Peripheral endocannabinoid system-mediated actions of rimonabant on growth hormone secretion are ghrelin-dependent.
The somatotroph axis is a crucial pathway regulating metabolism. Despite the fact that the endocannabinoid system has been also revealed as a potent modulator of energy homeostasis, little information is available concerning a putative interaction between these two systems. The aim of the present study was to determine the in vivo effects of the blockade of the cannabinoid receptor type 1 (CB1) over growth hormone (GH) secretion using the CB1 antagonist rimonabant. The results obtained show that the blockade of the CB1 peripheral receptor by i.p. injection of rimonabant significantly inhibited pulsatile GH secretion. Similarly, it was found that this injection significantly decreased ghrelin-induced GH secretion without any effect on growth hormone-releasing hormone (GHRH)-induced GH discharge. In situ hybridisation showed that the peripheral blockade of CB1 did not affect hypothalamic somatostatin mRNA levels; however, GHRH mRNA expression was significantly decreased. The blockade of the vagus nerve signal by surgical vagotomy eliminated the inhibitory action of rimonabant on GHRH mRNA and consequently on GH. On the other hand, the central CB1 blockade by i.c.v. rimonabant treatment was unable to reproduce the effect of peripheral blockade on GHRH mRNA, nor the GH response to ghrelin. In conclusion, the data reported in the present study establish, from a physiological point of view, the existence of a novel mechanism of GH regulation implicating the action of the cannabinoid receptor on the somatotroph axis.


Lulling the Cancer Cell into an Eternal Sleep.
A hallmark of metastasis is the ability of cancer cells to undergo the epithelial-to-mesenchymal transition to invade and disseminate to distal sites. More recently, the case has been made that the critical last step in metastasis is dependent on the ability to undergo reversion to an epithelial phenotype in a process known as the mesenchymal-to-epithelial transition (MET). It is this transition in the metastatic cascade that researchers are focusing on clinically to treat disseminated disease. Shinde and colleagues identified spleen tyrosine kinase (SYK) as a critical mediator of MET that facilitated the removal of P-bodies during autophagy. Remarkably, pharmacologic inhibition of SYK inhibited the clearance of P-bodies and autophagy in preclinical models of metastasis, arresting cancer cells in an indefinite dormant state and preventing tumor cell colonization and thus the establishment of aggressive metastatic disease.See related article by Shinde et al., p. 1831.


International expositions: a historiographic approach from Latin America.
This essay examines the historiography of international exhibitions, seen as geopolitical phenomena of modernity to which are associated the rise of middle classes, nationalist and colonialist movements, as well as an exhibitionary network connecting distinct spaces and times. Most of the recent studies analyses this repertoire and this pattern, and their relationship with political, economic, social and cultural issues. This study stresses, among ongoing approaches, the Latin American work - still barely visible or integrated into a field which is already consolidated -, and suggests how its visibility can be improved.


Transition metal-catalyzed C-H bond functionalization in multicomponent reactions: a tool toward molecular diversity.
Transition metal-catalyzed C-H bond functionalization has numerous applications in organic synthesis as a powerful type of bond transformation. In particular, the combination of C-H functionalization with other types of chemical transformations in the manner of multicomponent reactions is an even more beneficial tool in the synthesis of small organic molecules because such reactions provide a platform for the rapid generation of high molecular diversity and complexity by making use of the advantages of both latent C-H bond transformation and the multicomponent reaction. Herein, we provide a review highlighting the research advances in the multicomponent reactions built upon transition metal-catalyzed C-H bond functionalization. The content spans from the reactions featuring the functionalization of C(sp3)-H, C(sp2)-H and C(sp)-H bonds over the last decade.


Atypical adenomatous hyperplasia and bronchoalveolar lung carcinoma. Analysis by morphometry and the expressions of p53 and carcinoembryonic antigen.
Atypical adenomatous hyperplasia (AAH) of the lung is a putative precursor of bronchoalveolar carcinoma (BAC). To define the steps in its development and to clarify at which stage critical cellular events occur, we studied 65 lesions of AAH, early BAC, and overt BAC by morphometric analysis and immunohistochemical evaluation of expression of p53 protein and carcinoembryonic antigen (CEA). Both the nuclear area and lesion size increased from AAH to early BAC and to overt BAC; the standardized variation of nuclear area was smallest in overt BAC. Discriminant analysis using these morphometric parameters revealed high accuracy rates for the respective categories. Analysis of distribution of lung lesions in terms of nuclear area and lesion size yielded effective, potentially diagnostic cutoff values for distinction between AAH and early BAC. Both p53 and CEA expression tended to increase with the advance of atypia grade. In particular, high-level p53 expression was strongly correlated with overt BAC. These findings indicate that our classification of lung lesions is reproducible and thus useful for analyzing the development of BAC. Furthermore, some kinds of p53 gene abnormalities that are correlated with high-level p53 expression likely play an important role in the progression of early to overt BAC.


Divalent nutrient cations: Friend and foe during zinc stress in rice.
Zn deficiency is the most common micronutrient deficit in rice but Zn is also a widespread industrial pollutant. Zn deficiency responses in rice are well documented, but comparative responses to Zn deficiency and excess have not been reported. Therefore, we compared the physiological, transcriptional and biochemical properties of rice subjected to Zn starvation or excess at early and later treatment stages. Both forms of Zn stress inhibited root and shoot growth. Gene ontology analysis of differentially expressed genes highlighted the overrepresentation of Zn transport and antioxidative defense for both Zn stresses, whereas diterpene biosynthesis was solely induced by excess Zn. Divalent cations (Fe, Cu, Ca, Mn and Mg) accumulated in Zn-deficient shoots but Mg and Mn were depleted in the Zn excess shoots, mirroring the gene expression of non-specific Zn transporters and chelators. Ascorbate peroxidase activity was induced after 14 days of Zn starvation, scavenging H2 O2 more effectively to prevent leaf chlorosis via the Fe-dependent Fenton reaction. Conversely, excess Zn triggered the expression of genes encoding Mg/Mn-binding proteins (OsCPS2/4 and OsKSL4/7) required for antimicrobial diterpenoid biosynthesis. Our study reveals the potential role of divalent cations in the shoot, driving the unique responses of rice to each form of Zn stress.


Cortical State Fluctuations during Sensory Decision Making.
In many behavioral tasks, cortex enters a desynchronized state where low-frequency fluctuations in population activity are suppressed. The precise behavioral correlates of desynchronization and its global organization are unclear. One hypothesis holds that desynchronization enhances stimulus coding in the relevant sensory cortex. Another hypothesis holds that desynchronization reflects global arousal, such as task engagement. Here, we trained mice on tasks where task engagement could be distinguished from sensory accuracy. Using widefield calcium imaging, we found that performance-related desynchronization was global and correlated better with engagement than with accuracy. Consistent with this link between desynchronization and engagement, rewards had a long-lasting desynchronizing effect. To determine whether engagement-related state changes depended on the relevant sensory modality, we trained mice on visual and auditory tasks and found that in both cases desynchronization was global, including regions such as somatomotor cortex. We conclude that variations in low-frequency fluctuations are predominately global and related to task engagement.


[BTB allograft for revision surgery of the anterior cruciate ligament - part 2].
The study evaluates our experience with revision anterior cruciate ligament (ACL) surgery, with emphasis placed on the use of allografts. In the 2002-2004 period, 421 reconstructions of the anterior cruciate ligament, using patellar BTB or hamstring tendon autografts, were carried out in our orthopedic ward. In the same period we performed 24 revision ACL reconstructions (6 %) with BTB allografts; 19 were in men and five in women. Revision surgery after ACL reconstruction with a BTB graft fixed with a non-absorbable interference screw and with a hamstring tendon graft was performed in 18 and 5 patients, respectively. We distinguish four steps in the revision procedure: 1) diagnosis and analysis of the ACL reconstruction failure; 2) preoperative planning and surgery timing (one- or two-stage procedure, graft type, fixation method); 3) operative procedure; 4) postoperative care including rehabilitation. Revision surgery is indicated on the basis of subjective complaints (instability), and the results of clinical examination (Lachman's and pivot-shift tests) and imaging methods (X-ray, MRI, arthroscopy). Causes of failure are categorized as 1) traumatic (major trauma, too early weight-bearing, minor trauma due to rehabilitation); 2) surgery-related (erroneous position of the tibial and/or femoral tunnels, insufficient tensioning of the graft and its insufficient fixation); 3) biological (poor ;graft incorporation and restructuring, infection); and 4) combination of all previous causes. Errors in tunnel position are differentiated according to the part of the tunnel (tibial, femoral or both) tunnel direction (ventral, dorsal, lateral or medial) and the degree of malposition (mild, moderate or serious). We perform one-stage surgery when the position of tunnels is correct, with the exception of revision due to infection, and in all malpositions but for a dorsally positioned tibial tunnel. In a moderate degree of femoral tunnel ventral malposition, we make decisions individually. A two-stage procedure consists of removal of the failed graft and fixation material and spongioplasty followed by revision surgery. The results of revision reconstruction greatly depend on a correct isometric position. We extend the tunnel, if it is in a mild-degree malposition, and create a new, smaller tunnel, if the malposition is severe. Fixation, with either the Rigidfix system or interference screws, is also selected according to the direction and degree of malposition. In the last 3 years, we used exclusively grafts harvested from cadavers. In the group of 24 patients undergoing revision ACL reconstruction, the right knee was treated in 13. The previous ACL reconstruction was done with BTB grafts in 18 patients, with hamstring tendons in 5 patients and one patient underwent reconstruction by Harnach's method in an outside institution. The average time between the primary reconstruction and revision surgery was 27 months (range, 4 to 169 months). We found a surgery-associated error in 12 cases. poor graft restructuring in 3 and involvement of traumatic etiology in 11 cases. One patient underwent revision surgery because of infection. We used one-stage procedures in 20 patients and two-stage procedures in four patients. We fixed the graft with femoral interference screws and the Rigidfix system in 17 and 7 patients, respectively, and with tibial interference screws in 23 patients (absorbable screw completed with cancellous screw in one patient). Only in one patient did we use the tibial Rigidfix system. The average follow-up was 16 months. No infection, thromboembolic disease or synovialitis were recorded. One patient experienced a recurrent failure of the graft and one patient was treated for the Cyclops lesion. The average Lysholm scores were 78.25 (range, 48-97); 87.5 % of the patients were satisfied with the results and the same proportion of patients would undergo the surgery again. The overall results appeared poorer due to the patients in whom revision ACL reconstruction was performed on arthritic joints. The outcomes of revision surgery are worse than those in primary reconstruction. We regard allografts with massive bony blocks, adjusted as required, as an optimal method. The risk of disease transmission is low, operative time is shorter, incision is smaller and further trauma to the treated or the other, healthy knee due to graft harvest is avoided. Only patients without signs of gonarthrosis who have motivation are indicated for revision surgery, because they can be expected to cooperate well in the postoperative period. Revision ACL surgery should be performed by surgical teams with sufficient experience in this field. The crucial point is the analysis of ACL reconstruction failure with further procedure planning. The use of BTB allografts from the local tissue bank proved efficient in our hospital. In the hands of experienced surgeons, allograft offer great prospects for ACL reconstruction with good outcome.


Illness experience of Gulf War veterans possibly exposed to chemical warfare agents.
During the 1991 Gulf War, some Allied troops were potentially exposed to chemical warfare agents as the result of the detonation of Iraqi munitions at Khamisiyah. In 1999, we conducted a computer-assisted telephone survey of 2918 Gulf War veterans from Oregon, Washington, California, North Carolina, and Georgia to evaluate the prevalence of self-reported medical diagnoses and hospitalizations among this potentially exposed population and among comparison groups of veterans deployed and nondeployed to the Southwest Asia theater of operations. Troops reported to be within 50 kilometers of the Khamisiyah site did not differ from other deployed troops on reports of any medical conditions or hospitalizations in the 9 years following the Gulf War. Hospitalization rates among deployed and nondeployed troops did not differ. Deployed troops were significantly more likely to report diagnoses of high blood pressure (odds ratio [OR]=1.7); heart disease (OR=2.5); slipped disk or pinched nerve (OR=1.5); post-traumatic stress disorder (OR=14.9); hospitalization for depression (OR=5.1); and periodontal disease (OR=1.8) when compared to nondeployed troops. There was a trend for deployed veterans to report more diagnoses of any cancer (OR=3.0). These findings do not provide evidence of any long-term health effect associated with exposure to the detonation of chemical warfare agents, but support findings from other investigations of increased morbidity among deployed troops. The prevalence of cancer among this population of deployed troops merits ongoing attention.


The search for the ideal tendon repair in zone 2: strand number, anchor points and suture thickness.
This review article examines the mechanical factors involved in tendon repair by sutures. The repair strength, repair stiffness and gap resistance can be increased by increasing the number of core strands and anchor points, by increased anchor point efficiency and the use of peripheral sutures, and by using thicker sutures. In the future, laboratory tests could be standardized to a specific animal model and to a defined cyclic motion programme. Clinical studies support the use of multi-strand core and peripheral sutures, but two-strand core sutures are not adequate to ensure consistently good clinical results. Training surgeons in complex tendon repair techniques is essential.


Determination of Methomyl Residue in Tobacco Samples by Heart-Cutting Two-Dimensional Liquid Chromatography with Tandem Mass Spectrometry.
A novel heart-cutting two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) was developed for the qualitative and quantitative analysis of methomyl residue in tobacco. Compared to traditional methodologies, fairly high sensitivity and stability were achieved, and the sample procedure was simplified in the two-dimensional liquid chromatography (2D-LC) method. Although methomyl had poor retention performance in most of the reversed-phase liquid chromatography (RPLC) columns, an effective RP/RP strategy was successfully facilitated. An XB-Phenyl column was employed in the first dimension to effectively remove thousands of interference compounds in the matrix. In the second dimension, an ADME column was applied for further separation. After optimization of the separation conditions, a six-way valve was utilized for direct transformation of the target fraction from the 1st column to the 2nd column. A dynamic range of 2.5 ng/mL to 500 ng/mL was achieved with correlation coefficient (r 2) greater than 0.9995. The limit of detection and limit of quantification were determined to be 0.69 and 2.30 ng/mL, respectively. The 2D-LC method shows high sensitivity, good reproducibility, and recovery for methomyl in tobacco samples. Therefore, the new method was quite suitable for routine analysis.


A comparative study of anti-gastric cancer activity between aqueous extract and ethanol extract of Folium Cordylines Fruticosae.
The active components in Folium Cordylines Fruticosae were extracted by heat reflux method. The solvents used were distilled water and ethanol. The effects of two types of extracts on gastric cancer cells were compared; dry extract yields were calculated, as well as the inhibition rates of gastric cancer MGC-803 cell proliferation and the colony cell counts. The micro-Kjeldahl method was used to measure the cell protein contents and to make a comprehensive comparison. The results showed that the MGC-803 cell inhibition rates of three different concentrations (32.5, 75 and 150 mg/ml) of ethanol extracts increased with the increase of concentration, which was 48.9% at a concentration of 150 mg/ml; aqueous extract of Folium Cordylines Fruticosae had very low inhibitory activity at a low concentration (32.5 mg/ml), which was remained at about 20%. After being affected by two types of extracts, cells had uneven sizes, with very low brightness, while the normal cells presented a uniform full form, with high definition.


The respiratory syncytial virus transcription antiterminator M(2-1) is a highly stable, zinc binding tetramer with strong pH-dependent dissociation and a monomeric unfolding intermediate.
The human respiratory syncytial virus M(2-1) transcription antiterminator is an essential elongation factor required by the RNA polymerase for effective transcription beyond the first two nonstructural genes. Its exclusive presence in pneumovirus among all paramyxovirus suggests a unique function within this small genus. With the aim of understanding its biochemical properties, we investigated this α-helical tetramer by making use of a biophysical approach. We found that the tetramer hydrodynamic radius is considerably extended at high ionic strengths and determined its zinc content to be one atom per monomer. Dissociation-unfolding experiments show a fully reversible and concentration-dependent cooperative transition, but secondary and tertiary structural changes are uncoupled at lower protein concentrations. We detect the presence of a monomeric intermediate, which can be classified as a "late molten globule" with substantial secondary and tertiary structure. Global fittings of experiments from three different probes at two M(2-1) concentrations provide a free energy of dissociation-unfolding of -36.8 ± 0.1 kcal mol(-1), corresponding to a tight dissociation constant of 10(-28) M(3) at pH 7.0. The tetramer affinity is strongly governed by pH, with a free energy change of 13 kcal mol(-1) when pH decreases from 7.0 to 5.0 (K(D) = 10(-18) M(3)). The drastic changes that take place within a pH range compatible with a cellular environment strongly suggest a regulatory effect of pH on M(2-1) structure and biochemical properties, likely affecting transcription and interaction with proteins and RNA.


The size and fibre composition of the corpus callosum with respect to gender and schizophrenia: a post-mortem study.
In this study the cross-sectional area (in n = 14 female controls, 15 male controls, 11 female patients with schizophrenia, 15 male patients with schizophrenia) and fibre composition (in n = 11 female controls, 10 male controls, 10 female patients with schizophrenia, 10 male patients with schizophrenia) of the corpus callosum in post-mortem control and schizophrenic brains was examined. A gender x diagnosis interaction (P = 0.005) was seen in the density of axons in all regions of the corpus callosum except the posterior midbody and splenium. Amongst controls, females had greater density than males; in patients with schizophrenia this difference was reversed. A reduction in the total number of fibres in all regions of the corpus callosum except the rostrum was observed in female schizophrenic patients (P = 0.006; when controlling for brain weight, P = 0.053). A trend towards a reduced cross-sectional area of the corpus callosum was seen in schizophrenia (P = 0.098); however, this is likely to be no more than a reflection of an overall reduction in brain size. With age, all subregions of the corpus callosum except the rostrum showed a significant reduction in cross-sectional area (P = 0.018) and total fibre number (P = 0.002). These findings suggest that in schizophrenia there is a subtle and gender-dependent alteration in the forebrain commissures that may relate to the deviations in asymmetry seen in other studies, but the precise anatomical explanation remains obscure.


Antibiotic therapy 1985: what are the challenges?
Although antibiotic prescribing has historically been based on antimicrobial spectrum, the increasing numbers of agents with similar coverage have added new dimensions to antibiotic selection. P & T Committees must now evaluate antibiotics based on in vitro activity, pharmacokinetics, and resistance, as well as cost-effectiveness and dosing schedules. Issues may become confusing, and it is important to focus on what is most critical when making antibiotic formulary decisions. Perspectives are offered on the issues of antibiotic features, dosing schedules, and cost-containment; recommendations for optimal antibiotic therapy are made.


Integrated Comprehensive Care for Transcare and Gender Diverse Clinic Patients: An Assessment of Physical, Mental, and Social Needs.
Introduction There is a large body of research reporting the healthcare needs of groups identifying as lesbian, gay, bisexual, transgender, and/or queer (LGBTQ); however, a gap exists in the research literature because many epidemiological studies focus on sexual orientation rather than gender identify/incongruence. To address the lack of specific data from transgender and gender diverse (TGD) individuals, our organization designed and deployed a survey to assess the gender-affirming physical, mental, and social care needs of current patients. Methods A group of subspecialty physicians currently working with TGD patients created a list of questions and requested feedback from medical professionals familiar with the healthcare needs of this population. In addition, patients reviewed the survey for content and clarity. The final 68-item survey was distributed in April 2020 to patients or patients' representatives with an email address on file at the Nebraska Medicine Transgender Care Clinic (NMTCC). Participants were asked to respond to questions regarding their gender identity, their transition-related medical decisions, and their interest in services. Results Invitations were sent to 690 patients and 168 surveys were completed (response rate: 24.3%). Over 90% (n = 153) of the participants were patients and 9% (n = 15) answered survey questions on the patient's behalf. A majority (77.2%) had started the medical transition (hormones or puberty blockers) in the past four years. Nearly half (46.4%) identified as trans women, 43.4% identified as trans men, and 10.2% indicated they were nonbinary or gender expansive. Participants' sex assigned at birth was 50.9% female and 46.1% male. Most patients (n = 149; 92%) reported currently receiving hormone treatment within the Nebraska Medicine healthcare system. Results indicated the highest level of clinical services interest was primary care (38.4%), gender-affirming surgery (73.5%), voice therapy (49.0%), and hair removal (37.5%). In addition, participants were very likely to participate in support groups with "people of similar gender identity" (32.9%), with "others around my age" (28.6%), and "including a mix of ages and identities" (26.9%). Discussion This study suggests that our TGD patients would utilize integrated services to access a variety of clinical and non-clinical services. Ongoing community engagement and direct feedback from patients are critical to the success and growth of our gender-affirming care clinic. The results of this study will inform the planning and further evolution of a program designed to build trust and address health inequities for TGD individuals throughout the region.


Neurofilament phosphorylation regulates axonal transport by an indirect mechanism: a merging of opposing hypotheses.
Neurofilaments (NFs) are among the most abundant constituents of the axonal cytoskeleton. NFs consist of four subunits, termed NF-H, NF-M and NF-L, corresponding to heavy, medium and light in reference to their molecular mass and α-internexin. Phosphorylation of the C-terminal "sidearms" of NF-H and NF-M regulates the ability of NFs to form a cytoskeletal lattice that supports the mature axon. C-terminal phosphorylation events have classically been considered to regulate NF axonal transport. By contrast, studies demonstrating that NF axonal transport was not accelerated following sidearm deletion provided evidence that phosphorylation does not regulate NF transport. Herein, we demonstrate how comparison of transport and distribution of differentially phosphorylated NFs along axons identify common ground between these hypotheses and may resolve this controversy.


Management of infections after arthroscopy.
Management and evaluations of infections after arthroscopy of the knee and shoulder can be difficult and fraught with complications, both medical and legal. This article reviews the literature regarding arthroscopic infections from a historical perspective and discusses the treatment of knee and shoulder infections as well as the complications associated with delayed treatment. It is critical to make the diagnosis as soon as possible subsequent to the initial procedure to avoid postoperative sequelae consisting of stiffness and a decrease in function.


Motif-Based Exploration of Halide Classes of Li5M10.5M20.5X8 Conductors Using the DFT Method: Toward High Li-Ion Conductivity and Improved Stability.
The development of all-solid-state lithium-ion batteries (ASSLIBs) is highly dependent on solid-state electrolyte (SSEs) performance. However, current SSEs cannot satisfactorily meet the requirements for high interfacial stability and Li-ion conductivity, especially under high-voltage cycling conditions. To overcome the intractable problems, we theoretically develop the chemistry of structural units to build a series of MX6-unit mixed framework Li5M10.5M20.5X8 (total 184 halides) for use as SSEs and recommend six halide candidates that combine the (electro)chemical stability with a low Li-ion migration barrier. Among them, three Li5M10.5M20.5F8 compounds (M1 = Ca and Mg; M2 = Ti and Zr) exhibit expansive electrochemical windows with a high cathodic limit (6.3 V vs μLi) and three-dimensional Li diffusion associated with moderate Li-migration barriers. To discuss their stability and compatibility (and in turn as a reference for experiments), the energy above the convex hull, the electrochemical stability window, the predicted (electro)reaction products, and the calculated reaction energies of Li5M10.5M20.5X8 in combination with Li-metal and several cathodes are tabulated. We stress that the importance of the cation-mixed effect and specific moieties for the halide anion leads to a design principle for a halide class of Li-ion SSEs. We provide insight into selecting the optimal halide anion and cations and open a new avenue of broad compositional spaces for stable Li-ion SSEs.


Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials. Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis. The searches identified six trials; none of which met the inclusion criteria for the review. We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update. At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.


Microwave-Hydrothermal Rapid Synthesis of Cellulose/Ag Nanocomposites and Their Antibacterial Activity.
Silver-based antimicrobial nanomaterials are considered as the most promising antibacterial agents owing to their outstanding antimicrobial efficacy and their relatively low toxicity to human beings. In this work, we report on a facile and environment-friendly microwave-hydrothermal method to prepare cellulose/Ag nanocomposites using hemicellulose as the reductant. The influences of the microwave-hydrothermal heating time and temperature, as well as the hemicellulose concentration on the formation of cellulose nanocomposites, were investigated in detail. Experimental results indicated that the hemicellulose was an effective reductant for silver ions, with higher temperature and longer heating time favoring the formation of silver with higher crystallinity and mass content in the nanocomposites. Moreover, the antimicrobial properties of the as-prepared cellulose/Ag nanocomposites were explored using Gram-positive S. aureus ATCC 6538 and Gram-negative E. coli HB 101 by both disc diffusion method and agar dilution method, and the nanocomposites showed excellent antibacterial activity. These results demonstrate that the as-prepared cellulose/Ag nanocomposites, as a kind of antibacterial material, are promising for applications in a wide range of biomedical fields.


[Chemical constituents of the seed oil of Astragalus complanatus R. Brown].
beta-sitosterol and fatty acids were obtained from the oil of seeds of Astragalus complanatus. The fatty acids were separated and their molecular weights determined by GC-MS. Fourteen of them were identified as heptenoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, octadecenoic acid, octadecanoic acid, octadecadienoic acid, linolenic acid, eicosanoic acid, eicosenoic acid and docosanoic acid, etc.


[Retroauricular teratoma with congenital microtia and ankylotia: a case report].
Teratoma is a germ cell tumor, which is rare behind the ear. We described a rare case of retroauricular teratoma accompanied with congenital malformation of external and middle ear and cholesteatoma of middle ear in a 13-years-old girl. Congenital microtia and ankylotia of right ear was found since childhood, suppuration occurred repeatedly behind the right ear 1 year ago. Temporal bone CT and MRI scan revealed congenital malformation of middle ear and cholesteatoma of middle ear. Cystic mass containing a tooth was found intraoperatively. The pathological results showed that it was benign cystic teratoma. It showed no evidence of recurrence on the patient during 3 months follow-up.


Variations of the superficial peroneal nerve and its terminal branches in the Turkish newborn fetuses.
The topography of the superficial peroneal nerve (SPN) and its terminal branches were studied, with the aim of providing further anatomical details for leg and foot in the Turkish newborn fetuses. Limbs from twenty newborn cadavers were dissected. The course of the SPN on the leg and its terminal branches on the foot were investigated. The SPN was lateral (75%), anterior (15%), or branched in both areas (10%) of the cases. The SPN in the dorsum of the feet branched further into medial dorsal cutaneous nerve (MDCn) and intermediate dorsal cutaneous nerve (IDCn). In 82.5% of the cases the MDCn and the IDCn split into three and two branches, respectively. In 10% of the cases, the MDCn gave off three, and the IDCn one terminal branches. In 7.5% of the cases, the MDCn had three while the IDCn had two branches that communicated with the lateral dorsal cutaneous nerve. The course of SPN on the anterolateral surface of the leg and its terminal branches on the dorsal surface of the foot were quite different. This unusual variant location will enable the surgeon to find and preserve the SPN and its terminal branches.


Radical scavenging activity of tea catechins and their related compounds.
(-)-Epigallocatechin gallate was found to be the most effective scavenger among tea catechins for the superoxide anion, hydroxyl radical, and 1,1-diphenyl-3-picrylhydrazyl radical. Examination of the scavenging effects of tea catechins and their glucosides on superoxide anion showed that the presence of at least an ortho-dihydroxyl group in the B ring and a galloyl moiety at the 3 position was important in maintaining the effectiveness of the radical scavenging ability. Stoichiometric factors of tea catechins were estimated to be 2 for (+)-catechin and (-)-epicatechin, 5 for (-)-epigallocatechin, 7 for (-)-epicatechin gallate, and 10 for (-)-epigallocatechin gallate.


Cyclic nucleotide phosphodiesterase activity in bovine brain coated vesicles.
Cyclic AMP phosphodiesterase activity in bovine brain coated vesicles displayed a Km of approximately 22 microM for cyclic AMP, a Vmax of 3.2 nmol/min/mg protein, and a Hill coefficient of 1.5, suggesting positive cooperativity. The enzyme activity was stimulated by cyclic GMP with maximal indexes of stimulation ranging between 40 and 300%. Both basal and stimulated phosphodiesterase activities were immunotitrated with polyclonal antibodies against clathrin attached to heat-inactivated, formaldehyde-fixed Staphylococcus aureus cells. The main form of phosphodiesterase activity present in the immunoprecipitated brain coated vesicle preparation also is stimulated by cyclic GMP. The allosteric behavior was modulated by cyclic GMP. All of these properties are typical of type II or cyclic GMP-sensitive phosphodiesterases in addition to their calcium and calmodulin independence. Competition experiments with a series of phosphodiesterase inhibitors, papaverine, 1-methyl-3-isobutylxanthine, and theophylline, showed inhibition of cyclic AMP hydrolysis. Trifluoperazine was inactive at the highest concentration used, 100 microM. These compounds also inhibited the cyclic GMP-stimulated cyclic AMP hydrolysis with trifluoperazine practically inactive. At 5 microM cyclic AMP none of the inhibitors was seen to stimulate the cyclic AMP hydrolytic activity. The presence of an enzyme for the breakdown of cyclic nucleotides in brain coated vesicles may suggest a role for these second messengers in the in vivo functions of this organelle.


Genetic factors, viral infection, other factors and liver cancer: an update on current progress.
Primary liver cancer is one of the most common cancers at the global level, accounting for half of all cancers in some undeveloped countries. This disease tends to occur in livers damaged through alcohol abuse, or chronic infection with hepatitis B and C, on a background of cirrhosis. Various cancer-causing substances are associated with primary liver cancer, including certain pesticides and such chemicals as vinyl chloride and arsenic. The strong association between HBV infection and liver cancer is well documented in epidemiological studies. It is generally acknowledged that the virus is involved through long term chronic infection, frequently associated with cirrhosis, suggesting a nonspecific mechanism triggered by the immune response. Chronic inflammation of liver, continuous cell death, abnormal cell growth, would increase the occurrence rate of genetic alterations and risk of disease. However, the statistics indicated that only about one fifth of HBV carries would develop HCC in lifetime, suggesting that individual variation in genome would also influence the susceptibility of HCC. The goal of this review is to highlight present level of knowledge on the role of viral infection and genetic variation in the development of liver cancer.


[Multidisciplinary approach in urology. Current imaging studies in urology].
Imaging studies play a crucial role in the diagnosis of urologic diseases. X-ray and ultrasound studies are used as first-line diagnostic methods. Computed tomography and magnetic resonance imaging (MD-CT and MRI), radionuclide and hybrid methods allow to clarify diagnosis. Currently, the trend "from simple to complex" contributes to obtaining maximum information in the shortest possible time with a minimum cost.


[Cloning of beta-amylase gene from B. substitute and its expression in E. coli].
The gene coding for beta-amylase with raw starch-digestion ability was isolated from B. substitute R2 which was selected in this lab. The procedure used in this screening was developed in this work by the method named nutrition-restriction. The DNA fragment containing the beta-amylase gene was 5.25 kb in length. There was no difference in enzymological properties between the beta-amylase produced by the gene-donor strain and the expression product of E. coli. The yield of the cloned beta-amylase was over 500 IU/ml in our laboratory culture condition, the RDA value was 57%, and all of this enzyme were found to be secreted into medium.


Psychoanalytic peregrinations I: Transference and transference neurosis revisited.
The various meanings of transference and transference neurosis are reviewed with special attention to the various roles transference plays in the psychoanalytic process. A study of the provenance of transference is offered with some remarks on the crucial emphasis on understanding and interpreting the transference in psychoanalytic treatment. The danger of using other types of interventions as being manifestations of countertransference is suggested.


Mixed-mode reversed phase/positively charged repulsion chromatography for intact protein separation.
A mixed-mode reversed phase/positively charged repulsion stationary phase C8PN composed of octyl and amino group has been developed for separation of intact protein. Before the separation of proteins, a set of probe compounds were employed to evaluate the chromatographic properties of C8PN, demonstrating typical reversed phase/positively charged repulsion interaction on this stationary phase as estimated. Then the new C8PN stationary phase was used to separate a standard protein mixture on the reversed phase mode. Compared with a commercial C4 stationary phase, it showed different selectivity for some proteins. In order to better understand the properties of C8PN, the effect of acetonitrile content was investigated based on retention equation. Higher values of the equation parameters on C8PN demonstrated that the protein retentions were more sensitive to the change of acetonitrile content. Besides, the influences of buffer salt additives on the protein retentions were also studied. The retention factors of the proteins got larger with the increase of buffer salt concentration, which confirmed the positively charged repulsion interaction on the column. Finally, the C8PN was further applied to separate oxidized- and reduced- forms of Recombinant Human Growth Hormone. Our study indicated the advantages and application potential of mixed-mode reversed phase/positively charged repulsion stationary phase for intact protein separation.


Improving patient flow with a support service call center.
Using a call center model for central transport and housekeeping services is key to improving patient flow. Costs for creating a call center environment are incurred for labor and technology. The hospital's financial executive can help the planning team perform the cost-benefit analysis.


Carotid endarterectomy should not be based on consensus statement duplex velocity criteria.
Randomized trials support carotid endarterectomy (CEA) in asymptomatic patients with ≥60% internal carotid artery (ICA) stenosis. The widely referenced Society for Radiologists in Ultrasound Consensus Statement on carotid duplex ultrasound (CDUS) imaging indicates that an ICA peak systolic velocity (PSV) ≥230 cm/s corresponds to a ≥70% ICA stenosis, leading to the potential conclusion that asymptomatic patients with an ICA PSV ≥230 cm/s would benefit from CEA. Our goal was to determine the natural history stroke risk of asymptomatic patients who might have undergone CEA based on consensus statement PSV of ≥230 cm/s but instead were treated medically based on more conservative CDUS imaging criteria. All patients who underwent CDUS imaging at our institution during 2009 were retrospectively reviewed. The year 2009 was chosen to ensure extended follow-up. Asymptomatic patients were included if their ICA PSV was ≥230 cm/s but less than what our laboratory considers a ≥80% stenosis by CDUS imaging (PSV ≥430 cm/s, end-diastolic velocity ≥151 cm/s, or ICA/common carotid artery PSV ratio ≥7.5). Study end points included freedom from transient ischemic attack (TIA), freedom from any stroke, freedom from carotid-etiology stroke, and freedom from revascularization. Criteria for review were met by 327 patients. Mean follow-up was 4.3 years, with 85% of patients having >3-year follow-up. Four unheralded strokes occurred during follow-up at <1, 17, 25, and 30 months that were potentially attributable to the index carotid artery. Ipsilateral TIA occurred in 17 patients. An additional 12 strokes occurred that appeared unrelated to ipsilateral carotid disease, including hemorrhagic events, contralateral, and cerebellar strokes. Revascularization was undertaken in 59 patients, 1 for stroke, 12 for TIA, and 46 for asymptomatic disease. Actuarial freedom from carotid-etiology stroke was 99.7%, 98.4%, and 98.4% at 1, 3, and 5 years, respectively. Freedom from TIA was 98%, 96%, and 95%, freedom from any stroke was 99%, 96%, and 93%, and freedom from revascularization was 95%, 86%, and 81% at 1, 3, and 5 years, respectively. Patients with intermediate asymptomatic carotid stenosis (ICA PSV 230-429 cm/s) do well with medical therapy when carefully monitored and intervened upon using conservative CDUS criteria. Furthermore, a substantial number of patients would undergo unnecessary CEA if consensus statement CDUS thresholds are used to recommend surgery. Current velocity threshold recommendations should be re-evaluated, with potentially important implications for upcoming clinical trials.


The prevalence of the metabolic syndrome components and their combinations in men and women with acute ischemic syndromes.
During the last decade, it has been shown that the metabolic syndrome and its different components--arterial hypertension (AH), abdominal obesity (AO), diabetes mellitus (DM), atherogenic hypertriglyceridemia (HTG), and/or low concentration of high-density lipoprotein cholesterol (HDL-C))--increase the risk of cardiovascular diseases. There is increasing evidence that the incidence of the metabolic syndrome and the distribution of its components in combinations in the general male and female population differ. The aim of our study was to determine the incidence of the metabolic syndrome in men and women with acute ischemic syndromes and to evaluate the distribution of the metabolic syndrome component combinations in the presence of the metabolic syndrome. Contingent and methods. The study included 2756 patients (1670 males and 1086 females) with acute ischemic syndromes (1997 with myocardial infarction and 759 with unstable angina pectoris), in whom all five components of the metabolic syndrome were assessed. Women were significantly older than men (68.1+/-9.5 vs. 60.2+/-11.8 years, P<0.001). The metabolic syndrome was found (according to modified NCEP III) in 1641 (59.5%) patients (in 70.2% of females and in 52.6% of males, P<0.001). The most common components in both men and women were AH and AO (94.0% vs. 95.9% and 86.4% vs. 84.5%, respectively). HTG was significantly more common in men than in women (80.0% vs. 73.0%, P<0.001), while decreased HDL-C concentration was more common in women (82.8% and 59.2%, P<0.001). The DM component, detected in more than one-third of patients with acute ischemic syndromes, was significantly more common in women than in men (39.2% vs. 33.1%, P<0.05). Combinations of three components were significantly more common in men than in women, while combinations of four-five components were more common in women (55.6% vs. 41.4%, P<0.001; and 58.6% vs. 44.4%, P<0.01). The most common combination of three components in men was AH+AO+HTG and in women--AH+AO+low HDL-C; the most common combination of four components in both men and women was AH+AO+HTG+low HDL-C. CONCLUSION. In the metabolic syndrome, the differences between the components of atherogenic dyslipidemia in patients with acute ischemic syndromes were related to the patients' gender: men significantly more frequently had increased TG concentration and women--decreased HDL-C concentration; this is the problem to be addressed in further studies of dyslipidemia.


Effects of pancreas transplantation on late complications of diabetes and metabolic effects of pancreas and islet transplantation.
Pancreas transplantation has become an accepted therapeutic approach to treat insulin-dependent diabetes mellitus, successfully restoring normoglycemia. In contrast, islet transplantation is still in the experimental phase, only a few operations having being performed world-wide. The aim of this review is to analyze the effects of pancreas transplantation on the late complications of diabetes and to report the endocrino-metabolic effects of pancreas and islet transplantation.


The effect of a prospective intervention program with automated monitoring of hand hygiene performance in long-term and acute-care units at a Veterans Affairs medical center.
To measure the impact of an automated hand hygiene monitoring system (AHHMS) and an intervention program of complementary strategies on hand hygiene (HH) performance in both acute-care and long-term care (LTC) units. Prospective, nonrandomized, before-and-after intervention study. Single Veterans Affairs Medical Center (VAMC), with 2 acute-care units and 6 LTC units. An AHHMS that provides group HH performance rates was implemented on 8 units at a VAMC from March 2021 through April 2022. After a 4-week baseline period and 2.5-week washout period, the 52-week intervention period included multiple evidence-based components designed to improve HH compliance. Unit HH performance rates were expressed as the number of dispenses (events) divided by the number of patient room entries and exits (opportunities) × 100. Statistical analysis was performed with a Poisson general additive mixed model. During the 4-week baseline period, the median HH performance rate was 18.6 (95% CI, 16.5-21.0) for all 8 units. During the intervention period, the median HH rate increased to 21.6 (95% CI, 19.1-24.4; P < .0001), and during the last 4 weeks of the intervention period (exactly 1 year after baseline), the 8 units exhibited a median HH rate of 25.1 (95% CI, 22.2-28.4; P < .0001). The median HH rate increased from 17.5 to 20.0 (P < .0001) in LTC units and from 22.9 to 27.2 (P < .0001) in acute-care units. The intervention was associated with increased HH performance rates for all units. The performance of acute-care units was consistently higher than LTC units, which have more visitors and more mobile veterans.


Which therapy for which patient?
Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks, enhance response to acute medications, improve patient function and reduce disability. Sufficient evidence and consensus exist to recommend propranolol, timolol, amitriptyline, pizotifen, divalproex, sodium valproate and topiramate as first line agents for migraine prevention. These drugs can halve the frequency of attacks in 50% of patients. The anticipated benefit must be weighed against the adverse effects associated with each agent in determining the optimal preventive regimen for individual patients considering any comorbid conditions that are often present. The decision to treat and the choice of prophylactic drug must be taken with the patient. It is important to balance expectations and therapeutic realities for each particular drug. Recent data on the effect of prophylactic treatment on trigeminovascular activation and on cortical spreading depression emphasise the importance of developing research on migraine-preventive drugs.


Pancreatic intraepithelial neoplasms in the normal appearing pancreas: on their precise relationship with age.
Pancreatic intraepithelial neoplasms (PanINs) have been considered as age-related lesions as well as precancerous lesions. However, we do not know their true relationship with age because the former studies did not deal with all age groups. Moreover, the numbers of the patients in each age group were not the same. This study was done to examine the "true relationship" between PanINs and age. Ninety autopsied normal appearing pancreases from all age groups (from under 10s to 80s) were examined. Each group had 10 patients. The relationship between PanINs and age was studied. The sexual difference was also studied. Both the incidence of PanIN positive patients and the number of PanINs increased with age from under 10s to 40s, but they did not correlate with patient age after 40s. The number of PanIN positive patients in the under 10s, 40s and 80s were 2, 10 and 9, respectively. The number of PanINs in the under 10s, 40s and 80s were 11, 127 and 130, respectively. A sexual difference was not seen. The relationship between PanINs and age showed a biphasic correlation pattern before and after 40s. The presence of PanIN positive patients in their first year of age was also a new finding.


Biofilm management using monofilament fibre debridement technology: outcomes and clinician and patient satisfaction.
Best practice in wound bed preparation and biofilm-based wound management includes debridement to create a clean wound bed and to assist in minimising the redevelopment of biofilm. Biofilm that is not removed inhibits healing and redevelops if not prevented from doing so with topical antimicrobial agents. Monofilament fibre debriding technology (MFDT) is used for effective and rapid mechanical debridement of loose material, slough and biofilm. The objective of this evaluation was to determine the clinical effect and consequential levels of health professional and patient satisfaction with the results of a biofilm pathway that included MFDT to achieve debridement. This non-comparative, open label evaluation was conducted in static and non-static wounds that required debridement. MFDT was used to debride in a two-week evaluation of a biofilm pathway. Wounds were debrided three times in week one and twice in week two. Each debridement was followed by treatment with an antimicrobial dressing. Other care included secondary dressings and compression delivered according to local practice, guidelines and formularies. After the clinical evaluation, health professionals were invited to complete an online survey of the clinical outcomes and their satisfaction with the biofilm pathway. There were 706 health professionals who provided answers to the survey questions. Wound types evaluated were leg ulcers (67.4%), pressure ulcers (10%), dehisced surgical wounds (1.7%), diabetic foot ulcers (7.4%) and other wounds (13.4%). Of the wounds, 9% were reported as non-static despite the eligibility criteria. Not all wounds followed the pathway. The most frequently-used antimicrobial was silver. Non-antimicrobial products used included all-in-one dressings, other secondary dressings and compression. There was a change in 77% of wounds overall after two weeks. Change was reported almost equally for both static and non-static wounds. Health professionals who did or did not follow the pathway were 'completely satisfied' or 'satisfied' with the overall clinical outcome 96% and 95%, respectively. Of the patients, 77% were 'completely satisfied' or 'satisfied' with healing after following the pathway, as reported by the treating health professional. The biofilm pathway that includes MFDT appears effective. Wounds managed on the pathway were debrided effectively and healing progressed to the satisfaction of both health professionals and patients.


Antigenic Crossreactivity between Bacterial and Plant Cytochrome P-450 Monoxygenases.
Although cytochrome P-450 monoxygenases mediate critical reactions in plant microsomes, characterization of their activities has been difficult due to their inherent instability and the lack of a crossreacting P-450 antibody. We have surveyed the effects of protein stabilizing agents on t-cinnamic acid hydroxylase (t-CAH), a prominent microsomal P-450, and on total P-450 monoxygenase content. Trans-cinnamic acid is the most effective protecting agent for t-CAH activity. Leupeptin, a broad spectrum protease inhibitor, stabilizes t-CAH activity and increases the apparent P-450 content more than serine protease inhibitors such as phenylmethylsulfonyl fluoride. The combination of t-cinnamic acid and protease inhibitors increase the level of detectable t-CAH activity 4- to 14-fold over the levels detected by previously published procedures. In order to estimate the molecular weights and diversity of the plant P-450 monoxygenases in wounded pea epicotyls, we have prepared two polyclonal antibodies against the Pseudomonas putida camphor hydroxylase (P-450(cam)). One of the heterologous antibodies cross-reacts with constitutive microsomal polypeptides between 52 and 54 kilodaltons and several pea (Pisum sativum L.) mitochondrial proteins between 47 and 48 kilodaltons. The other polyclonal antibody cross-reacts strongly with two wound-induced polypeptides (65 and 47 kilodaltons) and weakly with one constitutive polypeptide (58 kilodaltons). We conclude that at least two subclasses of plant P-450 monoxygenases share common epitopes with the bacterial P-450 enzyme.


California Dentists' Opinions of the Interface Between Oral and Overall Health.
This cross-sectional study investigated California dentists' knowledge and opinion of the interface between oral and overall health. A questionnaire and cover letter explaining the purpose of the study were mailed to 1,100 randomly selected California licensed general dentists. The survey measured dentists' knowledge and opinions of the interface between oral and overall health as well as their recommendations for strengthening this interface. Dentists believed that there was minimal interface between oral and overall health care.


Synthesis and optoelectronic properties of indeno[1,2-b]fluorene-6,12-dione donor-acceptor-donor triads.
We report the synthesis of donor-acceptor-donor triads based on the indeno[1,2-b]fluorene-6,12-dione (IF) scaffold. Arylethynyl donor group attachment expands the light absorption of these molecules to the 600-700 nm region compared to derivatives with nondonating silylethynyl substituents yet does not affect the electron-accepting capabilities of the IF core. All triads show reduction potentials at similar or less negative potentials compared to the silylethynyl derivatives. Protonation studies using the bis(dibutylanilino) triad verify the charge transfer nature of the expanded absorption profile.


Factor XIII and surgical bleeding.
Factor XIII (FXIII) is the final factor in the coagulation cascade. It converts soluble fibrin monomers into a stable fibrin clot, prevents premature degradation of fibrin, participates in wound healing, and helps prevent the loss of the endothelial barrier function. FXIII deficiency is believed to be rare, and this may explain why clinicians do not routinely take it into consideration. Congenital FXIII deficiency is a rare disease with a reported prevalence of 1 per million. However, the prevalence of acquired FXIII deficiency is much higher. Acquired forms have been described in patients with decreased hepatic or bone marrow synthesis, overconsumption and increased degradation by autoantibodies. This review offers guidance on how to suspect and diagnose FXIII deficiency in both the preoperative consultation and different surgical settings. We also analyze current scientific evidence in order to clarify when and why this clinical situation should be suspected, and how it may be treated.


Nurse of the year 2002. An interview with Amanda Howarth.
Dawn Freshwater interviews Nurse of the Year (2002) Amanda Howarth and asks her about her work as a Clinical Nurse Specialist in Pain Management where she is using Complementary Therapies to help patients with Multiple Sclerosis cope with chronic pain.


Neonatal chemical sympathectomy attenuates fructose-induced hypertriglyceridemia and hypertension in rats.
Experiments were performed to determine the pathogenic contribution of the peripheral sympathetic nervous system to fructose-induced hypertriglyceridemia, hyperinsulinemia and hypertension in rats. Neonatal chemical sympathectomy was performed in neonatal Sprague-Dawley rats (1-week old) by administration of guanethidine (50 microg/g, i.p.) 5 times per week for consecutive 3 weeks and nerve-intact rats were served as controls. Both groups of rats were fed a fructose-enriched diet for 9 weeks. The systolic blood pressure (SBP) and body weight were measured weekly and arterial blood samples were taken weekly for determinations of plasma insulin, glucose and triglyceride levels. The results showed that fructose feeding for one week significantly increased SBP in intact rats and sympathectomized rats (116+/-1 to 119+/-1 mmHg and 116+/-1 to 120+/-1 mmHg, respectively). SBP further increased thereafter in both groups. However, the increased SBP levels were significantly higher in intact group than in sympathectomized group after 5 weeks of fructose feeding. Fructose feeding for one week concurrently produced hypertriglyceridemia that preceded the appearance of hyperinsulinemia in both groups. The elevated plasma triglyceride levels were significantly lower in sympathectomized rats than in intact rats after 3 weeks of fructose feeding, whereas the elevated plasma insulin concentrations were not different between groups throughout fructose feeding period. Plasma glucose concentrations of both groups were comparable and remained unchanged throughout the study. These data indicate that neonatal chemical sympathectomy attenuated, but did not prevent, fructose-induced elevations in blood pressure and plasma triglyceride levels, suggesting a partial dependency of fructose-induced hypertriglyceridemia and hypertension on the integrity of the peripheral sympathetic nervous system (SNS) in rats.


Multiscale community detection in Cytoscape.
Detection of community structure has become a fundamental step in the analysis of biological networks with application to protein function annotation, disease gene prediction, and drug discovery. This recent impact creates a need to make these techniques and their accompanying visualization schemes available to a broad range of biologists. Here we present a service-oriented, end-to-end software framework, CDAPS (Community Detection APplication and Service), that integrates the identification, annotation, visualization, and interrogation of multiscale network communities, accessible within the popular Cytoscape network analysis platform. With novel design principles, CDAPS addresses unmet new challenges, such as identifying hierarchical community structures, comparison of outputs generated from diverse network resources, and easy deployment of new algorithms, to facilitate community-sourced science. We demonstrate that the CDAPS framework can be applied to high-throughput protein-protein interaction networks to gain novel insights, such as the identification of putative new members of known protein complexes.


Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes.
Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic β-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated invariant T cells (MAIT cells) are innate-like T-cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I-related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology. In patients with T1D and mice of the non-obese diabetic (NOD) strain, we detected alterations in MAIT cells, including increased production of granzyme B, which occurred before the onset of diabetes. Analysis of NOD mice that were deficient in MR1, and therefore lacked MAIT cells, revealed a loss of gut integrity and increased anti-islet responses associated with exacerbated diabetes. Together our data highlight the role of MAIT cells in the maintenance of gut integrity and the control of anti-islet autoimmune responses. Monitoring of MAIT cells might represent a new biomarker of T1D, while manipulation of these cells might open new therapeutic strategies.


Halting viruses in scale-free networks.
The vanishing epidemic threshold for viruses spreading on scale-free networks indicate that traditional methods, aiming to decrease a virus' spreading rate cannot succeed in eradicating an epidemic. We demonstrate that policies that discriminate between the nodes, curing mostly the highly connected nodes, can restore a finite epidemic threshold and potentially eradicate a virus. We find that the more biased a policy is towards the hubs, the more chance it has to bring the epidemic threshold above the virus' spreading rate. Furthermore, such biased policies are more cost effective, requiring less cures to eradicate the virus.


UDI2Claims: Planning a Pilot Project to Transmit Identifiers for Implanted Devices to the Insurance Claim.
In response to problems with the current postmarket surveillance of medical devices, the U.S. Food and Drug Administration mandated device labelers to include a unique device identifier (UDI), composed of a device identifier (DI) and production identifier. Including the DI in insurance claims could be a potent method to monitor implanted devices, yet implementation has lagged because of questions of benefit and operational concerns. To illustrate the potential benefit of including DIs in claims, rates of 90-day adverse events after implantation using an electronic health record (EHR) were compared with the EHR plus claims, which capture utilization outside that EHR's health system. To explore operations, we planned a pilot project to transmit the DI of implanted devices from the point of care to the claim at two provider/payer pairs. By querying claims plus EHR, estimated rates of patients with potential adverse events were as much as 3.75 times higher. For our pilot, our multistakeholder team identified and resolved the following five challenges: (1) capturing the DI at the point of care; (2) selecting a location for the DI on the claim form; (3) transmitting the DI to the claim form; (4) analyzing the claim forms received by the payer; and (5) verifying the quality of the transmitted information. Including DIs on claims could allow more complete data capture of adverse events for implanted devices than the EHR data. We overcame challenges in transmitting the DI to the claim with attention to planning and multistakeholder involvement.


Autoxidation of Formaldehyde with Oxygen-A Comparison of Reaction Channels.
The autoxidation of formaldehyde through initiation by triplet oxygen is studied via two initial steps: (1) H-atom abstraction and (2) 3O2 addition reaction. The reaction energy profiles show that the reactions are thermodynamically and kinetically demanding. A comparison of the pathways of these initial reactions and the search for a less energy-demanding pathway is presented. The presence of a Brønsted acid has no effect on the energetics of the reaction, while the presence of a single water molecule catalyst enhances the initial reactions. The H-atom abstraction reaction from formaldehyde results in formyl and hydroperoxy radicals. These radicals on further reaction with the second equivalent of 3O2 lead to a CO + 2HO2 product channel. The 3O2 addition reaction to formaldehyde results in a triplet biradical intermediate which further leads to performic acid, the precursor in the synthesis of carboxylic acids from aldehydes. In the presence of water molecules, performic acid is formed in a single kinetic step, and this leads to a CO2 + OH + HO2 product channel upon subsequent reaction with 3O2 in a thermodynamically favorable reaction. The results show that the less established 3O2 addition reaction to aldehydes is a viable route for autoxidation in the absence of purpose-built initiators, in addition to the well-established H-atom abstraction route.


Getting the balance right: Scaling-up treatment and prevention.
The goals of the international response to control the HIV epidemic include high antiretroviral therapy (ART) coverage with HIV viral suppression, as well as reduction of new infections. ART use at individual and population levels reduces HIV morbidity and mortality and likely reduces HIV incidence. HIV viral suppression requires high levels of ART adherence, which necessitates support through behavioural and structural interventions to optimise effectiveness of the use of ART for prevention. Many people living with HIV remain unaware that they are HIV-infected, and HIV transmission risk is high during early infection, therefore ART expansion should be accompanied by other interventions in order to achieve the promise of treatment for prevention. Biomedical and behavioural prevention efforts focused on HIV-uninfected individuals at substantial risk of HIV acquisition are also needed to control the epidemic. Maintaining prevention programming is essential during the scale up of ART to reduce HIV transmission.


Anti-Inflammatory Effects of Aurantio-Obtusin from Seed of Cassia obtusifolia L. through Modulation of the NF-κB Pathway.
Aurantio-obtusin, an anthraquinone compound, isolated from dried seeds of Cassia obtusifolia L. (syn. Senna obtusifolia; Fabaceae) and Cassia tora L. (syn. Senna tora). Although the biological activities of Semen Cassiae have been reported, the anti-inflammatory mechanism of aurantio-obtusin, its main compound, on RAW264.7 cells, remained unknown. We investigated the anti-inflammatory effect of aurantio-obtusin on lipopolysaccharide- (LPS)-induced RAW264.7 cells in vitro and elucidated the possible underlying molecular mechanisms. Nitric oxide production (NO) and prostaglandin E₂ (PGE₂) were measured by the Griess colorimetric method and enzyme-linked immunosorbent assay (ELISA), respectively. Protein expression levels of cyclooxygenase 2 (COX-2) were monitored by cell-based ELISA. Interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) synthesis were analyzed using ELISA. The mRNA expression of nitric oxide synthase (iNOS), COX-2, and the critical pro-inflammatory cytokines (IL-6 and TNF-α) were detected by quantitative real-time PCR. Aurantio-obtusin significantly decreased the production of NO, PGE₂, and inhibited the protein expression of COX-2, TNF-α and IL-6, which were similar to those gene expression of iNOS, COX-2, TNF-α and IL-6 (p < 0.01). Consistent with the pro-inflammatory gene expression, the Aurantio-obtusin efficiently reduced the LPS-induced activation of nuclear factor-κB in RAW264.7 cells. These results suggested that aurantio-obtusin may function as a therapeutic agent and can be considered in the further development of treatments for a variety of inflammatory diseases. Further studies may provide scientific evidence for the use of aurantio-obstusin as a new therapeutic agent for inflammation-related diseases.


[Combined operations: trabeculectomy, crystalline lens extraction and insertion of a posterior chamber implant: a 3-year retrospective study].
Thirty-four eyes of 29 patients with coexisting cataract and glaucoma that underwent glaucoma triple procedure between 1991 et 1994 were retrospectively analyzed. Mean follow-up was 9 months. A phacotrabeculectomy (PHACO-TRAB) was performed in 21 eyes, 13 eyes received extracapsular cataract extraction with trabculectomy (ECCE-TRAB). In 26 eyes, adjunctive 5-FluoroUracil subconjunctival injections were administrated. Our results showed a mean decrease from preoperative intraocular pressure (IOP) baseline of 10.5 mmHg at 3 months. (Mean preoperative IOP = 25.6 mmHg, mean IOP 3 months = 15.1 mmHg). The mean IOP decrease appears equivalent in the PHACOTRAB group compared to the ECCE-TRAB group, with a stable IOP result during the follow-up. Overall mean visual acuity improved from 0.16 preoperatively to 0.6 at 3 months with a slightly better result in the PHACO-TRAB group. Postoperative hyphema and fibrinous anterior uveitis were seen more often in the ECCE-TRAB than in the PHACO-TRAB group. This observation, along with the rapidity of the surgery, the quicker visual rehabilitation and the technique that is less disruptive to the conjunctiva are arguments in favour of phacotrabeculectomy whenever a combined procedure is indicated.


[Effect of anti-Müllerian hormone on P450 aromatase mRNA expression in cultured human luteinized granulose cells].
To investigate the effect of anti-Müllerian hormone (AMH) on hormone secretion and P450 aromatase mRNA expression from cultured human luteinized granulosa cells. Human luteinized granulose cells were derived from 10 patients treated by in vitro fertilization-embryo transplantation (IVF-ET) in the Second Affiliated Hospital of Sun Yat-sen University from June to December 2006. Granulose cells were divided into group A, B, C, D, E depending on different concentration of AMH, testosterone group and blank group. 1x10(-7) mol/L testosterone and 1, 5, 10, 20, 50 microg/L AMH were added into the culture medium of group A, B, C, D and E. 1x10(-7) mol/L testosterone was added into the culture medium of testosterone group while no other ingredient was added into the medium of blank group. Estrogen levels in supernates were measured at 24, 48, 72 hours after cell incubation. RT-PCR was performed to detect the P450 aromatase mRNA expression in group B, C, D, E and testosterone group at 72 hours after cell incubation. (1) Estrogen levels in supernates of granulose cell culture at 24, 48, 72 hours were (8.529+/-0.381)x10(4), (10.977+/-0.436)x10(4), (13.309+/-0.506)x10(4) pmol/L in group A, (7.027+/-0.276)x10(4), (9.167+/-0.300)x10(4), (10.794+/-0.555)x10(4) pmol/L in group B, (6.039+/-0.226)x10(4), (7.585+/-0.548)x10(4), (8.797+/-0.518)x10(4) pmol/L in group C, (5.118+/-0.460)x10(4), (5.716+/-0.496)x10(4), (6.205+/-0.667)x10(4) pmol/L in group D, (4.932+/-0.148)x10(4), (5.323+/-0.184)x10(4), (5.629+/-0.212)x10(4) pmol/L in group E. When compared with blank group [(0.001+/-0.001)x10(4), (0.006+/-0.003)x10(4), (0.029+/-0.011)x10(4) pmol/L], the statistical differences were observed in group A, B, C, D, E (P<0.01); when compared with testosterone group [(8.418+/-0.569)x10(4), (10.841+/-0.689)x10(4), (13.301+/-0.637)x10(4) pmol/L], the statistical differences were observed in group B, C, D and E (P<0.01); statistical differences were also observed in group C, D and E when compared with group B, and also group D and E when compared with group C (P<0.01). No significant difference was observed between group D and E (P>0.05). In group A, B, C, D, E and testosterone group, the estrogen levels at 24 hours after cell culture were significantly lower than those at 48 and 72 hours (P<0.01); statistical difference was observed between estrogen levels at 48 and 72 hours (P<0.01). No significant difference was observed among 24, 48 and 72 hours in blank group (P>0.05). (2) Relative ratios of intensity of P450 aromatase/beta-actin at 72 hours of cell culture in group B, C, D and E were 0.6148+/-0.0046, 0.5156+/-0.0012, 0.4698+/-0.0027 and 0.4282+/-0.0017, respectively, which were statistically lower than that in testosterone group (0.8224+/-0.0021, P<0.01); statistical differences were also observed in group C, D and E when compared with group B, and also group D and E when compared with group C (P<0.01). No significant difference was observed between group D and E (P>0.05). It is suggested that AMH might affect estrogen synthesis by inhibiting P450 aromatose activity so that lead to hyperandrogenism microenvironment in local ovary.


Clinical characteristics and outcomes of patients with severe acute respiratory infections (SARI): results from the Egyptian surveillance study 2010-2014.
Respiratory viral and atypical bacterial infections data in Egyptian patients are sparse. This study describes the clinical features and outcomes of patients with severe acute respiratory infections (SARI) in hospitalized patients in Egypt. SARI surveillance was implemented at Cairo University Hospital (CUH) during the period 2010-2014. All hospitalized patients meeting the WHO case definition for SARI were enrolled. Nasopharyngeal/oropharyngeal (NP/OP) swabs were collected and samples were tested using RT-PCR for influenza A, B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza virus (PIV 1,2,3,4), adenovirus, bocavirus, coronavirus, enterovirus, rhinovirus, and atypical bacteria. Data were analyzed to calculate positivity rates for viral pathogens and determine which pathogens related to severe outcomes or resulted in death. Overall, 1,075/3,207 (33.5%) cases had a viral etiology, with a mean age of 5.74 (±13.87) years. The highest rates were reported for RSV (485 cases, 45.2%), PIV (125, 11.6%), and adenovirus (105, 9.8%). Children had a higher viral rate (981, 91.2%) compared to 94 (8.8%) cases in adults. Patients with identified viruses had significantly lower rates for ICU admission, hospital stay, mechanical ventilation, and overall mortality than those without identified viruses. No infections were independently associated with severe outcomes. Viral pathogens were encountered in one-third of hospitalized adult and pediatric Egyptian patients with SARI, while atypical bacteria had a minor role. Highest rates of viral infections were reported for RSV, PIV, and adenovirus. Viral infections had neither negative impacts on clinical features nor outcomes of patients with SARI in our locality.


Expression and prognostic value of the CD44 splicing variants v5 and v6 in gastric cancer.
In the present study, the expression and prognostic role of the CD44 splicing variants v5 and v6 were immunohistochemically investigated in 418 curatively resected gastric carcinomas. CD44v5 was expressed in 65.3 per cent (n = 273) and CD44v6 in 77.0 per cent (n = 322) of the tumours. Whereas the expression of CD44v5 was correlated with advanced pT categories, with lymph node involvement, and with the presence of blood and lymphatic vessel invasion, such a correlation could not be found for the variant v6. As shown by univariate analysis, patients with CD44v5-positive tumours had a significantly shorter overall survival than patients with CD44v5-negative tumours (P = 0.049). In contrast, expression of CD44v6 had no impact on prognosis (P = 0.574). In a multivariate analysis including the prognostic parameters pT category and pN category, as well as blood and lymphatic vessel invasion, the prognostic impact of CD44v5 expression could not, however, be maintained. Although in the present study the expression of CD44v5 was correlated with a more aggressive tumour type, these data suggest that neither CD44v5 nor CD44v6 can predict survival in patients with gastric cancer, nor is their expression a suitable tool for identifying subgroups of patients who may be at higher risk.


Mechanical valve replacement in congenital heart disease.
Mechanical valves are the prosthesis of choice in valve replacement in children. However, the problem of somatic growth leading to patient-valve mismatch remains present, and the appropriate anticoagulation regimen remains controversial. We present our experience of valve replacement in a young population over 20 years. Between 1972 and 1992, 48 patients (34 males and 14 females), mean age 11.2 years (range 0.4-27.4 years), underwent mechanical valve replacement at our institution. Aortic valve replacement was performed in 28 patients (58.3%), mitral valve replacement in 13 (27.1%), tricuspid valve replacement in six (12.5%) and pulmonary valve replacement in one patient (2.1%). The prostheses used were: St. Jude Medical (n = 2), Björk-Shiley (n = 14), Medtronic Hall (n = 16), Duromedics (n = 2) and CarboMedics (n = 14). Early mortality was 14.3%, 10.7% for aortic valve replacement and 30.8% for mitral valve replacement. Mean follow up for all patients was 8.3 years (range 0-22 years), with a total of 398 patient-years. Seven patients died during the follow up (17.1%). Survival after 10 years, including operative mortality, was 81% for aortic valve replacement, 33% for mitral valve replacement, 83% for tricuspid valve replacement and 100% for pulmonary valve replacement. All patients were anticoagulated with warfarin. In eight patients (16.7%) an antiplatelet drug (aspirin or dipyridamole) was added. Major events included paravalvular leak in six patients (1.5%/pty), valve thrombosis in five (mitral position in two, tricuspid in three) (1.3%/pty) and endocarditis in one patient (0.3%/pty). Minor thromboembolic events occurred in three patients (0.8%/pty) and minor hemorrhagic events in three (0.8%/pty). No patients developed hemolytic anemia and there was no case of structural failure. In our experience, mechanical prostheses in congenital heart disease were associated with significant morbidity and mortality, however long term survival after aortic valve replacement was good (81% at 10 years). Thromboembolic and hemorrhagic events were of minor significance. Atrio-ventricular valve replacement carried the highest risk of valve thrombosis and we now give warfarin and an antiplatelet drug to children undergoing mechanical valve implantation in this position.


Comparison of the antinociceptive profiles of morphine and oxycodone in two models of inflammatory and osteoarthritic pain in rat.
Oxycodone and morphine are two opioid drugs commonly used for the treatment of moderate to severe pain. However, their use in the management of noncancer pain remains a controversial issue and, in this respect, the evidence on their effectiveness and safety, particularly in osteoarthritis, is being questioned. In order to analyse their analgesic profile, two different pain models in rats were used: the formalin-induced inflammatory pain and the monosodium iodoacetate (MIA)-induced knee osteoarthritic pain. Drugs were administered systemically (i.p.) and their antinociceptive effect and potency were assessed. In the formalin test, both morphine and oxycodone produced a dose-dependent antinociceptive effect, but oxycodone outdid morphine in terms of effectiveness and potency (nearly two times) in the early (acute nociceptive) as in the late phase (inflammatory). In the osteoarthritis model, both drugs reduced movement-evoked pain (knee-bend test), mechanical allodynia (von Frey test) and heat hyperalgesia (Plantar test). Pretreatment with naloxone and naloxone methiodide reduced morphine and oxycodone effects. Peripheral mu-opioid receptors play a crucial role in the antinociceptive effect of both drugs on movement-evoked pain and heat hyperalgesia, but not on tactile allodynia. The main finding of our study is that oxycodone has a better antinociceptive profile in the inflammatory and osteoarthritic pain, being more effective than morphine at 14 days post-MIA injection (phase with neuropathic pain); it overcame the morphine effect by improving the movement-induced pain, tactile allodynia and heat hyperalgesia. Therefore, oxycodone could be an interesting option to treat patients suffering from knee osteoarthritis when opioids are required.


The brain-specific activator p35 allows Cdk5 to escape inhibition by p27Kip1 in neurons.
Cell cycle withdrawal in postmitotic cells involves cyclin-dependent kinase (Cdk) inhibitors that repress cell cycle Cdk activity. During mouse neurogenesis, cortical postmitotic neurons are shown here to accumulate high levels of the p27 Cdk inhibitor compared with their progenitor neuroblasts. Elevated p27 levels in staged embryo brain extracts correlate with p27 binding to Cdk2, and Cdk inactivation. Yet, Cdk5, which is associated with the noncyclin activator p35 in neurons, remains active in the presence of high p27 levels. Both in vitro and in vivo, p27 and related inhibitors can recognize a cyclin D-Cdk5 complex but not a p35-Cdk5 complex. The results indicate that the choice of activator determines the susceptibility of Cdk5 to p27 and related Cdk inhibitors, and thus its ability to act in postmitotic cells.


Pre-hospital airway management: guidelines from a task force from the Scandinavian Society for Anaesthesiology and Intensive Care Medicine.
This article is intended as a generic guide to evidence-based airway management for all categories of pre-hospital personnel. It is based on a review of relevant literature but the majority of the studies have not been performed under realistic, pre-hospital conditions and the recommendations are therefore based on a low level of evidence (D). The advice given depends on the qualifications of the personnel available in a given emergency medical service (EMS). Anaesthetic training and routine in anaesthesia and neuromuscular blockade is necessary for the use of most techniques in the treatment of patients with airway reflexes. For anaesthesiologists, the Task Force commissioned by the Scandinavian Society of Anaesthesia and Intensive Care Medicine recommends endotracheal intubation (ETI) following rapid sequence induction when securing the pre-hospital airway, although repeated unsuccessful intubation attempts should be avoided independent of formal qualifications. Other physicians, as well as paramedics and other EMS personnel, are recommended the lateral trauma recovery position as a basic intervention combined with assisted mask-ventilation in trauma patients. When performing advanced cardiopulmonary resuscitation, we recommend that non-anaesthesiologists primarily use a supraglottic airway device. A supraglottic device such as the laryngeal tube or the intubation laryngeal mask should also be available as a backup device for anaesthesiologists in failed ETI.


The functions and dysfunctions of laughter.
Laughter is not usually included in the curriculum of medical schools, therefore it is often neglected by physicians. Laughter is a reflex located in the reticular system of the hindbrain. Rich connections explain its complexity. Laughter appears very early in life and each individual has a very characteristic and stable laughing style. Laughter and speech differentiate human beings from the animal kingdom. Laughter is a unique communication media, common to all human societies speaking different languages. Laughter has a mood elevating and relaxing effect. Laughter dysfunction consists of inappropriate response to the meaning or to the stimulus intensity. In the present study, laughter's dysfunction and disorders are presented. The purpose of this study was to extricate laughter from the diffuse obscurity of information into a new area of interest for scientific research.


Optically Biaxial, Re-entrant and Frustrated Mesophases in Chiral, Non-symmetric Liquid Crystal Dimers and Binary Mixtures.
Sixteen optically active, non-symmetric dimers, in which cyanobiphenyl and salicylaldimine mesogens are interlinked by a flexible spacer, were synthesized and characterized. While the terminal chiral tail, in the form of either (R)-2-octyloxy or (S)-2-octyloxy chain attached to salicylaldimine core, was held constant, the number of methylene units in the spacer was varied from 3 to 10 affording eight pairs of (R & S) enantiomers. They were probed for their thermal properties with the aid of orthoscopy, conoscopy, differential scanning calorimetry and X-ray powder diffraction. In addition, the binary mixture study was carried out using chiral and achiral dimers with the intensions of stabilizing optically biaxial phase/s, re-entrant phases and important phase sequences. Notably, one of the chiral dimers as well as some mixtures exhibited a biaxial smectic A (SmAb ) phase appearing between a uniaxial SmA and a re-entrant uniaxial SmA phases. The mesophases such as chiral nematic (N*) and frustrated phases viz., blue phases (BPs) and twist grain boundary (TGB) phases, were also found to occur in most of the dimers and mixtures. X-ray diffraction studies revealed that the dimers possessing oxybutoxy and oxypentoxy spacers show interdigitated (SmAd ) phase where smectic periodicity is over 1.4 times the molecular length; whereas in the intercalated SmA (SmAc ) phase formed by a dimer having oxydecoxy spacer the periodicity was found to be approximately half the molecular length. The handedness of the helical structure of the N* phases formed by two enantiomers was examined with the aid of CD measurements; as expected, these enantiomers showed optical activities of equal magnitudes but with opposite signs. Overall, it appears that the chiral dimers and mixtures presented herein may serve as model systems in design and developing novel materials exhibiting the apolar SmAb phase possessing D2h symmetry and nematic-type biaxiality.


A pH-sensitive polymer based precise tumor targeting strategy with reduced uptake of nanoparticles by non-cancerous cells.
Drug-loaded nanoparticles can be specifically uptaken by tumor cells to realize active targeting due to the conjugated ligands or antibodies on their surface. However, some non-cancerous cells express non-specific receptors or antigens on their surface, which can react with the ligands or antibodies conjugated on the nanoparticle surface and then result in non-specific uptake of the nanoparticles by non-cancerous cells. In order to reduce the non-specific uptake of nanoparticles by non-cancerous cells, in this study, we proposed a pH-sensitive polymer based precise tumor targeting strategy and synthesized superparamagnetic iron oxide nanoparticle (SPION) encapsulated albumin nanoparticles (AN) with conjugation of folic acid (FA) and mPEG-DCA (SPION-AN-FA@mPEG), in which mPEG can shield FA, avoiding the non-specific recognition by normal cells under physiological conditions, and can be shed to expose FA in tumor microenvironments. The pH-sensitivity of mPEG-DCA was verified by HPLC characterization and 1H-NMR spectroscopy. The graft density and length of mPEG-DCA were optimized via the cellular uptake of SPION-AN-FA@mPEG measured by flow cytometry analysis. The r2 value and r2/r1 ratio of the optimized SPION-AN-FA@mPEG (i.e., SPION-AN-FA@mPEG4) are 168.6 mM-1 s-1 and 42.8, respectively, which are both much higher than that of the commercial contrast agent Resovist®. The in vitro T2-weighted MR images and in vivo MRI performance demonstrate that our SPION-AN-FA@mPEG4 nanoparticles can be used as an effective T2-weighted MRI contrast agent.


Effects of a dry acidulant addition to prevent Salmonella contamination in poultry feed.
Salmonella subs. serovar Enteritidis is a potential biological pathogen of concern in the poultry industry. Contamination of the bacterium on eggshells has led to human illnesses. With the implementation of new regulations, animal feed manufacturing continues to be under more stringent requirements. Specifically, there is zero tolerance for Salmonella Pullorum, Gallinarum, or Enteritidis in poultry feed. For this reason, it is important to determine an effective method of reducing or preventing Salmonella contamination in feed for poultry. Therefore, the objective of this study was to evaluate the impact of sodium bisulfate (SBS; Jones-Hamilton, Co., Walbridge, OH) added to poultry mash to reduce or prevent Salmonella growth over time. A single, commercially produced all-flock poultry mash was mixed with four different levels of SBS: 0.0%, 0.25%, 0.50%, and 0.70%. After SBS addition, the treated mash was inoculated with Salmonella enterica subsp, enterica serovar Enteritidis (ATCC 13076) and enumerated for Salmonella on days 0, 1, 2, 7, and 14 post-inoculation by plating on xylose lysine deoxycholate agar. There was no significant effect of SBS inclusion level on the reduction of Salmonella (P = 0.23); however, there was a significant effect of time across treatments (P < 0.0001). Additionally, there was no inclusion level × time interaction (P = 0.68). These results suggest that while SBS inclusion has no effect on Salmonella concentrations, storage time is effective at reducing or eliminating Salmonella contamination in poultry feed.


An intense, few-cycle source in the long-wave infrared.
For the last several decades, the wavelength range accessible for strong-field, few-cycle studies has remained limited to the visible, near infrared and mid-wave infrared regimes. In particular, sources in the long-wave infrared have been lacking. We report the development of a 1 kHz, few-cycle laser source with up to a 9 μm central wavelength and gigawatt peak powers. When focused, this source can ionize gas targets, which we demonstrate here through the ionization of atomic xenon at wavelengths ranging from 5 μm to 9 μm. This opens up new opportunities for fundamental atomic and molecular physics, enabling experimental tests of strong-field ionization theories in the extreme long-wavelength, few-cycle limit and the direct excitation of vibrational transitions in organic molecules.


Exogenous isoleucine and fatty acid shortening ensure the high content of anteiso-C15:0 fatty acid required for low-temperature growth of Listeria monocytogenes.
Previous studies have demonstrated that the branched-chain fatty acid anteiso-C15:0 plays a critical role in the growth of Listeria monocytogenes at low temperatures by ensuring sufficient membrane fluidity. Studies utilizing a chemically defined minimal medium revealed that the anteiso fatty acid precursor isoleucine largely determined the fatty acid profile and fatty acid response of the organism to lowered growth temperature. When isoleucine was sufficient, the fatty acid profile was very uniform, with anteiso fatty acids comprising up to 95% of total fatty acid, and the major fatty acid adjustment to low temperature was fatty acid chain shortening, which resulted in an increase of anteiso-C15:0 solely at the expense of anteiso-C17:0. When isoleucine was not supplied, the fatty acid profile became more complex and was readily modified by leucine, which resulted in a significant increase of corresponding iso fatty acids and an inability to grow at 10 degrees C. Under this condition, the increase of anteiso-C15:0 at low temperature resulted from the combined effect of increasing the anteiso:iso ratio and chain shortening. A branched-chain alpha-keto acid dehydrogenase-defective strain largely lost the ability to increase the anteiso:iso ratio. Cerulenin, an inhibitor of beta-ketoacyl-acyl carrier protein synthase (FabF), induced a similar fatty acid chain shortening as low temperature did. We propose that the anteiso precursor preferences of enzymes in the branched-chain fatty acid biosynthesis pathway ensure a high production of anteiso fatty acids, and cold-regulated chain shortening results in a further increase of anteiso-C15:0 at the expense of anteiso-C17:0.


The potential of oncogene products as tumour markers.
This paper discusses the possibilities of using the altered expression of oncogenes and their products in neoplastic tissues as markers for the diagnosis, prognosis and monitoring of human malignant disease. Results from our studies of the c-myc oncogene and its product in human solid tumours, using DNA and RNA hybridization and a set of monoclonal antibodies (MCAs) raised against synthetic peptides, are presented. These illustrate three important principles. Firstly, the level of expression of the gene correlates closely with histological grading. Secondly, the increased expression of an oncogene in a tumour can be used as a marker for imaging with radiolabelled MCA. Thirdly, the detection of a 40,000 dalton serum protein, which is immunologically related to the p62c-myc oncoprotein, and its quantitative analysis in patients with cancer and normal controls, suggests that oncogene-related serum proteins may provide novel markers for monitoring tumour activity. These data support the view that the detailed analysis of oncogene expression has the potential to predict a tumour's behaviour and response to different therapeutic modalities.


Effects of ractopamine, genotype, and growth phase on finishing performance and carcass value in swine: I. Growth performance and carcass merit.
A replicated factorial experiment using 183 individually fed crossbred barrows was conducted. Pigs were fed an 18.5% CP (.95% lysine) diet with 3,594 kcal of ME/kg. The effects of five genotypes (GT): 1) Hampshire (H) x (H x Duroc [D]), 2) synthetic terminal sire line, 3) (H x D) x (Landrace [L] x [Yorkshire (Y) x D]), 4) L x (Y x D), and 5) Y x L; two levels of ractopamine (RAC) treatment: 0 and 20 ppm; and three treatment weight periods (WT): 1) 59 to 100, 2) 73 to 114, and 3) 86 to 127 kg live weight on growth performance and carcass traits were evaluated. Ractopamine increased (P less than .0001) amount (FSL) and percentage (PFSL) of carcass lean standardized to 10% fat content, loin eye area (LEA), and dressing percentage (PDRES) and reduced (P less than .01) amount (DF) and percentage (PDF) of dissected fat. Magnitudes of RAC effects were smaller than those reported by other researchers. Effects of GT and WT on all growth and carcass traits were highly significant (P less than .001) except for those of WT on ADG (P less than .05) and GT on average feed intake (AFI) and backfat thickness at the last rib (BFLR; P less than .05). Genotype 3 performed better for most economically important traits than did GT 1 and 4, suggesting that heterosis existed in GT 3, which essentially was obtained by crossing GT 1 and 4. Among the three treatment periods, WT 2 had the highest ADG. As BW increased from WT 1 to 3, AFI and AFI/ADG ratio (FCR) increased and lean percentage decreased.(ABSTRACT TRUNCATED AT 250 WORDS)


EW-7197 Attenuates the Progression of Diabetic Nephropathy in db/db Mice through Suppression of Fibrogenesis and Inflammation.
Diabetic nephropathy (DN) is characterized by albuminuria and accumulation of extracellular matrix (ECM) in kidney. Transforming growth factor-β (TGF-β) plays a central role in promoting ECM accumulation. We aimed to examine the effects of EW-7197, an inhibitor of TGF-β type 1 receptor kinase (ALK5), in retarding the progression of DN, both in vivo, using a diabetic mouse model (db/db mice), and in vitro, in podocytes and mesangial cells. In vivo study: 8-week-old db/db mice were orally administered EW-7197 at a dose of 5 or 20 mg/kg/day for 10 weeks. Metabolic parameters and renal function were monitored. Glomerular histomorphology and renal protein expression were evaluated by histochemical staining and Western blot analyses, respectively. In vitro study: DN was induced by high glucose (30 mM) in podocytes and TGF-β (2 ng/mL) in mesangial cells. Cells were treated with EW-7197 (500 nM) for 24 hours and the mechanism associated with the attenuation of DN was investigated. Enhanced albuminuria and glomerular morphohistological changes were observed in db/db compared to that of the nondiabetic (db/m) mice. These alterations were associated with the activation of the TGF-β signaling pathway. Treatment with EW-7197 significantly inhibited TGF-β signaling, inflammation, apoptosis, reactive oxygen species, and endoplasmic reticulum stress in diabetic mice and renal cells. EW-7197 exhibits renoprotective effect in DN. EW-7197 alleviates renal fibrosis and inflammation in diabetes by inhibiting downstream TGF-β signaling, thereby retarding the progression of DN. Our study supports EW-7197 as a therapeutically beneficial compound to treat DN.