The results were disclosed by both mechanical and morphological evaluation of the pleural remodeling.


Scaling laws for van der Waals interactions in nanostructured materials.
Van der Waals interactions have a fundamental role in biology, physics and chemistry, in particular in the self-assembly and the ensuing function of nanostructured materials. Here we utilize an efficient microscopic method to demonstrate that van der Waals interactions in nanomaterials act at distances greater than typically assumed, and can be characterized by different scaling laws depending on the dimensionality and size of the system. Specifically, we study the behaviour of van der Waals interactions in single-layer and multilayer graphene, fullerenes of varying size, single-wall carbon nanotubes and graphene nanoribbons. As a function of nanostructure size, the van der Waals coefficients follow unusual trends for all of the considered systems, and deviate significantly from the conventionally employed pairwise-additive picture. We propose that the peculiar van der Waals interactions in nanostructured materials could be exploited to control their self-assembly.