Boosting Proton Conductivity in Highly Robust 3D Inorganic Cationic Extended Frameworks through Ion Exchange with Dihydrogen Phosphate Anions.
The limited long-term hydrolytic stability of rapidly emerging 3D-extended framework materials (MOFs, COFs, MOPs, etc.) is still one of major barriers for their practical applications as new solid-state electrolytes in fuel cells. To obtain hydrolytically stable materials, two H2 PO4 (-) -exchanged 3D inorganic cationic extended frameworks (CEFs) were successfully prepared by a facile anion-exchange method. Both anion-exchanged CEFs (YbO(OH)P and NDTBP) show significantly enhanced proton conductivity when compared with the original materials (YbO(OH)Cl and NDTB) with an increase of up to four orders-of-magnitude, reaching 2.36×10(-3) and 1.96×10(-2) S cm(-1) at 98 % RH and 85 °C for YbO(OH)P and NDTBP, respectively. These values are comparable to the most efficient proton-conducting MOFs. In addition, these two anion-exchanged materials are stable in boiling water, which originates from the strong electrostatic interaction between the H2 PO4 (-) anion and the cationic host framework, showing a clear advance over all the acid-impregnated materials (H2 SO4 @MIL-101, H3 PO4 @MIL-101, and H3 PO4 @Tp-Azo) as practical solid-state fuel-cell electrolytes. This work offers a new general and efficient approach to functionalize 3D-extended frameworks through an anion-exchange process and achieves water-stability with ultra-high proton conductivity above 10(-2) S cm(-1) .


Phenotypical manifestations of partial trisomy 9 and monosomy 4 in two siblings.
In this case report, we describe two siblings with a previously unreported partial monosomy 4q and partial trisomy 9q. The sibling karyotypes were determined to be 46,XX,der(4)t(4;9)(q33;q33)pat and 46,XY,der(4)t(4;9)-(q33;q33)pat. The siblings share several common pathological features, including VSD, PDA, low-set ears and digit anomalies as well as features consistent with Pierre-Robin syndrome and hydrocephalus. We review previously reported phenotypes associated with monosomy 4q and partial trisomy 9q and discuss potential mechanisms for these morphological insults with particular emphasis on neuropathology.


Preferences and Acceptability of Vaginal Delivery Forms for HIV Prevention Among Women, Male Partners and Key Informants in South Africa and Zimbabwe: Qualitative Findings.
The attributes of an HIV microbicide may affect its acceptability, uptake and use. Quatro, a clinical study with a qualitative component, was conducted to elicit input from end-users and key informants (KIs) on four different placebo vaginal microbicide delivery forms; fast dissolving insert, ring, film and gel. In-depth interviews and focus group discussions were conducted with young women, their male partners and KIs, to explore acceptability and preferences of the four placebo products, with the intention of improving product attributes, adherence, and consequently, long term effectiveness. None of the four microbicide delivery forms stood well above others as the most preferred. Product attributes; long-action, ease of use, invisibility, female initiated and non-interference during sex were favourable in both countries. Despite preference for the long-action, on-demand products were the most liked by women. Qualitative data from the Quatro study provided rich feedback on specific attributes important to the acceptability of four HIV prevention product platforms currently in development, enabling more informed and guided product development efforts moving forward.


Rate of Symptomatic Lymphocele Formation After Extraperitoneal vs Transperitoneal Robot-Assisted Radical Prostatectomy and Bilateral Pelvic Lymphadenectomy.
With the peritoneum acting as a natural surface for lymphatic reabsorption, transperitoneal robot-assisted radical prostatectomy (tRARP) is thought to be associated with a lower incidence of symptomatic lymphoceles (SLs) compared with its extraperitoneal counterpart (eRARP) when bilateral pelvic lymph node dissection (BPLND) is performed. In this study, we aim to determine if there is a difference in SL formation and characteristics between the two approaches. We retrospectively reviewed the records of patients who underwent eRARP or tRARP and BPLND by a single surgeon at a tertiary care academic center from July 1, 2003, to May 31, 2016. Patients with a history of prior pelvic radiotherapy, concomitant inguinal hernia repair, RARP without BPLND, or nonadenocarcinoma of the prostate were excluded. The resulting eRARP and tRARP groups were propensity matched for age, body mass index (BMI), American Association of Anesthesiologists (ASA) score, D'Amico risk classification, and pathological lymph node (LN) count. A total of 3183 RARPs were performed during this time period. After applying exclusion criteria and propensity score matching, 671 patients remained in each group. No statistically significant differences were noted between the groups with regard to age, BMI, ASA, pre-RARP prostate-specific antigen, D'Amico risk classification, biopsy and pathological Gleason sum score, pathological T stage, or margin status. The tRARP group had a higher clinical T stage (p = 0.0015), length of stay (LOS; p = 0.005), pathological N stage (4.92% vs 1.36%, p = 0.0002), and high total LN count (7.22 ± 5.54 vs 5.78 ± 4.18 LNs, p < 0.0001). The eRARP group had higher operating room times (197.4 ± 48.96 minutes vs 192.2 ± 44.12 minutes, p = 0.04) and estimated blood loss (218.4 ± 152.0 mL vs 179.9 ± 119.4 mL, p < 0.0001). No differences were noted in the frequency of SL formation [eRARP: 19/671 (2.83%) vs tRARP: 10/671 (1.49%), p = 0.09] or any clinical characteristics of the SL. Logistic regression analysis showed no effect of LN count (p = 0.071), pathological N stage (p = 0.111), or both combined (p = 0.085) on SL formation. In this cohort, the rate and clinical characteristics of SL were similar among patients treated with eRARP or tRARP and BPLND. The low event rate of SL in each group and trends favoring higher SL with LN yield and pN1 disease in the tRAPR group may deem the study underpowered to make definitive conclusions.


Modulation of voltage-gated ion channels on SH-SY5Y neuroblastoma by non-ionic surfactant, Cremophor EL.
Cremophor EL (CrEL) is a non-ionic surfactant widely used as a vehicle for insoluble drugs, including immunosuppressive and anticancer agents. Although CrEL has often been reported to induce sensory neuropathies, its action on voltage-gated ion channels remains unknown. We show here that CrEL modulates voltage-gated sodium current (INa) and potassium current (IK) of human neuroblastoma cells (SH-SY5Y). First, CrEL suppressed the amplitude of INa and that of IK. The suppression-concentration curve for INa was gradual but that for IK was steeper, indicating that INa remains incompletely blocked by high concentrations of CrEL, which greatly reduce IK. Thus, it is possible that CrEL paradoxically increases neuronal excitability at higher concentrations. Next, CrEL accelerated IK's inactivation process. The voltage-dependent inactivation of IK showed two time constants, τ(f) of 322±49 ms and τ(s) of 2925±184 ms, under the control condition. By applying 1000 ppm CrEL, three time constants-τ(u) of 23±2 ms, τ(f) of 196±19 ms, and τ(s) of 1396±127 ms-appeared in the inactivation process. This modified inactivation of IK probably disturbs the repolarizing phases of action potentials. These modulations of voltage-gated ion channels by CrEL may cause abnormal excitability involved in neuropathies.


Ageratum enation virus Infection Induces Programmed Cell Death and Alters Metabolite Biosynthesis in Papaver somniferum.
A previously unknown disease which causes severe vein thickening and inward leaf curl was observed in a number of opium poppy (Papaver somniferum L.) plants. The sequence analysis of full-length viral genome and associated betasatellite reveals the occurrence of Ageratum enation virus (AEV) and Ageratum leaf curl betasatellite (ALCB), respectively. Co-infiltration of cloned agroinfectious DNAs of AEV and ALCB induces the leaf curl and vein thickening symptoms as were observed naturally. Infectivity assay confirmed this complex as the cause of disease and also satisfied the Koch's postulates. Comprehensive microscopic analysis of infiltrated plants reveals severe structural anomalies in leaf and stem tissues represented by unorganized cell architecture and vascular bundles. Moreover, the characteristic blebs and membranous vesicles formed due to the virus-induced disintegration of the plasma membrane and intracellular organelles were also present. An accelerated nuclear DNA fragmentation was observed by Comet assay and confirmed by TUNEL and Hoechst dye staining assays suggesting virus-induced programmed cell death. Virus-infection altered the biosynthesis of several important metabolites. The biosynthesis potential of morphine, thebaine, codeine, and papaverine alkaloids reduced significantly in infected plants except for noscapine whose biosynthesis was comparatively enhanced. The expression analysis of corresponding alkaloid pathway genes by real time-PCR corroborated well with the results of HPLC analysis for alkaloid perturbations. The changes in the metabolite and alkaloid contents affect the commercial value of the poppy plants.


Increased nasal Streptococcus pneumoniae presence in Western environment associated with allergic conditions in Chinese immigrants.
Chinese immigrants living in Australia experience increased allergic conditions: asthma, eczema, hay fever and wheeze. Recently we reported diminished innate cytokine responses in long-term immigrants, potentially increasing their pathogenic viral load and microbial carriage. We hypothesise that a Western environment changes the nasal microbiome profile, and this altered profile may be associated with the development of allergic conditions. In this cross-sectional study, we aimed to examine the loading of viral and microbial respiratory pathogens in the upper airway. Adult Chinese immigrants were grouped depending on time spent in Australia: short-term (<6 years) or long-term (≥6 years). First, age- and gender-matched immigrants were selected for an initial screen using quantitative polymerase chain reaction (qPCR) micro-array panels. Then based on initial results the viruses, human parainfluenza 3 and rhinovirus, and the bacteria, Burkholderia spp., Staphylococcus aureus and Streptococcus pneumoniae, were validated using qPCR in the population. Associations for bacterial prevalence with atopic phenotypes were investigated. Pooling the initial screen and validation subjects, S. aureus and S. pneumoniae had higher prevalence in long-term compared with short-term subjects (25.0% vs 8.1%, P = 0.012; and 76.8% vs 48.4%, P = 0.002). Those immigrants with nasal S. pneumoniae presence resided longer (average time 90.4 months) in Australia than immigrants without S. pneumoniae (52.7 months; P = 0.001). After adjusting for confounders, Chinese immigrants with S. pneumoniae carriage have a five-fold increased risk of doctor-diagnosed eczema (odds ratio, OR 5.36, 95% CI: 1.10-26.14; P = 0.038) compared to immigrants without S. pneumoniae carriage. There was a trend of S. pneumoniae abundance correlating with reduced host Toll-like receptor gene expression. Our findings suggest that nasal S. pneumoniae may play a role in the development of allergic conditions in Chinese immigrants in a Western environment.


Disentangling Auger decays in O2 by photoelectron-ion coincidences.
In non-resonant Auger electron spectroscopies, multi core-ionized states lead to numerous energetically close-lying electronic transitions in Auger spectra, this hampering the assignment and interpretation of the experimental results. Here we reveal a new method to overcome this intrinsic limitation of non-resonant inner-shell spectroscopies. In a proof-of-principle experiment performed for the O2 molecule, most of the Auger final states are dissociative, and we measure in coincidence the kinetic energy of the photoelectron and the kinetic energy release of the (O+, O+) ion pairs produced after the Auger decay of the O 1s-1 core-ionized states. The Auger final states are assigned using energy conservation. We fully separate the contributions from the 4Σ- and 2Σ- intermediate ionic states and conclusively demonstrate that the Auger decay probability can dramatically depend on the different O2 1s -1 intermediate multiplet states. In addition, a metastable Auger final state also exists, with lifetime longer than 3.8 μs, and clear changes are observed in both branching ratio and spectral profile of the O 1s photoelectron spectrum when they are recorded in coincidence with either [Formula: see text] or with other ionic species. These changes are attributed to the population of the metastable [Formula: see text] Auger final state via different intermediate states.


Differential Activation of Programmed Cell Death in Patients with Severe SARS-CoV-2 Infection.
SARS-CoV-2 (SARS-2) causes severe lower airway disease and death in a subset of patients. Knowledge on the relative contribution of programmed cell death (PCD) to lung pathology is limited to few human autopsy studies with small sample size/scope, in vitro cell culture, and experimental model systems. In this study, we sought to identify, localize, and quantify activation of apoptosis, ferroptosis, pyroptosis, and necroptosis in FFPE lung tissues from patients that died from severe SARS-2 infection (n=28) relative to uninfected controls (n=13). Immunofluorescence (IF) staining, whole-slide imaging, and Image J software was used to localize and quantify expression of SARS-2 nucleoprotein and the following PCD protein markers: cleaved Caspase-3, pMLKL, cleaved Gasdermin D, and CD71, respectively. IF showed differential activation of each PCD pathway in SARS-2 infected lungs and dichotomous staining for SARS-2 nucleoprotein enabling distinction between high (n=9) vs low viral burden (n= 19). No differences were observed in apoptosis and ferroptosis in SARS-2 infected lungs relative to uninfected controls. However, both pyroptosis and necroptosis were significantly increased in SARS-2 infected lungs. Increased pyroptosis was observed in SARS-2 infected lungs, irrespective of viral burden, suggesting an inflammation-driven mechanism. In contrast, necroptosis exhibited a very strong positive correlation with viral burden (R2=0.9925), suggesting a direct SARS-2 mediated effect. These data indicate a possible novel mechanism for viral-mediated necroptosis and a potential role for both lytic programmed cell death pathways, necroptosis and pyroptosis, in mediating infection outcome.


Resting vagal control and resilience as predictors of cardiovascular allostasis in peacekeepers.
The body's adaptive reaction to a stressful event, an allostatic response, involves vigorous physiological engagement with and efficient recovery from stress. Our aim was to investigate the influence of individual predispositions on cardiac responses to and recovery from a standardized psychosocial stress task (Trier Social Stress Task) in peacekeepers. We hypothesized that those individuals with higher trait resilience and those with higher resting vagal control would be more likely to present an allostatic response: a vigorous cardiac response to stress (i.e., reduction in interbeat intervals and heart rate variability (HRV)) coupled with a significant cardiac recovery in the aftermath. Fifty male military personnel with a mean age of 25.4 years (SD ± 5.99) were evaluated after returning from a peacekeeping mission. Electrocardiogram recordings were made throughout the experimental session, which consisted five conditions: basal, speech preparation, speech delivery, arithmetic task, and recovery. Mean interbeat intervals and HRV were calculated for each condition. An Ego-Resilience Scale and resting vagal control assessed individual predispositions. Stress tasks reduced interbeat intervals (tachycardia) and HRV in comparison with basal, with return to basal in the aftermath (p < 0.001, for all comparisons). Resilience and resting vagal control correlated positively with cardiac parameters for both stress reactivity and recovery (r ≥ 0.29; p < 0.05). In conclusion, peacekeepers showing higher trait resilience and those with higher resting vagal control presented a more adaptive allostatic reaction characterized by vigorous cardiac response to stress (i.e., tachycardia and vagal withdrawal) and efficient cardiac recovery after stress cessation.


[A case of polyradiculoneuritis associated with dengue in a patient native to French Guiana].
An acute polyradiculoneuritis in a woman native of French Guiana has been observed with serologic conversion against flaviviruses by inhibition of hemagglutination test. Dengue's diagnostic was been kept in spite of lack of causal virus isolation and non-typical clinical symptoms. Association dengue-polyradiculoneuritis appears quite uncommon and is worthy of note, in view of frequency of infection by Flaviviruses.


Nanoscale Technologies in Highly Sensitive Diagnosis of Cardiovascular Diseases.
Cardiovascular diseases (CVD) are the leading cause of death and morbidity in the world and are a major contributor to healthcare costs. Although enormous progress has been made in diagnosing CVD, there is an urgent need for more efficient early detection and the development of novel diagnostic tools. Currently, CVD diagnosis relies primarily on clinical symptoms based on molecular imaging (MOI) or biomarkers associated with CVDs. However, sensitivity, specificity, and accuracy of the assay are still challenging for early-stage CVDs. Nanomaterial platform has been identified as a promising candidate for improving the practical usage of diagnostic tools because of their unique physicochemical properties. In this review article, we introduced cardiac biomarkers and imaging techniques that are currently used for CVD diagnosis. We presented the applications of various nanotechnologies on diagnosis within cardiac immunoassays (CIAs) and molecular imaging. We also summarized and compared different cardiac immunoassays based on their sensitivities and working ranges of biomarkers.


Marginal adaptation of dentin bonded ceramic inlays: effects of bonding systems and luting resin composites.
This in vitro study evaluated the marginal adaptation of bonded inlays of lucite-reinforced glass ceramic (Empress) to dentin as influenced by different bonding systems and by luting resin composites (LRCs) with different curing modes. Forty-eight Empress inlays etched with 5% hydrofluoric acid and treated with a silane-coupling agent (Monobond-S) were bonded to two-surface Class II cavities. Two total-etch bonding systems (OptiBond FL, Nexus) and one bonding system with selective enamel etching and a self-conditioning dentin primer (ART Bond) were included in the study. ART Bond was tested with and without the pre-curing of a first layer of adhesive resin selectively applied to the cervical cavity floor (selective double-bond technique). Each bonding system was used in combination with a light-cured resin composite (Prodigy) and a dual-cured LRC (Nexus or Vita Cerec Duo Cement). Marginal integrity was evaluated before and after thermocycling (TC) in a scanning electron microscope (SEM). Dye penetration tests were performed after TC was completed. The median percentages of continuous margin in dentin ranged from 80% to 100% before TC and from 53.5% to 96.1 % after TC. After TC, the influence of the bonding system was more pronounced than that of the LRC. In combination with the LC resin composite, ART Bond with precuring was significantly higher and the Nexus bonding system had significantly lower proportions of continuous margin than all the other bonding systems investigated. Swelling of the adhesive along the gingival margins was frequently found with the Nexus bonding system and with ART Bond without pre-curing. Microleakage was detected with all bonding system/LRC combinations, with somewhat lower rates in specimens completed using the selective double-bond technique. With the exception of the Nexus bonding system, post-TC marginal integrity was not influenced by the curing mode of the LRC (LC vs DC). In conclusion, the marginal quality of dentin bonded ceramic inlays can be improved by proper selection of the bonding sys- tem/LRC combination. The results of this study indicate the use of the Nexus luting system as directed without substitution.


Salivary cortisol responses to dexamethasone in adolescents with posttraumatic stress disorder.
Previous studies of adults with posttraumatic stress disorder (PTSD) have found various abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis, including enhanced suppression of cortisol following low-dose dexamethasone. The purpose of the present study was to investigate salivary cortisol responses to low-dose dexamethasone in adolescents with PTSD. Forty-eight adolescents (20 with current PTSD, 9 trauma controls without PTSD, and 19 healthy nontraumatized controls) were enrolled in the study. On day 1, baseline saliva samples were obtained at 8 a.m. and 0.5 mg of dexamethasone was administered at 11 p.m. Cortisol and dexamethasone levels were assessed at 8 a.m. the following day. Adolescents with current PTSD showed no difference in the suppression of salivary cortisol in response to low-dose (0.5 mg) dexamethasone compared to trauma controls without PTSD and nontraumatized controls. More severely affected PTSD subjects with co-occurring major depression showed higher pre- and post-dexamethasone salivary cortisol levels compared to controls. The present study did not find evidence for enhanced suppression of salivary cortisol at 8 a.m. following low-dose dexamethasone in multiply traumatized adolescents with PTSD. This result differs from findings in adults with PTSD. Further investigations of hypothalamic-pituitary-adrenal axis abnormalities in traumatized children and adolescents are needed.


The influence of CO2 in a space-like environment: study design.
For the operation of manned spacecraft, the removal of CO2 from the cabin atmosphere, produced by its inhabitants, is essential. This is accomplished by chemical absorption in a gas processing unit, a process which requires energy and consumables. Therefore, in terms of resource management, the CO2-level should be kept as high as possible. Otherwise, considering crew health and performance and also the interference with life science experiments, the CO2 load should be as on Earth, close to zero. In order to obtain more information about the permissible CO2 level for future space missions and also to clarify Space Station design criteria, NASA-ESA-DARA have initiated a ground-based simulation study with two different CO2 levels: 0.7% (first campaign) and 1.2% CO2 (second campaign). For this study the deep diving facility of DLR was used to provide atmospheric control and long-term habitation for the test subjects in studying the effect of increased CO2 on physiological and psychological functions. A number of experiments were implemented, which tested selected effects of raised CO2 on humans. Four male subjects stayed in the chamber for 26 d in each campaign, in order to perform the different tests in repeated trials, with the aim of evaluating possible long-term effects. CO2 was controlled by absorption with soda lime, flushing with fresh air and the addition of CO2, if necessary. Essentially, the CO2 produced by the subjects was used to maintain the level at 0.7 and 1.2%, respectively. Basic control of CO2 was carried out in the soda lime container of the Life Support System. In order to maintain the required level, the amount of gas flowing through the soda lime could be adjusted by a remote controlled bypass. With this set-up it was possible to keep CO2 at an average level between 0.67 and 0.73% in the first campaign and between 1.17 and 1.23% in the second campaign. The results of the experiments support the current CO2 limits for space operations, insofar as values around 1% do not impose any severe restrictions to human habitation for at least several weeks, whereas life sciences experiments especially sensitive to CO2 influences have to be carefully evaluated for possible interferences.


Glutamine ameliorates Bungarus multicinctus venom-induced lung and heart injury through HSP70: NF-κB p65 and P53/PUMA signaling pathways involved.
Bungarus multicinctus is one of the most dangerous venomous snakes prone to cardiopulmonary damage with extremely high mortality. In our previous work, we found that glutamine (Gln) and glutamine synthetase (GS) in pig serum were significantly reduced after Bungarus multicinctus bite. In the present study, to explore whether there is a link between the pathogenesis of cardiopulmonary injury and Gln metabolic changes induced by Bungarus multicinctus venom. We investigated the effect of Gln supplementation on the lung and heart function after snakebite. We supplemented different concentrations of Gln to mice that were envenomated by Bungarus multicinctus to observe the biological behavior, survival rate, hematological and pathological changes. Gln was supplemented immediately or one hour after the venom injection, and then changes in Gln metabolism were analyzed. Subsequently, to further explore the protective mechanism of glutamine on tissue damage, we measured the expression of heat-shock protein70 (HSP70), NF-κB P65, P53/PUMA by western blotting and real-time polymerase in the lung and heart. Gln supplementation delayed the envenoming symptoms, reduced mortality, and alleviated the histopathological changes in the heart and lung of mice bitten by Bungarus multicinctus. Additionally, Gln increased the activity of glutamine synthetase (GS), glutamate dehydrogenase (GDH) and glutaminase (GLS) in serum. It also balanced the transporter SLC7A11 expression in heart and lung tissues. Bungarus multicinctus venom induced the NF-κB nuclear translocation in the lung, while the HO-1 expression was suppressed. At the same time, venom activated the P53/PUMA signaling pathway and the BAX expression in the heart. Gln treatment reversed the above phenomenon and increased HSP70 expression. Gln alleviated the glutamine metabolism disorder and cardiopulmonary damage caused by Bungarus multicinctus venom. It may protect lungs and heart against venom by promoting the expression of HSP70, inhibiting the activation of NF-κB and P53/PUMA, thereby delaying the process of snake venom and reducing mortality. The present results indicate that Gln could be a potential treatment for Bungarus multicinctus bite.


Epitope Fingerprinting for Recognition of the Polyclonal Serum Autoantibodies of Alzheimer's Disease.
Autoantibodies (aAb) associated with Alzheimer's disease (AD) have not been sufficiently characterized and their exact involvement is undefined. The use of information technology and computerized analysis with phage display technology was used, in the present research, to map the epitope of putative self-antigens in AD patients. A 12-mer random peptide library, displayed on M13 phages, was screened using IgG from AD patients with two repetitions. Seventy-one peptides were isolated; however, only 10 were positive using the Elisa assay technique (Elisa Index > 1). The results showed that the epitope regions of the immunoreactive peptides, identified by phage display analysis, were on the exposed surfaces of the proteins. The putative antigens MAST1, Enah, MAO-A, X11/MINT1, HGF, SNX14, ARHGAP 11A, APC, and CENTG3, which have been associated with AD or have functions in neural tissue, may indicate possible therapeutic targets.


Haemodynamic limitations and exercise performance in peripheral arterial disease.
It has been frequently argued that haemodynamic limitations are poor predictors of exercise performance in people with peripheral arterial disease (PAD) and intermittent claudication. This review has tried to address this argument through a review of published data that appears to support or counterbalance it, brief consideration of some of the methodological limitations associated with these data, as well as some other considerations. The main argument rests primarily upon data about the resting ankle-brachial index (ABI) and/or blood flow after calf exercise or an ischaemic challenge; whereas the counter argument rests mainly on data about blood flow during walking or cyding exercise. Consideration of the limitations of all methods suggests that the measurement of blood flow during exercise has the greatest value in explaining differences in exercise performance amongst claudicants; whereas the other methods are relatively limited in their explanatory value. This strengthens the counter argument and undermines the main argument proposed by others. Consequently, asserting that haemodynamic limitations are poor predictors of exercise performance in claudicants is not justified in light of available evidence.


Transesophageal Echocardiography at the Golden Hour: Identification of Blunt Traumatic Aortic Injuries in the Emergency Department.
Although surface sonography has become an essential diagnostic tool in the evaluation of trauma patients, important limitations of this modality include the evaluation of retroperitoneal hemorrhage and mediastinal pathology, such as blunt traumatic aortic injuries (BTAI). As in other emergency applications where surface sonography can't provide the information needed, focused transesophageal echocardiography (TEE) may represent a valuable diagnostic tool in the evaluation of hemodynamically unstable trauma patients with suspected thoracic pathology such as BTAI. We present a series of five cases that illustrate the diagnostic value of emergency physician-performed resuscitative TEE in the diagnosis of BTAI in patients presenting with blunt thoracic trauma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: As the use of point-of-care TEE during resuscitation continues to expand in emergency medicine, the evaluation of patients with BTAI represents a novel application where this emerging modality can allow early diagnosis of these injuries in hemodynamically unstable patients.


Terminal phosphanido rhodium complexes mediating catalytic P-P and P-C bond formation.
Complexes with terminal phosphanido (M-PR2) functionalities are believed to be crucial intermediates in new catalytic processes involving the formation of P-P and P-C bonds. We showcase here the isolation and characterization of mononuclear phosphanide rhodium complexes ([RhTp(H)(PR2)L]) that result from the oxidative addition of secondary phosphanes, a reaction that was also explored computationally. These compounds are active catalysts for the dehydrocoupling of PHPh2 to Ph2P-PPh2. The hydrophosphination of dimethyl maleate and the unactivated olefin ethylene is also reported. Reliable evidence for the prominent role of mononuclear phosphanido rhodium species in these reactions is also provided.


From favours to entitlements: community voice and action and health service quality in Zambia.
Social accountability is increasingly invoked as a way of improving health services. This article presents a theory-driven qualitative study of the context, mechanisms and outcomes of a social accountability program, Citizen Voice and Action (CVA), implemented by World Vision (WV) in Zambia. Primary data were collected between November 2013 and January 2014. It included in-depth interviews and focus group discussions with program stakeholders. Secondary data were used iteratively-to inform the process for primary data collection, to guide primary data analysis and to contextualize findings from the primary data. CVA positively impacted the state, society, state-society relations and development coordination at the local level. Specifically, sustained improvements in some aspects of health system responsiveness, empowered citizens, the improved provision of public goods (health services) and increased consensus on development issues appeared to flow from CVA. The central challenge described by interviewees and FGD participants was the inability of CVA to address problems that required central level input. The mechanisms that generated these outcomes included productive state-society communication, enhanced trust, and state-society co-production of priorities and the provision of services. These mechanisms were activated in the context of existing structures for state-society interaction, willing political leaders, buy-in by traditional leaders, and WV's strong reputation and access to resources. Prospective observational research in multiple contexts would shed more light on the context, mechanisms and outcomes of CVA programs. In addition to findings that are intuitive and well supported in the literature we identified new areas that are promising areas for future research. These include (1) the context of organizational reputation by the organization(s) spearheading social accountability efforts; (2) the potential relationship between social accountability efforts and making ambitious national programs operational at the frontlines of the health system and (3) the feasibility of scale up for certain types of local level responsiveness.


Clinical validation of an open-access SARS-COV-2 antigen detection lateral flow assay, compared to commercially available assays.
Rapid tests for SARS-COV-2 infection are important tools for pandemic control, but current rapid tests are based on proprietary designs and reagents. We report clinical validation results of an open-access lateral flow assay (OA-LFA) design using commercially available materials and reagents, along with RT-qPCR and commercially available comparators (BinaxNOW® and Sofia®). Adult patients with suspected COVID-19 based on clinical signs and symptoms, and with symptoms ≤7 days duration, underwent anterior nares (AN) sampling for the OA-LFA, Sofia®, BinaxNOW ™, and RT-qPCR, along with nasopharyngeal (NP) RT-qPCR. Results indicate a positive predictive agreement with NP sampling as 69% (60% -78%) OA-LFA, 74% (64% - 82%) Sofia®, and 82% (73% - 88%) BinaxNOW™. The implication for these results is that we provide an open-access LFA design that meets the minimum WHO target product profile for a rapid test, that virtually any diagnostic manufacturer could produce.


Amelioration of accelerated collagen induced arthritis by a novel calcineurin inhibitor, ISA(TX)247.
To examine the efficacy and toxicity of ISA(TX)247, a novel calcineurin inhibitor, in comparison to cyclosporine (cyclosporin A, CSA) and placebo in established collagen induced arthritis. ISA(TX)247 has up to 3-fold greater potency than CSA in an in vitro whole blood calcineurin inhibition assay and in in vivo solid organ and cell transplantation models. Phase I clinical trials show no discernible nephrotoxicity. Type II collagen immunized DBA/Lac J mice with established arthritis were randomized to treatment with ISA(TX)247 (125/250/500 microg/mouse), CSA (250/500 microg/mouse), or drug vehicle, by daily intraperitoneal injection for 10 days from the onset of clinical arthritis. A significant dose dependent reduction in clinical severity was observed in ISA(TX)247 treated but not in CSA treated animals 10 days after the onset of established arthritis, and when examined by area under the curve analysis during the treatment period. Significant improvement in paw swelling (p < 0.001), synovial histology (p < 0.001), and articular cartilage damage scores (p = 0.002) was also noted in ISA(TX)247 treated animals, even in the 125 pg dose group (p = 0.03 for paw swelling and synovial histology). By comparison, CSA had no significant effect on either synovial inflammation or articular cartilage damage. ISA(TX)247 (500 microg dose group) was the only treatment to significantly decrease the development of proximal interphalangeal joint erosions (p < 0.05). A significant reduction in Type II collagen antibody titer was noted in ISA(TX)247 animals in both 250 microg (p = 0.02) and 500 microg (p = 0.004) dosage groups, but only in the 500 microg group for CSA (p = 0.004). Treatment was well tolerated, with no significant toxicity in ISA(TX)247 groups. ISA(TX)247 demonstrates efficacy and safety in the treatment of established collagen induced arthritis. Together with its improved potency and nephrotoxicity profile in comparison to CSA, this agent warrants further clinical investigation in autoimmune disease. Phase II studies in rheumatoid arthritis have been initiated.


Average entropy of a subsystem from its average Tsallis entropy.
In the non-extensive Tsallis scenario, Page's conjecture for the average entropy of a subsystem [Phys. Rev. Lett. 71, 1291 (1993)] as well as its demonstration are generalized, i.e., when a pure quantum system, whose Hilbert space dimension is mn, is considered, the average Tsallis entropy of an m-dimensional subsystem is obtained. This demonstration is expected to be useful to study systems where the usual entropy does not give satisfactory results.


Activation of G protein-coupled receptor 39 alleviates neuropathic pain and chronic inflammation.
Neuropathic pain (NP) is mainly caused by lesions or diseases of the somatosensory nervous system and triggers severe physical burdens to patients. It is claimed that activated microglia-mediated neuroinflammation participates in the development of NP, which is regulated by p38 mitogen-activated protein kinase (MAPK)/nuclear factor-κappa B (NF-κB) p65 signaling. G protein-coupled receptor 39 (GPR39) is a trans-membrane protein involved in the activation of cellular transduction pathways, and TC-G 1008, a GPR39 agonist, is believed to have inhibitory effects on neuroinflammation. Our study will explore the possible alleviatory function of TC-G 1008 on NP in a rat model. GPR39 was found markedly downregulated in the spinal dorsal horn of chronic constriction injury (CCI)-stimulated rats. Rats were treated with CCI, followed by intranasal administration with 7.5 and 15 mg/kg TC-G 1008 at 1, 25, 49, and 73 h postmodeling, respectively. Drastically lowered values of paw withdrawal threshold and paw withdrawal latency, upregulated ionized calcium-binding adapter molecule 1, increased release of inflammatory cytokines, elevated spinal malondialdehyde levels, and reduced spinal glutathione peroxidase levels were observed in CCI-stimulated rats, all of which were markedly alleviated and rescued by TC-G 1008. Furthermore, the levels of p-p38/p38 and p-NF-κB p65 were found signally repressed in the spinal dorsal horn of CCI-stimulated rats, which was notably reversed by TC-G 1008. Collectively, TC-G 1008 markedly alleviated NP and neuroinflammation in CCI-treated rats. Our findings provide an attractive future direction for the treatment of NP.


Doing molecular biophysics: finding, naming, and picturing signal within complexity.
A macromolecular structure, as measured data or as a list of coordinates or even on-screen as a full atomic model, is an extremely complex and confusing object. The underlying rules of how it folds, moves, and interacts as a biological entity are even less evident or intuitive to the human mind. To do science on such molecules, or to relate them usefully to higher levels of biology, we need to start with a natural history that names their features in meaningful ways and with multiple representations (visual or algebraic) that show some aspect of their organizing principles. The two of us have jointly enjoyed a highly varied and engrossing career in biophysical research over nearly 50 years. Our frequent changes of emphasis are tied together by two threads: first, by finding the right names, visualizations, and methods to help both ourselves and others to better understand the 3D structures of protein and RNA molecules, and second, by redefining the boundary between signal and noise for complex data, in both directions-sometimes identifying and promoting real signal up out of what seemed just noise, and sometimes demoting apparent signal into noise or systematic error. Here we relate parts of our scientific and personal lives, including ups and downs, influences, anecdotes, and guiding principles such as the title theme.


Evaluation of lung tumor motion management in radiation therapy with dynamic MRI.
Surrogate-based tumor motion estimation and tracing methods are commonly used in radiotherapy despite the lack of continuous real time 3D tumor and surrogate data. In this study, we propose a method to simultaneously track the tumor and external surrogates with dynamic MRI, which allows us to evaluate their reproducible correlation. Four MRI-compatible fiducials are placed on the patient's chest and upper abdomen, and multi-slice 2D cine MRIs are acquired to capture the lung and whole tumor, followed by two-slice 2D cine MRIs to simultaneously track the tumor and fiducials, all in sagittal orientation. A phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body area as a respiratory surrogate and group-wise registration. The 4D-MRI provides 3D template volumes for different breathing phases. 3D tumor position is calculated by 3D-2D template matching in which 3D tumor templates in 4D-MRI reconstruction and the 2D cine MRIs from the two-slice tracking dataset are registered. 3D trajectories of the external surrogates are derived via matching a 3D geometrical model to the fiducial segmentations on the 2D cine MRIs. We tested our method on five lung cancer patients. Internal target volume from 4D-CT showed average sensitivity of 86.5% compared to the actual tumor motion for 5 min. 3D tumor motion correlated with the external surrogate signal, but showed a noticeable phase mismatch. The 3D tumor trajectory showed significant cycle-to-cycle variation, while the external surrogate was not sensitive enough to capture such variations. Additionally, there was significant phase mismatch between surrogate signals obtained from fiducials at different locations.


Legal Theories, Disability Models and Principles of Disability Assessment.
In the personal injury compensation system, the protection and relief of the injured people's rights to life, rights to health, and body rights are generally based on the results of disability assessment. Over the years, with the increased number of personal injury compensation cases, the practice of disability assessment have been greatly developed, and the development of disability assessment standards tends to be mature. However, the lack of basic theories for disability assessment has seriously affected the construction and unification of standards. Starting from the tort legal system of personal injury compensation, this article systematically analyzes the legal theories of disability assessment, and holds that the loss of labor ability is the legal basis for disability assessment in China, and the essence of disability assessment should be understood as the quantitative assessment of an individual's permanent loss of labor ability. This article combines the international disability assessment models and the primary concepts of American Medical Association's Guides to the Evaluation of Permanent Impairment to refine the basic concepts of disability assessment in China, such as impairment, disability, handicap, disabled people and self-care ability, etc. At the same time, it sorts out the critical issues of identification time, promotion principles and compound calculation of multiple injuries in disability assessment. It is expected to be beneficial to the theory and practice of disability assessment in personal injury compensation.


Ventilatory response to spontaneous resistive load variations during sleep.
We investigated the ventilatory response to spontaneous changes in resistive load during sleep in nine adult asthmatic patients, four of whom were snorers. All patients had a history of nocturnal worsening of respiratory symptoms and were submitted to a nocturnal polysomnographic study in a sleep laboratory. During the night, all patients showed spontaneous increases in pulmonary resistance due to bronchoconstriction. A temporary additional increase in inspiratory resistance (RI) was observed as a result of snoring. In all patients, a highly significant inverse linear relationship was found between ventilation (VE) and RI, but the slopes of the regressions varied considerably among patients; the decrease in VE was due to a reduced mean inspiratory flow. The most effective ventilatory compensation to increasing resistive load (lowest absolute values in the VE/RI slopes) was observed in two patients: one nonsnorer and one snorer. Effective VE compensation appeared to be dependent on the individual's combined adjustments of transpulmonary pressure (Ptp) and duty cycle (TI/TT). In fact, an increase in Ptp, linearly related to RI, was observed in all patients except one (a snorer during nonsnoring breathing); however, the Ptp increase was able to compensate VE only when TI/TT increased. We conclude that, in sleeping asthmatic patients, VE adaptation to increased spontaneous load is highly variable among patients and its effectiveness is related to individual strategies on the basis of adequate adjustments of neuromuscular output and timing of the breathing cycle.


[Childhood and adolescent depression].
Depression is a common, chronic and recurrent disorder in children and adolescents. This article reviewed the epidemiology, clinical characteristics, natural course and treatment (pharmacological and psychotherapeutic treatment) of major depressive disorder (MDD) in children and adolescents. Several randomized controlled trials have shown that the selective serotonin reuptake inhibitors (SSRIs), in particular fluoxetine, and psychotherapeutic treatments such as cognitive behavioral therapy and interpersonal therapy are efficacious in children and adolescents with MDD. However, in Japan only three SSRIs (fluvoxamine, paroxetine and sertraline) are currently available, and few clinicians are trained to deliver psychotherapeutic treatment. Further clinical researches on the treatment to children and adolescents with MDD are needed in Japan.


Chemopreventive activity of hydroethanolic Murraya koenigii leaves extract (HEMKLE) against chemically induced skin carcinogenesis in mice.
The present study aimed to examine the chemoprotective effect of Hydroethanolic Murraya koenigii leaves extract (HEMKLE) on murine skin carcinogenesis model. For the study, male LACA mice divided into four groups (n = 15 per group). Group I (Control), Group II (DMBA/TPA), Group III (HEMKLE), and Group IV (HEMKLE + DMBA/TPA). Skin tumors were induced in Group II (DMBA/TPA) and Group IV (HEMKLE + DMBA/TPA) by topical application of 7, 12 dimethylbenz[a]anthracene (DMBA) [500 nmol/100 μL of acetone, twice a week for two weeks] and 12-O-tetradecanoyl phorbol-13-acetate (TPA) [1.7 nmol/100 μL of acetone, twice a week for eighteen weeks] and HEMKLE (200 mg/kg b. w.) was administered orally (instilled by oral gavage). The chemoprotective response of HEMKLE was evident by inhibition in tumor incidence, mean tumor volume, mean tumor burden, total number of tumors, and tumor size in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA). HEMKLE administration also decreased the reactive oxygen species (ROS) and lipid peroxidation (LPO) levels and increased the antioxidants enzyme activities in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA) that suggests its antioxidant potential. HEMKLE administration also increased the mRNA and protein expression of caspase-9 and caspase-3 and decreased the mRNA and protein expression of Bcl-2 in Group IV (HEMKLE + DMBA/TPA) when compared to Group II (DMBA/TPA) that suggest its apoptosis-inducing effect on DMBA/TPA induced skin carcinogenesis.


Comparative effectiveness of antibiotic-impregnated shunt catheters in the treatment of adult and pediatric hydrocephalus: analysis of 12,589 consecutive cases from 287 US hospital systems.
The real-world effectiveness of antibiotic-impregnated shunt catheters to reduce the incidence of shunt infections is still debated. The literature to date consists mostly of small, single-institution studies. The aim of this study was to assess the incidence of infection for antibiotic-impregnated catheters (AICs) versus standard shunt catheters in a large nationwide administrative database. The authors retrospectively reviewed hospital discharge and billing records from the Premier Perspective Database from April 2003 to July 2009 to identify all adult and pediatric patients undergoing de novo ventricular shunt placement. The primary end point was the incidence of shunt infection within 1 year of implantation. Multivariate logistical regression was performed to determine factors associated with increased incidence of infection. A total of 10,819 adult (AIC, 963; standard catheter, 9856) and 1770 pediatric (AIC, 229; standard catheter, 1541) patients underwent ventricular shunt placement in 287 US hospitals. Overall, the incidence of infection was 3.5% in adults (n=380) and 6.6% in pediatric patients (n=116). AICs were associated with significant reduction in infection for both adult (2.2% vs 3.6%, p=0.02) and pediatric (2.6% vs 7.1%, p<0.01) patients. AIC use was associated with reduced infection regardless of hospital size, annual shunt volume, hospital location, or patient risk factors and remained associated with a reduced infection in multivariate analysis for both adult (p=0.02) and pediatric (p=0.02) patients. The use of antibiotic-impregnated shunt catheters was associated with a reduction in shunt infections for both adult and pediatric patients. This provides further support that AICs may represent a reliable means of reducing shunt infections for both adult and pediatric patients.


Effects of neurotensin on norepinephrine release in blood vessels of spontaneously hypertensive rats.
The present study was performed to investigate the effects of neurotensin on noradrenergic transmission in blood vessels of hypertension. In the perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats, we examined the influences of neurotensin on vascular responsiveness and norepinephrine release from adrenergic neurons. In studies with male standard Wistar rats, endogenous norepinephrine release during periarterial nerve stimulation was inhibited by neurotensin in a dose-dependent manner. Vasoconstrictor responses to electrical nerve stimulation were also inhibited by neurotensin. In SHR, the stimulation-evoked pressor responses and norepinephrine release were enhanced compared with WKY rats. The suppression of these responses by neurotensin was significantly less in SHR than in WKY rats. These results show that neurotensin could have a modulatory effect on noradrenergic activity and cause a decrease in stimulation-evoked norepinephrine release from vascular adrenergic neurons. The lesser reduction of pressor responses and norepinephrine release by neurotensin in SHR might suggest an insufficient regulation of vascular adrenergic transmission by the peptide hormone in hypertension.


Basolateral glucose transport by intestine of teleost, Oreochromis mossambicus.
Transport characteristics of D-glucose by isolated basolateral membrane vesicles of the teleost fish, Oreochromis mossambicus, were measured. Specific activity of the vesicle Na-K-adenosinetriphosphatase was increased 11-fold, whereas specific activities of brush-border and organelle membrane enzymes were enriched only 0.3- to 0.8-fold. Vesicles had diameters of 0.1-0.4 micron, 70% of vesicles were leaky (unsealed), and 60% of sealed vesicles were inside out. D-Glucose transport occurred by stereospecific facilitated diffusion, independent of 120 mM gradients of either NaCl or KCl, and was inhibited by sulfhydryl reagents, phloretin, and cytochalasin B, but not by phloridzin. Competition studies with a range of sugars demonstrated that aldohexoses in the C-1 chair conformation were preferred substrates and probably share the same carrier. Kinetic analysis of glucose influx yielded a Kt of 10 mM and a Jmax of 3,910 pmol X mg protein-1 X min-1. Fish intestinal basolateral D-glucose transport closely resembles that of mammalian or avian intestinal epithelia and of red blood cell plasma membrane. The magnitude of transport is much lower in fish than in other vertebrates, which may be related to lower metabolic rates in these poikilotherms.


Uredinorubellins and caeruleoramularin, photodynamically active anthraquinone derivatives produced by two species of the genus ramularia.
Both the phytopathogenic fungus Ramularia collo-cygni and the hyperparasite R. uredinicola biosynthesize a number of red and yellow anthraquinone derivatives called rubellins. The new compounds uredinorubellins I and II, which were isolated from R. uredinicola, contribute to understanding the biosynthesis pathway that leads from simple anthraquinones to the rubellins. In addition, we isolated for the first time such simple compounds as chrysophanol and helminthsporin from both Ramularia species. A blue compound isolated from the mycelium of R. collo-cygni was revealed to be a unique 9,4-anthracenedione derivative. Structure elucidation by (1)H and (13)C NMR of the new but unstable compound caeruleoramularin was possible only by feeding the fungus different labeled (13)C acetates. The photodynamic activity of the uredinorubellins was comparable to rubellin D, whereas chrysophanol and caeruleoramularin did not display such activity.


Use of Cherenkov-type detectors for measurements of runaway electrons in the ISTTOK tokamak.
Gas, fluid, or solid Cherenkov-type detectors have been widely used in high-energy physics for determination of parameters of charged particles, which are moving with relativistic velocities. This paper presents experimental results on the detection of runaway electrons using Cherenkov-type detectors in the ISTTOK tokamak discharges. Such detectors have been specially designed for measurements of energetic electrons in tokamak plasma. The technique based on the use of the Cherenkov-type detectors has enabled the detection of energetic electrons (energies higher than 80 keV) and determination of their spatial and temporal parameters in the ISTTOK discharges. Obtained experimental data were found in adequate agreement to the results of numerical modeling of the runaway electron generation in ISTTOK.


Temperature and Alternative Hosts Influence Aceria tosichella Infestation and Wheat Streak Mosaic Virus Infection.
Wheat streak mosaic, caused by Wheat streak mosaic virus (WSMV; family Potyviridae), is the most important and common viral disease of wheat (Triticum aestivum L.) in the Great Plains of North America. WSMV is transmitted by the wheat curl mite (WCM; Aceria tosichella). We evaluated how mean daily temperatures, cumulative growing degree-days, day of the year, and surrounding alternative host identity affected WCM infestation and WSMV infection of wheat from late summer through early autumn in Montana, United States. Cumulative growing degree-days, warm mean daily temperatures (i.e., >10°C), and surrounding alternative hosts interacted to alter risk of WCM infestation and WSMV infection. Wheat surrounded by Bromus tectorum L. and preharvest volunteer wheat had WCM infestation and WSMV infection rates of 88% in years when the mean daily temperature was 15°C in October, compared with 23% when surrounded by bare ground, and <1% when the temperature was 0°C regardless of surrounding alternative host. Mean daily temperatures in the cereal-growing regions of Montana during autumn are marginally conducive to WCM population growth and movement. As the region continues to warm, the period of WCM movement will become longer, potentially increasing the frequency of WSMV outbreaks.


Impact of antigen-unloaded immature dendritic cells on antileukemic T-cell cytotoxicity.
Immature dendritic cells (iDC) loaded with antigens are able to induce tolerance in antigen-specific T-cells. The potential of antigen-unloaded iDC to regulate the antileukemic cytotoxicity of autologous T-cells was determined. iDC generated with 50 U/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) and very immature DC (viDC) generated with 10 U/ml GM-CSF from the bone marrow of Balb/c mice were used for T-cell co-culture. The measurement of cellular cytotoxicity against the syngeneic murine B-cell leukemia line A20 revealed that T-cells without co-culture or after co-culture with iDC exerted a similar cytotoxicity, whereas T-cells co-incubated with viDC showed a significantly diminished lysis of A20 cells (p<0.05). Antigen-unloaded iDC in contrast to antigen-loaded iDC may not affect antileukemic T-cell cytotoxicity, whereas antigen-unloaded DC cultures generated with a low dose of GM-CSF are able to impair the T-cell-mediated cytolysis of leukemic cells.


Ion-selective membrane electrode for rapid automated determinations of total carbon dioxide.
Previously described ion-selective membrane electrodes useful for determination of total carbon dioxide in biological fluids in automated analyzers show interference from several sources--e.g., fatty acids, keto acids, salicylate, heparin. Judicious selection of membrane components has produced a membrane with superior performance characteristics: short conditioning time, long lifetime in storage, rapid and stable response, low drift, and significantly less susceptibility to interference than other electrodes thus far reported. Samples can be analyzed at 240 samples or more per hour and results correlate well with those by, e.g., the Technicon SMAC II method for total carbon dioxide. Mounted on the Technicon RA-1000, the carbon dioxide sensor is arranged in tandem with sodium and potassium ion-selective electrodes. When all three species are measured in the same buffered sample stream, the sampling rate thus becomes 720 tests per hour, done on 25-microL samples.


The role of micronutrients in pregnancy.
The antenatal shared care model has become increasingly popular among Australian women as the preferred mode of pregnancy care. General practitioners are often asked by their pregnant women patients about the nutrients needed during pregnancy. This article discusses the role of various micronutrients and trace elements needed in pregnancy, and provides daily intake recommendations of these nutrients as a reference point. Much attention has been given to micronutrients such as folate and iron, but less regard to other trace elements that are also important in pregnancy. Encouraging a balanced diet and ensuring the adequacy of these micronutrients is essential for minimising pregnancy complications. However, GPs should also be aware of the maximum level of recommended intakes and any possible adverse effects.


Laparoscopic resection of ileal lipoma diagnosed by multidetector-row computed tomography.
Intussusception is rare in adults and it is difficult to diagnose on admission. We present the case of a 43-year-old woman with the chief complaint of nausea and upper abdominal pain. Abdominal multidetector-row computed tomography showed ileo-ileal small bowel intussusception with an intraluminal soft tissue mass with attenuation numbers suggestive of a lipoma. The patient was treated with a laparoscopic-assisted extracorporeal partial resection of the small bowel including ileal lipoma, followed by a functional end-to-end anastomosis. Histologic diagnosis of the resected tumor, 2.4×2.0×2.0 cm, was an intestinal lipoma. This case serves as the basis of a review of small bowel intussusception in adults secondary to lipomas. It focuses on the utility of multidetector-row computed tomography and the cosmetic, physical, and economic benefits of laparoscopic surgery as well as the rarity of the disease.


Religious restrictions and the trauma patient.
This article discusses some of the dilemmas the Certified Registered Nurse Anesthetist (CRNA) faces when the patient refuses potential life-saving blood products or a blood transfusion. Even if the CRNA disagrees with the patient's decision, the patient's right to refuse is taken very seriously in the legal arena. Without a court order, the patient cannot be forced to receive blood or blood products. It would be easier if there were clear guidelines; unfortunately, these do not exist. In the past, courts were more likely to agree with the anesthesia provider and order the transfusion, even if the patient were competent. Today, courts are less likely to do so in these cases. However, there are circumstances in which obtaining a court order for the transfusion is more predictable, such as if the patient is a child in a true emergency situation, or if the patient is pregnant and the fetus is viable.


Sporozoite malaria vaccine. Where do we stand?
A sporozoite malaria vaccine which elicits high levels of antibodies to the circumsporozoite (CS) protein may protect part of the human population in areas of low endemicity. Other possible targets of a sporozoite vaccine are the liver stages, but in this case the effector cells are T-lymphocytes which recognize sporozoite-derived peptides in association with products of the major histocompatibility complex. There is no evidence that the variation observed in the CS protein of P. falciparum is driven by immunological pressure, nor that this variation will be a major impediment to vaccine development.


Dermatomyositis revealing breast cancer: report of a case.
Dermatomyositis (DM) is a rare connective corresponding to an inflammatory disease of skeletal muscles. Paraneoplastic origin must always be sought, primarily gynecological tumor in women, but the investigations are often made difficult by the fact that a primary tumor is often not detectable at the time of the cutaneous manifestations. This approach includes in addition to the monitoring report at regular intervals of 6 to 12 months for two years after diagnosis. We report a case of Dermatomyositis revealing breast cancer.


Do potassium channel openers compete with ATP to activate ATP sensitive potassium channels?
Potassium channel openers are a class of chemically heterogeneous compounds that produce vasodilatation by opening vascular smooth muscle potassium channels. Using various configurations of the powerful patch clamp technique, the molecular pharmacology of potassium channel openers has been largely explored in different cellular systems. These studies have revealed that the primary molecular target for potassium channel openers is this class of potassium channel proteins that close under the influence of intracellular ATP and have thus been named ATP sensitive potassium channels. Direct recordings of unitary ATP sensitive potassium channels in cell detached membrane patches support the view that potassium channel openers compete with intracellular ATP to prevent channel inhibition. However, there also exists experimental evidence that contradicts the competition hypothesis and suggests the involvement of phosphorylation-dephosphorylation mechanisms. The aim of the present article is to review experimental data that support, or inversely, contradict the potassium channel opener-ATP competition theory.


Full experimental modelling of a liver tissue mimicking phantom for medical ultrasound studies employing different hydrogels.
Tissue mimicking phantoms have been widely reported to be an important tool for development, optimisation and performance testing of ultrasound-based diagnostic techniques. In particular, modern applications of tissue mimicking phantoms often include characterisation of the nonlinear behaviour of experimental ultrasound contrast agents. In such cases, the tissue-mimicking materials should be chosen not only based on the values of their density, speed of sound and attenuation coefficient, but also considering their effect on the appearance of "native harmonics" due to nonlinear distortion of ultrasound signal during propagation. In a previous paper it was demonstrated that a cellulose-based hydrogel is suitable to simulate nonlinear acoustical behaviour of liver tissue for thicknesses up to 8 cm. In this paper we present the experimental characterisation of the nonlinear acoustical behaviour of a different polyethylene glycol diacrylate (PEGDA)-based hydrogel, in order to assess whether and how it can improve the performances and overcome some limitations of the cellulose-based hydrogel as liver tissue-mimicking material. Samples of pig liver tissue, cellulose-based hydrogel and PEGDA-based hydrogel were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values. Second harmonic and first harmonic amplitudes were extracted from the spectra of received signals and their difference was then used to compare sample behaviours. Obtained results show how a new more accurate and combined experimental model of linear and nonlinear acoustical behaviour of liver tissue is feasible. In fact, a further confirmation of the cellulose-based hydrogel effectiveness to precisely simulate the liver tissue for penetration depths up to 8 cm was provided, and it was also shown that the employment of the PEGDA-based hydrogel can extend the range of useful tissue-mimicking material thicknesses up to 11 cm, moreover allowing a considerable improvement of the time stability and behaviour reliability of the corresponding manufactured phantoms.


Statins and Angiotensin-Converting Enzyme Inhibitors are Associated with Reduced Mortality and Morbidity in Chronic Liver Disease.
Liver fibrosis is a common response to many chronic liver diseases. The aim of our study was to explore whether pharmacotherapy for concurrent diseases affects overall mortality, liver-related mortality and liver-related morbidity in patients with chronic liver disease. We performed a register-based cohort study of all patients with a first-time diagnosis of chronic liver disease between 2005 and 2012 in Sweden (n = 70 546). Data from the Patient Register, the Prescribed Drug Register and the Death Certificate Register were linked. We studied whether the use of statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and antibiotics affected the risk of total mortality, liver-specific mortality and morbidity. We found a reduction in mortality risk for statin users (n = 11,245) with hazard ratios from 0.57 (95% CI: 0.32-0.99) for patients with autoimmune hepatitis to 0.84 (95% CI: 0.75-0.95) for patients with alcoholic liver disease. There was a significantly reduced liver-related mortality for patients with alcoholic liver disease who used angiotensin-converting enzyme inhibitors, 0.85 (95% CI: 0.65-0.96). There were increased overall mortality risks for antibiotic users (n = 44,572), with hazard ratios up to 1.67 (95% CI, 1.55-1.80) for viral hepatitis. Statin use was associated with decreased risks of liver-specific mortality and morbidity, and reduced total mortality foremost among patients with alcoholic liver disease. Angiotensin -converting enzyme inhibitors was associated with reduced liver-related mortality among patients with alcoholic liver disease.


[Effect of chronic disconnection between septal area and hypothalamus on modulation of background activity of septal neurons by biologically-active substances in hibernators].
Our previous work demonstrated paradoxically increased excitability of the medial septal (MS) neurons during hibernation of ground squirrels in comparison to waking animals. Recently this was supported by demonstration of higher efficacy of the neuropeptides identified in the brain of hibernators in septal slices of hibernating animals. To decide whether this increased excitability is determined by endogenous properties of the pacemaker septal neurons, or it depends on the influences of thermoregulatory-circadian mechanisms of preoptico-hypothalamic area, testing of the neuropeptides (TSKYR, TSKY, DY) and neurotransmitters participating in control of hibernation (serotonin and noradrenaline) was repeated on septal slices taken from the brain of hibernating animals two weeks after operation disconnecting it from the hypothalamus. Effects of neuropeptides in the deafferented hibernating animals neither quantitatively (low reactivity level), nor qualitatively (distribution of inhibitory and excitatory responses) differed from the data obtained in waking animals. Decrease of reactivity occurred at the expense of the neurons with regular pacemaker-like spontaneous activity. Thus, increased reactivity of the MS neurons to neuropeptides in hibernating animals depends mainly on influence of the hypothalamic centres controlling hibernation behavior upon pacemaker neurons of the MS. Contrary to the neuropeptides, serotonin and noradrenaline were highly effective in deafferented septum. They evoked stronger changes of background activity (shorter latencies and more rapid development of maximal shifts), presumably as a result of development of denervation hypersensitivity after deafferentation.


Bacillus subtilis rRNA promoters are growth rate regulated in Escherichia coli.
rRNA promoters from the rrnB locus of Bacillus subtilis and from the rrnB locus of Escherichia coli were fused to the gene for chloramphenicol acetyltransferase (CAT). The level of expression of CAT in E. coli showed growth rate dependence when the CAT gene was linked to either E. coli or B. subtilis tandem promoters. The downstream promoter of the tandem Bacillus pair showed growth rate regulation, while the upstream promoter did not, whereas for the E. coli tandem promoters, only the upstream promoter was growth rate regulated.


Influenza Vaccine Effectiveness in a Low-Income, Urban Community Cohort.
In this community-based cohort study of 275 primarily low-income, urban households in New York City, overall 2013-2014 influenza vaccine effectiveness (VE) was 62.5% (95% confidence interval, 21.7%-82.0%). VE point estimates were highest against 2009 H1N1 and for those who were vaccinated in 2013-2014 but not in 2012-2013.


Will a quadruple multiplexed point-of-care screening strategy for HIV-related co-infections be feasible and impact detection of new co-infections in at-risk populations? Results from cross-sectional studies.
Multiplexed point-of-care (POC) devices can rapidly screen for HIV-related co-infections (eg, hepatitis C (HCV), hepatitis B (HBV), syphilis) in one patient visit, but global evidence for this approach remains limited. This study aimed to evaluate a multiplex POC testing strategy to expedite screening for HIV-related co-infections in at-risk populations. A multiplex strategy was developed with two subsequent versions of an investigational device Miriad. It was evaluated in two non-comparable settings and populations in two countries for feasibility of conduct, detection of new infections, preference and accuracy. Version 1 was evaluated in 375 sexually transmitted disease clinic attendees in Mumbai, India; version 2 was evaluated in 119 injection drug users in Montreal, Canada. Feasibility (completion rate) of the multiplex strategy was high (86.1% Mumbai; 92.4% Montreal). A total of 170 new infections were detected in Mumbai (56 HIV, 75 HBV, 37 syphilis, 2 HCV) versus 2 in Montreal. Preference was 60% in Mumbai and 97% in Montreal. Miriad version 1 specificities were high: HIV 99.7% (98.3% to 100%), HBV 99.3% (97.6% to 99.9%), HCV 99.7% (98.5% to 99.9%), syphilis 85.2% (80.9% to 88.8%); sensitivities were as follows: HIV 100% (94.8% to 100%), HBV 13.3% (6.6% to 23.2%), HCV 50% (1.3% to 98.7%), syphilis 86.1% (70.5% to 95.3%). With version 2, specificities improved: HIV 100% (97.2% to 100%), HBV 100% (97.3% to 100%), HCV 85.3% (73.8% to 93.0%), syphilis 98.1% (93.3% to 99.8%); sensitivities were: HIV 100% (47.3% to 100%), HCV 80.4% (66.1% to 90.6%), syphilis 100% (22.4% to 100%). A quad multiplex POC strategy for HIV and co-infections was feasible to operationalise and preferred by patients in both settings. Many new infections were identified in Mumbai and accuracy improved with version 2 of the assay. Such a strategy will help expedite screening for co-infections, particularly where baseline screening is low. These findings are valuable to practitioners, researchers, policymakers and funders involved in initiatives for all four diseases with implications for scale-up.


Potential for improving fiber digestion in the rumen of cattle (Bos taurus) through microbial inoculation from bison (Bison bison): In situ fiber degradation.
The objective of this experiment was to determine if partial replacement of cattle rumen contents with those from bison would increase in situ ruminal fiber degradation of various forages. The second objective was to examine individual variation among cattle in their ability to degrade forage and their responses to inoculation. In situ degradation of barley straw, canola straw, alfalfa hay, and timothy hay was measured in 16 ruminally cannulated heifers fed a barley straw-based diet before and after inoculation with combined rumen contents from 32 bison (performed twice, 14 d apart). Each feed was incubated in the rumen of each heifer for 0, 4, 8, 12, 24, 48, 96, and 120 h, and the degradation parameters were determined as washout fraction (), potentially degradable fraction (), rate of digestion of fraction (), and total potentially degradable fraction (). The of barley straw decreased ( = 0.04) after inoculation, whereas fraction of NDF increased ( = 0.03) and fraction of NDF and ADF decreased ( ≤ 0.02) by inoculation. In contrast, of alfalfa hay NDF and ADF decreased ( = 0.002) after inoculation, but fraction of NDF and ADF ( ≤ 0.02) increased. There were no major effects ( > 0.06) of inoculation on the fiber degradation of timothy hay or canola straw. The differential response between barley straw and alfalfa hay may have occurred because the cattle were previously adapted to a barley straw diet, whereas the bison were fed barley silage and oats. Some animals consistently ranked higher or lower for or across at least 3 of the 4 feeds incubated, but the rankings changed after inoculation. In conclusion, inoculation of cattle with bison rumen contents failed to improve degradation of fiber from barley straw, canola straw, or timothy hay in cattle well adapted to a barley straw diet, although there were small improvements in the extent of degradation of fiber from alfalfa hay. Cattle varied both in their ability to degrade various forages and in their responses to inoculation with bison rumen contents.


A Systematic Review of Naltrexone for Attenuating Alcohol Consumption in Women with Alcohol Use Disorders.
Several clinical trials have evaluated naltrexone as a treatment for alcohol use disorders (AUDs), but few have focused on women. The aim of this review was to systematically review and summarize the evidence regarding the impact of naltrexone compared to placebo for attenuating alcohol consumption in women with an AUD. A systematic review was conducted using PubMed, Cochrane, Web of Science, CINAHL, and Alcohol Studies Database to identify relevant peer-reviewed randomized controlled trials (RCTs) published between January 1990 and August 2016. Seven published trials have evaluated the impact of naltrexone on drinking outcomes in women distinct from men; 903 alcohol-dependent or heavy drinking women were randomized to receive once daily oral or depot (injectable) naltrexone or placebo with/without behavioral intervention. Two studies examining the quantity of drinks per day observed trends toward reduction in drinking quantity among women who received naltrexone versus placebo. The 4 studies examining the frequency of drinking had mixed results, with 1 study showing a trend that favored naltrexone, 2 showing a trend that favored placebo, and 1 that showed no difference. Two of the 3 studies examining time to relapse observed trends that tended to favor naltrexone for time to any drinking and time to heavy drinking among women who received naltrexone versus placebo. While the growing body of evidence suggests a variety of approaches to treat AUD, the impact of naltrexone to combat AUD in women is understudied. Taken together, the results suggest that naltrexone may lead to modest reductions in quantity of drinking and time to relapse, but not on the frequency of drinking in women. Future research should incorporate sophisticated study designs that examine gender differences and treatment effectiveness among those diagnosed with an AUD and present data separately for men and women.


Family care-giving for people with dementia: some implications for policy and professional practice.
The objective of this paper is to describe one study undertaken in the north of England which sought an understanding of family care-giving for people with dementia. Data were collected by interview and diary with 14 family carers, by questionnaire with 60 professional carers, and by interview and diary from nine case studies. Family carers were found to value their continuing relationship with the person with dementia. This emphasis on their relationship together influenced the contact which they had with professional carers. The implications of this research for policy and professional practice are explored through illumination of the tensions in professional responses to family carers.


Various plus unique: Viral protein U as a plurifunctional protein for HIV-1 replication.
Human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, encodes four accessory genes, one of which is viral protein U (Vpu). Recently, the study of Vpu has been of great interest. For instance, various cellular proteins are degraded (e.g. CD4) and down-modulated (e.g. tetherin) by Vpu. Vpu also antagonizes the function of tetherin and inhibits NF-κB. Moreover, Vpu is a viroporin forming ion channels and may represent a promising target for anti-HIV-1 drugs. In this review, we summarize the domains/residues that are responsible for Vpu's functions, describe the current understanding of the role of Vpu in HIV-1-infected cells, and review the effect of Vpu on HIV-1 in replication and pathogenesis. Future investigations that simultaneously assess a combination of Vpu functions are required to clearly delineate the most important functions for viral replication. Impact statement Viral protein U (Vpu) is a unique protein encoded by human immunodeficiency virus type 1 (HIV-1) and related lentiviruses, playing multiple roles in viral replication and pathogenesis. In this review, we briefly summarize the most up-to-date knowledge of HIV-1 Vpu.


Luteoprotective roles of luteinizing hormone are mediated by not only progesterone production but also glucocorticoid conversion in bovine corpus luteum.
Luteinizing hormone (LH) is known as a key regulator of corpus luteum (CL) function, but the luteoprotective mechanisms of LH in the maintenance of bovine CL function are not well understood. The current study investigated if LH increases cell viability and induces cortisol conversion, and if the luteoprotective action of LH is mediated by stimulating the local production and action of progesterone (P4) and/or cortisol. Cultured bovine luteal cells obtained at the mid-luteal stage (Days 8-12 of the estrous cycle) were treated for 24 hr with LH (10 ng/ml) with/without onapristone (OP, a specific P4 receptor antagonist; 100 µM), cortisone (1 µM), and aminoglutethimide (AGT, a specific inhibitor of cytochrome P450 side-chain cleavage; 100 µM). LH with and without OP significantly increased the mRNA and protein expressions of 11β-hydroxysteroid dehydrogenase (HSD11B) 1, but did not affect the mRNA or protein expression of HSD11B2. These treatments also significantly increased HSD11B1 activity. Cell viability was significantly increased by LH alone or by LH in combination with cortisone and OP. LH in combination with OP or AGT significantly decreased cell viability as compared to LH alone. The overall results suggest that LH stimulates not only P4 production but also HSD11B1 expression, thereby increasing the cortisol concentration in the bovine CL, and that LH prevents cell death through these survival pathways. LH may consequently support CL function during the luteal phase in cattle.


Basilar artery blood flow in subclavian steal.
Subclavian "steal", when blood siphons from one vertebral artery to the other, has been suggested as a cause of brain stem ischaemia and stroke. We investigated 33 patients using transcranial Doppler to determine the direction and velocity of basilar blood flow. All patients had severe subclavian stenosis with reversed vertebral blood flow in the ipsilateral artery previously demonstrated by extracranial Doppler. Basilar flow was normal in direction in all cases, but its velocity was significantly increased (p less than 0.0008) compared to age- and sex-matched controls. These findings, in conjunction with previous observations using extracranial Doppler techniques, suggest that subclavian steal is little more than a harmless haemodynamic phenomenon.


coliSNP database server mapping nsSNPs on protein structures.
We have developed coliSNP, a database server (http://yayoi.kansai.jaea.go.jp/colisnp) that maps non-synonymous single nucleotide polymorphisms (nsSNPs) on the three-dimensional (3D) structure of proteins. Once a week, the SNP data from the dbSNP database and the protein structure data from the Protein Data Bank (PDB) are downloaded, and the correspondence of the two data sets is automatically tabulated in the coliSNP database. Given an amino acid sequence, protein name or PDB ID, the server will immediately provide known nsSNP information, including the amino acid mutation caused by the nsSNP, the solvent accessibility, the secondary structure and the flanking residues of the mutated residue in a single page. The position of the nsSNP within the amino acid sequence and on the 3D structure of the protein can also be observed. The database provides key information with which to judge whether an observed nsSNP critically affects protein function and/or stability. As far as we know, this is the only web-based nsSNP database that automatically compiles SNP and protein information in a concise manner.


Plasma Extracellular Vesicles Enriched for Neuronal Origin: A Potential Window into Brain Pathologic Processes.
Our team has been a pioneer in harvesting extracellular vesicles (EVs) enriched for neuronal origin from peripheral blood and using them as a biomarker discovery platform for neurological disorders. This methodology has demonstrated excellent diagnostic and predictive performance for Alzheimer's and other neurodegenerative diseases in multiple studies, providing a strong proof of concept for this approach. Here, we describe our methodology in detail and offer further evidence that isolated EVs are enriched for neuronal origin. In addition, we present evidence that EVs enriched for neuronal origin represent a more sensitive and accurate base for biomarkers than plasma, serum, or non-enriched total plasma EVs. Finally, we proceed to investigate the protein content of EVs enriched for neuronal origin and compare it with other relevant enriched and non-enriched populations of plasma EVs. Neuronal-origin enriched plasma EVs contain higher levels of signaling molecules of great interest for cellular metabolism, survival, and repair, which may be useful as biomarkers and to follow response to therapeutic interventions in a mechanism-specific manner.


2010 Trauma Association of Canada presidential address: why the Trauma Association of Canada should care about space medicine.
The Trauma Association of Canada is now 27 years old, having been officially founded in 1983, at the meetings of the Royal College as a maturation of the trauma committee of the Canadian Association of General Surgeons. The first page of the official minutes also stressed the need to welcome other disciplines into the fold. Personally, it has taken me years of involvement, as well as the Presidency, to truly appreciate the depth of our Founding Members commitment. These individuals set lofty mission goals for the organization, namely: to strive to improve the quality of care provided to the injured patient, including prehospital management and transport, acute care hospitalization, and reintegration into society; to support, conduct, and apply basic science and clinical and outcome research related to trauma; to encourage effective and efficient use of healthcare resources in the delivery of trauma care; and to foster professional and community education in the field of injury prevention and in the care of the injured patient. As daunting as these responsibilities are, I am suggesting one more: to overcome the great penalty of geography that challenges our nation and penalizes many of our citizens by aspiring to optimize these four goals, for all Canadians, irrespective of where they live--our potential fifth mission. Furthermore, I believe that lessons from space medicine may offer some strategies to accomplish this goal.


Retinoblastoma: revisiting the model prototype of inherited cancer.
Hereditary retinoblastoma is an autosomal dominant disorder caused by mutations in the RB1 gene. Analysis of this rare condition has helped to elucidate the mechanisms underlying hereditary cancer predisposition in general. As identification of RB1 gene mutations has become a part of clinical management of patients with retinoblastoma, there is now a wealth of data. In this article, we summarize the current knowledge on the relations between the genotype and phenotypic expression. Moreover, detailed analysis of genotype-phenotype relations shows that hereditary retinoblastoma has features of a complex trait.


Spontaneous healing of duodenal ulcers.
Ninety-one patients with duodenal, pyloric, or prepyloric ulcers were studied endoscopically. Spontaneous ulcer healing was seen in 29 patients within 2 weeks (rapid healing) and in 23 patients within 6 weeks (slow healing). More ulcers healed spontaneously in women than in men (P less than 0.05). Spontaneous healing in men was related to a low gastric peak acid output (P less than 0.05). During follow-up study for 2 years of patients with spontaneously healed ulcers 13 patients had no recurrence, whereas 19 patients had 1 or 2 recurrences, which also healed spontaneously; 11 patients had to be given active treatment, and 9 patients did not complete the study. Cigarette smoking was more frequently recorded in the group receiving active treatment than in the group with spontaneous healing. In men ulcers needing active treatment during the follow-up period were related to a high peak acid output (P less than 0.05).


The effectiveness of a mutual support group for family caregivers of a relative with dementia.
This experimental study compared the effectiveness of providing a mutual support group program for family caregivers of a relative with dementia with that of conventional family service available to this group in Hong Kong. Fifty-two family caregivers from two centers participated in the study. A protocol, specifically designed to guide the mutual support group process and the facilitator and peer leader training, was based on evidence from other family support group intervention studies. Significant differences were found for distress levels and quality of life, with the mutual support group having greater improvements than the control group. The results of this study show the importance of psychosocial support beyond conventional services generally offered to family caregivers in dementia care.


[FAS- and TNF-dependent ways participation in apoptosis mechanisms in hypotalumus in physiological and pathological aging.]
The cell resistance to apoptosis can be related to the activity of cytokine-dependent signaling. So, the aim of the work is to investigate the mechanisms of cytokine-dependent FAS/TNF-mediated regulation of apoptosis of neurosecretory cells in the physiological and pathological (overexpression of the oncogene HER-2/Neu) aging. HER2/Neu transgenic accelerated aged mice of different ages and wild type FVB/N were examined. The apoptosis level of neurons in hypothalamic sections (supraoptic and paraventricular nuclei) (TUNEL) and expression of caspase-8, CD178 (FASL), FAS, FADD, TRADD (Western blotting) was determined. Participation of the proinflammatory component in the aging process is shown. FAS, adapter proteins associated with the death domain (FADD and TRADD), caspase-8 expression is activated in hypothalamus in FVB/N mice (wild type) during aging, and it correlates with an increase in the apoptosis level. HER-2/Neu expression leads to the extrinsic apoptotic pathway suppression. In this case, the reception of an apoptotic signal (FAS-receptor expression) and its further transmission (expression of FADD and TRADD) is suppressed. However, in young transgenic mice, increased expression of TRADD can activate one of the survival ways - NF-κB, ERK or PI3K-AKT cascade. Thus, the HER-2/Neu tyrosine kinase receptor plays a role in the mechanism of cell resistance to age-dependent apoptosis, and the FAS/TNF-signaling pathway is one of the targets of HER-2/Neu.


Coupling effect of reaction conditions on the catalytic activity of Cu-Mn composite oxide catalysts for toluene.
Volatile organic compounds (VOCs) are one of the major components of air pollution. Catalytic combustion is a promising technology for the treatment of VOCs and at its center is the preparation of efficient and cheap catalysts. In this study, by loading copper (Cu) and manganese (Mn) on Santa Barbara Amorphous-15 (SBA-15) molecular sieve, the Cux-Mny/SBA-15 (x = 1, 2; y = 1, 2) composite metal oxide catalyst was prepared using the equal volume impregnation method. Their performance in the toluene catalytic combustion reaction was investigated by adjusting the molar ratio (x : y), and the loading of Cu and Mn. The results of the Brunner-Emmett-Teller (BET), X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) analyses show that the CuMnO spinel phase can be detected in the Cu-Mn composite metal oxide catalyst doped with a low concentration of Cu. The overall rod-like structure of the fibrous network structure provides a large specific surface area, and the particle crystallinity is low and the dispersion is good. Due to the synergistic effect of Cu and Mn, the greater the amount of Mn3+ and adsorbed oxygen species (Oads) that are available, and the higher the turnover frequency (TOF) value, the better and more superior catalytic performance and excellent stability is obtained, when compared with the single-component oxides used in toluene catalytic combustion. After a continuous catalytic reaction for 12 h, the toluene conversion rate remained above 95%. The coupling effect of the catalytic reaction temperature and concentration of oxygen on the catalytic combustion of toluene was also studied. At a low reaction temperature (<250 °C), the increase of the concentration of oxygen played a superior role in promoting the conversion of toluene. The kinetic analysis of the toluene catalytic combustion process showed that the catalytic combustion of toluene by Cu-Mn/SBA-15 followed both the Mars-Van Krevelen (MVK) and Langmuir-Hinshelwood (L-H) reaction mechanisms. With the increase of the Oads amount caused by the decrease of the Cu ratio, the proportion of the L-H reaction mechanism increases.


The intestinal TORC2 signaling pathway contributes to associative learning in Caenorhabditis elegans.
Several types of associative learning are dependent upon the presence or absence of food, and are crucial for the survival of most animals. Target of rapamycin (TOR), a kinase which exists as a component of two complexes, TOR complex 1 (TORC1) and TOR complex 2 (TORC2), is known to act as a nutrient sensor in numerous organisms. However, the in vivo roles of TOR signaling in the nervous system remain largely unclear, partly because its multifunctionality and requirement for survival make it difficult to investigate. Here, using pharmacological inhibitors and genetic analyses, we show that TORC1 and TORC2 contribute to associative learning between salt and food availability in the nematode Caenorhabditis elegans in a process called taste associative learning. Worms migrate to salt concentrations experienced previously during feeding, but they avoid salt concentrations experienced under starvation conditions. Administration of the TOR inhibitor rapamycin causes a behavioral defect after starvation conditioning. Worms lacking either RICT-1 or SINH-1, two TORC2 components, show defects in migration to high salt levels after learning under both fed and starved conditions. We also analyzed the behavioral phenotypes of mutants of the putative TORC1 substrate RSKS-1 (the C. elegans homolog of the mammalian S6 kinase S6K) and the putative TORC2 substrates SGK-1 and PKC-2 (homologs of the serum and glucocorticoid-induced kinase 1, SGK1, and protein kinase C-α, PKC-α, respectively) and found that neuronal RSKS-1 and PKC-2, as well as intestinal SGK-1, are involved in taste associative learning. Our findings shed light on the functions of TOR signaling in behavioral plasticity and provide insight into the mechanisms by which information sensed in the intestine affects the nervous system to modulate food-searching behaviors.


[Alterations of myocardial ultrastructure and gene expression of calcium handling proteins in diabetic rat heart].
To investigate the ultrastructure of myocardium and gene expression of calcium handling proteins in diabetic rat heart. Diabetes was induced in male Sprague-Dawley rats by a single injection of alloxanm (40 mg/kg ) and the rats in control group were injected with normal saline. At the end of 2, 4, 6 weeks after the induction of diabetes, the animals were sacrificed. The expression of calcium handling proteins was detected by reverse transcription-polymerase chain reaction (RT-PCR) and actin mRNA was used as internal standard. Heart tissue at the apex was obtained for light and electron microscope study. At the end of 4 and 6 weeks, cardiosomatic ratio of diabetic rats was higher than that of control. Electron microscopy revealed a spectrum of subcellular remodeling in myocardium which was characterized by damaged myofibrils and mitochondria, dilated and swollen sarcoplasmic reticulum. Expression of phospholamban mRNAs was significantly increased, but 1,4,5-trisphosphate inositol receptor type 2, ryanodine receptor type 2 mRNAs were significantly decreased compared with those in the age-matched control rats. In contrast, the expression of sarco/endoplasmic reticulum Ca(2+)-ATPase mRNAs was not affected. In diabetic rat heart, gene expression of calcium handling proteins was characterized by up-regulation of phospholamban and down-regulation of sarcoplasmic reticulum calcium release channel while electron microscopic analysis of myocardium revealed a spectrum of subcellular remodeling.


Tibial Plateau Fractures Complicated by Compartment Syndrome Are Associated With a 3 Times Higher Cost of Care.
To determine the impact of acute compartment syndrome (ACS) and identify cost drivers of 1-year total treatment costs for operative tibial plateau fractures. Retrospective review. Level 1 trauma center. 337 patients with tibial plateau fractures, 24 of which were complicated by ACS. The primary outcome was total treatment cost over the first year for operatively treated tibial plateau fractures. The secondary objective was to use regression analysis to identify significant cost drivers. The diagnosis of ACS was associated with 2.85 times higher total treatment cost ( P < 0.001). ACS demonstrated increased total treatment cost when controlling for polytrauma ( P < 0.001) and postoperative infection ( P < 0.001). Regression analysis identified 5 variables significantly associated with total cost of care: body mass index, injury severity score, ACS, staged external fixation, and locking fixation ( P < 0.001; R 2 = 0.57). The diagnosis of ACS had the largest impact on total cost with a 3.5× greater impact on cost compared with the next highest variable, staged external fixation. Tibial plateau fractures complicated by ACS are associated with 2.85 times higher treatment costs over a 1-year period. There were 5 significant variables identified by regression analysis with ACS having the highest impact on total treatment. Together, these 5 factors account for 57% of treatment cost variability. Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Synthesis of Oxatricyclooctanes via Photoinduced Intramolecular Oxa-[4+2] Cycloaddition of Substituted o-Divinylbenzenes.
The photolysis of substituted o-divinylbenzenes promotes a one-step and metal-free conversion to oxatricycles at room temperature. Irradiation o-divinylbenzenes results in an pericyclic reaction to form cyclic o-quinodiemthane intermediates, which subsequently undergo intramolecular oxa-[4+2] cycloaddition to form oxacyclic derivatives.


Components and physical properties of hydrogels modulate inflammatory response and cartilage repair.
Collagen and hyaluronic acid are commonly applied in cartilage tissue engineering, yet there has been limited investigation into their inflammatory response, a crucial factor in articular cartilage repair. This study aimed to evaluate the impact of components and physical properties of hydrogels on inflammatory response and cartilage repair. Three kinds of hydrogels with comparable storage moduli at low frequencies were designed and fabricated, namely, methacrylic anhydride-modified hyaluronic acid hydrogel (HAMA), methacrylic anhydride-modified type I collagen hydrogel (CMA) and unmodified type I collagen hydrogel (Col). HAMA hydrogel was unfavorable for adhesion and spreading of BMSCs. Furthermore, HAMA hydrogel stimulated rapid migration and pro-inflammatory M1 polarization of macrophages, leading to persistent and intense inflammation, which was unfavorable for cartilage repair. CMA and Col hydrogels possessed the same component and facilitated the adhesion, spreading and proliferation of BMSCs. Compared with CMA hydrogel, Col hydrogel induced rapid migration and moderate M1 polarization of macrophages at the early stage of injury, which was mainly influenced by its fast dissolution rate, small pore size fiber network structure and rapid stress relaxation. In addition, the phenotype of macrophages timely transformed into anti-inflammatory M2 due to the properties of the collagen component, which shortened the duration of inflammation and enhanced cartilage repair. The results indicated that moderate macrophage activation adjusted by hydrogel components and physical properties was critical in modulating inflammation and cartilage regeneration.