Multiple time scales in solvation dynamics of DNA in aqueous solution: the role of water, counterions, and cross-correlations.
Recent time domain experiments have explored solvation dynamics of a probe located inside a DNA duplex, in an effort to gain information, e.g., on the dynamics of water molecules in the DNA major and minor grooves and their environment. Multiple time constants in the range of a few picoseconds to several nanoseconds were obtained. We have carried out 15 ns long atomistic molecular dynamics simulations to study the solvation dynamics of bases of a 38 base-pair long DNA duplex in an aqueous solution containing counterions. We have computed the energy-energy time correlation function (TCF) of the four individual bases (A, T, G, and C) to characterize the solvation dynamics. All the TCFs display highly nonexponential decay with time. When the trajectories are analyzed with 100 fs time resolution, the TCF of each base shows initial ultrafast decay (with tau1 approximately equal 60-80 fs) followed by two intermediate components (tau2 approximately equal 1 ps, tau3 approximately equal 20-30 ps), in near complete agreement with a recent time domain experiment on DNA solvation. Interestingly, the solvation dynamics of each of the four different nucleotide bases exhibit rather similar time scales. To explore the existence of slow relaxation at longer times reported recently in a series of experiments, we also analyzed the solvation TCFs calculated with longer time trajectories and with a larger time resolution of 1 ps. In this case, an additional slow component with a time constant of the order of 250 ps is observed. Through an analysis of partial solvation TCFs, we find that the slow decay originates mainly from the interaction of the nucleotides with the dipolar water molecules and the counterions. An interesting negative cross-correlation between water and counterions is observed, which makes an important contribution to relaxation at intermediate to longer times.


Hypoxic pulmonary vasoconstriction: mechanisms of oxygen-sensing.
Hypoxic pulmonary vasoconstriction (HPV) is driven by the intrinsic response to hypoxia of pulmonary arterial smooth muscle and endothelial cells. These are representatives of a group of specialized O2-sensing cells, defined by their acute sensitivity to relatively small changes in pO2, which have evolved to modulate respiratory and circulatory function in order to maintain O2 supply within physiological limits. The aim of this article is to discuss recent investigations into the mechanism(s) of hypoxia-response coupling and, in light of these, provide a critical assessment of current working hypotheses. Upon exposure to hypoxia state-of-the-art technologies have now confirmed that mitochondrial oxidative phosphorylation is inhibited in all O2-sensing cells, including pulmonary arterial smooth muscle cells. Thereafter, evidence has been presented to indicate a role as principal effector for the 'gasotransmitters' carbon monoxide and hydrogen sulphide, reactive oxygen species or, in marked contrast, reduced cellular redox couples. Considering recent evidence in favour and against these proposals we suggest that an alternative mechanism may be key, namely the activation of adenosine monophosphate-activated protein kinase consequent to inhibition of mitochondrial oxidative phosphorylation. HPV supports ventilation-perfusion matching in the lung by diverting blood flow away from oxygen-deprived areas towards regions rich in O2. However, in diseases such as emphysema and cystic fibrosis, widespread HPV leads to hypoxic pulmonary hypertension and ultimately right heart failure. Determining the precise mechanism(s) that underpins hypoxia-response coupling will therefore advance understanding of the fundamental processes contributing to related pathophysiology and provide for improved therapeutics.


Effect of shoe flexibility on plantar loading in children learning to walk.
In a previous pilot study of "cruisers" (nonindependent ambulation), "early walkers" (independent ambulation for 0-5 months), and "experienced walkers" (independent ambulation for 6-12 months), developmental age significantly affected the children's stability when walking and performing functional activities. We sought to examine how shoe structural characteristics affect plantar pressure distribution in early walkers. Torsional flexibility was evaluated in four shoe designs (UltraFlex, MedFlex, LowFlex, and Stiff based on decreasing relative flexibility) with a structural testing machine. Plantar pressures were recorded in 25 early walkers while barefoot and shod at self-selected walking speeds. Peak pressure was calculated over ten masked regions for the barefoot and shod conditions. Torsional flexibility, the angular rotation divided by the applied moment about the long axis of the shoe, was different across the four shoe designs. As expected, UltraFlex was the most flexible and Stiff was the least flexible. As applied moment increased, torsional flexibility decreased in all footwear. When evaluating early walkers during gait, peak pressure was significantly different across shoe conditions for all of the masked regions. The stiffest shoe had the lowest peak pressures and the most flexible shoe had the highest. It is likely that increased shoe flexibility promoted greater plantar loading. Plantar pressures while wearing the most flexible shoe are similar to those while barefoot. This mechanical feedback may enhance proprioception, which is a desirable attribute for children learning to walk.


A cognitive psychometric model for assessment of picture naming abilities in aphasia.
Picture naming impairments are a typical feature of stroke-induced aphasia. Overall accuracy and rates of different error types are used to make inferences about the severity and nature of damage to the brain's language network. Currently available assessment tools for picture naming accuracy treat it as a unidimensional measure, while assessment tools for error types treat items homogenously, contrary to findings from psycholinguistic investigations of word production. We created and tested a new cognitive psychometric model for assessment of picture naming responses, using cognitive theory to specify latent processing decisions during the production of a naming attempt, and using item response theory to separate the effects of item difficulty and participant ability on these internal processing decisions. The model enables multidimensional assessment of latent picture naming abilities on a common scale, with a relatively large cohort for normative reference. We present the results of 4 experiments testing our interpretation of the model's parameters, as they apply to picture naming predictions, lexical properties of the items, statistical properties of the lexicon, and participants' scores on other tests. We also created a website for researchers and clinicians to analyze item-level data using our model, providing estimates of latent abilities and percentile scores, as well as credible intervals to help gauge the reliability of the estimated model parameters and identify meaningful changes. To the extent that the model is successful, the estimated parameter values may aid in treatment decisions and progress monitoring, or they may help elucidate the functional properties of brain networks. (PsycINFO Database Record


IL-10 and IL-12 production in response to Mycobacterium tuberculosis total lipid antigens in multidrug resistant tuberculosis.
Mycobacterium tuberculosis lipid antigens take part in pathogenicity of the bacterium but the response of monocytes/macrophages to these antigens in tuberculosis is not well known. The aim of current investigation was to study the M. tuberculosis lipid antigens in tuberculosis pathogenesis. In the present study M. tuberculosis lipid antigens were extracted. Monocytes and macrophages from multidrug-resistant tuberculosis (MDR-TB), TB patients, asymptomatic healthy individuals with positive tuberculin skin test positive and healthy individuals with negative tuberculin skin test were collected using magnetic cell sorting. The cells were stimulated by M. tuberculosis total lipid antigens and IL-12 and IL-10 in their supernatants were measured by enzyme-linked immunosorbent assay. The IL-12 production by monocytes in response to M. tuberculosis total sonicate antigens in the MDR-TB patients did not show a considerable difference with the PPD positive healthy subjects, whereas in the active TB patients, IL-12 levels significantly decreased (p<0.05). IL-10 production by monocytes in TB patients in response to total lipid antigens showed a significant increase in comparison to MDR-TB patients and healthy individuals. In the MDR-TB patients, IL-10 and IL-12 production by monocytes in response to M. tuberculosis lipid antigens are similar to the healthy subjects.


A Novel, Low-cost, Low-fidelity Pericardiocentesis Teaching Model.
Pericardiocentesis is a high-risk/low-frequency procedure important to emergency medicine (EM). However, due to case rarity it is not often performed on a patient during residency training. Because the coronavirus disease 2019 pandemic limited cadaver-based practice, we developed a novel, low-cost, low-fidelity pericardiocentesis model using three dimensional-printing technology to provide advances on prior home-made models. Residents watched a 20-minute video about performing a pericardiocentesis and practiced both a blind and ultrasound-guided technique. We assessed model fidelity, convenience, and perceived provider competence via post-workshop questionnaire. A total of 24/26 (93%) individuals practicing on the ultrasound-guided model and 22/24 (92%) on the blind approach model agreed or strongly agreed that the models reasonably mimicked a pericardial effusion. Our low-cost, low-fidelity model is durable, mimics the clinical case, and is easy to use. It also addresses known limitations from prior low-fidelity models.


Lessons Learned Designing and Using an Online Discussion Forum for Care Coordinators in Primary Care.
While an increasing number of researchers are using online discussion forums for qualitative research, few authors have documented their experiences and lessons learned to demonstrate this method's viability and validity in health services research. We comprehensively describe our experiences, from start to finish, of designing and using an asynchronous online discussion forum for collecting and analyzing information elicited from care coordinators in Patient-Centered Medical Homes across the United States. Our lessons learned from each phase, including planning, designing, implementing, using, and ending this private online discussion forum, provide some recommendations for other health services researchers considering this method. An asynchronous online discussion forum is a feasible, efficient, and effective method to conduct a qualitative study, particularly when subjects are health professionals.


Mentalization-Based Treatment From the Patients' Perspective - What Ingredients Do They Emphasize?
Objective: The aim of this study was to explore how patients with personality disorder (PD) and substance use disorder (SUD) experience mentalization-based treatment (MBT), in particular what they consider useful and less useful elements of the therapy. Method: Semi-structured qualitative interviews with 13 participants were conducted. Participants were interviewed on their experience of the different elements of MBT, their experience of working in the transference, and their view on MBT as a whole. Thematic analyses were performed within a hermeneutical-phenomenological epistemology, with an emphasis on researcher reflexivity. Results: The following themes were found in the material: "I am not alone," "Taking blinders off," "Just say it," "The paradox of trust," and "Follow me closely." Three of these themes concerned therapist interventions; these involved addressing the relationship with the patients, addressing negative or unspoken feelings in the sessions, and validating and tolerating patients' affect. Two themes concerned group therapy experiences; these were the experience of sameness with co-patients in group and the experience of discovering different perspectives in group. Conclusions: Patients' experiences of useful elements in MBT resonate with theoretical tenets of (borderline) personality pathology, in particular attachment disturbances and emotional dysregulation. Patients highlight what we would label working in the therapeutic relationship, addressing transferential and counter-transferential processes explicitly, emotional validation, and enhancing mentalizing in its own right.


Quorum sensing in plant-associated bacteria.
N-acyl homoserine lactone (AHL)-mediated quorum sensing by bacteria regulates traits that are involved in symbiotic, pathogenic and surface-associated relationships between microbial populations and their plant hosts. Recent advances demonstrate deviations from the classic LuxR/LuxI paradigm, which was first developed in Vibrio. For example, LuxR homologs can repress as well as activate gene expression, and non-AHL signals and signal mimics can affect the expression of genes that are controlled by quorum sensing. Many bacteria utilize multiple quorum-sensing systems, and these may be modulated via post-transcriptional and other global regulatory mechanisms. Microbes inhabiting plant surfaces also produce and respond to a diverse mixture of AHL signals. The production of AHL mimics by plants and the identification of AHL degradative pathways suggest that bacteria and plants utilize this method of bacterial communication as a key control point for influencing the outcome of their interactions.


A comparison of cyclic guanosine 3':5'-monophosphate and muscarinic excitatory responses in the superior cervical ganglion of the rat.
The relationship between the magnitude of atropine-sensitive afterdischarge (AD), which is generated from slow excitatory postsynaptic potentials and the ganglionic cyclic guanosine 3':5'-monophosphate (cGMP) concentration was investigated in the rat superior cervical ganglion in vitro. Parallel increases in the magnitude of atropine-sensitive AD and cGMP concentration occurred with increasing frequency of preganglionic nerve stimulation up to 40 Hz for 10 sec. However, AD was completely antagonized by atropine, 0.1 to 1 microM, whereas the cGMP response was not significantly affected by up to 25 microM atropine. Although bethanechol, 0.5 mM, causes an asynchronous firing which can be recorded from the postganglionic nerve, bethanechol had no effect on the ganglionic cGMP concentration even in ganglia preincubated with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, 1 mM. The methylxanthine did increase the resting cGMP concentration and the concentration of cGMP immediately after stimulation of the preganglionic nerve. It is concluded that muscarinic AD and the slow excitatory postsynaptic potentials of rat sympathetic ganglia are not generated by a mechanism involving an increase in ganglionic cGMP.


[Rapunzel syndrome as a cause of obstruction and intestinal perforation].
The following is a case report involving a 16 year old female with trichotillomania as an antecedent. This patient presented to the Emergency Room with a chief complaint of early satiety and persistent abdominal pain for the past 3 months. However, recently her abdominal pain has worsened and it is now complicated by nausea and vomiting. The physical exam was notable for epigastric pain on deep palpation. The biochemical analysis and abdominal ultrasound were otherwise unremarkable. An esophagogastroduodenoscopy was subsequently performed where a trichobezoar was discovered. It extended from the gastric fundus to the third portion of the duodenum. A surgical extraction of the trichobezoar was then performed. The trichobezoar was found to be 130 cm in length and 8 cm wide at its most cephalad aspect. It is important to note that they also found five mall perforations throughout the duodenum and jejunum. The patient was discharged with outpatient follow up with psychiatry. In this report we describe the case of a patient with Rapunzel syndrome that was complicated by small bowel perforation and we provide a review of the salient literature concerning this syndrome and its associated complications.


Body shaping under water stress: osmosensing and osmoregulation of solute transport in bacteria.
Fluctuation of external osmolarity is one of the most common types of environmental stress factors for all kind of cells, both of prokaryotic and of eukaryotic origin. Cells try to keep their volume and/or turgor pressure constant; consequently, both a decrease (hypoosmotic stress) and an increase (hyperosmotic stress) of the solute concentration (correctly: increase or decrease in water activity) in the surrounding area, respectively, are challenges for cellular metabolism and survival. A common example from the prokaryotic world is the fate of a soil bacterium that, after a sunny day has dried out the soil (hyperosmotic stress), is suddenly exposed to a drop of distilled water from a rain cloud (hypoosmotic stress). The immediate and inevitable passive response to the sudden osmotic shift in the surroundings is fast water efflux out of the cell in the former situation and water influx in the latter. In the worst case, these responses may lead to either loss of cell turgor and plasmolysis or to cell burst. In order to overcome such drastic consequences cells have developed effective mechanisms, namely osmoadaptation, to cope with the two different types of osmotic stress. For a graded reaction to osmotic shifts, cells must be able (1) to sense stimuli related to osmotic stress, (2) to transduce corresponding signals to those systems that properly respond (3) by activating transport or enzymatic functions or (4) by changing gene expression profiles. In this review, membrane proteins involved in the cell's active response to osmotic stress are described. Molecular details of structure, function, and regulation of mechanosensitive efflux channels from various organisms, as well as of osmoregulated uptake systems are discussed.


Rapid suppression of plasma testosterone levels and tumor growth in the dunning rat model treated with degarelix, a new gonadotropin-releasing hormone antagonist.
Degarelix (FE 200486) is a member of a new class of water-soluble (>50 mg/ml) gonadotropin-releasing hormone (GnRH) antagonists in clinical development for prostate cancer. Upon subcutaneous administration, degarelix forms a gel that results in a sustained release of the compound into the circulation, immediately blocking GnRH receptors in the pituitary and inducing a fast and sustained suppression of gonadotrophin secretion in rats and primates. One of the few animal models of prostate adenocarcinoma is the Dunning R-3327H rat carcinoma transplanted into Copenhagen rats. The growth of the Dunning tumor can be inhibited by various treatments reported to be effective in the clinic, such as GnRH superagonists, antiandrogens, 5-alphareductase inhibitors, tyrosine kinase inhibitors, and surgical castration. We report in this study that degarelix produces a fast and sustained suppression of the pituitary gonadal axis in rats and a similar inhibition of tumor growth compared with surgical castration in the Dunning R-3327H rat carcinoma model. First, degarelix as been compared with d-Trp(6)-luteinizing hormone-releasing hormone and surgical castration on a short-term study (2 months); and second, degarelix has been compared with leuprolide and surgical castration on a long-term study (12 months). In both studies, degarelix demonstrated a sustained inhibition of tumor growth at least comparable with surgical castration. These data provide a convincing profile of degarelix as a potential candidate for the clinical management of sex steroid-dependent pathologies, such as prostate cancer, where long-term reversible chemical castration is required.


A longitudinal study of accommodative changes in biometry during incipient presbyopia.
To profile accommodative biometric changes longitudinally and to determine the influence of age-related ocular structural changes on the accommodative response prior to the onset of presbyopia. Twenty participants (aged 34-41 years) were reviewed at six-monthly intervals over two and a half years. At each visit, ocular biometry was measured with the LenStar biometer (www.Haag-Streit.com) in response to 0.00, 3.00 and 4.50 D stimuli. Accommodative responses were measured by the WAM 5500 Auto Ref/Keratometer (www.grandseiko.com). During accommodation, anterior chamber depth reduced (F = 29, p < 0.001), whereas crystalline lens thickness (F = 39, p < 0.001) and axial length (F = 5.4, p = 0.009) increased. The accommodative response (F = 5.5, p = 0.001) and the change in anterior chamber depth (F = 3.1, p = 0.039), crystalline lens thickness (F = 3.0, p = 0.042) and axial length (F = 2.5, p = 0.038) in response to the 4.50 D accommodative target reduced after 2.5 years. However, the change in anterior chamber depth (F = 2.2, p = 0.097), crystalline lens thickness (F = 1.7, p = 0.18) and axial length (F = 1.0, p = 0.40) per dioptre of accommodation exerted remained invariant after 2.5 years. The increase in disaccommodated crystalline lens thickness with age was not significantly associated with the reduction in accommodative response (R = 0.32, p = 0.17). Despite significant age-related structural changes in disaccommodated biometry, the change in biometry per dioptre of accommodation exerted remained invariant with age. The present study supports the Helmholtz theory of accommodation and suggests an increase in lenticular stiffness is primarily responsible for the onset of presbyopia.


[An outbreak of measles among unvaccinated migrant population in Zhejiang province, from June to August, 2010].
On July 6, 2010, the parents of a patient with confirmed measles reported several suspected measles patients with fever and rash in their village. An investigation was carried out to verify and understand the cause of the outbreak. Several suspected cases had an onset of fever and rash in this and other neighboring villages during June 1 to August 3, 2010. A confirmed case was a suspected case with measles-specific IgM identified in the serum. We conducted door-to-door visits and searched the Chinese Center for Disease Control and Prevention Information System to identify cases, also conducted a retrospective cohort study among migrant children aged 8 months-14 years to identify risk factors related to measles. We identified 19 measles cases (17 confirmed case, 2 suspected cases) in the village, and all of them were migrants. Children aged 1-2 years had the highest attack rate (13%). The primary case-patient had onset on the day she arrived in this village (June 4, 2010). Caretakers from an unlicensed private clinic were providing service in the village but did not report the outbreak to the public health authority. The outbreak was identified only after receiving a report from the parents of one of the patients, by that time the outbreak had lasted for one month. The measles vaccine coverage rate was 81% among the 315 migrant children aged 8 months-14 years. Among the 61 unvaccinated children, those who reportedly being contacted a measles patient had a higher attack rate (14/16, 88%) than those who did not (2/45, 4.4%) (Relative risk = 20, Fisher's exact 95% confidence interval: 5.7-94). The low measles vaccine coverage among migrant children and lack of measures taken on the incident, timely isolation diagnosis/reporting by the caretakers from the unlicensed private clinic etc. had contributed to this prolonged outbreak. Measures need to be taken to improve the immunization services for migrant populations and to enhance measles surveillance programs in the area.


Microarray analysis of di-n-butyl phthalate and 17α ethinyl-oestradiol responses in three-spined stickleback testes reveals novel candidate genes for endocrine disruption.
Phthalate esters are plasticizers frequently found in wastewater effluents. Previous studies on phthalates have reported anti-androgenic activity in mammals, causing concerns of their potential effects on the reproduction of aquatic organisms. Another group of environmental endocrine disrupters, steroidal estrogens, are known to inhibit steroid biosynthesis in the gonads, but the effects related to spermatogenesis are not well understood in fish. In this study, three-spined sticklebacks were exposed to di-n-butyl phthalate (DBP) and 17α ethinyl-oestradiol (EE2) at nominal concentrations 35μg/L and 40ng/L, respectively, for four days. The aim of the study was to obtain insight into the acute transcriptional responses putatively associated with endocrine disruption. RNA samples from eight individual male fish per treatment (including controls) were used in microarray analysis, covering the expression of approximately 21,000 genes. In the EE2 treatment the results show transcriptional downregulation of genes associated with steroid biosynthesis pathway and up-regulation of genes involved in pathways related to epidermal growth factor signaling and xenobiotic metabolism. The transcriptional response to DBP was in general weaker than to EE2, but based on enrichment analysis, we suggest adverse effects on retinoid metabolism, creatine kinase activity and cell adhesion. Among the genes showing highest fold changes after DBP treatment compared to control was the teleost fish -specific cytochrome P450 17A2. Overall, this study promotes our understanding on molecular responses to anti-androgens and estrogens in fish testes.


Topical rapamycin (sirolimus) for facial angiofibromas.
Rapamycin (sirolimus) is a fungal fermentation product that inhibits the proper functioning of a serine/threonine protein kinase in mammalian cells eponymously named mammalian target of rapamycin, or mTOR. Rapamycin is a novel class of anticancer and immunosuppressant drugs targeting the proteins at molecular level. Rapamycin (sirolimus) is routinely incorporated in drug-eluting stents used for cardiac angioplasty. In recent years, rapamycin was found to be efficacious in managing the symptom complex of tuberous sclerosis, i.e. renal angiomyolipoma, giant cell astrocytoma and pulmonary lymphangiomyomatosis. Various investigators have also proved that topically applied rapamycin causes regression of facial angiofibromas, giving better cosmetic results.


[Duplex Sonography of the Brain-Supplying Arteries - Pitfalls].
This CME article presents a structured examination of duplex sonography of the brain-supplying arteries, especially focusing on difficulties and pitfalls. Criteria for stenosis grading and common mistakes as well as anatomical and methodical characteristics are described in detail.


Fibrinogen coating density affects the conformation of immobilized fibrinogen: implications for platelet adhesion and spreading.
Adhesion of platelets to immobilized fibrinogen appears to play an important role in a variety of physiologic and pathologic phenomena. We previously observed that the fibrinogen concentration used to coat polystyrene wells affected the morphology and distribution of GP IIb/IIIa receptors on the surface of platelets adherent to the fibrinogen. One possible explanation for these differences is that fibrinogen immobilized at high density adopts a different conformation than fibrinogen immobilized at low density. To address this possibility, we studied the binding of a panel of anti-fibrinogen monoclonal antibodies (mAbs) to fibrinogen immobilized at different coating densities. Three different patterns of binding were observed: 1) a linear increase in binding to wells coated with 1-10 microg/ml fibrinogen, followed by a lesser increase or plateau at higher fibrinogen concentrations (mAbs Fd4-4E1, Fd4-7B3, 1D4, 4-2); 2) minimal reactivity at all fibrinogen concentrations (mAbs GC4-1A12, 2C34); 3) a biphasic response, with a linear increase up to 10 microg/ml fibrinogen and then a significant decline in binding at higher fibrinogen concentrations (mAbs 311, 31A9, FPA 19/7, 9C3, 1C5-A5/2, 44-3). The patterns of mAb binding to fibrinogen immobilized from plasma were similar. Most mAbs that demonstrated a biphasic response bound poorly or not at all to soluble fibrinogen, while mAbs that demonstrated a linear/plateau response were able to bind soluble fibrinogen. At equal surface densities, mAbs that bound biphasically, particularly mAb 1C5-A5/2, were more reactive to urea-denatured than native fibrinogen. mAbs 1C5-A5/2 and 44-3 are specific for gamma 1-78 and 95-265, respectively, suggesting that the fibrinogen gamma-chain may be sensitive to changes in conformation induced by immobilization. In summary, these data suggest that fibrinogen immobilized at 1-10 microg/ml adopts a conformation unlike soluble fibrinogen, while fibrinogen immobilized at > 30 microg/ml adopts a more solution-like conformation. These differences in fibrinogen conformation may partially account for the ability of platelets to bind to immobilized fibrinogen without the addition of agonist, as well as the differences in spreading and GPIIb/IIIa distribution on platelets adherent to high- versus low-density immobilized fibrinogen.


Mercury uptake by Paspalum distichum L. in relation to the mercury distribution pattern in rhizosphere soil.
Paspalum distichum L. was tested to evaluate their phytoremediation capacity for Hg contaminated soil through analyzing the dissipation of Hg in soil through a greenhouse study by using self-made rhizos box. Original soil samples were collected at Hg mining site with serious Hg contamination and a control site, respectively. Planting of P. distichum. L last for 60 days. Soil and plant samples were collected from four periods (0 d, 20 d, 40 d, and 60 d) and soil samples were collected from five different rhizosphere distance in horizontal direction (0-2 cm, 2-4cm, 4-6cm, 6-8cm, 8-10cm). The results showed that the presence of P. distichum. L significantly accelerated the Hg dissipation in soil compared with control. Hg concentration in the rhizospheric soil was affected by the plant growth period and the distance to the plant roots. The closer of soil to the root of P. distichum. L, the lower mercury concentration in soil. During the 60-day growing period, the concentrations of total Hg (THg) and methylmercury (MeHg) reduced by 45% and 64%, respectively, in the rhizosphere (0-2cm) of Hg contaminated soil. However, MeHg concentration was increased near the roots (0-4 cm) during the initial growing period (0-20 d), which may be attributed to the influence of root exudates. Root is the major part for Hg accumulation in P. distichum. L. The low ratio between Hg concentrations in underground and aboveground tissues indicated that it seemed difficult for Hg translocation from root to shoot. The highest THg (9.71 ± 3.09 μg·g-1) and MeHg (26.97 ± 0.98 ng·g-1) value in root of P. distichum. L were observed at the 20th day when P. distichum. L grown in Hg contaminated soil. The results of chemical fractions analyses showed that elemental Hg and residual Hg were the two major speciations followed by organic bound Hg in the Hg contaminated soil, which indicated the high bioavailability and ecological potential risk of Hg in Hg contaminated soil.


[Swedish practice routines for fluid therapy are considerably changing].
The optimal fluid therapy for plasma volume support at major surgical procedures and in the treatment of critically ill patients has been a matter of considerable controversy during the last few years. The impact of the ongoing debate on Swedish routines has been assessed from a detailed questionnaire sent to all operation (OP) and intensive care units (ICU) in Sweden (n=130) in September 2004. Response was obtained from 92% of the units. It was found that major changes in fluid treatment regimes had occurred in recent years. In spite of the anti-colloid debate in the 1990s the continued use of colloids was evident. The use of albumin was reduced while that of other colloids had increased. Dextran was no longer the dominating colloid since a majority of the departments reported a switch to hydroxyethyl starch (HES). The switch was based on recent information on the advantages and disadvantages of the various products available. Gelatin was only marginally used since it was no longer available on the market. The fluid treatment profile documented on the basis of the responses to the questionnaire agreed well with the recent sale figures of albumin and artificial colloids. A restrictive fluid therapy at surgical procedures is recently advocated based on administration of colloid but only a rather limited volume of crystalloid. Some caution in the application of such a fluid therapy approach seems justified. More liberal fluid administration has recently been found rather to improve recovery after laparoscopic surgery.


Robustness of neuronal tuning to binaural sound localization cues against age-related loss of inhibitory synaptic inputs.
Sound localization relies on minute differences in the timing and intensity of sound arriving at both ears. Neurons of the lateral superior olive (LSO) in the brainstem process these interaural disparities by precisely detecting excitatory and inhibitory synaptic inputs. Aging generally induces selective loss of inhibitory synaptic transmission along the entire auditory pathways, including the reduction of inhibitory afferents to LSO. Electrophysiological recordings in animals, however, reported only minor functional changes in aged LSO. The perplexing discrepancy between anatomical and physiological observations suggests a role for activity-dependent plasticity that would help neurons retain their binaural tuning function despite loss of inhibitory inputs. To explore this hypothesis, we use a computational model of LSO to investigate mechanisms underlying the observed functional robustness against age-related loss of inhibitory inputs. The LSO model is an integrate-and-fire type enhanced with a small amount of low-voltage activated potassium conductance and driven with (in)homogeneous Poissonian inputs. Without synaptic input loss, model spike rates varied smoothly with interaural time and level differences, replicating empirical tuning properties of LSO. By reducing the number of inhibitory afferents to mimic age-related loss of inhibition, overall spike rates increased, which negatively impacted binaural tuning performance, measured as modulation depth and neuronal discriminability. To simulate a recovery process compensating for the loss of inhibitory fibers, the strength of remaining inhibitory inputs was increased. By this modification, effects of inhibition loss on binaural tuning were considerably weakened, leading to an improvement of functional performance. These neuron-level observations were further confirmed by population modeling, in which binaural tuning properties of multiple LSO neurons were varied according to empirical measurements. These results demonstrate the plausibility that homeostatic plasticity could effectively counteract known age-dependent loss of inhibitory fibers in LSO and suggest that behavioral degradation of sound localization might originate from changes occurring more centrally.


Charged-coupled device (CCD) detectors for Lab-on-a Chip (LOC) optical analysis.
A critical element of any Lab-on-a-Chip (LOC) is a detector; among the many detection approaches, optical detection is very widely used for biodetection. One challenge for advancing the development of LOC for biodetection has been to enhance the portability and lower the cost for Point-of-Care diagnostics, which has the potential to enhance the quality of healthcare delivery for underserved populations and for global health. We describe a simple and relatively low cost charged-coupled device (CCD)-based detector that can be integrated with a conventional microtiter plate or a portable LOC assay for various optical detection modalities including fluorescence, chemiluminescence, densitometry, and colorimetric assays. In general, the portable battery-operated CCD-based detection system consists of four modules: (1) a cooled CCD digital camera to monitor light emission, (2) a LOC or microtiter plate to perform assays, (3) a light source to illuminate the assay (such as electroluminescence (EL) or light emitting diode (LED)), and (4) a portable computer to acquire and analyze images. The configuration of the fluorescence detector presented here was designed to measure fluorogenic excitation at 490 nm and to monitor emission at 523 nm used for FITC detection.The LOC used for this detection system was fabricated with laminated object manufacturing (LOM) technology, and was designed to detection activity of botulinum neurotoxin serotype A (BoNT-A) using a fluorogenic peptide substrate (SNAP-25) for botulinum neurotoxin serotype A (BoNT-A) labeled with FITC. The limit of detection (LOD) for the CCD detector is 0.5 nM (25 ng/ml). The portable system is small and is powered by a 12 V source. The modular detector was designed with easily interchangeable LEDs, ELs, filters, lenses, and LOC, and can be used and adapted for a wide variety of densitometry, florescence and colorimetric assays.


Changes in cross-resistance spectrum resulting from methyl parathion selection of Culex tarsalis Coq.
Larvae of a field strain of Culex tarsalis Coq. manifesting a broad spectrum of resistance to organophosphorus (OP) insecticides were selected further by methyl parathion pressure in the laboratory. There was a 6.9 times further increase in resistance to methyl parathion in larvae, i.e., from 13.4 times level of resistance in the parental strain to 93.5 times level in the F11 generation. With the exception of fenthion and malathion, cross resistance in larvae the parental strain. The F11 larval population exhibited high levels of cross-resistance to chlorpyrifos (29.6 times), fenitrothion (49.4 times), parathion (55.6 times), fenthion (76.8 times), and chlorpyrifos-methyl (253.8 times). The high levels and broad spectrum of resistance to diverse OP compounds suggest the involvement of more than one mechanism in resistance. Larval selection also affected the spectrum of OP resistance in adults. The F11 adult population exhibited high levels of resistance to dichlorvos (48 times) and chlorpyrifos-methyl (40.1 times) insecticides propoxur, Mobam, Landrin or carbaryl, or to the chrysanthemate insecticide cismethrin. Resistance to the OP insecticides methyl parathion, parathion, fentirothion, fenthion and chlorpyrifos-methyl was found to be fairly stable over nine generations in the absence of methyl parathion selection pressure.


Effect of phorbol esters and hormones on rat hepatoma cells producing alpha-fetoprotein.
Effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on rat AH66 hepatoma cells was studied with a reference to that of insulin and the epidermal growth factor (EGF). In a short term cell incubation, TPA and EGF caused an approximately 2-fold increase in the production of alpha-fetoprotein (AFP) and other acid-precipitable materials, while the same concentration of insulin brought a 3-fold increase. In a long term culture using a low serum medium, TPA as well as insulin and EGF caused remarkable proliferation of AH66 cells, but the increase in cell number was not accompanied by a proportional increase in the levels of AFP of the culture media. These biological effects of TPA, insulin and EGF appeared to resemble each other, and subsequent hormone binding studies showed that TPA inhibited 125I-EGF binding to its membrane receptors without affecting 125I-insulin binding. Scatchard analysis of TPA effect on EGF binding indicated that TPA altered the affinity of the membrane receptors for EGF without changing the total number of available receptors per cell. From these data, it is suggested that some of the biological effects of TPA on AH66 cells may result from alterations in the functions of cell membrane.


High resolution laser beam induced current images under trichromatic laser radiation: approximation to the solar irradiation.
A laser beam induced current (LBIC) map of a photoactive surface is a very useful tool when it is necessary to study the spatial variability of properties such as photoconverter efficiency or factors connected with the recombination of carriers. Obtaining high spatial resolution LBIC maps involves irradiating the photoactive surface with a photonic beam with Gaussian power distribution and with a low dispersion coefficient. Laser emission fulfils these characteristics, but against it is the fact that it is highly monochromatic and therefore has a spectral distribution different to solar emissions. This work presents an instrumental system and procedure to obtain high spatial resolution LBIC maps in conditions approximating solar irradiation. The methodology developed consists of a trichromatic irradiation system based on three sources of laser excitation with emission in the red, green, and blue zones of the electromagnetic spectrum. The relative irradiation powers are determined by either solar spectrum distribution or Planck's emission formula which provides information approximate to the behavior of the system if it were under solar irradiation. In turn, an algorithm and a procedure have been developed to be able to form images based on the scans performed by the three lasers, providing information about the photoconverter efficiency of photovoltaic devices under the irradiation conditions used. This system has been checked with three photosensitive devices based on three different technologies: a commercial silicon photodiode, a commercial photoresistor, and a dye-sensitized solar cell. These devices make it possible to check how the superficial quantum efficiency has areas dependent upon the excitation wavelength while it has been possible to measure global incident photon-to-current efficiency values approximating those that would be obtained under irradiation conditions with sunlight.


Performance of recombinant chimeric proteins in the serological diagnosis of Trypanosoma cruzi infection in dogs.
Dogs are considered sentinels in areas of Trypanosoma cruzi transmission risk to humans. ELISA is generally the method of choice for diagnosing T. cruzi exposure in dogs, but its performance substantially depends on the antigenic matrix employed. In previous studies, our group has developed four chimeric antigens (IBMP-8.1, 8.2, 8.3, and 8.4) and evaluated their potential for diagnosing T. cruzi exposure in humans. For human sera, these chimeric antigens presented superior diagnostic performances as compared to commercial tests available in Brazil, Spain, and Argentina. Therefore, in this study we have evaluated the potential of these antigenic proteins for detection of anti-T. cruzi IgG antibodies in dog sera. The IBMP-ELISA assays were optimized by checkerboard titration. Subsequently, the diagnostic potential was validated through analysis of ROC curves and the performance of the tests was determined using double entry tables. Cross-reactivity was also evaluated for babesiosis, ehrlichiosis, dirofilariosis, anaplasmosis, and visceral leishmaniasis. Best performance was shown by IBMP-8.3 and IBMP-8.4, although all four antigens demonstrated a high diagnostic performance with 46 positive and 149 negative samples tested. IBMP-8.3 demonstrated 100% sensitivity, followed by IBMP-8.4 (96.7-100%), IBMP-8.2 (73.3-87.5%), and IBMP-8.1 (50-100%). The highest specificities were achieved with IBMP-8.2 (100%) and IBMP-8.4 (100%), followed by IBMP-8.3 (96.7-97.5%) and IBMP 8.1 (89.1-100%). The use of chimeric antigenic matrices in immunoassays for anti-T. cruzi IgG antibody detection in sera of infected dogs was shown to be a promising tool for veterinary diagnosis and epidemiological studies. The chimeric antigens used in this work allowed also to overcome the common hurdles related to serodiagnosis of T. cruzi infection, especially regarding variation of efficiency parameters according to different strains and cross-reactivity with other infectious diseases.


Differential functional regulation of protein kinase C (PKC) orthologs in fission yeast.
The two PKC orthologs Pck1 and Pck2 in the fission yeast Schizosaccharomyces pombe operate in a redundant fashion to control essential functions, including morphogenesis and cell wall biosynthesis, as well as the activity of the cell integrity pathway and its core element, the MAPK Pmk1. We show here that, despite the strong structural similarity and functional redundancy of these two enzymes, the mechanisms regulating their maturation, activation, and stabilization have a remarkably distinct biological impact on both kinases. We found that, in contrast to Pck2, putative in vivo phosphorylation of Pck1 within the conserved activation loop, turn, and hydrophobic motifs is essential for Pck1 stability and biological functions. Constitutive Pck activation promoted dephosphorylation and destabilization of Pck2, whereas it enhanced Pck1 levels to interfere with proper downstream signaling to the cell integrity pathway via Pck2. Importantly, although catalytic activity was essential for Pck1 function, Pck2 remained partially functional independent of its catalytic activity. Our findings suggest that early divergence from a common ancestor in fission yeast involved important changes in the mechanisms regulating catalytic activation and stability of PKC family members to allow for flexible and dynamic control of downstream functions, including MAPK signaling.


Same-Sex and Race-Based Disparities in Statutory Rape Arrests.
This study tests a liberation hypothesis for statutory rape incidents, specifically that there may be same-sex and race/ethnicity arrest disparities among statutory rape incidents and that these will be greater among statutory rape than among forcible sex crime incidents. 26,726 reported incidents of statutory rape as defined under state statutes and 96,474 forcible sex crime incidents were extracted from National Incident-Based Reporting System data sets. Arrest outcomes were tested using multilevel modeling. Same-sex statutory rape pairings were rare but had much higher arrest odds. A victim-offender romantic relationship amplified arrest odds for same-sex pairings, but damped arrest odds for male-on-female pairings. Same-sex disparities were larger among statutory than among forcible incidents. Female-on-male incidents had uniformly lower arrest odds. Race/ethnicity effects were smaller than gender effects and more complexly patterned. The findings support the liberation hypothesis for same-sex statutory rape arrest disparities, particularly among same-sex romantic pairings. Support for race/ethnicity-based arrest disparities was limited and mixed.


Low-frequency electroacupncture improves locomotor function after sciatic crushed nerve injury in rats.
Sciatic crushed nerve injury (SCI) causes pain-related gait and swelling in the affected limb. Electroacupuncture (EA) is a modified acupuncture technique, and analgesic effect of EA on different types of pain has been documented. Scientific functional index (SFI) is a mathematical formula to represent parameters of normal and experimental footprints. We investigated the effect of low-frequency EA on functional recovery following SCI in rats. For this study, immunohistochemistry for c-Fos in the ventral lateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN) and western blot for neurofilament (NF) and brain-derived neurotrophic factor (BDNF) in the sciatic nerve were conducted. To induce crush injury on the sciatic nerve, sciatic nerve was crushed for 30 sec using a surgical clip. The rats in the acupuncture groups received acupuncture bilaterally at respective site, once a day for 14 days. The rats in the EA group received 100-Hz electrical stimulation for 10 min once a day during 14 days. SCI decreased SFI value, in contrast, EA increased SFI value. c-Fos expression in the vlPAG and PVN was increased following SCI, in contrast, EA suppressed c-Fos expression. NF expression in the sciatic nerve was decreased by SCI, in contrast, EA increased NF expression. BDNF expression in the sciatic nerve was increased by SCI, in contrast, EA suppressed BDNF expression. In the present study, EA showed effectiveness on functional recovery from SCI.


Anti-cancer vaccines - a one-hit wonder?
Immunization against common bacterial and viral diseases has helped prevent millions of deaths worldwide. More recently, the concept of vaccination has been developed into a potentially novel strategy to treat and prevent cancer formation, progression, and spread. Over the past few years, a handful of anti-cancer vaccines have been licensed and approved for use in clinical practice, thus providing a breakthrough in the field. However, the path has not always been easy, with many hurdles that have had to be overcome in order to reach this point. Nevertheless, with more anti-cancer vaccines currently in development, there is still hope that they can eventually become routine tools used in the treatment and prevention of cancer in the future. This review will discuss in detail both types of anti-cancer vaccine presently used in clinical practice - therapeutic and preventive - before considering some of the more promising anti-cancer vaccines that are currently in development. Finally, the issue of side effects and the debate surrounding the overall cost-effectiveness of anti-cancer vaccines will be examined.


Unexpected ubiquity of heart-shaped scale morphotype in Centroplasthelida (Haptista): Ancestral trait or multiple acquisitions?
Centrohelids (Haptista: Centroplasthelida) are axopodial protists with a remarkable diversity of external siliceous scale morphologies. It is believed that the last common ancestor of centrohelids had a double layer of siliceous scales composed of plate scales closer to a cell surface and spine scales radiating outwards. The characteristic morphotype of spine scales with a heart-shaped base was once believed to be a unique feature of the genus Choanocystis, as it was defined by Siemensma and Roijackers (1988). Further research revealed that this morphology is present in different and sometimes distantly related lineages: Ozanamiidae, Meringosphaeridae, and Marophryidae. Here, we report the fourth clade, Pterocystidae, which is also revealed to contain representatives having this phenotype. Cernunnos gen. nov. is erected here to place Cernunnos uralica sp. nov., Cernunnos arctica sp. nov., Cernunnos america sp. nov., and Cernunnos antarctica Tikhonenkov et Mylnikov, 2010, Gerasimova comb. nov. C. uralica was studied with scanning electron microscopy and SSU rDNA sequencing. Molecular phylogenetic analysis placed it into marine environmental clade P within Pterocystida. The ubiquity of spine scales with heart-shaped bases could be an example of parallel evolution, but taking into account the considerable similarity it is likely an ancestral trait, acquired from the last common ancestor of centrohelids.


Indirect immunofluorescent detection of oocysts of Cryptosporidium parvum in the feces of naturally infected raccoons (Procyon lotor).
Fecal samples from 100 wild raccoons were examined for the presence of oocysts of Cryptosporidium parvum using a commercially available indirect immunofluorescent detection procedure. Thirteen (13%) of the samples were positive for oocysts. All positive samples were from juvenile raccoons. Over 61% of the infected samples contained moderate to large numbers of oocysts. Raccoons may serve as potential reservoirs for transmission of C. parvum.


Increasing trend of antibiotic resistance in Shigella in Bangladesh: a plasmid-mediated transfer of mphA macrolide resistance gene.
Shigellosis remains a common gastrointestinal disease mostly in children <5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.


Sliding window analyses for optimal selection of mini-barcodes, and application to 454-pyrosequencing for specimen identification from degraded DNA.
DNA barcoding remains a challenge when applied to diet analyses, ancient DNA studies, environmental DNA samples and, more generally, in any cases where DNA samples have not been adequately preserved. Because the size of the commonly used barcoding marker (COI) is over 600 base pairs (bp), amplification fails when the DNA molecule is degraded into smaller fragments. However, relevant information for specimen identification may not be evenly distributed along the barcoding region, and a shorter target can be sufficient for identification purposes. This study proposes a new, widely applicable, method to compare the performance of all potential 'mini-barcodes' for a given molecular marker and to objectively select the shortest and most informative one. Our method is based on a sliding window analysis implemented in the new R package SPIDER (Species IDentity and Evolution in R). This method is applicable to any taxon and any molecular marker. Here, it was tested on earthworm DNA that had been degraded through digestion by carnivorous landsnails. A 100 bp region of 16 S rDNA was selected as the shortest informative fragment (mini-barcode) required for accurate specimen identification. Corresponding primers were designed and used to amplify degraded earthworm (prey) DNA from 46 landsnail (predator) faeces using 454-pyrosequencing. This led to the detection of 18 earthworm species in the diet of the snail. We encourage molecular ecologists to use this method to objectively select the most informative region of the gene they aim to amplify from degraded DNA. The method and tools provided here, can be particularly useful (1) when dealing with degraded DNA for which only small fragments can be amplified, (2) for cases where no consensus has yet been reached on the appropriate barcode gene, or (3) to allow direct analysis of short reads derived from massively parallel sequencing without the need for bioinformatic consolidation.


A cadaver model evaluating femoral intramedullary reaming: a comparison between new reamer design (Pressure Sentinel) and a novel suction/irrigation reamer (RIA).
To compare the intramedullary pressures developed during reaming of cadaveric femurs with the Synthes Reamer/Irrigator/Aspirator (RIA) reamer and the Zimmer Pressure Sentinel (PS) reamer, controlling for the force and speed of reaming. Fifteen matched pairs of frozen unpreserved femurs were used in the study. Two pressure transducers and two thermocouples were screwed into holes drilled into the femoral shaft. The femurs were stabilized in the vertical position by mechanically attaching them to a custom jig equipped with a load cell to detect the vertical component of force applied to the reamer. Proximally a linear voltage displacement transducer (LVDT) was attached to the reamer to record the continuous position of the reamer. All femurs were reamed to a diameter 2 mm larger than the narrowest point of the canal. Proximal and distal pressures, proximal and distal temperatures, applied vertical force and displacement were measured continuously throughout the reaming process. Maximum and minimum, and average proximal and distal pressures for each reamer were obtained and compared using paired t-tests. Averages were also calculated and compared in the same manner. A p-value of <0.05 was considered statistically significant. The maximum, minimum and average intramedullary pressures during reaming were significantly lower with the RIA system than the PS reamer. In general, the pressures produced by the RIA system were consistently below atmospheric pressure for the majority of the reaming time. This was not true for the PS system. No appreciable temperature changes were observed during any of the trials. The RIA reaming system significantly reduces the intramedullary pressures produced during the reaming process compared to the PS reaming system.


The periodic table and the intrinsic barrier in s(n)2 reactions.
The identity S(N)2 reactions on nitrogen (see eq 3) with nucleophiles having the general structure H(n)()X(-) where X belongs to the group of nonmetallic elements which do not border the line separating them from the metallic elements (X = F, Cl, Br, I, O, S, Se, N, P, and C) were studied at the G2+ level. The results show that, similarly to the previously observed phenomenon for S(N)2 reaction on carbon (J. Am. Chem. Soc. 1999, 121, 7724), the Periodic Table, through the valence of the element X, controls the intrinsic barrier for the reaction. The average intrinsic barriers obtained for nitrogen substrates were 20, 27, 39, and 57 kcal/mol for the mono-, di-, tri-, and tetravalent X's, respectively. It is also concluded that the intrinsic barriers are similar for N- and C-based substrates and dimethyl substitution on both raises the intrinsic barrier by ca. 10 kcal/mol.


West Nile virus activity--United States, 2007.
West Nile virus (WNV) is the leading cause of arboviral encephalitis in the United States. Originally identified in Africa in 1937, WNV was first detected in the western hemisphere in 1999 in New York City. Since then, WNV has caused seasonal epidemics of febrile illness and neurologic disease in the United States. This report summarizes national WNV surveillance data for 2007. WNV transmission to humans or animals expanded into 19 counties that had not reported transmission previously and recurred in 1,148 counties where transmission had been reported in previous years. A total of 1,227 cases of WNV neuroinvasive disease (WNND) and 117 deaths were reported. These findings highlight the need for ongoing surveillance, mosquito control, promotion of personal protection from mosquito bites, and research into additional prevention strategies, including a WNV human vaccine.


Long-term efficacy of phototherapeutic keratectomy on recurrent corneal erosion syndrome.
To assess the long-term sequelae, principally time-to-first-recurrence, of phototherapeutic keratectomy (PTK) for the treatment of recurrent corneal erosion syndrome (RCES). A retrospective case series was performed. Thirty-nine eyes in 33 patients with RCES required PTK and were treated using the VISX STAR Excimer Laser System. The data were analyzed with the Kaplan-Meier survival estimate. Patients were characterized by the cause of their RCES. More than 50% had epithelial corneal dystrophies, 31% were posttraumatic, and 15% were idiopathic. Overall, 25% of eyes had a recurrence by 3 months, and 36% had a recurrence by 9 months. The mean follow-up time was 17.4 months (range, 0.4-67.6 months). Of those who had a primary recurrence, 38% had a second and 15% had a third. Visual acuity was slightly decreased within 2 weeks after surgery, and 10% of patients developed transient haze. No serious adverse effects were reported. PTK is an important treatment of RCES refractory to other therapies. Long-term data suggest that most patients treated with PTK do not develop recurrences, and side effects from PTK are minimal.


Pigment epithelium-derived factor protects retinal ganglion cells from hypoxia-induced apoptosis by preventing mitochondrial dysfunction.
To investigate the potential of pigment epithelium-derived factor (PEDF) to protect the immortalized rat retinal ganglion cells-5 (RGC-5) exposed to CoCl2-induced chemical hypoxia. After being differentiated with staurosporine (SS), RGC-5 cells were cultured in four conditions: control group cells cultured in Dulbecco's modified eagle medium (DMEM) supplemented with 10% fetal bovine serum, 100 µmol/mL streptomycin and penicillin (named as normal conditions); hypoxia group cells cultured in DMEM containing 300 µmol/mL CoCl2; cells in the group protected by PEDF were first pretreated with 100 ng/mL PEDF for 2h and then cultured in the same condition as hypoxia group cells; and PEDF group cells that were cultured in the presence of 100 ng/mL PEDF under normal conditions. The cell viability was assessed by MTT assay, the percentage of apoptotic cells was quantified using Annexin V-FITC apoptosis kit, and intra-cellar reactive oxygen species (ROS) was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) probe. The mitochondria-mediated apoptosis was also examined to further study the underlying mechanism of the protective effect of PEDF. The opening of mitochondrial permeability transition pores (mPTPs) and membrane potential (Δψm) were tested as cellular adenosine triphosphate (ATP) level and glutathione (GSH). Also, the expression and distribution of Cyt C and apoptosis inducing factor (AIF) were observed. SS induced differentiation of RGC-5 cells resulting in elongation of their neurites and establishing contacts between outgrowths. Exposure to 300 µmol/mL CoCl2 triggered death of 30% of the total cells in cultures within 24h. At the same time, pretreatment with 100 ng/mL PEDF significantly suppressed the cell death induced by hypoxia (P<0.05). The apoptosis induced by treatment of CoCl2 was that induced cell death accompanied with increasing intra-cellar ROS and decreasing GSH and ATP level. PEDF pre-treatment suppressed these effects (P<0.05). Additionally, PEDF treatment inhibited the opening of mPTPs and suppressed decreasing of Δψm in RGC-5 cells, resulting in blocking of the mitochondrial apoptotic pathway. Pretreatment of RGC-5 cells with 100 ng/mL PEDF significantly decreases the extent of apoptosis. PEDF inhibits the opening of mPTPs and suppresses decreasing of Δψm. Moreover, PEDF also reduces ROS production and inhibits cellular ATP level's reduction. Cyt C and AIF activation in PEDF-pretreated cultures are also reduced. These results demonstrate the potential for PEDF to protect RGCs against hypoxic damage in vitro by preventing mitochondrial dysfunction.


Differences in stereoselectivity and catalytic efficiency of three human glutathione transferases in the conjugation of glutathione with 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene.
The kinetics of the enzyme-catalyzed conjugation of glutathione with (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha -oxy-7,8,9,10 -tetrahydrobenzo(a)pyrene [(+/-)-anti-BPDE] have been studied with the following human cytosolic glutathione transferases: the basic (alpha-epsilon) and near-neutral (mu) isoenzymes from liver, and the acidic (pi) isoenzyme from placenta. When the BPDE concentration was varied (using 5 mM glutathione) the apparent Vmax values for transferases alpha-epsilon, mu, and pi were 38, 570, and 825 nmol X mg-1 X min-1, respectively, with corresponding apparent Km values of 88, 27, and 54 microM. The apparent Km values for glutathione [using 80 microM (+/-)-anti-BPDE] were 0.4, 0.7, and 0.1 mM for transferase alpha-epsilon, mu, and pi, respectively. The glutathione conjugates formed with the two enantiomers of (+/-)-anti-BPDE were resolved by high performance liquid chromatography. The percentages of conjugates derived from the highly carcinogenic (+)-enantiomer were 59, 60, and greater than or equal to 90% for transferases alpha-epsilon, mu, and pi, respectively. The separate enantiomers of anti-BPDE were assayed in experiments with transferases mu and pi. Both enantiomers were substrates for transferase mu, but only the (+)-enantiomer gave measurable activity with transferase pi. A 3-fold increase in Vmax and Km values for transferase pi was obtained with (+)-anti-BPDE as compared with the racemic substrate and could be quantitatively accounted for by the finding that (-)-anti-BPDE serves as a competitive inhibitor for transferase pi.


[Applications and perspectives of ketone body D-β-hydroxybutyrate in the medical fields].
Human body can obtain energy from either carbohydrate or fat digestion. Although glucose metabolism derived from carbohydrate-based diets has long been utilized for energy supply, it has been recently discovered that shifting from glucose to fatty acid metabolism may become a novel way for improving human health especially when carbohydrate is deprived. In recent years, intermittent fasting and ketogenic diets have received a lot of attention in respect to favoring fatty acid metabolism. In all cases, fatty acid metabolism produces D-β-hydroxybutyrate (D3HB), which is a natural ketone body, as well as, a monomer of microbial poly-D-β-hydroxybutyrate (PHB). D3HB can be utilized by different cells of the body as an alternative energy fuel or an intracellular signaling molecule with multiple downstream signaling pathways. Usually, the serum level of D3HB is increased during ketogenic diets, however, requires a very long period of adaptation (over 3-months) and exhibits unwanted adverse effects. Hence, exogenous ketone supplements using D3HB have become a more effective approach to induce and maintain nutritional ketosis for subsequent functional effects. This review describes how D3HB is produced and metabolized within the body, the functional roles played by D3HB, and a detailed summary of the different applications of exogenous ketones that have been explored to date in both nutritional and therapeutical context.


A randomized clinical trial comparing the efficacy of ibuprofen and paracetamol in the control of orthodontic pain.
Previous research has shown that ibuprofen provides effective relief from orthodontic pain. The aim of this study was to ascertain whether paracetamol (also known as acetaminophen) provided pain relief of equivalent or greater magnitude. A multicenter, noninferiority, randomized clinical trial was conducted in 3 orthodontic clinics; 159 patients aged 12 to 16 years attending for routine orthodontic treatment were randomly allocated to receive either 400 mg of oral ibuprofen or 1 g of oral paracetamol an hour before and again 6 hours after separator placement. Pain scores were recorded on 7 visual analog scales (10 cm) over a week. The margin of equivalence was defined as 10 mm. Mean orthodontic pain from 2 hours after separation to bedtime was 8.5 mm (90% CI: lower, 3.7; upper,13.2) higher in the paracetamol group. This confidence interval lies partly outside the margin of equivalence, suggesting that paracetamol is not equivalent, and excludes the value 0, suggesting that ibuprofen is superior. From day 1 onward, there was a trend for patients who had taken ibuprofen to experience less pain at most time intervals compared with the paracetamol group. Two doses of ibuprofen, taken on the day of separator placement, were insufficient to control orthodontic pain on day 1 after placement. A combination of preoperative and postoperative ibuprofen is more effective than paracetamol in the control of orthodontic pain.


Circulating delta-like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus-based immunosuppression.
Cardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx. We studied circulating delta-like Notch ligand 1 (DLL1) and periostin (POSTN) and CAV in de novo HTx recipients (n = 70) randomized to standard or EVR-based, calcineurin inhibitor-free immunosuppression and in maintenance HTx recipients (n = 41). Compared to healthy controls, plasma DLL1 and POSTN were elevated in de novo (P < .01; P < .001) and maintenance HTx recipients (P < .001; P < .01). Use of EVR was associated with a treatment effect for DLL1. For de novo HTx recipients, a change in DLL1 correlated with a change in CAV at 1 (P = .021) and 3 years (P = .005). In vitro, activation of T cells increased DLL1 secretion, attenuated by EVR. In vitro data suggest that also endothelial cells and vascular smooth muscle cells (VSMCs) could contribute to circulating DLL1. Immunostaining of myocardial specimens showed colocalization of DLL1 with T cells, endothelial cells, and VSMCs. Our findings suggest a role of DLL1 in CAV progression, and that the beneficial effect of EVR on CAV could reflect a suppressive effect on DLL1. Trial registration numbers-SCHEDULE trial: ClinicalTrials.gov NCT01266148; NOCTET trial: ClinicalTrials.gov NCT00377962.


[Occipital tumor simulating pericranial sinus (author's transl)].
A case of occipital tumor simulating sinus pericranii was reported. The patient was a 4-year-old girl who suffered from headache and nausea following head injury on midoccipital tumor, but had no remarkable neurological deficit. Her occipital tumor was soft, compressible redish and cyst-like without bruit. Conray cystography of this tumor showed superior sagittal sinus like shadow (Fig. 4). Total removal of the tumor associated with epidural hematoma was performed. Histologically this tumor was confirmed as eosinophilic granuloma. Pathogenesis of this case is following, since patient's tumor was blowed, intratumor-bleeding occurred cosequently and the bleeding flowed into epidural space. So the tumor simulated sinus pericranii (Fig. 5.).


Factors affecting the structure and properties of an injectable self-setting calcium phosphate foam.
One of the main challenges in the investigation on calcium phosphate cements (CPC) lies in the introduction of macroporosity, without loosing the self-setting ability and injectability, characteristic of the cement-type materials. The benefits of macroporosity are related to the enhancement of bone regeneration mechanisms, such as angiogenesis and tissue ingrowth. In this work, the feasibility to obtain self-setting injectable macroporous hydroxyapatite foams by the incorporation of a protein-based foaming agent to a CPC is demonstrated. Albumen is combined with an alpha-tricalcium phosphate [Ca3(PO4)2, alpha-TCP] paste, which hydrolyzes to a calcium deficient hydroxyapatite during the setting reaction. A systematic study is presented, where the effect of different processing parameters is analyzed in terms of porosity, setting properties, injectability, and compressive strength. Self-setting foams with porosities up to 70%, which maintain their porous structure after injection, are obtained. These injectable foams can be used both for direct in vivo applications and for the fabrication of low temperature tissue engineering scaffolds.


Evidence for cooperative vibrational relaxation of the NH-, OH-, and OD-stretching modes in hydrogen-bonded liquids using infrared pump-probe spectroscopy.
Vibrational energy relaxation of the NH-, OH-, and OD-stretching modes in hydrogen-bonded liquids has been investigated by means of infrared pump-probe spectroscopy. The relaxation rates have been determined both in neat liquids and in isotopic mixtures with systematically varied isotope fractions. In all liquids, the vibrational relaxation rate increases as the isotope fraction is increased and reaches a maximum in the neat liquid. The dependence of the relaxation rate on the isotope fraction suggests a relaxation channel in which the vibrational energy is partitioned between accepting modes of two neighboring molecules.


Schleyer hyperconjugative aromaticity and Diels-Alder reactivity of 5-substituted cyclopentadienes.
Schleyer's discovery of hyperconjugative aromaticity and antiaromaticity in 5-substituted cyclopentadienes further expanded our understanding of the pervasive influence of aromaticity. Acceptors induce antiaromatic character by Schleyer's negative hyperconjugative aromaticity, and donors have the opposite effect. We computationally explored the Diels-Alder reactivity of 5-substituted cyclopentadienes with ethylene and maleic anhydride. The predicted billionfold difference in the computed gas phase rate constants at room temperature for the Diels-Alder reactions of 5-substituted cyclopentadienes with ethylene or maleic anhydride results from differences in the transition state distortion energies, which are directly related to the hyperconjugative aromaticity of these molecules.


Physicochemical evaluation of the Upper Litani River watershed, Lebanon.
This study aims to determine the extent of groundwater damage in the Upper Litani River Basin (ULRB) after years of water mismanagement and overfertilization in what is considered to be Lebanon's largest fertile area. Physical and chemical samples were collected between 2005 and 2010 and analyzed using "The Standard Methods for the Examination of Water and Wastewater" (APHA, AWWA) in order to determine the extent of this pollution. The parameters included pH, ammonia, nitrate, nitrite, sulfate, phosphate, dissolved oxygen, and total dissolved solids.


Nonspeech oral motor treatment issues related to children with developmental speech sound disorders.
This article examines nonspeech oral motor treatments (NSOMTs) in the population of clients with developmental speech sound disorders. NSOMTs are a collection of nonspeech methods and procedures that claim to influence tongue, lip, and jaw resting postures; increase strength; improve muscle tone; facilitate range of motion; and develop muscle control. In the case of developmental speech sound disorders, NSOMTs are employed before or simultaneous with actual speech production treatment. First, NSOMTs are defined for the reader, and there is a discussion of NSOMTs under the categories of active muscle exercise, passive muscle exercise, and sensory stimulation. Second, different theories underlying NSOMTs along with the implications of the theories are discussed. Finally, a review of pertinent investigations is presented. The application of NSOMTs is questionable due to a number of reservations that include (a) the implied cause of developmental speech sound disorders, (b) neurophysiologic differences between the limbs and oral musculature, (c) the development of new theories of movement and movement control, and (d) the paucity of research literature concerning NSOMTs. There is no substantive evidence to support NSOMTs as interventions for children with developmental speech sound disorders.


Phototriggered sulfoxide isomerization in [Ru(pic)2(dmso)2].
We report the characterization and photochemistry of a simple ruthenium coordination complex containing only picolinate (pic) and dmso, which exhibits a large isomerization quantum yield (Phi(SS-->OO) = 0.50) in various solvents. The picolinate ligands of [Ru(pic)(2)(dmso)(2)] are in a cis arrangement so that the carboxylate oxygen of one pic ligand (O1) is trans to the pyridine of the second picolinate (N2). One dmso ligand (S1) is trans to a pyridine nitrogen (N1), while the second dmso (S2) is trans to a carboxylate oxygen (O3). The cyclic voltammetry, (1)H NMR, IR, and UV-vis spectroscopy data suggest that while both dmso ligands isomerize photochemically, only one dmso ligand isomerizes electrochemically. Isomerization quantum yields for each dmso ligand differ by an order of magnitude (Phi(SS-->SO) = 0.46 and Phi(SO-->OO) = 0.036). In agreement with previous results, the isomerization quantum yield for each dmso is dependent on the ligand that is trans to the dmso.


A 23911 bp region of the Bacillus subtilis genome comprising genes located upstream and downstream of the lev operon.
Within the framework of the European project to sequence the whole Bacillus subtilis 168 genome, a 23911 bp long chromosomal DNA fragment located around 233 degrees on the B. subtilis genetic map was cloned and sequenced. From the generated sequencing data and the results of the homology search, the primary structure of this region was determined. In addition to the whole lev operon, the region contains putative genes for an amino acid permease, two different alcohol dehydrogenases, a chitosanase, a protein belonging to the LysR family of transcriptional regulators, a protein related to the MerR transcriptional regulator, up to four proteins related to the product of the spoF gene, and genes coding for nine more inferred proteins of unknown function.


[Inhaled steroids in COPD. Do they modify the disease?].
The use of inhaled steroids in the treatment of chronic obstructive lung disease is controversial. It is becoming ever more clear that a differentiated approach to treatment determined by the clinical presentation and the specific cell profile is needed. More inflammation, poorer lung function and more frequent exacerbation benefit from steroids, while early stages of the disease with few symptoms, and patients with predominance of emphysema but little bronchitis are unlikely to benefit from this form of treatment. Particular attention must be paid to mixed types with an asthma-like component. While the combination of long-acting beta-mimetic drugs and inhalative steroids might appear to be of benefit, the outcome of currently ongoing studies must be awaited.


Intrauterine fetal demise in multiple gestation.
Fifteen cases were reviewed over a five-year period at a perinatal centre with intrauterine demise of one member of a multiple gestation. Nine cases were monozygotic twin pairs, two were dizygotic, and two were triples . Gestational age ranged from 27 to 39 weeks. The management protocol consisted of delivery in all cases after confirmation of the diagnosis. In 4 cases delivery was immediate because of spontaneous labor. In the other cases elective delivery was performed if the gestational age was 37 weeks or greater or there was evidence of preeclampsia or if amniocentesis revealed a mature lecithinsphingomyelin (L/S) ratio. Steroids were given if the L/S was immature or the attempt at amniocentesis was unsuccessful and delivery was performed 48 hours after initiation of steroid therapy. Cesarean section was the mode of delivery in 14 of the 15 cases. All of the cotwins and cotriplets survived. One survivor of a monozygous twin pair has multicystic encephalomalacia possibly implicating perinatal arterial occlusion or in utero disseminated intravascular coagulation (DIC). The intrauterine deaths are categorized into possibly avoidable deaths (2/15), unavoidable due to congenital anomalies (3/15), and unknown or unavoidable deaths (8/15).


Hyperspectral Nanoimaging of van der Waals Polaritonic Crystals.
Phonon polaritons (PhPs) in van der Waals (vdW) crystal slabs enable nanoscale infrared light manipulation. Specifically, periodically structured vdW slabs behave as polaritonic crystals (vdW-PCs), where the polaritons form Bloch modes. Because the polariton wavelengths are smaller than that of light, conventional far-field spectroscopy does not allow for a complete characterization of vdW-PCs or for revealing their band structure. Here, we perform hyperspectral infrared nanoimaging and analysis of PhPs in a vdW-PC slab made of h-BN. We demonstrate that infrared spectra recorded at individual spatial positions within the unit cell of the vdW-PC can be associated with its band structure and local density of photonic states (LDOS). We thus introduce hyperspectral infrared nanoimaging as a tool for the comprehensive analysis of polaritonic crystals, which could find applications in the reconstruction of complex polaritonic dispersion surfaces in momentum-frequency space or for exploring exotic electromagnetic modes in topological photonic structures.


Iron-modified biochar improves plant physiology, soil nutritional status and mitigates Pb and Cd-hazard in wheat (Triticum aestivum L.).
Environmental quality and food safety is threatened by contamination of lead (Pb) and cadmium (Cd) heavy metals in agricultural soils. Therefore, it is necessary to develop effective techniques for remediation of such soils. In this study, we prepared iron-modified biochar (Fe-BC) which combines the unique characteristics of pristine biochar (BC) and iron. The current study investigated the effect of pristine and iron modified biochar (Fe-BC) on the nutritional values of soil and on the reduction of Pb and Cd toxicity in wheat plants (Triticum aestivum L.). The findings of present study exhibited that 2% Fe-BC treatments significantly increased the dry weights of roots, shoots, husk and grains by 148.2, 53.2, 64.2 and 148%, respectively compared to control plants. The 2% Fe-BC treatment also enhanced photosynthesis rate, transpiration rate, stomatal conductance, intercellular CO2, chlorophyll a and b contents, by 43.2, 88.4, 24.9, 32.5, 21.4, and 26.7%, respectively. Moreover, 2% Fe-BC treatment suppressed the oxidative stress in wheat plants by increasing superoxide dismutase (SOD) and catalase (CAT) by 62.4 and 69.2%, respectively. The results showed that 2% Fe-BC treatment significantly lowered Cd levels in wheat roots, shoots, husk, and grains by 23.7, 44.5, 33.2, and 76.3%. Whereas, Pb concentrations in wheat roots, shoots, husk, and grains decreased by 46.4, 49.4, 53.6, and 68.3%, respectively. Post-harvest soil analysis showed that soil treatment with 2% Fe-BC increased soil urease, CAT and acid phosphatase enzyme activities by 48.4, 74.4 and 117.3%, respectively. Similarly, 2% Fe-BC treatment significantly improved nutrients availability in the soil as the available N, P, K, and Fe contents increased by 22, 25, 7.3, and 13.3%, respectively. Fe-BC is a viable solution for the remediation of hazardous Cd and Pb contaminated soils, and improvement of soil fertility status.


Charge Shielding-Oriented Design of Zinc-Based Nanoparticle Liquids for Controlled Nanofabrication.
Metal-containing nanoparticles possess nanoscale sizes, but the exploitation of their nanofeatures in nanofabrication processes remains challenging. Herein, we report the realization of a class of zinc-based nanoparticle liquids and their potential for applications in controlled nanofabrication. Utilizing the metal-core charge shielding strategy, we prepared nanoparticles that display glass-to-liquid transition behavior with glass transition temperature far below room temperature (down to -50.9 °C). Theoretical calculations suggest the outer surface of these unusual nanoparticles is almost neutral, thus leading to interparticle interactions weak enough to give them liquefaction characteristics. Such features endow them with extraordinarily high dispersibility and excellent film-forming capabilities. Twenty-two types of nanoparticles synthesized by this strategy have all shown good lithographic properties in the mid-ultraviolet, electron beam, or extreme ultraviolet light, and these nanoparticle liquids have achieved controlled top-down nanofabrication with predesigned 18 or 16 nm patterns. This proposed strategy is synthetically scalable and structurally extensible and is expected to inspire the design of entirely new forms of nanomaterials.


Shared phylogeographic patterns between the ectocommensal flatworm Temnosewellia albata and its host, the endangered freshwater crayfish Euastacus robertsi.
Comparative phylogeography of commensal species may show congruent patterns where the species involved share a common history. Temnosewellia is a genus of flatworms, members of which live in commensal relationships with host freshwater crustaceans. By constructing phylogenetic trees based on mitochondrial COI and 28S nuclear ribosomal gene sequences, this study investigated how evolutionary history has shaped patterns of intraspecific molecular variation in two such freshwater commensals. This study concentrates on the flatworm Temnosewellia albata and its critically endangered crayfish host Euastacus robertsi, which have a narrow climatically-restricted distribution on three mountaintops. The genetic data expands upon previous studies of Euastacus that suggested several vicariance events have led to the population subdivision of Euastacus robertsi. Further, our study compared historical phylogeographic patterning of these species. Our results showed that phylogeographic patterns shared among these commensals were largely congruent, featuring a shared history of limited dispersal between the mountaintops. Several hypotheses were proposed to explain the phylogeographic points of differences between the species. This study contributes significantly to understanding evolutionary relationships of commensal freshwater taxa.


Purification and properties of dihydrogeodin oxidase from Aspergillus terreus.
The last step of (+)-geodin biosynthesis is a phenol oxidative coupling, which is one of the most important reactions in biosynthesis of natural products. The enzyme named dihydrogeodin oxidase catalyzes the regio- and stereospecific phenol oxidative coupling reaction to form (+)-geodin from dihydrogeodin. The enzyme was purified from the cell-free extract of Aspergillus terreus, a (+)-geodin producer, by ammonium sulfate fractionation, acid treatment, and column chromatographies on DEAE-cellulose, Hydroxyapatite, chromatofocusing, and Toyopearl HW-55S. The purified enzyme was homogeneous as judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The molecular weight of the enzyme was estimated to be 153,000 by gel filtration on a Toyopearl HW-55S column and 76,000 by SDS-polyacrylamide gel electrophoresis, indicating that the enzyme is a dimer. The purified enzyme showed an intense blue color and had absorption maxima at 280 and 600 nm, which suggested it to be a blue copper protein. The copper content was found to be 8 atoms per subunit by atomic absorption analysis and no significant amount of other metals was detected by ICP emission spectrometry. The electron paramagnetic resonance spectrum showed the presence of type 1 and type 2 copper atoms in the enzyme molecule. Sodium azide and ethylxanthate inhibited the enzyme activity, but potassium cyanide and diethyldithiocarbamate, both known as potent copper enzyme inhibitors, were not inhibitory.


Myocardial infarction treated with two lymphagogues, calcium dobesilate (CLS 2210) and hyaluronidase: a coded, placebo-controlled animal study.
The effects on the evolution of canine myocardial infarction (MI) of the lymphagogues hyaluronidase (hyaluronate glucanohydrolase) (known to reduce the size of MIs) and calcium dobesilate (calcium, 2,5-dihydroxybenzenesulfonate, CLS 2210) were compared in a coded, placebo-controlled study in 48 dogs, during the first 24 h after coronary occlusion. MI was induced by embolization of the anterior descending branch of the left coronary artery. The animals were given either a placebo, CLS 2210, or hyaluronidase by intravenous infusion begun immediately after embolization and continued for 24h. The volume of myocardial tissue at risk was evaluated at 2 and 24 h by ungated computed tomography (CT), and after necropsy by staining myocardial sections with triphenyl tetrazolium chloride (TTC). Electrocardiography and estimation of serum creatine kinase (CK) activity were also performed. In the 25 animals that survived 24 h, the results of all tests showed that there was less myocardial damage in the animals treated with the two lymphagogues than in those treated with placebo, and less damage with CLS 2210 than with hyaluronidase. The good correlation between the volume of ischemic tissue as assessed by CT in vivo and as assessed by TTC staining after necropsy (r = 0.959) confirms that the CT perfusion phase defect accurately reflects the volume of tissue at risk during the evolution of MI. This study has shown that CLS 2210 is at least as effective as hyaluronidase in reducing myocardial damage due to coronary artery occlusion in dogs.


Impaired brain functions due to diazepam and meprobamate abuse in a 53-year-old-male.
The following case study demonstrates the important influence of diazepam and meprobamate on a patient's neuropsychological test performance. This article includes: a brief medical history and summary of previous physical examinations; brief description of the neuropsychological test battery; formulation of the original neuropsychological test findings; follow-up neuropsychological testing; and discussion. The profound interaction effect of these prescribed drugs revealed severe cognitive, memory, and motor function deficits in a 53-year-old male. These findings are in contrast to reports in the literature.


TrkB gene transfer protects retinal ganglion cells from axotomy-induced death in vivo.
Injury-induced downregulation of neurotrophin receptors may limit the response of neurons to trophic factors, compromising their ability to survive. We tested this hypothesis in a model of CNS injury: retinal ganglion cell (RGC) death after transection of the adult rat optic nerve. TrkB mRNA rapidly decreased in axotomized RGCs to approximately 50% of the level in intact retinas. TrkB gene transfer into RGCs combined with exogenous BDNF administration markedly increased neuronal survival: 76% of RGCs remained alive at 2 weeks after axotomy, a time when >90% of these neurons are lost without treatment. Activation of mitogen-activated protein kinase, but not phosphatidylinositol-3 kinase, was required for TrkB-induced survival. These data provide proof-of-principle that enhancing the capacity of injured neurons to respond to trophic factors can be an effective neuroprotective strategy in the adult CNS.


Does the National Health Service want hospital-at-home?
There has been increasing interest in the development of hospital-at-home within the National Health Service (NHS) as a way of shifting resources from secondary to primary care. We describe the development of hospital-at-home schemes in London and draw on data from an evaluation of five such schemes to discuss support for hospital-at-home within the NHS. The study has identified a small but important group of patients who do not want hospital-at-home, as well as resistance to it from some health care professionals and managers, particularly in hospitals. These organizational issues must be taken into account in any evaluation of hospital-at-home, along with issues of quality, outcome and cost. Feasibility studies are needed to identify possible organizational barriers to hospital-at-home and the development work that is required. This service innovation should not be considered in isolation from other services, but rather within the context of a wider debate about the pattern of acute care.


In vitro binding of free cdc2 and raf kinase to membrane vesicles: a possible new regulatory mechanism for cdc2 kinase activation in Xenopus oocyte.
The G2-M transition of the cell cycle is under the control of the M-phase promoting factor (MPF) formed of cdc2 kinase and cyclin B. The Xenopus prophase-blocked oocyte contains a stockpile of cyclin B2-cdc2 complexes that are maintained inactive by a double inhibitory phosphorylation on Thr-14 and Tyr-15 of cdc2. Free cdc2 molecules that are not associated with cyclin, are present in excess as compared to cyclin B2-associated cdc2. This pool of free cdc2 is permanently recruited to associate with neosynthetized cyclin B2 in the resting prophase oocyte, to feed up the pre-MPF stockpile. During re-entry into meiosis, free cdc2 could generate with newly synthesized cyclin B a small level of active MPF, that could serve as starter to initiate the conversion of pre-MPF into MPF. It was, therefore, of high interest to investigate whether free cdc2 interacts with other proteins and what could be its intracellular localization. To address these questions, we developed an in vitro system of membrane vesicles. We demonstrate here that free cdc2 is recovered in association with the external layer of membrane vesicles, whereas cyclin B2-associated cdc2 is not. Cyclin is able to associate in vitro with cdc2-containing membrane vesicles. This association does not induce the inhibitory cdc2 phosphorylations. However, it does not lead to active complexes, suggesting that membrane vesicles prevent cdc2 activation. C-Raf1, another kinase activated during reentry into meiosis, is also totally recovered in association with the membrane vesicles.


Physiopathology and clinical considerations of laparoscopic surgery in the elderly.
The marked improvements in medical technology and healthcare, lead an increasing number of elderly patients to take advantage of even complex surgical. Recently, laparoscopic surgery has been accepted as a minimally invasive treatment to reduce the morbidity after conventional surgery, and a number of studies have demonstrated the feasibility of laparoscopy with significant advantages also in the elderly. On the other side, the laparoscopic procedure has some drawbacks, including prolonged operation time and impact of carbon dioxide pneumoperitoneum on circulatory and respiratory dynamics. This paper will review the physiopathological implications of laparoscopy, as well as the current literature concerning the most common laparoscopic procedures that are increasingly performed in elderly patients. A systematic review of the current literature was performed using the search engines EMBASE and PubMed to identify all studies reporting the physiopathological implications of laparoscopy in the elderly. The MeSH search terms used were "laparoscopy in the elderly", "physiopathology of laparoscopy", and "pneumoperitoneum". Multiple combinations of the keywords and MeSH terms were used with particular reference to elderly patients. Although laparoscopy is minimally invasive in its dissection techniques, the increased physiologic demands present particular challenges among elderly patients. Laparoscopy and its safety in the elderly patients remains a challenge and the evaluation of this approach is therefore mandatory. Although many studies have demonstrated the applicability and advantages of the laparoscopy also in the geriatric population, with low rates of morbidity and mortality, in elderly patients undergoing general surgical procedures the physiologic demands of laparoscopy should be carefully considered.


A biomechanical comparison of vascularized and conventional autogenous bone grafts.
Vascularized and conventional autogenous rib grafts were used to reconstruct 6-cm ulnar defects in the forelegs of the nine dogs. Each dog served as its own control. Biomechanical torsional testing of the grafted ulnas showed that vascularized grafts were 234 percent stronger than the conventional grafts. Bone toughness (energy absorbed) was 483 percent greater in the vascularized grafts, and elastic modulus and proportional limits were 263 and 246 percent greater, respectively. We conclude that vascularized bone grafts are significantly stronger than conventional autogenous bone grafts after 3 months of healing in the dog ulna model.


Action of taurine, 3-aminopropanesulfonic acid, and GABA on the hindgut and heart of the cockroach, Leucophaea maderae.
Taurine, glycine, glutamate, and gamma-aminobutyric acid (GABA) were all present in concentrations of greater than 1% of the total free amino acid content in the brain, thoracic, and abdominal ganglia of Leucophaea maderae. Hemolymph, subesophageal ganglia, and hindgut had substantial amounts of glutamate and glycine, but less than 0.3% taurine or GABA. Taurine, 3-aminopropanesulfonic acid (3-APS), cysteine-sulfinic acid (CSA), and GABA each had myotropic activity on the isolated cockroach hindgut, with 3-APS having the most consistent effect (ED50 = 0.63 mM), while taurine and CSA activities were similar to that of GABA on the hindgut. Both taurine and 3-APS had anti-arrhythmic effects on semi-isolated heart preparations of L. maderae, while GABA was inhibitory and induced arrhythmia. Bicuculline was antagonistic to the effects of GABA, taurine, and 3-APS on the hindgut, and induced arrhythmia in heart preparations; this arrhythmia was reversible by taurine, but not by GABA or 3-APS.


IgA autoreactivity: a feature common to inflammatory bowel and connective tissue diseases.
The immunopathogenic mechanisms in inflammatory bowel disease (IBD) are not yet fully established. The aim of this study was to determine the profile and magnitude of IgA and IgG autoantibodies in IBD patients. The autoantigen profile defined by IgA and IgG antibodies from 24 IBD (14 Crohn's disease CD], 10 ulcerative colitis UC]), three coeliac, 12 connective tissue disease (CTD) patients and 10 healthy individuals was studied in human cellular extracts by Western blotting. The magnitude of the IgA and IgG1-4 subclass responses was measured by ELISA. IBD patients could not be distinguished from healthy individuals on the basis of IgG autoantibodies to Western blotted proteins. IgG subclass analysis indicated no clear bias towards Th1 or Th2 immune responses in IBD or CTD. In accordance with previous work, we found that IgA autoreactivity was strongest in coeliac disease patients. Unexpectedly, IBD as well as CTD patients exhibited strong IgA autoantibody reactivities to components of similar molecular weights (16-80 kD) in intestinal and non-intestinal epithelial cell lines. Our data indicate immunopathogenic similarities between IBD and CTD.