Pathways Associating Childhood Trauma to the Neurobiology of Schizophrenia.
While researchers have for decades considered the role of social factors, endocrinology, neural function, hippocampal integrity, and cognition in the development of schizophrenia, there has been a relative paucity of studies considering the participation of the stress cascade in the interplay of these elements. As described in this review, stressful exposures and stress sensitivity may plausibly be argued to play a role in the etiology, neurobiology, and course of schizophrenia and related psychotic disorders. Notably, research conducted over the last decade has made it increasingly clear that childhood traumatic experiences represent a prominent risk factor for the development of psychotic disorders, including schizophrenia. Accumulating evidence suggests that this relationship is mediated by the development of a neuropathological stress response, involving HPA axis dysregulation, aberrant functioning of different neurotransmitter systems, hippocampal damage, and memory deficits. However, it remains difficult to identify exact causal pathways linking early trauma to schizophrenia, including to the individual symptoms associated with the disorder. In addition to the strong association among early trauma, stress sensitization, and positive symptoms in schizophrenia, there is also evidence indicating that the negative and cognitive symptoms are related to these factors. However, the emergence of these symptoms may lie on a distinct and non-interacting pathway in relation to the development of the positive symptoms. The natural increases in stress sensitivity and HPA axis activity during adolescence may act on already maladaptive stress circuitry resulting from early trauma and/or a genetic predisposition to produce full blown stress sensitization and cause epigenetic effects, such as the altered methylation of different genes, that lead to schizophrenia or other psychiatric illnesses.


Collateral coronary circulation in the absence of obstructive coronary artery disease.
The presence of collateral coronary circulation almost always accounts for significant obstructive coronary artery disease and its development remains unclear. We present two cases wherein there was a large collateral artery in a patient with angiographically normal coronary arteries. In both cases, the vessel ran in the atrioventricular groove, between the distal right coronary artery and the circumflex artery. We believe that this vessel is of congenital origin and after reviewing the literature we describe the angiographic features that distinguish such a vessel from collaterals that are secondary to coronary stenosis or hypoxia.


Adolescent mothers' relationship with their children's biological fathers: social support, social strain, and relationship continuity.
Two-hundred and eighteen low-income, minority, adolescent mothers were interviewed during the perinatal period and 3 years later about their social networks, including their relationships with their children's fathers. Few adolescents were involved with fathers at both time points. Relationships with fathers were, in general, less supportive and less problematic over time. Moreover, although father support was not associated with adolescent mothers' psychological adjustment, father absence and father strain had negative associations with psychological adjustment. Maternal grandmother support buffered the negative effects of strain in the adolescents' relationships with biological fathers. Perceptions of less social support from maternal grandmothers and more social support from fathers during the perinatal period as well as less social support from a new male partner at 3 years postpartum predicted relationship continuity between adolescent mothers and fathers at 3 years postpartum. Implications for intervention and policy are discussed.


The Induction of Pro-IL-1β by Lipopolysaccharide Requires Endogenous Prostaglandin E2 Production.
PGE2 has been shown to increase the transcription of pro-IL-1β. However, recently it has been demonstrated that PGE2 can block the maturation of IL-1β by inhibiting the NLRP3 inflammasome in macrophages. These apparently conflicting results have led us to reexamine the effect of PGE2 on IL-1β production. We have found that in murine bone marrow-derived macrophages, PGE2 via the cAMP/protein kinase A pathway is potently inducing IL-1β transcription, as well as boosting the ability of LPS to induce IL-1β mRNA and pro-IL-1β while inhibiting the production of TNF-α. This results in an increase in mature IL-1β production in macrophages treated with ATP. We also examined the effect of endogenously produced PGE2 on IL-1β production. By blocking PGE2 production with indomethacin, we made a striking finding that endogenous PGE2 is essential for LPS-induced pro-IL-1β production, suggesting a positive feedback loop. The effect of endogenous PGE2 was mediated by EP2 receptor. In primary human monocytes, where LPS alone is sufficient to induce mature IL-1β, PGE2 boosted LPS-induced IL-1β production. PGE2 did not inhibit ATP-induced mature IL-1β production in monocytes. Because PGE2 mediates the pyrogenic effect of IL-1β, these effects might be especially relevant for the role of monocytes in the induction of fever. A positive feedback loop from IL-1β and back to PGE2, which itself is induced by IL-1β, is likely to be operating. Furthermore, fever might therefore occur in the absence of a septic shock response because of the inhibiting effect of PGE2 on TNF-α production.


Sex dependent effects of post-natal penicillin on brain, behavior and immune regulation are prevented by concurrent probiotic treatment.
There is increasing awareness of the need to consider potential long-term effects of antibiotics on the health of children. In addition to being associated with immune and metabolic diseases, there is evidence that early-life antibiotic exposure can affect neurodevelopment. Here we investigated the effect of low dose of penicillin V on mice when administered for 1 week immediately prior to weaning. We demonstrated that exposure to the antibiotic during the pre-weaning period led to long-term changes in social behaviour, but not anxiety-like traits, in male mice only. The change in behaviour of males was associated with decreased hippocampal expression of AVPR1A and AVPR1B while expression of both receptors was increased in females. Spleens of male mice also showed an increase in the proportion of activated dendritic cells and a corresponding decrease in regulatory T cells with penicillin exposure. All changes in brain, behaviour and immune cell populations, associated with penicillin exposure, were absent in mice that received L. rhamnosus JB-1 supplementation concurrent with the antibiotic. Our study indicates that post-natal exposure to a clinically relevant dose of antibiotic has long-term, sex dependent effects on the CNS and may have implications for the development of neuropsychiatric disorders. Importantly, we also provide further evidence that probiotic based strategies may be of use in counteracting detrimental effects of early-life antibiotics on neurodevelopment.


Factors affecting the level and localization of the transferrin receptor in Trypanosoma brucei.
Transfer of bloodstream-form Trypanosoma brucei variant 221a from calf serum to dog serum-based medium induces acute iron starvation, as the transferrin receptor (Tf-R) of variant 221a binds dog Tf poorly. We show here that transfer to dog serum induces a 3-5-fold increase in Tf-R mRNA and protein within one doubling time (8 h). Because iron stores are still high 8 h after transfer, we infer that the signal for Tf-R overproduction is the decreased availability of cytosolic iron when cellular iron import drops. Up to 30% of the extra Tf-R spills out of the flagellar pocket onto the pellicular surface. Because the 5-fold increase in Tf-R is accompanied by a 5-fold increase in bovine Tf uptake, the up-regulation of Tf-R levels in response to Tf starvation helps the trypanosome to compete for limiting amounts of Tf. We noted that Tf-R levels also vary in calf serum medium. Cells in dense cultures contain up to 5-fold more Tf-R mRNA and protein than in dilute cultures. Only one-tenth of the extra Tf-R reaches the pellicular surface. The increase cannot be explained by a lack of Tf or to cell density sensing but is due to pericellular hypoxia. Our results show that bloodstream-form trypanosomes can regulate the expression of the two Tf-R subunit genes and the localization of their gene products in a flexible manner. This flexibility is made possible by the promoter-proximal position of the two genes in the variant surface glycoprotein expression site.


Measuring Nurses' Experiences With Unintended Adverse Consequences in EMR Use in Acute Care Settings.
Adverse effects of EMR use have been rarely reported in South Korea. This study examined nurses' experiences with unintended adverse consequences associated with EMR implementation. The participants were 155 nurses using the EMR for patient care in three public hospitals. The statistically tested 21-item instrument and the same 21 open-ended questions were used for data collection. The data collected were analyzed using descriptive statistics and two-way analysis of variance, and the descriptions were grouped by meaning. The participants frequently experienced unintended adverse consequences that resulted from EMR use, and their experiences were organized into 11 subgroups under four dimensions of the unintended consequences instrument including the malfunction and inefficient design of EMR screens dimension (two groups), extra work from EMR implementation dimension (three groups), EMR incompatibility and changes in the prescription pattern dimension (three groups), and patient safety and EMR dependence (three groups). Successful implementation of EMRs is possible when unintended adverse consequences identified by the users are corrected and EMRs are tailored to user needs. Healthcare organizations should provide administrative support, timely technical remedy, and user training to increase user acceptance on a system.


Visible and near-infrared spectroscopy as a technique for screening the inorganic arsenic content in the red crayfish (procambarus clarkii Girard).
The potential of near-infrared spectroscopy (NIRS) for screening the inorganic arsenic (i-As) content in the red crayfish (Procambarus clarkii Girard 1852) was assessed. Sixty-two samples belonging to this species were freeze-dried and scanned by NIRS. The i-As contents of the samples were obtained by acid digestion-solvent extraction followed by hydride generation atomic absorption spectrometry and were regressed against different spectral transformations by modified partial least-squares (MPLS) regression. Second derivative transformation equations of the raw optical data, previously standardized by applying standard normal variate and de-trending algorithms, resulted in a coefficient of determination in the cross-validation (1-VR) of 0.84, indicative of equations of good quantitative information. The standard error of cross-validation to standard deviation ratio, shown by the second derivative equation, was similar to those obtained for other trace metal calibrations reported in NIRS reflectance. Spectral information related to chromophores and lipids of the red crayfish tissues, and also the plant matter contained in their stomachs, were the main organic components used by MPLS for modeling the selected prediction equation. This pioneering use of NIRS to predict the i-As content in red crayfish represents an important savings in time and cost of analysis.


Selective Gas Sensing under a Mixed Gas Flow with a One-Dimensional Copper Coordination Polymer.
Structural changes of the coordination polymer associated with gas adsorption (gate opening-type adsorption) can be linked to bulk physical properties such as magnetism, electrical conductivity, and dielectric properties. To enable real-space sensing applications, it is imperative to have a system where the selective adsorption of mixed gases can be correlated with physical properties. In this report, we demonstrate that a crystalline sample of one-dimensional (1D) coordination polymer exhibits selective CO2 adsorption while simultaneously displaying dielectric switching behavior in a mixed N2/CO2 gas environment. In the crystal of {[Cu2(2-TPA)4(pz)]·CH3CN}n (1·CH3CN), where 2-TPA and pz are 2-thiophencarboxylate and pyrazine, respectively, paddle wheel-type units of [Cu2(2-TPA)4] are bridged by pz, forming a 1D chain structure. One of the two crystallographically independent 2-TPA units was interacted with the pz moiety of the adjacent 1D chain by π···π interactions, forming a two-dimensional (2D) layer parallel to the ab plane. Activated 1 shows selective CO2 adsorption by a gate opening-type adsorption mechanism, indicating that the CO2 adsorption process is accompanied by a structural change. The change in the real part of dielectric permittivity (ε') under the mixed N2/CO2 gas flow is a result of the selective CO2 adsorption, which was supported by the enthalpy changes (ΔH) associated with CO2 adsorption in two methods: CO2 adsorption isotherms and temperature-dependent measurements of ε' under a mixed N2/CO2 gas flow. The calculated ΔH values were found to be in good agreement across both methods. The CO2 ratio in the mixed N2/CO2 gas flow increased, and the switching ratio of ε' (Δε') also increased. Notably, Δε' exhibited a marked increase beyond the pressure required for gate opening adsorption.


Regional scale analysis for the design of storage tanks for domestic rainwater harvesting systems.
A regional scale analysis for the design of storage tanks for domestic rain water harvesting systems is presented. The analysis is based on the daily water balance simulation of the storage tank by the yield-after-spillage algorithm as tank release rule. Water balances are applied to 17 rainfall gauging stations in Sicily (Italy). Compared with literature existing methods, a novel dimensionless parameter is proposed to better describe the intra-annual character of the rainfall patterns. As a result, easy-to-use regional regressive models to evaluate the water saving performance and the overflow discharges from the tank are provided along with a stepwise procedure for practical application. The regional models demonstrate good fits between model predictions and simulated values of both water savings and overflows from the tank.


Effect of human autologous serum and fetal bovine serum on human corneal epithelial cell viability, migration and proliferation in vitro.
To analyze the concentration-dependent effects of autologous serum (AS) and fetal bovine serum (FBS) on human corneal epithelial cell (HCEC) viability, migration and proliferation. AS was prepared from 13 patients with non-healing epithelial defects Dulbecco's modified eagle medium/Ham's F12 (DMEM/F12) with 5% FBS, 0.5% dimethyl sulphoxide (DMSO), 10 ng/mL human epidermal growth factor, 1% insulin-transferrin-selenium, then were incubated in serum media: DMEM/F12 supplemented by 5%, 10%, 15% or 30% AS or FBS. HCEC viability was analyzed using cell proliferation kit XTT, migration using a wound healing assay, proliferation by the cell proliferation enzyme-linked immunosorbent assay (ELISA) BrdU kit. Statistical analysis was performed using the generalized linear model, the values at 30% AS or 30% FBS were used as the baselines. HCEC viability was the highest at 30% AS or 15% FBS and the lowest at 10% AS or 30% FBS application. HCEC migration was the quickest through 30% AS or 30% FBS and the slowest through 5% AS or 5% FBS concentrations. Proliferation was the most increased through 15% AS or 5% FBS and the least increased through 30% AS or 30% FBS concentrations. HCEC viability at 10% and 15% AS was significantly worse (P=0.001, P=0.023) compared to baseline and significantly better at 15% FBS (P=0.003) concentrations. HCEC migration was significantly worse (P≤0.007) and HCEC proliferation significantly better (P<0.001) in all concentration groups compared to baseline. For the best viability of HCEC 30% AS or 15% FBS, for HCEC migration 30% AS or 30% FBS, for proliferation 15% AS or 5% FBS should be used. Therefore, we suggest the use of 30% AS in clinical practice.


Electrical perception of the 'death message' in Chara: analysis of K+-sensitive depolarization.
Wounding electrical responses were studied in Chara corallina. Specimens comprising two adjoining internodal cells were prepared. When one cell (victim cell) was cut, the other cell (receptor cell) generated four kinds of depolarization: (i) rapid depolarization; (ii) long-lasting depolarization; (iii) action potentials; and (iv) small spikes. In the present study, attention was focused on the long-lasting depolarization. A decrease in the electrical resistance suggested activation of ion channel(s). The duration of the depolarization was sensitive to the external ions. K(+) significantly prolonged the depolarization. On the other hand, Ca(2+), Mg(2+) and Na(+) had a tendency to shorten the duration prolonged by K(+). When a nodal end was continuously flushed with a medium lacking K(+), the depolarization was significantly shortened. Treatment of the nodal end with artificial cell sap for 2 min induced a long-lasting depolarization similar to that induced by cutting the victim cell. These findings suggested the involvement of K(+) released from the victim cell in generating the long-lasting depolarization by the receptor cell.


The actin-polymerizing activity of SipA is not essential for Salmonella enterica serovar Typhimurium-induced mucosal inflammation.
Salmonella enterica serovar Typhimurium depends on type III secretion systems to inject effector proteins into host cells to promote bacterial invasion and to induce intestinal inflammation. SipA, a type III effector, is known to play important roles in both the invasion and the elicitation of intestinal inflammation. The actin-modulating activity of SipA has been shown to promote Salmonella entry into epithelial cells. To investigate whether the actin-modulating activity of SipA is required for its ability to induce an inflammatory response in vivo, we generated the SipA(K635A E637W) mutant, which is deficient in actin-modulating activity. Salmonella strains expressing the chromosomal SipA(K635A E637W) point mutation had reduced invasion abilities but still caused colitis similar to that caused by the wild-type strain in a mouse model of infection. Our data indicate that the SipA actin-polymerizing activity is not essential for the SipA-induced inflammatory response in the mouse model of infection.


Opening of mitochondrial KATP channels enhances cardioprotection through the modulation of mitochondrial matrix volume, calcium accumulation, and respiration.
Previously, we have shown that the pharmacological opening of the mitochondrial ATP-sensitive K channels with diazoxide (DZX) enhances the cardioprotection afforded by magnesium-supplemented potassium (K/Mg) cardioplegia. To determine the mechanisms involved in the cardioprotection afforded by K/Mg + DZX cardioplegia, rabbit hearts (n=24) were subjected to isolated Langendorff perfusion. Control hearts were perfused for 75 min. Global ischemia (GI) hearts were subjected to 30 min of equilibrium, 30 min of GI, and 15 min of reperfusion. K/Mg and K/Mg + DZX cardioplegia hearts received either K/Mg or K/Mg + DZX for 5 min before GI and reperfusion. Tissue was harvested for mitochondrial isolation and transmission electron microscopy (TEM). Mitochondrial structure, area, matrix volume, free calcium, and oxygen consumption were determined. TEM demonstrated that GI mitochondria were damaged and that K/Mg and K/Mg + DZX preserved mitochondrial structure. TEM and light scattering demonstrated separately that mitochondrial matrix and cristae area and matrix volume were significantly increased after GI and reperfusion with GI > K/Mg + DZX > K/Mg hearts (P <0.05 vs. control). Mitochondrial free calcium was significantly increased in GI and K/Mg hearts. K/Mg + DZX significantly decreased mitochondrial free calcium accumulation (P <0.05 vs. GI and K/Mg). State 3 oxygen consumption and respiratory control index in malate (complex I substrate)- and succinate (complex II substrate)-energized mitochondria were significantly decreased (P <0.05 vs. control) in the GI and K/Mg + DZX groups. These data indicate that the enhanced cardioprotection afforded by K/Mg + DZX cardioplegia occurs through the preservation of mitochondrial structure and the significant decrease in mitochondrial free calcium accumulation and mitochondrial state 3 oxygen consumption.


Reducing Postoperative Bleeding After Craniosynostosis Repair Utilizing a Low-Dose Transexamic Acid Infusion Protocol.
Craniosynostosis surgery is associated with large volume blood loss and the need for blood transfusion. Recently, the use of tranexamic acid (TXA) has been demonstrated to be helpful in reducing perioperative blood loss in many pediatric procedures. This study used a low-dose pharmacokinetic TXA dosing protocol and assessed its ability to limit perioperative blood loss for craniosynostosis repairs. A retrospective chart review was conducted of pediatric craniosynostosis surgeries performed at our institution between September 2011 and December 2014. Outcome measures included comparisons of perioperative blood loss and transfusion rates in patients who had surgery with or without TXA. Twenty-five patients met inclusion criteria. Nine patients had craniosynostosis surgery without TXA (no-TXA group) and 16 patients received TXA (TXA group). The TXA group had significantly higher postoperative hemoglobin levels than the no-TXA group (P = 0.009). This finding was supported by significantly higher postoperative estimated red cell volume in the TXA group (P = 0.017). Postoperative 24-hour drain output was significantly lower in the TXA group (P = 0.042). The volume of packed red blood cells transfused perioperatively was not significantly different between groups. Patients who received TXA during craniosynostosis surgery at our institution had higher postoperative hemoglobin levels and lower 24-hour drain output. However, TXA was not associated with lower perioperative blood transfusion rates.


Enhanced enantioselectivity of native α-cyclodextrins by the synergy of chiral ionic liquids in capillary electrophoresis.
In the cyclodextrins family, the native α-cyclodextrin has almost been abandoned in capillary electrophoresis chiral separation due to its much weaker enantioselectivity compared with β-cyclodextrin and their derivatives. In this work, several amino acid chiral ionic liquids were selected to establish synergistic enantioseparation systems with native α-cyclodextrin. Enhanced enantioselectivities were observed in the chiral ionic liquids/α-cyclodextrin synergistic systems compared with single α-cyclodextrin system. A series of comparison experiments were performed to demonstrate the superiority of the synergistic systems. Primary parameters affecting the enantioseparation were systematically optimized, including the type and concentration of chiral ionic liquids, α-cyclodextrin concentration, buffer pH, and applied voltage. Best separations of the model enantiomers were obtained in a 20 mM Tris/H3 PO4 buffer at pH 2.5 containing 3% (m/v) α-cyclodextrin and 30 mM tetramethylammonium-l-arginine. The results show that the α-cyclodextrin is also worth our attention when selecting chiral selectors for capillary electrophoresis enantioseparation of specific racemic compound.


Medial patellofemoral ligament reconstruction in patellar instability.
Medial patellofemoral ligament (MPFL) is one of the major static medial stabilising structures of the patella. MPFL is most often damaged in patients with patellar instability. Reconstruction of MPFL is becoming a common surgical procedure in treating patellar instability. We hypothesised that MPFL reconstruction was adequate to treat patients with patellar instability if the tibial tubercle and the centre of the trochlear groove (TT-TG) value was less than 20 mm and without a dysplastic trochlea. 30 patients matching our inclusion criteria and operated between April 2009 and May 2011 were included in the study. MPFL reconstruction was performed using gracilis tendon fixed with endobutton on the patellar side and bio absorbable interference screw or staple on the femoral side. Patients were followed up with subjective criteria, Kujala score and Lysholm score. The mean duration of followup was 25 months (range 14-38 months). The mean preoperative Kujala score was 47.5 and Lysholm score was 44.7. The mean postoperative Kujala score was 87 and Lysholm score was 88.06. None of the patients had redislocation. MPFL reconstruction using gracilis tendon gives excellent results in patients with patellar instability with no redislocations. Some patients may have persistence of apprehension.


Heart rate during myocardial infarction: relationship with one-year global mortality in men and women.
Elevated heart rate (HR) has been found to be related to an increased death rate in patients with acute myocardial infarction (AMI), but sex differences and optimal timing for HR measurement have not been sufficiently investigated. To verify the predictive value of HR for one-year mortality in a cohort of subjects hospitalized for AMI, with men and women considered separately. HR was measured in 424 patients (303 men and 121 women) with constant sinus HR, on the first, third and seventh days after hospital admission for AMI. Clinical and laboratory data were obtained on the same days. All patients were followed up for one year. Among the men, the one-year mortality rate was 5% for the subjects with a seven-day HR of less than 80 beats/min, and the one-year mortality rate was 39% for patients with a seven- day HR of 80 beats/min or more (P<0.0001). Among the women, the differences in mortality related to HR were not significant. In a multivariate Cox regression analysis, the relative risks of mortality in men who had an HR of 80 beats/min or more were 3.1 (CI=1.4 to 7.0, P=0.003) on the first day, 4.1 (CI=1.8 to 9.8, P=0.001) on the third day and 8.6 (CI=2.9 to 27.0, P<0.0001) on the seventh day. In the 203 men in whom echocardiographic left ventricular ejection fraction was measured, an interactive effect of high HR with depressed ejection fraction on mortality was found. Beta-blocking therapy influenced HR during AMI but did not influence the HR-mortality association. The results of the present prospective study show that HR measured during the first week after admission for AMI is an important predictor of mortality in men. The predictive power of HR increased from the first to the seventh day after AMI.


Control of Tire Wear Particulate Matter through Tire Tread Prescription.
This study aims to analyze tire wear particulate matter (TWP) from tread rubber with different formulations and to compare the concentration of TWP with different wear devices. The TWP generated during the abrasion of truck and bus radial (TBR) tires were examined, and the effect of using different types of rubber and carbon black (CB) were investigated. When natural rubber (NR) was solely used as the tire tread rubber material, there was a higher concentration of 5-10 µm TWP. However, when the tread formulation consisted of NR mixed with butadiene rubber, the TWP concentration decreased. Changing the type of CB also reduced the amount of TWP in the 2.5 µm size range. The TWP concentration in the specimens increased with increasing speed and vertical load. The TWP generated during the abrasion tests using wear testers and tire simulators exhibited similar trends. These findings suggest that modifying tire tread formulations can effectively control the distribution and amount of TWP generation.


Virulence of Entomopathogenic Nematodes to Pupae of Frankliniella fusca (Thysanoptera: Thripidae).
Tobacco thrips, Frankliniella fusca (Hinds) is an economically significant pest. Entomopathogenic nematodes (EPNs) have shown promise as biocontrol agents against certain thrips species, but they have not been explored for suppression of F. fusca. We investigated the potential of EPNs to manage F. fusca by conducting three different bioassays: 1) a small cup dose-response bioassay (25, 50, and 100 IJs cm-2) with four EPN species, 2) a broad virulence bioassay with eight EPN species at 100 IJs cm-2, and 3) a potted soil bioassay testing with four EPN species (100 IJs cm-2). In the dose-response bioassay, all treatments showed relatively lower adult emergence when compared with the control group, but the minimum adult emergence (30%) was observed at 7 d post-treatment when Heterorhabditis bacteriophora (FL1-1) was applied at the highest rate (100 IJs cm-2). In the broad virulence study, all EPN treatments caused significant reductions in F. fusca adult emergence (18.3-75.0%) in comparison with the control. H. bacteriophora (Fl1-1) was more virulent than other nematode treatments but statistically not different from Steinernema feltiae and Steinernema riobrave, while Steinernema rarum was the least virulent. In the potted soil bioassay, the lowest emergence (10.6%) was observed in H. bacteriophora (Fl1-1) treatment, followed by S. feltiae (SN), S. riobrave (355), and Heterorhabditis indica (HOM1) treatments. These results indicate that EPNs have the ability to suppress the soil dwelling stage of F. fusca and should be explored further under greenhouse and field conditions for biocontrol potential within an integrated pest management (IPM) context.


Liver transplant for metastatic neuroendocrine tumor.
Generally, the results of liver transplantation for metastatic liver disease have not been favorable. One exception has been the unique group of neuroendocrine tumors, the slow growth of which allows liver transplantation to effectively palliate and control symptoms. We report two cases: (a) A 51-year-old man who underwent orthotopic liver transplantation and resection of the pancreatic primary tumor for a nonfunctioning malignant neuroendocrine tumor with features of both carcinoid and islet-cell glucagonoma remains symptom-free and without evidence of tumor recurrence at 13 months follow-up. (b) A 47-year-old man who underwent orthotopic liver transplantation and Whipple resection for a metastatic islet-cell tumor in the head of the pancreas is fully recovered at 5 months follow-up.


Tuning the Solid Electrolyte Interphase for Selective Li- and Na-Ion Storage in Hard Carbon.
Solid-electrolyte interphase (SEI) films with controllable properties are highly desirable for improving battery performance. In this paper, a combined experimental and theoretical approach is used to study SEI films formed on hard carbon in Li- and Na-ion batteries. It is shown that a stable SEI layer can be designed by precycling an electrode in a desired Li- or Na-based electrolyte, and that ionic transport can be kinetically controlled. Selective Li- and Na-based SEI membranes are produced using Li- or Na-based electrolytes, respectively. The Na-based SEI allows easy transport of Li ions, while the Li-based SEI shuts off Na-ion transport. Na-ion storage can be manipulated by tuning the SEI layer with film-forming electrolyte additives, or by preforming an SEI layer on the electrode surface. The Na specific capacity can be controlled to < 25 mAh g-1 ; ≈ 1/10 of the normal capacity (250 mAh g-1 ). Unusual selective/preferential transport of Li ions is demonstrated by preforming an SEI layer on the electrode surface and corroborated with a mixed electrolyte. This work may provide new guidance for preparing good ion-selective conductors using electrochemical approaches.


Antimicrobial activity of root canal filling pastes used in pediatric dentistry.
This study evaluated the antimicrobial activity of root canal filling pastes commonly used in primary teeth: iodoform paste, zinc oxide-eugenol (ZOE), and analytical grade calcium hydroxide (Ca[OH]2). The materials were evaluated in the following 6 combinations: iodoform paste (Rifocort [prednisolone + rifampicin] + iodoform + camphorated paramonochlorophenol); zinc oxide + eugenol in a proportion of 1:3; zinc oxide + eugenol in a proportion of 1:5; Ca(OH)2 + water; iodoform paste + ZOE (1:3) + Ca(OH)2; and ZOE (1:3) + Ca(OH)2. Chlorhexidine gel (0.2%) served as the positive control. A commercial strain of Enterococcus faecalis (ATCC 25175) was plated in petri dishes containing 10 mL of brain-heart infusion agar culture medium with a hole in the center. The filling pastes (3 g) were manipulated and inserted in the hole. The plates were incubated at 37°C for 48 hours, and then the inhibition zone associated with each paste was measured. The experiments were carried out in triplicate (n = 3 per group). The data were submitted to analysis of variance and Tukey tests (P < 0.05). Iodoform paste resulted in the largest mean (SD) inhibition zone, 7.06 (0.74) mm. The smallest was obtained with Ca(OH)2 + water, the mean (SD) of 0.00 (0.00) mm indicating that these specimens did not form an inhibition zone. The ZOE pastes in proportions of 1:3 and 1:5 resulted in statistically similar mean (SD) inhibition zones of 1.86 (0.50) and 1.30 (0.18) mm, respectively (P > 0.05). Of the test materials, the combination of iodoform paste + ZOE + Ca(OH)2 presented the second largest inhibition zone, 6.27 (3.08) mm, significantly different from that of the non-iodoform pastes (P < 0.05). It can be concluded that iodoform paste, alone or in combination with ZOE + Ca(OH)2, demonstrates high antimicrobial activity, while the combination of ZOE + Ca(OH)2 demonstrates moderate activity.


Influence of menopausal status on the main contributors of muscle quality.
Muscle quality is a strong independent predictor of physical function. Body mass and fatness, muscle mass and cardiorespiratory fitness are known to influence muscle quality. To identify the contributors of muscle quality in young and postmenopausal women and whether hormone replacement therapy (HT) could influence this relationship at the age of menopause. Fifty-four postmenopausal women, 27 not on HT (PMW) and 27 on HT (PMW-HT), and 33 young women (YW) were evaluated for (1) body composition (body mass index, BMI), total fat mass (FM, %), appendicular lean mass (ALM, in kg and %), and appendicular skeletal mass index (ASMI = ALM/height2 in kg/m2); (2) absolute peak oxygen uptake (VO2peak, in ml/min) and relative peak oxygen uptake (VO2peakRel in ml/kg/min); and (3) absolute isometric knee extension strength (iKES in kg) and relative isometric knee extension strength (iKES/BMI and iKES/ALM). YW, PMW and PMW-HT had similar BMI (32.1 ± 10.2, 27.3 ± 4.7 and 26.7 ± 4 kg/m2) and FM (39.8 ± 10.0, 39.8 ± 7.3 and 39.9 ± 7.1%), respectively. Correlations were found between iKES/BMI index and FM (r = -0.52), ALM (r = 0.32) and VO2peak (r = 0.31). Regression analysis demonstrated that, in YW, total amount of variance in iKES/BMI was mostly explained by ALM (42%), whereas, in PMW and PMW-HT, it was cumulatively explained by FM along with VO2peakRel (34 and 46%, respectively). The main contributors of muscle quality differ between young and postmenopausal women and HT does not seem to influence this relationship.


Structural requirements of FGF-1 for receptor binding and translocation into cells.
FGF-1 binds to and activates specific transmembrane receptors (FGFRs) and is subsequently internalized and translocated to the interior of the cell. To elucidate the role of the receptor in the translocation process, we studied the effects of the elimination of distinct sites of the ligand-receptor interaction. On the basis of the structure of the FGF-1-FGFR1 complex, we substituted four key amino acid residues of FGF-1 from the FGF-receptor binding site with alanines, constructing four point mutants and one double mutant. We determined by in vivo assays in NIH 3T3 cells the ability of the mutants to bind to specific FGF receptors, to stimulate DNA synthesis, and to activate downstream signaling pathways. We found that correct binding to the receptor is necessary for optimal stimulation of DNA synthesis. All four single mutants became phosphorylated to different extents, indicating that they were translocated to the cytosol/nucleus with varying efficiency. This indicates that despite a low affinity for FGFR, translocation to the cytosol/nucleus can still occur. However, simultaneous substitution in two of the positions led to a total loss of biological activity of the growth factor and prevented its internalization, implying that there is only one strongly receptor-dependent, productive way of translocating FGF-1. We also found that the process of translocation did not correlate with the thermal stability of the protein. Additionally, we observed a clear negative correlation between the stability of the FGF-1 mutants and the efficiency of their phosphorylation, which strongly suggests that protein kinases prefer the unfolded state of the protein substrate.


A four-disc version of the Tower of London for clinical use.
Three studies are reported on the development of a four-disc version of the Tower of London test of planning ability. The first (n = 138) involved the selection of items based on rational and empirical criteria to provide a short test of graded difficulty suitable for use with children and clinical populations. The second study (n = 480) checked the properties of the 10-item test on a new sample and in addition examined the internal consistency and factor structure of the test. The third study (n = 61) examined the test-retest reliability of the test over a period of 1 month. The difficulty level of the test remained relatively stable from sample to sample and was sensitive to linear trend in performance from age 5 years up to 30 years. Total score did not reflect the action of a single underlying construct but rather appeared to index a number of factors. Scores were reasonably stable over the 1-month period studied, at least for the children's sample employed. The four-disc version is a promising method of assessing planning in children and adolescents in clinical situations.


Pheochromocytoma and paraganglioma: genotype versus anatomic location as determinants of tumor phenotype.
To date, germline or somatic genetic events can be detected for at least 60% of paragangliomas. Strong genotype-phenotype associations have been recognized and become increasingly refined. Characteristics closely linked with genotype include syndromic presentation, age of onset, risk of metastatic disease and predominant anatomic site. In contrast, profiles of catecholamine secretion appear to be largely determined by anatomic location or cell type of origin. This review summarizes current knowledge of genotype-phenotype correlations for paragangliomas in different locations and scrutinizes previous publications on the respective tissues of origin to find potential explanations for site-related differences. We hypothesize that differential sensitivities of distinct chromaffin cell populations to hypoxia are major determinants of these differences, with increased sensitivity to hypoxia likely exacerbating vulnerability to mutation-derived disruption of hypoxic signaling pathways. Potential involvement of endothelin-1, tumor necrosis factor type 1 receptor-associated protein and the hypoxia-inducible miR-210 in the development of abdomino-thoracic or head and neck paragangliomas are discussed. Recognition of factors that predispose to chromosomal losses, or amplify sub-threshold molecular alterations towards tumorigenic events in different (chromaffin) cell types, may facilitate the leap from developing targeted therapies towards establishment of tumor preventative measures.


Barriers to training family medicine residents in community health centers.
Training partnerships between family medicine residencies (FMRs) and community health centers (CHCs) are a potential solution to the chronic problem of health workforce shortages in CHCs. We conducted a national survey to identify the barriers to training family medicine residents in CHCs. We asked US family medicine residency directors to identify barriers to training residents in CHCs. Using grounded theory, three coders grouped responses by theme. We examined differences in barriers between residency programs that currently train in CHCs with programs that do not currently train in CHCs. A total of 51% (226/439) of residency program directors responded. Of these, 29% cited governance as a barrier to affiliation, 26% cited administrative complexity, 24% cited financial considerations, 21% cited leadership, and 18% cited access. Programs that trained in CHCs were more likely to cite financial considerations and administrative complexity than programs that did not train in CHCs. Governance and administrative complexity are the most commonly cited barriers to effective CHC-FMR partnerships. Financial consideration and leadership issues are also common barriers.


CACNA1S expression in mouse retina: Novel isoforms and antibody cross-reactivity with GPR179.
Cacna1s encodes the α1S subunit (Cav1.1) of voltage-dependent calcium channels, and is required for normal skeletal and cardiac muscle function, where it couples with the ryanodine receptor to regulate muscle contraction. Recently CACNA1S was reported to be expressed on the tips of retinal depolarizing bipolar cells (DBCs) and colocalized with metabotropic glutamate receptor 6 (mGluR6), which is critical to DBC signal transduction. Further, in mGluR6 knockout mice, expression at this location is down regulated. We examined RNAseq data from mouse retina and found expression of a novel isoform of Cacna1s. To determine if CACNA1S was a functional component of the DBC signal transduction cascade, we performed immunohistochemistry to visualize its expression in several mouse lines that lack DBC function. Immunohistochemical staining with antibodies to CACNA1S show punctate labeling at the tips of DBCs in wild type (WT) retinas that are absent in Gpr179 nob5 mutant retinas and decreased in Grm6 -/- mouse retinas. CACNA1S and transient receptor potential cation channel, subfamily M, member 1 (TRPM1) staining also colocalized in WT retinas. Western blot analyses for CACNA1S of either retinal lysates or proteins after immunoprecipitation with the CACNA1S antibody failed to show the presence of bands expected for CACNA1S. Mass spectrometric analysis of CACNA1S immunoprecipitated proteins also failed to detect any peptides matching CACNA1S. Immunohistochemistry and western blotting after expression of GPR179 in HEK293T cells indicate that the CACNA1S antibody used here and in the retinal studies published to date, cross-reacts with GPR179. These data suggest caution should be exercised in conferring a role for CACNA1S in DBC signal transduction based solely on immunohistochemical staining.


[Physiology and pathology of the immune system of reproduction].
The Authors describe in detail the complex immunological mechanisms thanks to which the maternal organism does not reject the embryo, constituting an allogenic transplant. They examine the modifications, referring to both natural and adoptive immunity, occurring in the pregnant without ignoring the important contribution the foetus itself and adnexa make to the gestation positive termination. In the second part of the paper all the pregnancy pathologies, originating from an imbalance proper to the immunity system, are considered. The following pathologies are particularly described: a) the spontaneous recurrent abortion, both primary and secondary; b) the gestosis; c) the maternal-foetal isoimmunization towards transferable antigens present on red corpuscles, white corpuscles and blood platelets. At last Authors describe all the autoimmune illnesses in pregnancy and their influence on the foetus. Such illnesses may be: a) organ-specifics (immunological thrombocytopenic purpura, thyrotoxicosis, myxedema, serious myasthenia); b) systemics (rheumatoid arthritis, lupus erythematous). The course of each pathology, its influence on the embryo and, the present therapeutic protocols are examined.


Pre-operative investigations: yield and conformity to national guidelines.
Routine ordering of pre-operative investigations yields a low true positive rate and is not cost effective. In this study, case notes of 251 adults who underwent elective surgery were reviewed. Pre-operative investigations were classified as 'indicated' or 'not indicated', based on the national guidelines. Only 56% of all tests done were indicated. The overall rates of expected and unexpected abnormal values from pre-operative blood investigations were 51.1% and 34.4% respectively. This study found that selective testing based on guidelines was beneficial. However, the results also suggest that the local guidelines need to be reviewed.


Rigorous force field optimization principles based on statistical distance minimization.
We use the concept of statistical distance to define a measure of distinguishability between a pair of statistical mechanical systems, i.e., a model and its target, and show that its minimization leads to general convergence of the model's static measurable properties to those of the target. We exploit this feature to define a rigorous basis for the development of accurate and robust effective molecular force fields that are inherently compatible with coarse-grained experimental data. The new model optimization principles and their efficient implementation are illustrated through selected examples, whose outcome demonstrates the higher robustness and predictive accuracy of the approach compared to other currently used methods, such as force matching and relative entropy minimization. We also discuss relations between the newly developed principles and established thermodynamic concepts, which include the Gibbs-Bogoliubov inequality and the thermodynamic length.


The P2X7 Receptor in Tumor Immunity.
Extracellular adenosine triphosphate (eATP) is a potent mediator of the immune response via stimulation of purinergic P2 receptors. ATP concentration in the extracellular space increases dramatically during tissue damage and eATP acts as a danger-associated molecular pattern (DAMP) to alert innate immune system cells for tissue repair. Similarly, eATP is present at hundreds of micromolar concentration in the tumor microenvironment (TME). However, its impact on antitumor immune response is still not well established, probably because of the complexity of the responses it induces in different cells constituting the TME. On one hand, ATP released by tumor cells concomitantly to cell death can contribute to immunogenic cell death (ICD) that is proinflammatory for the innate immune compartment and beneficial for tumor control, while on the other hand, eATP can foster immune-suppressive mechanisms within the TME, thus contributing to tumor progression and metastasis. It is well established that T-cell immunity is pivotal in limiting tumor growth and possibly eradicating neoplastic cells. T cells are limited though in their antitumor activity through different mechanisms, such as exhaustion, anergy, and senescence; the pathways resulting in these cellular outcomes are not clear. Here, we review the function of P2X7 receptor in conditioning T cell-dependent immunity against cancer.


Survival following investigational treatment of amanita mushroom poisoning: thistle or shamrock?
We report the first case, to our knowledge, of amatoxin hepatotoxicity in Iowa and explore the ethical and decisional challenges of offering an investigational treatment of a rare disease. Acute liver failure due to ingestion of amatoxin-containing mushrooms is a relatively rare entity. Once amatoxin poisoning is identified, there is no clearly effective treatment, leading to a broad range of theoretically beneficial, anecdotally successful, or investigational options. The evolution of hepatotoxicity led us to offer investigational treatment with silibinin, an extract of Mediterranean milk thistle. We explore the pitfalls in medical decision-making experienced by both the patient and the physician in the face of ambiguity. The patient did well following silibinin infusion, but we are left uncertain as to whether the patient truly responded to treatment or was simply destined to recover.


Pathophysiological changes of the cochlea during ageing--a review.
Research of the pathophysiology of the age-related human presbycusis was largely initiated by those investigations in which the cochlea's damages were experimentally induced by various acoustic exposures. It became apparent that the outer hair cells are more vulnerable to different noise influences than the inner hair cells. On the other hand, the role of the altered ultrastructural elements of various types, cannot be ruled out. The evolving of the age-related presbycusis was to a great extent established using large-scale model experiments, including mainly rodents. It seems that the age-bound presbycusis (cf. intrinsic degeneration of the cochlea) begins at the apical regions which will be later more worsening by various extrinsic traumas. It is suggested that the damages gradually taking part in the inner ear structures are bound to the age-dependent processes in which the ever-increasing formation of cross-linkages plays an important role as ageing progresses.


A comparison of regional and systemic humoral immune responses to a nematode infection.
The kinetics of humoral immune response against Trichinella spiralis (TS) was characterized with immunofluorescence assay. The mesenteric lymph nodes (MLN) and the spleen of infected rats were examined for concurrent expression of multiple antibody (Ab) isotypes from day 1 to day 15 after infection. The tissues were processed and stained with either a pan-B cell marker (OX33) conjugated with rhodamine (XRITC) or combinations of dual monoclonal Ab probes plus A secondary Ab conjugated with XRITC or fluorescein (FITC). As compared to the uninfected controls, the spleen and the MLN showed significant proliferation of dual-Ab expressing B cells (Debc) on days 5 and 7, respectively. During the immune response, only minimal numbers of B cells expressed single Ab isotype while most B cells expressed more than one isotypes of Ab. When combining all the numbers of Debc within each tissue for each respective days, and comparing those numbers with the total numbers of B cells that were OX33+ in the serial sections of the same tissue specimens, the combined Debc in the spleen were > 6 times higher than the OX33 labeled B cells on day 10, and the Debc in MLN were > 3 times higher than the OX33+ B cells on day 10. Our results thus indicate that the Debc most likely expressed more than two Ab isotypes during the peak days of the humoral immune response to the parasite and this phenomenon occurred in both regional and systemic lymphoid tissues.


Computed tomography of fatal hepatic rupture due to peliosis hepatis.
Hepatic rupture with subcapsular hematoma and hemoperitoneum is shown by CT in a patient with peliosis hepatis. Peliosis hepatis is pathologically characterized by blood-filled cystic spaces in the liver associated with the administration of anabolic androgenic steroids or oral contraceptive agents, particularly those with large components of estrogen. We report a fatal case in a patient receiving diethylstilbestrol for 3 years. In patients receiving these medications, peliosis hepatis should be considered in the differential diagnosis of low attenuation areas in the liver by CT. These patients are subject to increased risk of spontaneous hepatic rupture.


Role of FGF3 in otic capsule chondrogenesis in vitro: an antisense oligonucleotide approach.
Initiation of otic capsule chondrogenesis depends on interactions between the otocyst and surrounding periotic mesenchyme. We previously reported localization of endogenous basic fibroblast growth factor (FGF2) to the epithelium of the mouse otocyst, and initiation of chondrogenesis in cultured periotic mesenchyme by this epithelial-derived signaling molecule. We now report that FGF3, related to FGF2, can also initiate otic capsule chondrogenesis. We show localization of endogenous FGF3 to the otocyst, and suppression of chondrogenesis by antisense oligonucleotides complementary to different regions of the murine FGF3 gene. Our results support a role for FGF3 in otic capsule formation in situ.


Impact of long-term exposure to mosquito coils: residual deposition and dissipation of D-trans-allethrin in a room.
A D-trans-allethrin-based mosquito repellent coil formulation was used continuously in a room for 30 d. Two different experiments were conducted and the deposition of residues on different surfaces of the room was determined. Studies were conducted continuously for a period of 30 d in a fully closed room and in another room kept open for 14 h per day. The residues deposited on different surfaces, ceiling, side walls and floor, were measured. The results showed the accumulation of high concentrations of allethrin on all the surfaces of the room when the room was in a fully closed condition. Samples collected from the ceiling showed residues of D-trans-allethrin of 6.34-148.63 microg m(-2) during the 30 d study, the side walls 4.68-170.72 microg m(-2) and the floor 20.00-184.52 microg m(-2) Maximum residues were observed in 30 d samples collected from the ceiling and floor. The residual concentrations were nearly 10 times higher in samples collected from the closed room. Discontinuation of the use of the mosquito repellent after 30 d led to a gradual decrease in the concentrations of residues on all the surfaces. The influence of environmental parameters on the dissipation of residues was also studied.


Carbenicillin in the first nine months of unrestricted use. A chapter in the natural history of an antibiotic.
During the first nine months following its release for general use, carbenicillin was administered to forty-two patients in Hahnemann Hospital. Thirty-nine available records of patients receiving the drug for other than urinary infection were reviewed. Among children, all but one had mucoviscidosis: most were given acceptable therapeutic regimens; survival rate was 80%, and their physicians were favorably impressed. Among adults, underlying disease was usually life threatening; most were inadequately treated; survival rate was 31%, and their physicians were not favorably impressed. The multiplicity of variables precludes objective evaluation of the drug under the circumstances of its use, but one that could have been avoided was the inconsistency of the therapeutic regimen, which in adult patients was too often insufficient. As used, therefore, carbenicillin has not provided the benefits predicted from its earlier controlled evaluation, and the large expenditure of money, particularly by adult patients, has been largely wasted.


Hyman J. Weiner's use of systems and population approaches: their relevance to social work practice in health care today.
In the course of his creative career, Hyman J. Weiner (August 22, 1926-December 2, 1980) exerted a particularly profound, distinct and dynamic influence on social work practice in health care settings. This tribute to him reviews the theoretical perspective and action guides he formulated to help social workers in these settings apply systems and population approaches to the shaping of their missions, functions and services. Their current applicability is discussed.


Interleukin-29 induces receptor activator of NF-κB ligand expression in fibroblast-like synoviocytes via MAPK signaling pathways.
We previously reported that interleukin-29 (IL-29) was highly expressed in the blood and synovium of rheumatoid arthritis (RA) patients and contributed to synovial inflammation by induction of proinflammatory cytokine production. Given chronic inflammation can trigger the process of bone erosion, and receptor activator of nuclear factor-κB ligand (RANKL) plays a crucial role in bone erosion of RA, we hypothesize that IL-29 mediates bone erosion in RA by regulation of RANKL expression. Here, we investigated the effect of IL-29 on RANKL expression in RA fibroblast-like synoviocytes (FLS) and the relevant signaling pathways involved in it. Primary fibroblast cells isolated from RA patients were stimulated by recombinant IL-29 in the presence or absence of anti-IL-29 antibody, and the expression levels of RANKL were assessed using real-time polymerase chain reaction and immunostaining. Furthermore, the IL-29 signaling pathway for regulation of RANKL was also examined by Western blotting assay. IL-29 upregulated RANKL expression in a dose-dependent manner, and blockade of IL-29 resulted in a significantly reduced RANKL expression in RA-FLS. Incubation RA-FLS with IL-29 (100 ng/mL) led to phosphorylation of ERK (extracellular signal-regulated kinase), p38 and JNK (c-Jun N-terminal kinase). The expression of RANKL induced by IL-29 could be completely blocked by the inhibitors of mitogen-activated protein kinase (MAPK) signal pathway, including PD98059 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor). These findings indicate, for the first time, that IL-29 could directly induce RANKL expression in RA-FLS via MAPK signaling pathway, suggesting IL-29 might be a new target in the prevention of joint destruction in RA.


[Measuring leg length and leg length difference with the method of real time sonography].
A brief presentation of the clinical and radiological methods to measure the leg length and the leg length difference is followed by an outline of the new diagnostic method for measuring the leg length and the leg length difference by means of real-time sonography. Tests conducted on corpses, as well as clinical examples, show that sonography is an ideal method for determining the exact lengths of the femur and tibia. The joint gaps on the hip joint, knee joint and upper ankle joint can be visualised by means of a 5 MHz linear scanner. A 1 mm strong metal bar on the skin and under the scanner are positioned at a right angle to the longitudinal axis of the body so that the bar can be seen in the centre of each joint gap by means of real-time sonography. A measuring device gives the distances of the joint gaps in cm so that the differences correspond to the real length of femur and tibia. This standardised measuring procedure is done by a specially developed bearing and measuring device. The results of the sonographical measurings on 20 corpses and checking after consecutive dissections showed in 75% of the cases a 100% sonographic measuring accuracy of the total leg length. The separately considered results for femur (85%) and tibia (90%) were even better. The maximum sonographic measuring fault was 1.0 cm for the femur (in one case) and 0.5 cm for the tibia, respectively. Thus, sonographic measuring of the leg length offers a reliable, non-invasive and easily performed new method that can be repeated any number of times. It is ideal for the development control of therapeutically influenced as well as spontaneous transformations of leg length differences.


Thermogenic responses to selective and nonselective beta-adrenerg agonists in hypothyroidism of Sprague-Dawley rats.
Resting oxygen consumption (VO2) and mitochondrial GDP binding were measured in hypothyroid and euthyroid rats after administration of selective and nonselective beta-adrenoceptor agonists (BRL 35135A and Isoprenaline--BRL, ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-agonists were lower in hypothyroid rats than in the euthyroid group. The reduced response was more marked for ISO than for BRL. These results suggest that BRL is acting on a beta-adrenoceptor which differs from beta-1 and beta-2 adrenoceptors, responsible for the effect of ISO. Activation of thermogenesis via this beta-3 adrenoceptor seems to be less dependent on permissive levels of thyroid hormones than on activation via beta-1 and/or beta-2 adrenoceptors.


Rab GTPases in Parkinson's disease: a primer.
Parkinson's disease is a prominent and debilitating movement disorder characterized by the death of vulnerable neurons which share a set of structural and physiological properties. Over the recent years, increasing evidence indicates that Rab GTPases can directly as well as indirectly contribute to the cellular alterations leading to PD. Rab GTPases are master regulators of intracellular membrane trafficking events, and alterations in certain membrane trafficking steps can be particularly disruptive to vulnerable neurons. Here, we describe current knowledge on the direct links between altered Rab protein function and PD pathomechanisms.


"Tell Me About Your Child": A Grounded Theory Study of Mothers' Understanding of Language Disorder.
Purpose The purpose of this study was to generate a theory grounded in data explaining caregivers' understanding of their child's language disorder and the perceived role of speech-language pathologists in facilitating this knowledge. Method This study employed grounded theory as a conceptual framework. Qualitative data were generated based on semistructured interviews conducted with 12 mothers of children who had received speech-language pathology services. Results The following themes emerged from the data analysis: (a) Many mothers reported receiving confusing or irrelevant diagnostic terms for language disorder, (b) mothers of children with language disorders were distressed about their children's language problems, (c) mothers did not always trust or understand their children's speech-language pathologist, and (d) mothers were satisfied with the interventions their child had been receiving. Mothers described their children's language disorder using a total of 23 labels, most of which were not useful for accessing meaningful information about the nature of their child's communication problem. Generally, mothers reported they did not receive language-related diagnostic labels from speech-language pathologists for their child's language disorder. Conclusions Two theories were generated from the results: (a) Lack of information provided to mothers about their child's language disorder causes mothers psychological harm that appears to be long lasting. (b) Difficulties in successfully relaying information about language disorders to parents result in negative perceptions of speech-language pathology. Implications and future directions are discussed. Supplemental Material https://doi.org/10.23641/asha.12177390.


Student and intern awareness of ionising radiation exposure from common diagnostic imaging procedures.
This study aims to evaluate medical student and intern awareness of ionising radiation exposure from common diagnostic imaging procedures and to suggest how education could be improved. Fourth to sixth year medical students enrolled at a Western Australian university and interns from three teaching hospitals in Perth were recruited. Participants were asked to complete a questionnaire consisting of 26 questions on their background, knowledge of ionising radiation doses and learning preferences for future teaching on this subject. A total of 331 completed questionnaires were received (95.9%). Of the 17 questions assessing knowledge of ionising radiation, a mean score of 6.0 was obtained by respondents (95% CI 5.8-6.2). Up to 54.8% of respondents underestimated the radiation dose from commonly requested radiological procedures. Respondents (11.3 and 25.5%) incorrectly believed that ultrasound and MRI emit ionising radiation, respectively. Of the four subgroups of respondents, the intern doctor subgroup performed significantly better (mean score 6.9, P < 0.0001, 95% CI 6.5-7.3) than each of the three medical student subgroups. When asked for the preferred method of teaching for future radiation awareness, a combination of lectures, tutorials and workshops was preferred. This study has clearly shown that awareness of ionising radiation from diagnostic imaging is lacking among senior medical students and interns. The results highlight the need for improved education to minimise unnecessary exposure of patients and the community to radiation. Further studies are required to determine the most effective form of education.


Using a theatre-based programme to prevent gender-based violence: evidence from Australia.
Bystander interventions play an important contribution to efforts to prevent violence against women and arts-based interventions have been effective as part of a range of health promotion programmes. You the Man is a theatre-based programme, which contributes to violence prevention efforts in community settings. Requiring a single actor and minimal props, the programme consists of a 30-35 min play about intimate partner violence and sexual assault followed by a moderated post-performance panel discussion including staff from local support agencies. Although it has received positive feedback in a range of settings, the only previously published evaluation involved establishing short and long-term impacts on American high school students. This article examines the short-term impacts from attending You the Man events on a different audience, i.e. Australian adults. Anonymous online surveys conducted prior and 4 weeks after events were completed by 41 participants of whom 29 were female and 12 were male, three-quarters of whom were aged between 18 and 49, and who attended events at university campuses (46.3%), in workplaces (34.1%), at sporting clubs (12.2%) and community centres (7.3%). At follow up, participants regarded the severity of abusive and coercive behaviours as being higher than at baseline, their capacity to intervene as a bystander had increased, as had the number of sources of support they would recommend to someone experiencing gender-based violence. Hence, theatre-based programmes can positively affect attitudes in relation to gender-based violence, increase bystander knowledge about safe ways to intervene and positively affect intended bystander intervention.


Effects of prolonged mental work on functional brain topography.
Topographic patterns of event-related covariance between electrodes were measured from subjects performing a difficult memory and fine-motor control task for 10-14 h. Striking changes occurred in the patterns after subjects performed the task for an average of 7-9 h, but before performance deteriorated. Pattern strength was reduced in a fraction-of-a-second-long response preparation interval over midline precentral areas and over the entire left hemisphere. By contrast, pattern strength in a succeeding response inhibition interval was reduced over all areas. The pattern changed least in an intervening interval associated with visual-stimulus processing. This suggests that, in addition to the well-known global reduction in neuroelectric signal strength, functional neural networks are selectively affected by sustained mental work in specific fraction-of-a-second task intervals.


K2S as Sulfur Source and DMSO as Carbon Source for the Synthesis of 2-Unsubstituted Benzothiazoles.
We describe a three-component reaction of o-iodoanilines with K2S and DMSO that provides 2-unsubstituted benzothiazoles in moderate to good isolated yields with good functional group tolerance. Electron-rich aromatic amines and o-phenylenediamines instead of o-iodoanilines provided 2-unsubstituted benzothiazoles and 2-unsubstituted benzimidazoles with and without K2S under similar conditions. Notably, DMSO plays three vital roles: carbon source, solvent, and oxidant.


Discrimination of stable isotopes in fin whale tissues and application to diet assessment in cetaceans.
In stable isotope research, the use of accurate, species-specific diet-tissue discrimination factors (i.e., Δ(13)C and Δ(15)N) is central to the estimation of trophic position relative to primary consumers and to the identification of the dietary sources of an individual. Previous research suggested that the diet of fin whales from the waters off northwestern Spain is overwhelmingly based on krill, thus permitting reliable calculation of discrimination values in this wild population. After confirming that the stable isotope ratios (δ(13)C and δ(15)N values) in muscle from 65 aged fin whales remained constant through age classes (4-65 years), the signatures were determined in muscle, bone protein, skin, liver, kidney, baleen plates and brain, as well as food (krill), from a subset of individuals to calculate discrimination factors. Signatures were determined by means of elemental analysis isotope ratio mass spectrometry (EA-IRMS) using a ThermoFinnigan Flash 1112. The isotopic values remained constant regardless of age. The mean Δ(15)N values between krill and whale tissues ranged from 2.04 in bone protein to 4.27‰ in brain, and those of Δ(13)C ranged from 1.28 in skin to 3.11‰ in bone protein. This variation was consistent with that found in other groups of mammals, and is attributed to variation in tissue composition and physiology. Because discrimination factors are relatively constant between taxonomically close species, the results here obtained may be reliably extrapolated to other cetaceans to improve dietary reconstructions. The skin discrimination factors are of particular relevance to monitoring diet through biopsies or other non-destructive sampling methods. The large difference in bone protein discrimination factors from those of other tissues should be taken into consideration when bone collagen is used to determine trophic level or to assess diet in paleodietary isotopic reconstructions.


Understanding Refractive Index Changes in Homologous Series of Unbranched Organic Compounds Based on Beer's Law.
Changes of the refractive index for homologous series of hydrocarbons are usually plotted versus the density. While there is a clear linear dependence for alkanes and alkenes, the linearity deteriorates for homologous series with functional groups involving heteroatoms. The slope can even become negative, e. g., for carboxylic acids. For gaining a deeper understanding and to establish a more general correlation, we reinvestigate the corresponding theories starting with the Newton-Laplace, Gladstone-Dale and the Lorentz-Lorenz rules. We revisit the concept of molar refractivity pioneered by Landolt and Brühl and show that it is closely connected with a twin of Beer's law. We conclude that the refractive index of homologues series should better be plotted versus the molar concentration of the main UV-chromophore, the C-H bond, which actually causes the refractive index changes. This new approach is not limited to alkanes and alkenes but holds for homologous series with functional groups including heteroatoms.


Flow cytometric identification of microorganisms by dual staining with FITC and PI.
The identification of microorganisms by flow cytometry was evaluated by using a double staining technique with propidium iodide and fluorescein isothiocyanate and a two dimensional analysis. A diverse group of 19 different species and strains of microorganisms was tested to determine if they could be differentiated by flow cytometry. The organisms tested displayed characteristic and distinct two dimensional fluorescent patterns which allowed ready grouping and differentiation into subsets of organisms. The slopes and correlation coefficients of the histograms and the ratio of red to green signals expressed these differences quantitatively and allowed organisms to be placed into one of three groups based on these values. In some instances, as with Streptococcus pneumoniae and pyogenes and Staphylococcus aureus and epidermidis, it was possible to distinguish between species of bacteria from the same genus. The use of dual dye labeling and flow cytometry provided a rapid method of identifying selected microorganisms and may be broadly applicable for the detection and identification of many bacteria and fungi.


Psoriasis of the Lips: A Case Report with Review of the Literature.
Psoriasis is a chronic inflammatory dermatosis, which progresses by relapses-remissions, of a multifactorial etiology which involves genetic, immunological, and environmental factors. Skin lesions are mainly localized in areas of friction: elbows, knees, pre-tibial, lumbosacral regions, scalp, and nails. Although the appearance of the skin lesions is sufficient for a diagnosis, diagnostic difficulties may be found in case of unusual topography. We report a case of a 45-year-old female patient with psoriatic cheilitis with a review of the literature.


Effect of micronutrient-enriched sunflower oils on plasma lipid profile and antioxidant status in high-fat-fed rats.
The main objective of this study was to evaluate in vivo whether micronutrient-enriched high-oleic sunflower oils (optimized oils) obtained using different crushing and refining procedures could have any beneficial effect on plasma lipid profile and antioxidant status. Sprague-Dawley rats were fed a high-fat diet for 4 weeks. The lipid source consisted of 20% optimized sunflower oils with different quantities and qualities of micronutrients. The control group received traditional refined high-oleic sunflower oil. The experimental optimized oils in the diets had a hypolipidemic effect. The reduction in plasma triglyceride and total cholesterol levels was 43% and 20%, respectively, in the group fed the diet with the highest levels of micronutrients. The serum ferric antioxidant capacity, superoxide dismutase, glutathione peroxidase and reduced glutathione significantly increased and lipid peroxidation decreased in parallel with the enhancement of micronutrients. These results suggest that a regular intake of optimized sunflower oils can help to improve lipid status and reduce lipid peroxidation in plasma.


[Recombinant expression of human fibrogenic factors and preparation of polyclonal antibodies].
To express the recombinant proteins of human fibrogenic factors and prepare the polyclonal antibodies of rabbit-anti-human fibrogenic factors. The human fibrogenic factors were variant splicing forms of one gene. Their consensus sequence (ChS) was cloned into plasmid pQE30 to construct recombinant prokaryotic expression system. The recombinant expression vectors were transformed into E.coli M15, and then the expression vectors were induced by IPTG and many insoluble inclusion body proteins was obtained. The obtained proteins were used to immunize rabbits to obtain polyclonal antiserum with high titer and specificity. The eukaryotic expression of the recombinants of human fibrogenic factors was detected by Western blot. The insoluble inclusion body proteins were also used to prepare polyclonal antibodies with high titer and specificity. The expression of the recombinant proteins of human fibrogenic factors and the preparation of polyclonal antiserum provide a useful tool for further study of the expression and function of human fibrogenic factors.


Identification of methylation markers for diagnosis of autism spectrum disorder.
Autism spectrum disorder (ASD) is a hereditary heterogeneous neurodevelopmental disorder characterized by social and speech dysplasia. We collected the expression profiles of ASD in GSE26415, GSE42133 and GSE123302 from the gene expression omnibus (GEO) database, as well as methylation data of GSE109905. Differentially expressed genes (DEGs) between ASD and controls were obtained by differential expression analysis. Enrichment analysis identified the biological functions and signaling pathways involved by common genes in three groups of DEGs. Protein-protein interaction (PPI) networks were used to identify genes with the highest connectivity as key genes. In addition, we identified methylation markers by associating differentially methylated positions. Key methylation markers were identified using the least absolute shrink and selection operator (LASSO) model. Receiver operating characteristic curves and nomograms were used to identify the diagnostic role of key methylation markers for ASD. A total of 57 common genes were identified in the three groups of DEGs. These genes were mainly enriched in Sphingolipid metabolism and PPAR signaling pathway. In the PPI network, we identified seven key genes with higher connectivity, and used qRT-PCR experiments to verify the expressions. In addition, we identified 31 methylation markers and screened 3 key methylation markers (RUNX2, IMMP2L and MDM2) by LASSO model. Their methylation levels were closely related to the diagnostic effects of ASD. Our analysis identified RUNX2, IMMP2L and MDM2 as possible diagnostic markers for ASD. Identifying different biomarkers and risk genes will contribute to the diagnosis of ASD and the development of new clinical and drug treatments.


Caring for a child with asthma: pre-registration education.
Management abilities enhance the care delivered to patients in the NHS. Students need to acquire these competencies to meet the Nursing and Midwifery Council requirements at registration. This article explores the management skills used by a third-year child branch nursing student in the assessment and care of a child with acute asthma in a paediatric emergency department.


Developmental expression of endothelin receptors in postnatal swine mesenteric artery.
Studies were conducted to determine whether endothelin (ET) ETA and ETB receptor protein and mRNA expression is developmentally regulated in the postnatal swine mesenteric circulation. To this end, Western blotting and real-time reverse PCR were performed on protein and total RNA isolated from the mesenteric artery harvested from 3-, 10-, and 30-d-old swine. Western blot analysis revealed that ETA and ETB receptor protein expression in the swine mesenteric artery decreased over the age range studied; thus, ETA and ETB receptor protein expression was significantly greater in the 3-d-old group then progressively declined over the first postnatal month. Similar to the Western data, real-time PCR analysis revealed that ETA and ETB receptor mRNA expression also decreased over the age range studied; thus, ETA and ETB receptor mRNA expression was significantly greater in the 3-d-old group then progressively declined over the first postnatal month. Immunohistochemistry localized the ETA receptor to the vascular smooth muscle and the ETB receptor to the endothelial cell layer. Additionally, we report a partial cDNA sequence for the swine ETB receptor. We conclude that ETA and ETB receptor protein and mRNA expression is developmentally regulated in the postnatal swine mesenteric artery, being expressed to a greater degree in younger animals.


Handheld UV fluorescence spectrophotometer device for the classification and analysis of petroleum oil samples.
Oil spills can be environmentally devastating and result in unintended economic and social consequences. An important element of the concerted effort to respond to spills includes the ability to rapidly classify and characterize oil spill samples, preferably on-site. An easy-to-use, handheld sensor is developed and demonstrated in this work, capable of classifying oil spills rapidly on-site. Our device uses the computational power and affordability of a Raspberry Pi microcontroller and a Pi camera, coupled with three ultraviolet light emitting diodes (UV-LEDs), a diffraction grating, and collimation slit, in order to collect a large data set of UV fluorescence fingerprints from various oil samples. Based on a 160-sample (in 5x replicates each with slightly varied dilutions) database this platform is able to classify oil samples into four broad categories: crude oil, heavy fuel oil, light fuel oil, and lubricating oil. The device uses principal component analysis (PCA) to reduce spectral dimensionality (1203 features) and support vector machine (SVM) for classification with 95% accuracy. The device is also able to predict some physiochemical properties, specifically saturate, aromatic, resin, and asphaltene percentages (SARA) based off linear relationships between different principal components (PCs) and the percentages of these residues. Sample preparation for our device is also straightforward and appropriate for field deployment, requiring little more than a Pasteur pipette and not being affected by dilution factors. These properties make our device a valuable field-deployable tool for oil sample analysis.


School-based mental health: a de facto mental health system for children.
As the nation's schools seek to fulfill the academic imperatives of the federal No Child Left Behind Act and associated state imperatives, they may be forgetting an important missing element in boosting academic achievement: directly confronting the mental health and psychosocial needs that impede a significant percentage of children and adolescents. This article explores the available research on mental health services in schools and the theoretical basis for multiple approaches to the problem. Creating a comprehensive solution to address mental and behavioral barriers to learning could significantly improve academic performance in U.S. primary and secondary schools.


Effects of Body Positioning When Assessing Lymphedema of the Lower Limb Using Bioimpedance Spectroscopy.
Background: Bioimpedance spectroscopy (BIS) measurements are conventionally performed in supine position with a lead device attached to gel-backed electrodes, and more recently, with a stand-on device that uses fixed stainless-steel electrodes under the hands and feet. The aim of this study was to assess and compare BIS measurements made in supine, sitting, and standing positions using lead and stand-on impedance devices in participants with and without unilateral leg lymphedema. Materials and Methods: Participants with self-ascribed unilateral leg lymphedema (n = 24) and healthy controls (n = 71) were recruited using a cross-sectional study design. Triplicate BIS measurements were taken for each device in each position. Results: Impedance measurements with either device were reliable with coefficient of variation of 0.6% or lower. The magnitude of mean differences in absolute impedance values between devices were between 1% and 6% dependent on condition. L-Dex scores between the two devices were highly correlated (r = 0.82) and ∼70% of participants in the lymphedema group were classified as having lymphedema using the recommended cut-off with either device. There was no significant interleg difference of controls using the lead device; however, small, but significant differences (p = 0.0001) were found when using the stand-on device. Conclusion: The findings demonstrate that reliable impedance measurements of the legs can be made with either device in lying, sitting, or standing positions. However, data between the devices were not directly interchangeable. Although the risk of misidentification was small, reference ranges appropriate to the device and measurement position should be used when converting data to L-Dex scores.


Influence of substrate morphology on the growth of gold nanoparticles.
We have simulated the vacuum deposition and subsequent growth of gold nanoparticles on various substrates in order to explore the effects that substrate morphology has on the resultant morphology of gold nanoparticles. The substrates and conditions explored included, the three low index faces, namely, (111), (100), and (110) for both fcc and bcc crystalline substrate structures, including various substrate lattice constants and temperatures. Firstly, we cataloged the major nanoparticle morphologies produced overall. While some substrates were found to produce a mixture of the main nanoparticle morphologies we were successful in identifying certain substrates and temperature conditions for which only I(h), D(h), or certain fcc crystalline nanoparticles can be grown almost exclusively. The substrate characteristics, temperature conditions, and governing growth dynamics are analyzed. We shed light on the balance between substrate influences and vacuum growth tendencies. From observations we can speculate that a substrate alters both the free energy stability of gold nanoparticles and/or the free energy barriers to transformation between certain morphologies. As such we find that substrates are an effective tool in templating the selective growth of desired nanoparticles or surface nanostructures.


Acetylated diamines inhibit endotoxin-induced lymphocyte activation.
Fully acetylated diamines hexamethylenebisacetamide (HMBA) and diacetylputrescine (tetramethylenebisacetamide, TMBA) cause inhibition of murine B lymphocyte activation in the absence of ruminant serum. Mitogenesis induced by LPS, LAP, and 8-BrcGMP was profoundly inhibited in the presence of 3 mM HMBA and TMBA. PHA-stimulated thymidine uptake was not affected. Higher levels of the acetylated polyamines were toxic to lymphocytes. Immunoglobulin secretion by LPS-stimulated spleen cells was inhibited in similar fashion. This inhibition requires the early addition of the polyamines and does not appear to be associated with direct inhibition of DNA synthesis. These data support the hypothesis that polyamines represent immunomodulatory agents and suggest that acetylated derivatives of polyamines may also have activity in regulating B lymphocyte activation.


Arundic Acid Prevents Developmental Upregulation of S100B Expression and Inhibits Enteric Glial Development.
S100B is expressed in various types of glial cells and is involved in regulating many aspects of their function. However, little is known about its role during nervous system development. In this study, we investigated the effect of inhibiting the onset of S100B synthesis in the development of the enteric nervous system, a network of neurons and glia located in the wall of the gut that is vital for control of gastrointestinal function. Intact gut explants were taken from embryonic day (E)13.5 mice, the day before the first immunohistochemical detection of S100B, and cultured in the presence of arundic acid, an inhibitor of S100B synthesis, for 48 h. The effects on Sox10-immunoreactive enteric neural crest progenitors and Hu-immunoreactive enteric neurons were then analyzed. Culture in arundic acid reduced the proportion of Sox10+ cells and decreased cell proliferation. There was no change in the density of Hu+ enteric neurons, however, a small population of cells exhibited atypical co-expression of both Sox10 and Hu, which was not observed in control cultures. Addition of exogenous S100B to the cultures did not change Sox10+ cell numbers. Overall, our data suggest that cell-intrinsic intracellular S100B is important for maintaining Sox10 and proliferation of the developing enteric glial lineage.


Endogenous testosterone and mortality risk.
In men, obesity and metabolic complications are associated with lower serum testosterone (T) and dihydrotestosterone (DHT) and an increased risk of, and mortality from, multiple chronic diseases in addition to cardiovascular disease (CVD). The causal interrelationships between these factors remain a matter of debate. In men with untreated congenital and lifelong forms of hypogonadotropic hypogonadism, there appears to be no increased risk. Men with Klinefelter's syndrome have an increased risk of various types of cancers, as well as CVD, which persist despite T therapy. In the absence of pathology of the hypothalamic-pituitary-gonadal axis, the effect of modest reductions in serum T in aging men is unclear. The prevalence of low serum T concentrations is high in men with cancer, renal disease, and respiratory disease and is likely to be an indicator of severity of systemic disease, not hypogonadism. Some population-based studies have found low serum T to be associated with a higher risk of deaths attributed to cancer, renal disease, and respiratory disease, while others have not. Although a meta-analysis of longitudinal studies has shown an association between low serum T and all-cause mortality, marked heterogeneity between studies limited a firm conclusion. Therefore, while a decrease in T particularly occurring later in life may be associated with an increase in all-cause and specific types of mortality in men, the differential effects, if any, of T and other sex steroids as compared to health and lifestyle factors are unknown at the current time.


Granulomatous prostatitis: mimicking locally advanced prostate adenocarcinoma.
We report the case of a 63-year-old male who came to the urology clinic with an increasing value of the prostate specific antigen and an asymmetrical enlargement at the digital rectal examination. The man was subjected to an MRI of the prostate following which a convincing radiological diagnosis of prostate cancer was made. The patient was assigned a provisional stage of disease T3a N0. In order to confirm this diagnosis, a prostate biopsy was performed but the histological analysis reported non-specific granulomatous prostatitis (GP). It is an uncommon condition that both clinically and radiologically on TRUS and MRI usually mimics prostate cancer (PCa), representing a diagnostic challenge due to its non-specific symptoms and aspecific radiological findings. In this case report we discuss the magnetic resonance imaging features of this rare clinical condition in order to help radiologists in the timely diagnosis for a correct diagnostic framing.


The potent Cdc7-Dbf4 (DDK) kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds.
Cdc7-Dbf4 kinase or DDK (Dbf4-dependent kinase) is required to initiate DNA replication by phosphorylating and activating the replicative Mcm2-7 DNA helicase. DDK is overexpressed in many tumor cells and is an emerging chemotherapeutic target since DDK inhibition causes apoptosis of diverse cancer cell types but not of normal cells. PHA-767491 and XL413 are among a number of potent DDK inhibitors with low nanomolar IC50 values against the purified kinase. Although XL413 is highly selective for DDK, its activity has not been extensively characterized on cell lines. We measured anti-proliferative and apoptotic effects of XL413 on a panel of tumor cell lines compared to PHA-767491, whose activity is well characterized. Both compounds were effective biochemical DDK inhibitors but surprisingly, their activities in cell lines were highly divergent. Unlike PHA-767491, XL413 had significant anti-proliferative activity against only one of the ten cell lines tested. Since XL413 did not effectively inhibit DDK in multiple cell lines, this compound likely has limited bioavailability. To identify potential leads for additional DDK inhibitors, we also tested the cross-reactivity of ∼400 known kinase inhibitors against DDK using a DDK thermal stability shift assay (TSA). We identified 11 compounds that significantly stabilized DDK. Several inhibited DDK with comparable potency to PHA-767491, including Chk1 and PKR kinase inhibitors, but had divergent chemical scaffolds from known DDK inhibitors. Taken together, these data show that several well-known kinase inhibitors cross-react with DDK and also highlight the opportunity to design additional specific, biologically active DDK inhibitors for use as chemotherapeutic agents.


[Malabsorption and developmental retardation due to secondary trypsin deficiency].
A 1.5-year-old girl was admitted with chronic diarrhea of 10 months duration and retarded physical and psychomotor development. Duodenal tryptic activity was absent on testing with secretin and cholecystokinin. With pancreatic enzyme replacement diarrhea ceased and growth recommenced. Duodenal tryptic activity returned to normal within 6 months. A 10-year follow-up revealed normal physical and mental growth. Secondary deficiency of trypsin is a rare cause of malabsorption in childhood; correct and timely treatment can avoid severe, irreversible developmental defects.


Block copolypeptide nanoparticles for the delivery of ocular therapeutics.
Self-assembling block copolypeptides were prepared by sequential ring-opening polymerization of N-carboxyanhydride (NCA) derivatives of γ-benzyl-L-glutamic acid and ε-carbobenzyloxy-L-lysine, followed by selective deprotection of the benzyl glutamate block. The synthesized polymers had number average molecular weights close to theoretical values, and had low dispersities (ĐM = 1.15-1.28). Self-assembly of the amphiphilic block copolymers into nanoparticles was achieved using the "solvent-switch" method, whereby the polymer was dissolved in THF and water and the organic solvent removed by rotary evaporation. The type of nanostructures formed varied from spherical micelles to a mixture of spherical and worm-like micelles, depending on copolymer composition. The spherical micelles had an average diameter of 43 nm by dynamic light scattering, while the apparent diameter of the mixed phase system was around 200 nm. Reproducibility of nanoparticle preparation was demonstrated to be excellent; almost identical DLS traces were obtained over three repeats. Following qualitative dye-solubilization experiments, the nanoparticles were loaded with the ocular anti-inflammatory drug dexamethasone. Loading efficiency of the nanoparticles was 90% and the cumulative drug release was 94% over 16 d, with a 20% burst release in the first 24 h.


Human coronary artery remodeling, beginning and end of the atherosclerotic process.
BACKGROUND, AIMS OF THE STUDY: The objective of the study was to relate the progress of coronary artery remodeling to the earliest stages of the atherosclerotic process. For this purpose, a mathematical model for description of dimensional change of the coronary artery wall and its constituent components was developed and applied. The study used coronary artery samples randomly taken from each of 83 consecutive, unselected postmortems. All samples were routinely fixed and processed to paraffin for the preparation of right-angled, 5-micron sections, routinely stained and mounted for subsequent analysis. Computer assisted image analysis, using 32 systematic random, radial sampling lines, was used for interactive measurements of distance from centre of lumen to points defining intima, media and adventitia thickness along the radial intercept, which were subsequently tabled for analysis of variance, calculations of (group-vessel) means, and related to stage of pathology. Pre-atherosclerotic changes, before any localised changes in especially intima dimensions, are found, consisting of a process of gradual vascular widening, associated with temporally at least partly dissociated increases in width, which as a fraction of total vessel radius show a phased process. In these, the intima first increases, subsequently remains stable, and finally reduces in width proportionally to the increasing diameter. The media shows a similar initial increase, on average stabilising in the third phase after reaching a plateau value in the second. The adventitia, already increasing in phase 1, continues to increase in phase 2, accelerating in phase 3. The complex process, as found, occurs systematically in all vessels, is distributed circumferentially, and precedes the development of localised lesions of the intima. The findings suggest the existence of a diffuse complex of changes, consisting of a gradual vascular widening followed by narrowing, with associated mural changes reflecting the atherosclerotic process.


Follow-up of tibialis posterior transfer surgery (TPT) for drop-foot in leprosy.
Prevention of Disability (POD) service needs to be expanded for future reducing the leprosy burden. Tibialis Posterior Transfer Surgery (TPT) is an established procedure and relatively easy to do at district level general hospitals. It can protect further damages of affected foot and consequently reduce patient's social burden as well. Totally 70 TPT surgeries were done during a joint project of JICA on leprosy control and basic health service in Myanmar for training purpose (Jan/2002-Jan/2006). A follow-up assessment was done for exploring the effectiveness of foot drop surgery, in Nov/2006 at 9-selected townships in Mid-Myanmar. 33 cases (Male 22, Female 11) were reviewed and the mean of follow up period was 29.1 months (SD=7.1, 10-48 months). Total results were; good: 25 cases (76%), fair: 4 cases (12%) and poor: 4 cases (12%). In good and fair cases, patients were satisfied with the results and TPT improved the QOL of patients. In almost all cases (32/33, 97%) after TPT, patients are free from plantar ulcer. Most serious complication of operation (4 cases, 12%) identified was inversion deformity due to loosed tension of lateral tail of grafted TP tendon sutured to Extensor Digitorum Longus. From the results of TPT surgery follow-up, it can benefit much to the patients if resources permit to make it as a routine service in more places.


A path model of smoking cessation in women smokers of low socio-economic status.
The goals of this study were to (i) determine how factors commonly implicated in smoking cessation processes influenced smoking cessation in low socio-economic status (SES) women and (ii) elucidate the pathways through which these factors may lead to quitting smoking. Secondary analysis was conducted on data from 644 women smokers aged 18-45 years who had participated in an earlier experimental evaluation of a smoking cessation program, were still smokers at the 2-month post-intervention survey and completed an interview 6 months later. Path analysis (LISREL 8) was used to test a conceptual model in which (i) factors considered as precursors to quitting (motivation, self-efficacy, confidence, action and intention to quit) directly predicted subsequent quitting and (ii) health concerns, social pressure to quit and daily stress influenced quitting indirectly through their effects on the precursor factors and (iii) mediated the effects of background characteristics (race, education, single motherhood, pregnancy and exposure to the earlier smoking cessation intervention) on quitting. Overall, results supported this conceptual model and its applicability to low-SES women smokers and indicated significant pathways among specific factors. In particular, (i) only plans to quit, confidence and social pressure to quit directly predicted quitting; (ii) both health concerns and social pressure increased motivation to quit and (iii) the negative effect of daily stress on quitting was mediated through decreased self-efficacy.