D2-40/podoplanin expression in cancer stroma by immunohistochemical staining is associated with poor prognosis in bladder cancer patients after radical cystectomy.
We assessed whether D2-40/podoplanin (PDPN) could be used to identify bladder cancer patients with a higher probability of benefiting from cisplatin-based combination chemotherapy. We investigated PDPN expression by immunohistochemical analysis of cystectomy specimens from 96 bladder cancer patients who had undergone radical cystectomy without neoadjuvant or adjuvant cisplatin-based combination chemotherapy until recurrence. We classified the cases into 2 groups according to the achievement of 2-year recurrence-free survival (RFS) and evaluated whether PDPN expression was associated with patient prognosis. We also classified the 96 cases into 3 groups according to the possible need for perioperative chemotherapy based on the response to chemotherapy after recurrence as "unnecessary" (achieving 2-year RFS), "responder" (recurring within 2 years and responding to chemotherapy after recurrence), and "non-responder" (not responding chemotherapy following recurrence) and compared PDPN expression between these groups. Among 13 cases diagnosed with clinically <T2 disease, all 13 cases achieved 2-year RFS. Only 6 (8.7%) and 9 cases (13.0%) were classified as "responders" and "non-responders," respectively, out of 69 cases with clinical T2 or higher disease who received cisplatin-based chemotherapy after recurrence. We identified PDPN expression in cancer stroma cells were morphologically fibroblasts, but not in cancer cells. Cases with <1% PDPN staining positivity ratios showed significantly better prognosis compared to that in cases with ≧1% (log-rank tests). Moreover, the positive predictive value and specificity of a <1% PDPN positive staining ratio were 89.5% and 86.7%, respectively, for "unnecessary" perioperative chemotherapy in the 69 cases. Our results confirmed that cisplatin-based perioperative chemotherapy is unnecessary in many cases requiring radical cystectomy. To our knowledge, this is the first report of PDPN expression in bladder cancer stroma cells that are morphologically fibroblasts. Although PDPN expression might be associated with poor prognosis after surgery, we did not find that it helped to predict chemotherapy response. Whether PDPN expression by fibroblasts in high-risk bladder cancer cases is a marker for prognosis after radical cystectomy and response to perioperative cisplatin-based chemotherapy to avoid unnecessary chemotherapy warrants further investigation.


Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis.
To study the biologic role of migration inhibitory factor (MIF), a pleiotropic cytokine, we generated a mouse strain lacking MIF by gene targeting in embryonic stem cells. Analysis of the role of MIF during sepsis showed that MIF-/- mice were resistant to the lethal effects of high dose bacterial lipopolysaccharide (LPS), or Staphylococcus aureus enterotoxin B (SEB) with D-galactosamine and had lower plasma levels of tumor necrosis factor alpha (TNF-alpha) than did wild-type mice, but normal levels of interleukin (IL)-6 and IL-10. When stimulated with LPS and interferon gamma, macrophages from MIF-/- mice showed diminished production of TNF-alpha, normal IL-6 and IL-12, and increased production of nitric oxide. MIF-/- animals cleared gram-negative bacteria Pseudomonas aeruginosa instilled into the trachea better than did wild-type mice and had diminished neutrophil accumulation in their bronchoalveolar fluid compared to the wild-type mice. Thioglycollate elicited peritoneal exudates in uninfected MIF-/- mice, but showed normal neutrophil accumulation. Finally, the findings of enhanced resistance to P. aeruginosa and resistance to endotoxin-induced lethal shock suggest that the counteraction or neutralization of MIF may serve as an adjunct therapy in sepsis.


Determinants of quality of life in adults with epilepsy: a multicenter, cross-sectional study from Germany.
Assessment of quality of life (QoL) has become an important indicator for chronic neurological diseases. While these conditions often limit personal independence and autonomy, they are also associated with treatment-related problems and reduced life expectancy. Epilepsy has a tremendous impact on the QoL of patients and their families, which is often underestimated by practitioners. The aim of this work was to identify relevant factors affecting QoL in adults with epilepsy. This cross-sectional, multicenter study was conducted at four specialized epilepsy centers in Germany. Patients diagnosed with epilepsy completed a standardized questionnaire focusing on QoL and aspects of healthcare in epilepsy. Univariate regression analyses and pairwise comparisons were performed to identify variables of decreased QoL represented by the overall Quality of Life in Epilepsy Inventory (QOLIE-31) score. The variables were then considered in a multivariate regression analysis after multicollinearity analysis. Complete datasets for the QOLIE-31 were available for 476 patients (279 [58.6%] female, 197 [41.4%] male, mean age 40.3 years [range 18-83 years]). Multivariate regression analysis revealed significant associations between low QoL and a high score on the Liverpool Adverse Events Profile (LAEP; beta=-0.28, p < 0.001), Hospital Anxiety and Depression Scale - depression subscale (HADS-D; beta=-0.27, p < 0.001), Neurological Disorders Depression Inventory in Epilepsy (NDDI-E; beta=-0.19, p < 0.001), revised Epilepsy Stigma Scale (beta=-0.09, p = 0.027), or Seizure Worry Scale (beta=-0.18, p < 0.001) and high seizure frequency (beta = 0.14, p < 0.001). Epilepsy patients had reduced QoL, with a variety of associated factors. In addition to disease severity, as measured by seizure frequency, the patient's tolerability of anti-seizure medications and the presence of depression, stigma, and worry about new seizures were strongly associated with poor QoL. Diagnosed comorbid depression was underrepresented in the cohort; therefore, therapeutic decisions should always consider individual psychobehavioral and disease-specific aspects. Signs of drug-related adverse events, depression, fear, or stigmatization should be actively sought to ensure that patients receive personalized and optimized treatment. German Clinical Trials Register (DRKS00022024; Universal Trial Number: U1111-1252-5331).


Modified Parkes tenodesis in claw hand.
The purpose of this report is to present observations on a modified Parkes tenodesis operation for correction of paralytic claw fingers. The long-term results were evaluated in eight adult patients with an observation time of two to six years. As compared to the findings four months after the operation, the results had not deteriorated with time and were found to be good in six patients and fair in two patients.


Morphology of branching trees related to entropy.
Analyses of river systems by geomorphologists have suggested that for minimal entropy production in the movement of water down the river the fall in altitude should be equal in each order of branching of the tributaries. In this paper the same concepts have been applied to the bronchial tree and pulmonary arterial tree, assuming that the energy associated with pressure difference is analogous to that associated with altitude difference in rivers. The morphology of the bronchial tree is such that, given laminar flow or air, the calculated pressure difference across each order is equal. This may indicate that the bronchial tree is designed for minimal entropy production. In the arterial tree, however, this result is not obtained, probably because we do not know how to calculate the pressure drop in blood flowing through a branching system. It is therefore not currently possible, on the basis of this approach, to say whether the pulmonary arterial tree is designed for minimal entropy production or not.


Transient orthostatic hypertension after partial cerebellar resection.
An effective baroreflex and autonomic pathways normally ensure that blood pressure (BP) is satisfactorily maintained, despite various stimuli in daily life that include postural changes. We describe a 20-year-old man with a cerebellar hematoma and acute hydrocephalus, who had a vermian and partial right cerebellar hemisphere resection followed by orthostatic hypertension (OHT) and mutism. On standing his systolic BP rose over 60 mmHg with a fivefold increase in plasma noradrenaline. After a period of 8 weeks, postural BP regulation improved along with his ability to communicate. We conclude that transient impairment of cerebellar autonomic modulation or dysfunction of the baroreflex medullary circuit, may have resulted in OHT.


The inimitable mouth: task-dependent kinematic differences are independent of terminal precision.
Previous studies in our lab have described kinematic difference between grasp-to-eat and grasp-to-place movements, whereby participants produce smaller maximum grip apertures (MGAs) when grasping to bring the item to the mouth than when grasping to bring the item to a container near the mouth. This task difference is limited to right-handed movements, regardless of handedness; it has, therefore, been interpreted as evidence of left-hemisphere lateralization of the grasp-to-eat and other hand-to-mouth grasping movements. However, the difference in end-goal aperture may have accounted for both the kinematic signature (smaller MGAs) and their lateralized expression. Specifically, if the right hand is more sensitive to the precision requirements of secondary movements, it may have produced more precise MGAs for actions whose ultimate goal is the small-aperture mouth rather than a comparatively large aperture container. The current study addresses this question by replacing the previously-used bib with a small drinking glass whose aperture more closely resembles that of the mouth. 25 adult participants reached-to-grasp small cereal items to either (a) eat them, or (b) place them into a small-aperture glass hanging beneath their chin. Results once more showed a lateralised kinematic signature in the form of smaller MGAs for the eat action, demonstrating that the signature is not a result of lateralized sensitivity to a movement's secondary precision requirements. We discuss these results in terms of their impact on predominant theories regarding visual guidance of grasping movements.


Amyloid fibrillation in native and chemically-modified forms of carbonic anhydrase II: role of surface hydrophobicity.
Chemical modification or mutation of proteins may bring about significant changes in the net charge or surface hydrophobicity of a protein structure. Such events may be of major physiological significance and may provide important insights into the genetics of amyloid diseases. In the present study, fibrillation potential of native and chemically-modified forms of bovine carbonic anhydrase II (BCA II) were investigated. Initially, various denaturing conditions including low pH and high temperatures were tested to induce fibrillation. At a low pH of around 2.4, where the protein is totally dissociated, the apo form was found to take up a pre-molten globular (PMG) conformation with the capacity for fibril formation. Upon increasing the pH to around 3.6, a molten globular (MG) form became abundant, forming amorphous aggregates. Charge neutralization and enhancement of hydrophobicity by methylation, acetylation and propionylation of lysine residues appeared very effective in promoting fibrillation of both the apo and holo forms under native conditions, the rates and extents of which were directly proportional to surface hydrophobicity, and influenced by salt concentration and temperature. These modified structures underwent more pronounced fibrillation under native conditions, than the PMG intermediate form, observed under denaturing conditions. The nature of the fibrillation products obtained from intermediate and modified structures were characterized and compared and their possible cytotoxicity determined. Results are discussed in terms of the importance of surface net charge and hydrophobicity in controlling protein aggregation. A discussion on the physiological significance of the observations is also presented.


Bayesian Techniques in Predicting Frailty among Community-Dwelling Older Adults in the Netherlands.
Background Frailty is a syndrome that is defined as an accumulation of deficits in physical, psychological, and social domains. On a global scale, there is an urgent need to create frailty-ready healthcare systems due to the healthcare burden that frailty confers on systems and the increased risk of falls, healthcare utilization, disability, and premature mortality. Several studies have been conducted to develop prediction models for predicting frailty. Most studies used logistic regression as a technique to develop a prediction model. One area that has experienced significant growth is the application of Bayesian techniques, partly due to an increasing number of practitioners valuing the Bayesian paradigm as matching that of scientific discovery. Objective We compared ten different Bayesian networks as proposed by ten experts in the field of frail elderly people to predict frailty with a choice from ten dichotomized determinants for frailty. Methods We used the opinion of ten experts who could indicate, using an empty Bayesian network graph, the important predictors for frailty and the interactions between the different predictors. The candidate predictors were age, sex, marital status, ethnicity, education, income, lifestyle, multimorbidity, life events, and home living environment. The ten Bayesian network models were evaluated in terms of their ability to predict frailty. For the evaluation, we used the data of 479 participants that filled in the Tilburg Frailty indicator (TFI) questionnaire for assessing frailty among community-dwelling older people. The data set contained the aforementioned variables and the outcome "frail". The model fit of each model was measured using the Akaike information criterion (AIC) and the predictive performance of the models was measured using the area under the curve (AUC) of the receiver operator characteristic (ROC). The AUCs of the models were validated using bootstrapping with 100 repetitions. The relative importance of the predictors in the models was calculated using the permutation feature importance algorithm (PFI). Results The ten Bayesian networks of the ten experts differed considerably regarding the predictors and the connections between the predictors and the outcome. However, all ten networks had corrected AUCs >0.700. Evaluating the importance of the predictors in each model, "diseases or chronic disorders" was the most important predictor in all models (10 times). The predictors "lifestyle" and "monthly income" were also often present in the models (both 6 times). One or more diseases or chronic disorders, an unhealthy lifestyle, and a monthly income below 1800 euro increased the likelihood of frailty. Conclusions Although the ten experts all made different graphs, the predictive performance was always satisfying (AUCs >0.700). While it is true that the predictor importance varied all the time, the top three of the predictor importance consisted of "diseases or chronic disorders", "lifestyle" and "monthly income". All in all, asking for the opinion of experts in the field of frail elderly to predict frailty with Bayesian networks may be more rewarding than a data-driven forecast with Bayesian networks because they have expert knowledge regarding interactions between the different predictors.


Single-cell profiling of Arabidopsis leaves to Pseudomonas syringae infection.
Plant response to pathogen infection varies within a leaf, yet this heterogeneity is not well resolved. We expose Arabidopsis to Pseudomonas syringae or mock treatment and profile >11,000 individual cells using single-cell RNA sequencing. Integrative analysis of cell populations from both treatments identifies distinct pathogen-responsive cell clusters exhibiting transcriptional responses ranging from immunity to susceptibility. Pseudotime analyses through pathogen infection reveals a continuum of disease progression from an immune to a susceptible state. Confocal imaging of promoter-reporter lines for transcripts enriched in immune cell clusters shows expression surrounding substomatal cavities colonized or in close proximity to bacterial colonies, suggesting that cells within immune clusters represent sites of early pathogen invasion. Susceptibility clusters exhibit more general localization and are highly induced at later stages of infection. Overall, our work shows cellular heterogeneity within an infected leaf and provides insight into plant differential response to infection at a single-cell level.


Surgery for intestinal graft-versus-host disease: report of two cases.
With allogeneic bone marrow transplantation becoming increasingly common, intestinal graft-versus-host disease often is seen within specialized transplant units. Surgeons are involved infrequently in the management of such patients, and yet occasionally are called upon to operate on critically ill patients with refractory disease. This article reviews the salient features of this condition and discusses possible indications for surgery. Two cases of intestinal graft-versus-host disease that required laparotomy are presented. A 24-year-old male with severe, unremitting, acute intestinal graft-versus-host disease underwent small-bowel and large-bowel resections for massive bleeding. A 35-year-old male with recurrent symptoms of small-bowel obstruction after allogeneic bone marrow transplantation underwent small-bowel resection and multiple strictureplasties for chronic intestinal graft-versus-host disease. Surgery can be performed for complications of intestinal graft-versus-host disease not responding to medical therapy, with successful outcome.


Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients.
The novel coronavirus pneumonia COVID-19 caused by SARS-CoV-2 infection could lead to a series of clinical symptoms and severe illnesses, including acute respiratory distress syndrome (ARDS) and fatal organ failure. We report the fundamental pathological investigation in the lungs and other organs of fatal cases for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. The autopsy and pathological investigations of specimens were performed on bodies of two deceased cases with COVID-19. Gross anatomy and histological investigation by Hematoxylin and eosin (HE) stained were reviewed on each patient. Alcian blue/periodic acid-Schiff (AB-PAS) staining and Masson staining were performed for the examinations of mucus, fibrin and collagen fiber in lung tissues. Immunohistochemical staining was performed on the slides of lung tissues from two patients. Real-time PCR was performed to detect the infection of SARS-CoV-2. Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages. The main pathological features in lungs included extensive impairment of type I alveolar epithelial cells and atypical hyperplasia of type II alveolar cells, with formation of hyaline membrane, focal hemorrhage, exudation and pulmonary edema, and pulmonary consolidation. The mucous plug with fibrinous exudate in the alveoli and the dysfunction of alveolar macrophages were characteristic abnormalities. The type II alveolar epithelial cells and macrophages in alveoli and pulmonary hilum lymphoid tissue were infected by SARS-CoV-2. S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction. Infection of alveolar macrophage by SARS-CoV-2 might be drivers of the "cytokine storm", which might result in damages in pulmonary tissues, heart and lung, and lead to the failure of multiple organs . Shanghai Guangci Translational Medical Research Development Foundation, Shanghai, China.


Carbonic anhydrase inhibition affects contraction of directly stimulated rat soleus.
We have studied the contractile parameters of directly stimulated isolated rat soleus muscles incubated in media containing the carbonic anhydrase inhibitors chlorzolamide (5.10(-4)M) or cyanate (10(-2)M). Both inhibitors caused a decrease in isometric twitch and tetanic (5s) tensions and an increase in muscle relaxation time. It is speculated that among the three types of skeletal muscle carbonic anhydrase it may be the enzyme associated with the sarcoplasmatic reticulum whose inhibition caused the observed changes in contractile parameters.


"People Like Us": News Coverage of Food Assistance During the COVID-19 Pandemic.
To understand how the public discourse around food assistance and social responsibility evolved during the first year of the COVID-19 pandemic by analyzing news coverage. We conducted an ethnographic content analysis of news articles and photographs about food insecurity or food assistance published by U.S. newspapers and wire services between December 1, 2019, and November 30, 2020. We analyzed a random sample of 241 articles and 223 photographs to assess how they depicted food assistance programs, the program participants, and whether they included cues for deservingness. Before the pandemic, news about food assistance was dominated by stories about abuse and fraud. Once COVID-19 began, news coverage contained cues known to engender beliefs about the deservingness of people receiving assistance. During the pandemic, news also highlighted misconceptions about food assistance programs, called for policy changes to reduce logistical barriers, and described the plight of families and other "people like us" in need of food assistance. News coverage during the pandemic cued audience empathy, highlighted the logistical strains faced by food assistance programs, and elevated values of government accountability. The narrative about society's obligation to care for communities in need can be transferred to other safety net programs that protect the public's health. As the pandemic evolves, public health leaders can maintain the narrative about the importance of food assistance and expand the characteristics of this narrative to challenge well-entrenched, but false, narratives about those who need help.


Tracheal Stenosis: Evaluation of an Institutional Protocol and Introduction of Novel Surgical Criteria and Scoring System.
Treatment modalities for treatment of post intubation and post tracheostomy tracheal stenosis are many. However, well defined surgical criteria and prognostic classification eluding us till date. A prospective study of 57 cases of post intubation and post tracheostomy tracheal stenosis managed as per well defined surgical criteria followed in our institution. Patients were divided into three groups as per the primary surgical procedure used. The stenosis was classified into mild, moderate and severe based on our proposed prognostic classification. The success rate of endoscopic procedure was 81% with average 1.6 number of procedures per patient, for tracheoplasty success rate was 63% with 1.4 number of procedure per patient, and similarly for tracheal resection and anastomosis was 90% with 1.1 procedure per patient. The patient score as per our proposed classification correlated well with the prognosis. Our surgical criteria correlates well with success rate reported by other authors and can be helpful for institutions or surgeons dealing with tracheal stenosis occasionally. Our prognostic classification can be used to predict prognosis.


Dopaminergic control of the cough reflex as demonstrated by the effects of apomorphine.
The effect of apomorphine on the cough reflex induced by electrical stimulation of the superior laryngeal nerve was studied in cats anesthetized with pentobarbital. Intravenous administration of apomorphine in doses which ranged from 0.1 to 1.0 mg/kg decreased the number of coughs in a dose-dependent manner. Haloperidol (0.3 mg/kg i.v.) did not significantly change the number of coughs. However, haloperidol administered 15 min prior to administration of apomorphine abolished the apomorphine-induced decrease in the number of coughs. These results suggest that dopaminergic mechanisms could have an important role in the regulation of the cough reflex.


Interactions of conventional or photopolymerized liposomes with platelets in vitro.
We have examined the effects of liposomes on in vitro platelet aggregation. Liposomes were prepared from various conventional lipids and from a novel photopolymerizable phosphatidylcholine derivative (DPL, bis[1,2-(methacryloyloxy)dodecanoyl]-L-alpha-phosphatidylcholine). None of the liposome preparations studied caused marked platelet aggregation in either plasma or buffer solution. However, positively charged vesicles impaired the ability of platelets in plasma to aggregate in response to ADP, whereas negatively charged vesicles impaired the ability of platelets in buffer to aggregate in response to thrombin. DPL vesicles had only modest effects on platelets in plasma or buffer.


MGMT is frequently inactivated in pancreatic NET-G2 and is associated with the therapeutic activity of STZ-based regimens.
O6-methylguanine-DNA methyltransferase (MGMT) has been linked with alkylating agent resistance and tumor growth suppression. However, its role remains undetermined in pancreatic neuroendocrine tumors (Pan-NET). The MGMT expression was examined by immunohistochemistry in 142 patients to evaluate MGMT immunoreactivity and clinicopathological factors. We analyzed the relationship between MGMT expression and treatment efficacy in 19 patients who received STZ-based regimens. In 142 Pan-NET, 97 cases (68.3%) were judged as MGMT-positive and 45 cases (31.6%) as negative. MGMT negativity was significantly more common in NET-G2 (62.5%) than in NET-G1 (11.2%, p < 0.001). MGMT-negative cases were associated significantly with larger tumor size (p < 0.01), higher Ki-67 index (p < 0.01), higher mitotic index (p < 0.05), and more frequent liver metastasis (p < 0.05). Of the 19 cases treated with STZ, 6 cases were determined as SD and 4 cases as PD in MGMT-positive patients (N = 10), while 5 cases were determined as PR and 4 cases as SD in MGMT-negative patients (N = 9). Progression-free survival in MGMT-negative cases was significantly better than in MGMT-positive cases (p < 0.05). MGMT expression was lower in NET-G2 than in NET-G1, and STZ-based regimens improved the therapeutic outcomes of MGMT-negative Pan-NET. These findings indicate that NET-G2 may represent a better therapeutic target for STZ treatment.


Pexophagy is induced by increasing peroxisomal reactive oxygen species in 1'10-phenanthroline-treated cells.
Although autophagy regulates the quality and quantity of cellular organelles, the regulatory mechanisms of peroxisomal autophagy remain largely unknown. In this study, we developed a cell-based image screening assay, and identified 1,10-phenanthroline (Phen) as a novel pexophagy inducer from chemical library screening. Treatment with Phen induces selective loss of peroxisomes but not endoplasmic reticulum and Golgi apparatus in hepatocytes. In addition, Phen increases autophagic engulfment of peroxisomes in an ATG5 dependent manner. Interestingly, treatment of Phen excessively produces peroxisomal reactive oxygen species (ROS), and inhibition of the ROS suppresses loss of peroxisome in Phen-treated cells. Taken together, these results suggest that Phen triggers pexophagy by enhancing peroxisomal ROS.


New registered nurse and registered psychiatric nurse graduates' transition-to-practice amid the pandemic: An art-based grounded theory study.
According to the Transition Shock theory, new Registered Nurses face formidable obstacles within their first year of practice. However, little is known about the experience of new Registered Psychiatric Nurses entering the workforce. The aim was to explore how new graduates from nursing and psychiatric nursing experience their transition into the workplace that included identifying mediating factors that assist or challenge these entry-level professionals within their transition. Constructivist grounded theory methodology developed by Charmaz was utilized to explore the first-year transition period using art-based methods. A total of 13 new graduates practicing as Registered Nurses and Registered Psychiatric Nurse in a western Canadian province were recruited to participate in the study. Three art-based workshops occurred at four, eight, and 12-months starting in the fall of 2020 through the Spring of 2021 during the novel coronavirus pandemic with subsequent member checks in the Spring of 2022. A total of 38 interview and focus group data were collected. Art-based activities included sand tray and figurine object exercises, collaging, reflective and thematic writing, as well as group concept mapping. Through co-creation of knowledge using Charmaz's methodology, participants selected the major themes throughout their first year of transition with guided researcher facilitation. Data were analyzed using the constant comparative method of analysis for each workshop drawing on the art creations, discussion, and narrative reflective writing pieces generated by participants. Participants were in a basic psychosocial process of growing personal and professional self. Through co-construction of knowledge with the participants, three substantive interconnected categories were identified: (1) Being thrown into the fire; (2) Adjusting and adapting to the team environment; and (3) Nurturing self and others. The findings revealed many recommendations for employers hiring new graduates and nursing education programs preparing graduates for the practice arena.


Thioesterase domain swapping of a linear polyketide tautomycetin with a macrocyclic polyketide pikromycin in Streptomyces sp. CK4412.
Tautomycetin (TMC) is a linear polyketide metabolite produced by Streptomyces sp. CK4412 that has been reported to possess multiple biological functions including T cell-specific immunosuppressive and anticancer activities that occur through a mechanism of differential inhibition of protein phosphatases such as PP1, PP2A, and SHP2. We previously reported the characterization of the entire TMC biosynthetic gene cluster constituted by multifunctional type I polyketide synthase (PKS) assembly and suggested that the linear form of TMC could be generated via free acid chain termination by a narrow TMC thioesterase (TE) pocket. The modular nature of the assembly presents a unique opportunity to alter or interchange the native biosynthetic domains to produce targeted variants of TMC. Herein, we report swapping of the TMC TE domain sequence with the exact counterpart of the macrocyclic polyketide pikromycin (PIK) TE. PIK TE-swapped Streptomyces sp. CK4412 mutant produced not only TMC, but also a cyclized form of TMC, implying that the bioengineering based in vivo custom construct can be exploited to produce engineered macrolactones with new structural functionality.


Modeling Clot Formation of Shear-Injured Platelets in Flow by a Dissipative Particle Dynamics Method.
The regions with high non-physiological shear stresses (NPSS) are inevitable in blood-contacting medical devices (BCMDs) used for mechanically assisted circulatory support. NPSS can cause platelet activation and receptor shedding potentially resulting in the alteration of hemostatic function. In this study, we developed a dissipative particle dynamics model to characterize clot formation (platelet-collagen and inter-platelet adhesion) of NPSS-traumatized blood at a vascular injury site. A rectangular tube of 50 × 50 × 200 µm with an 8 × 8 µm collagen-coated area was modeled as a small blood vessel and perfusion with blood. Clot formation dynamics during perfusion was simulated. NPSS-traumatized blood was modeled to have more activated platelet and fewer adhesion receptors with weakened inter-platelet binding. Computational results showed that clots grew at a faster rate while the structure of the clots was less stable and collapsed more frequently for NPSS-traumatized blood compared with normal blood. The finding that NPSS-traumatized platelets could result in quicker but more easily breakable blood clots at injury sites may explain why increased risks of thrombotic and bleeding complications occurred concurrently in patients implanted with BCMDs.


Suppression of nitric oxide oxidation to nitrite by curcumin is due to the sequestration of the reaction intermediate nitrogen dioxide, not nitric oxide.
Curcumin, a phytochemical with antioxidant and other cytoprotective properties, has been reported to reduce nitrite formation during nitric oxide (NO) oxidation in solution. This decrease in nitrite production was attributed to the direct sequestration of NO by curcumin. In this report, we confirm that curcumin inhibits nitrite formation from DEA/NO-derived NO in a concentration-dependent manner. However, curcumin over a concentration range of 3-50 microM had no effect on the concentration of free NO (0.5 microM) in solution at 37 degrees C as assessed using an NO electrode. We conclude that the inhibitory effect of curcumin on the oxidation of NO to nitrite is due to its known sequestration of the reaction intermediate nitrogen dioxide (NO(2)). The ability of curcumin to sequester NO(2), but not NO, suggests that curcumin may be useful for separating the actions of NO(2) from those of NO in various biological systems.


Long thoracic nerve release for scapular winging: clinical study of a continuous series of eight patients.
Scapular winging secondary to serratus anterior muscle palsy is a rare pathology. It is usually due to a lesion in the thoracic part of the long thoracic nerve following violent upper-limb stretching with compression on the nerve by the anterior branch of thoracodorsal artery at the "crow's foot landmark" where the artery crosses in front of the nerve. Scapular winging causes upper-limb pain, fatigability or impotence. Diagnosis is clinical and management initially conservative. When functional treatment by physiotherapy fails to bring recovery within 6 months and electromyography (EMG) shows increased distal latencies, neurolysis may be suggested. Muscle transfer and scapula-thoracic arthrodesis are considered as palliative treatments. We report a single-surgeon experience of nine open neurolyses of the thoracic part of the long thoracic nerve in eight patients. At 6 months' follow-up, no patients showed continuing signs of winged scapula. Control EMG showed significant reduction in distal latency; Constant scores showed improvement, and VAS-assessed pain was considerably reduced. Neurolysis would thus seem to be the first-line surgical attitude of choice in case of compression confirmed on EMG. The present results would need to be confirmed in larger studies with longer follow-up, but this is made difficult by the rarity of this pathology. III.


Effects of pyruvate on post-ischemic myocardial recovery at various workloads.
In the present study the hemodynamic and metabolic effects of pyruvate (5 mM), added as cosubstrate to glucose (11 mM) perfused, transiently ischemic, isolated working rat hearts, were evaluated. During 2 h of normoxic perfusion pyruvate improved functional stability, prevented depletion of glycogen and triacylglycerol stores, and increased non-esterified fatty acid (NEFA) levels, even at relatively high workloads. The elevated NEFA levels are in line with the notion that pyruvate competes with endogenously produced fatty acids for oxidative energy production. After 45 min of global ischemia pyruvate was found (a) to affect markedly the relative contribution of ATP, ADP and AMP to the total adenine nucleotide content and (b) to stimulate the degradation of glycogen and to enhance the accumulation of lactate, suggesting enhanced anaerobic ATP production. After restoration of flow pyruvate reduced the incidence of fibrillation and markedly improved recovery of cardiac output at both normal and high workload. Pyruvate did neither attenuate the release of lactate dehydrogenase, a marker for cell death, nor improve the conservation of the total adenine nucleotide and ATP content of hearts reperfused for 30 min. The latter findings indicate that hemodynamic recovery during reperfusion in the presence of pyruvate is neither related to the absolute tissue content of ATP nor to a reduction of irreversible cell damage, and suggest that pyruvate exerts its advantageous hemodynamic effects rather by improving the condition of reversibly damaged cells during reperfusion.


Adhesiveness and morphology of Lewis lung carcinoma variants influence their sensitivity to natural killer cytolysis and their metastatic capacity.
Cloned metastatic Lewis lung carcinoma cells, C3, were more resistant to natural killer (NK) lysis than were nonmetastatic variant cells, C8. This was influenced by the tumor cell adhesiveness and morphology. When the nonadherent round C3 cells were cultured with dimethylsulfoxide, they became adherent and spread, sensitive to NK lysis and less metastatic. When the adherent and spread C8 cells were made nonadherent and round with cytochalasin B, they became more resistant to NK lysis and more metastatic. These metastatic differences were not observed in 3-week-old NK-deficient mice.


Tracheitis: the 'other' cause of upper airway obstruction.
A 22-year-old woman presented to an ear, nose, and throat clinic with an upper respiratory infection and sudden stridorous respirations. Aerosolized isoethrane therapy was beneficial and fiber-optic nasolaryngoscopy revealed a normal supraglottis and purulent intratracheal secretions. Secretions were cultured and grew Staphylococcus aureus and alpha hemolytic Streptococcus. IV cefazolin was initiated and the patient recovered without sequelae. This case illustrates a rare cause of upper airway obstruction, tracheitis. Tracheitis has been found in the pediatric literature. This is the first adult case reported in the literature.


Significant clinical and radiological resolution of a spinal cord syrinx following the release of a tethered cord in a patient with an anatomically normal conus medullaris. Case report.
The authors describe a case of progressive neurological deficit caused by syringomyelia in a 7-year-old boy with a normally positioned conus medullaris. This deficit responded favorably to surgical untethering of the filum terminale, with subsequent clinical and radiological improvement. The authors discuss the implications of their findings in the context of the current understanding of the pathophysiology of tethered cord syndrome, particularly in relation to the ongoing debate in the neurosurgical literature.


Cytomegalovirus infection in ulcerative colitis: a prospective, comparative study on prevalence and diagnostic strategy.
Cytomegalovirus (CMV) infection has been reported in ulcerative colitis (UC), especially in severe, steroid-refractory disease. However, its role in steroid-refractoriness remains unknown. Our goals were to evaluate the prevalence of CMV disease in UC, the best diagnostic strategy, and the influence of disease activity and/or treatment in its development. Prospective, observational study including 114 subjects with active UC requiring intravenous steroids, steroid-refractory UC, inactive UC on mesalamine, inactive UC on azathioprine, and healthy controls. CMV antibodies, pp65-antigenemia, and rectal biopsies for hematoxylin and eosin staining, immunohistochemistry, and CMV-pp67 mRNA were performed. These procedures were repeated after medical treatment only in patients with active UC. CMV disease was defined by the presence of inclusion bodies and/or positive immunohistochemistry in colonic biopsies. CMV disease was found in 6 steroid-refractory, CMV-IgG-positive UC patients but not among controls, inactive UC, or steroid-responding UC patients. In 5 out of the 6 patients, CMV disease was diagnosed after 7-10 days on cyclosporine. CMV disease in UC only affects seropositive, steroid-refractory UC patients. Steroid/cyclosporine treatment together with disease activity may predispose to latent colonic CMV reactivation. The impact of antiviral therapy on the clinical outcome of these patients remains to be elucidated.


Gordonia sp.: a salt tolerant bacterial inoculant for growth promotion of pearl millet under saline soil conditions.
In the resent study, a diazotrophic bacterial isolate JPA2 having the ability to tolerate salinity (6 % NaCl) and plant growth-promoting features was isolated from rhizospheric soil of weed Chenopodium murale growing in saline soil of Pindara (EC 11.47 dS m-1), district Jind (Haryana). The nitrogen fixing ability of the isolate was confirmed by nifH gene amplification and acetylene reduction assay (38.9 nmol ethylene h-1 mg-1 protein). The potential of strain JPA2 to promote growth of pearl millet was investigated by inoculation experiment which showed significant increase in plant height (51.1, 39.9 and 28.8 %) and dry weight (55.9, 36.4 and 35.5 %) over uninoculated control plants at EC 0, 6, 8 dS m-1, respectively. The strain JPA2 was Gram +ve and identified as Gordonia sp. on the basis of partial 16S rRNA gene sequencing and biochemical characterization. It is concluded that salt tolerant diazotrophic Gordonia sp. can be considered as a beneficial microbe for agriculture in saline soils.


Corrigendum to "Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho-/- mouse".
[This corrects the article DOI: 10.1038/mtm.2015.16.].


Ionic partial molar volumes of density gradient salts at finite concentrations.
A general method is presented for estimating concentration-dependent partial molar volumes for individual ions of heavy density gradient salts used in the isopycnic ultracentrifugation of charged macromolecules.


Stratified microbial communities in Australia's only anchialine cave are taxonomically novel and drive chemotrophic energy production via coupled nitrogen-sulphur cycling.
Anchialine environments, in which oceanic water mixes with freshwater in coastal aquifers, are characterised by stratified water columns with complex physicochemical profiles. These environments, also known as subterranean estuaries, support an abundance of endemic macro and microorganisms. There is now growing interest in characterising the metabolisms of anchialine microbial communities, which is essential for understanding how complex ecosystems are supported in extreme environments, and assessing their vulnerability to environmental change. However, the diversity of metabolic strategies that are utilised in anchialine ecosystems remains poorly understood. Here, we employ shotgun metagenomics to elucidate the key microorganisms and their dominant metabolisms along a physicochemical profile in Bundera Sinkhole, the only known continental subterranean estuary in the Southern Hemisphere. Genome-resolved metagenomics suggests that the communities are largely represented by novel taxonomic lineages, with 75% of metagenome-assembled genomes assigned to entirely new or uncharacterised families. These diverse and novel taxa displayed depth-dependent metabolisms, reflecting distinct phases along dissolved oxygen and salinity gradients. In particular, the communities appear to drive nutrient feedback loops involving nitrification, nitrate ammonification, and sulphate cycling. Genomic analysis of the most highly abundant members in this system suggests that an important source of chemotrophic energy is generated via the metabolic coupling of nitrogen and sulphur cycling. These findings substantially contribute to our understanding of the novel and specialised microbial communities in anchialine ecosystems, and highlight key chemosynthetic pathways that appear to be important in these energy-limited environments. Such knowledge is essential for the conservation of anchialine ecosystems, and sheds light on adaptive processes in extreme environments. Video Abstract.


Chromosome abnormalities in a pancreatic adenocarcinoma.
Short-term cultures initiated from a pancreatic adenocarcinoma were cytogenetically investigated. The composite karyotype was 74-76,XX,+X,+2,+3,+del(3)(p21),+5,+5,+der(7) t(1;7)(q21;p22),+der(7),del(8)(p21),+del(8)(p21),+der(8)t(8;?)(q24; +),+9,+9,+10,+10,+11,+11,+12,+13,+14,+der(14)t(14; +)(p11;?),+der(16)t(15;16)(q11;p13),+der(16),+der(17)t(17;?) (p11;?),+der(17),+18,+20,+20,-21,-21,+22,+22,+1-3mar. A comparison with the few previously cytogenetically characterized cases of this tumor type reveals no consistent abnormalities.


Immune Response and Protective Efficacy of Inactivated and Live Influenza Vaccines Against Homologous and Heterosubtypic Challenge.
Inactivated (whole-virion, split, subunit, and adjuvanted) vaccines and live attenuated vaccine were tested in parallel to compare their immunogenicity and protective efficacy. Homologous and heterosubtypic protection against the challenge with influenza H5N1 and H1N1 viruses in a mouse model were studied. Single immunization with live or inactivated whole-virion H5N1 vaccine elicited a high level of serum antibodies and provided complete protection against the challenge with the lethal A/Chicken/Kurgan/3/05 (H5N1) virus, whereas application of a single dose of the split vaccine was much less effective. Adjuvants increased the antibody levels. Addition of the Iso-SANP adjuvant to the split vaccine led to a paradoxical outcome: it increased the antibody levels but reduced the protective effect of the vaccine. All tested adjuvants shifted the ratio between IgG1 and IgG2a antibodies. Immunization with any of the tested heterosubtypic live viruses provided partial protection against the H5N1 challenge and significantly reduced mouse mortality, while inactivated H1N1 vaccine offered no protection at all. More severe course of illness and earlier death were observed in mice after immunization with adjuvanted subunit vaccines followed by the challenge with the heterosubtypic virus compared to challenged unvaccinated animals.


A novel identification method using perceptual degree of concordance of occlusal surfaces calculated by a Python program.
One of the important issues during the response to a mass disaster is the identification of victims. In this study, we verified the use of the occlusal morphology of molars for individual identification. The aim of this study was to establish a simple new method for identifying individuals from molar data. Using Python, we developed programming that included the perceptual Hash (pHash) function and the Hamming distance (HD) between antemortem data (AMD) and postmortem data (PMD). The AMD comprised 2,215 dental models. The PMD were selected from the AMD set and comprised 17 models from the same individual with changes over time. As a result, 16 PMD models (over 90%) were ranked in the top 5%. Although identification using only a single molar is difficult, there is the possibility of narrowing down victims' identity with high accuracy through verification using multiple teeth. This system is expected to be useful as a very simple method of identification.


[Evaluation of regional anesthesia procedure in an emergency department].
Evaluation of regional anaesthesia procedures for limb traumatic surgery performed in an emergency department. Anaesthetic procedures concerning traumatic emergencies have been studied from 1995 to 2000. A 32% increase in anaesthesia practice was observed from 1995 (221) to 2000 (292) with a 52% increase in regional anaesthesia. Since 1996, regional anaesthesia represents more than 80% of the anaesthetic procedures and 90% for the upper limb surgery (66% of the surgical procedures). Axillary block (50%), interscalene brachial plexus block (15%) and combined sciatic and femoral nerve block (17%) were the main regional anaesthesia procedures. Spinal anaesthesia (9 cases) and intravenous locoregional anaesthesia (12 cases) were rarely used. In our study, regional anaesthesia is the most used technique when compared to general anaesthesia for emergency procedure. The anaesthetic staff has to be motivated and trained.


Underlying mechanism of Qiling Jiaogulan Powder in the treatment of broiler ascites syndrome.
Broiler ascites syndrome (AS), is a nutritional and metabolic disease that occurs in fast-growing commercial broiler chickens. AS can cause poor growth and a significant increase in the rate of broiler deaths, which has resulted in serious economic losses to the poultry industry. The classic traditional Chinese medicine Qiling Jiaogulan Powder (QLJP) has been demonstrated to have a certain therapeutic effect on broiler AS. However, its pharmacological mechanism remains to be elucidated. This study was performed to investigate the multitarget action mechanism of QLJP in the treatment of broiler AS based on network pharmacology analysis using a broiler AS model. First, all chemical components and targets of QLJP were obtained from the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP). Targets related to broiler AS were further obtained through the GeneCards database and the NCBI Gene sub-database. A protein-protein interaction (PPI) network was constructed. Then, enrichment analyses were performed to predict the potential mechanisms of QLJP in the treatment of broiler AS. Finally, the treatment effect of QLJP on AS was verified in a broiler AS model. Network pharmacology analysis generated 49 active ingredients and 167 core targets of QLJP, and a QLJP-single drug-target-disease network was successfully constructed. Gene enrichment analysis indicated that the core targets have played major roles in the Cell cycle, FOXO signaling pathways, etc. We demonstrated that QLJP improved clinical and organ damage symptoms and significantly reduced the ascites heart index in broilers with AS induced by administration of high-energy, high-protein diets and high-sodium drinking water in a low-temperature environment. QLJP may regulate lung oxidative stress, the cell cycle and apoptosis by activating the FOXO3a signaling pathway to interfere with the occurrence and development of AS in broilers. QLJP administration may be a good clinical strategy for the prevention and treatment of broiler AS.


Fetal MRI: what's new? A short review.
Fetal magnetic resonance imaging (fetal MRI) is usually performed as a second-level examination following routine ultrasound examination, generally exploiting morphological and diffusion MRI sequences. The objective of this review is to describe the novelties and new applications of fetal MRI, focusing on three main aspects: the new sequences with their applications, the transition from 1.5-T to 3-T magnetic field, and the new applications of artificial intelligence software. This review was carried out by consulting the MEDLINE references (PubMed) and including only peer-reviewed articles written in English. Among the most important novelties in fetal MRI, we find the intravoxel incoherent motion model which allow to discriminate the diffusion from the perfusion component in fetal and placenta tissues. The transition from 1.5-T to 3-T magnetic field allowed for higher quality images, thanks to the higher signal-to-noise ratio with a trade-off of more frequent artifacts. The application of motion-correction software makes it possible to overcome movement artifacts by obtaining higher quality images and to generate three-dimensional images useful in preoperative planning.Relevance statementThis review shows the latest developments offered by fetal MRI focusing on new sequences, transition from 1.5-T to 3-T magnetic field and the emerging role of AI software that are paving the way for new diagnostic strategies.Key points• Fetal magnetic resonance imaging (MRI) is a second-line imaging after ultrasound.• Diffusion-weighted imaging and intravoxel incoherent motion sequences provide quantitative biomarkers on fetal microstructure and perfusion.• 3-T MRI improves the detection of cerebral malformations.• 3-T MRI is useful for both body and nervous system indications.• Automatic MRI motion tracking overcomes fetal movement artifacts and improve fetal imaging.


Time Trend and Prevalence Analysis of Transfusion Transmitted Infections among Blood Donors: A Retrospective Study from 2001 to 2016.
Transfusion-transmitted infections (TTIs) remain a major threat to the patients receiving blood. The incidence of the transmission of various infectious agents has reduced ever since the introduction of various molecular techniques for detection. The study tried to figure out accurate estimates of risk and trend of TTI over a period of sixteen years, essential for monitoring the safety of blood supply and evaluating the efficacy of the currently employed screening procedures. A total of 57942 blood donors' records were analyzed for the period from January 2001 to December 2016. Chi-square test (χ2) was used to evaluate the relationship between serological positivity and particular donor characteristics. A P value of less than 0.05 was considered statistically significant. Of the 57942 donations, overall prevalence of TTI was 2.7%. Of these, the reactivity rate of hepatitis B (HBV), hepatitis C, HIV, syphilis, and malaria was 1.8%, 0.42%, 0.2%, 0.31%, and 0.017%, respectively with significant P value (P < 0.05, CI: 95%). Overall prevalence was higher in replacement donors as compared to voluntary blood donors. Trend of TTI prevalence decreased from 2001 to 2016. This epidemiological research on TTI is important for the region, as estimated disease burden based on comprehensive epidemiological research provides the foundation for public policy to ensure an easily accessible and adequate supply of safe and quality blood and blood components to the needy patients.


Reliability of measured tidal volume in mechanically ventilated young pigs with normal lungs.
This study examined whether volumes can be accurately measured at the expiratory valve of a conventional ventilator using pressure support ventilation and positive end expiratory pressure with software compensation for circuit compliance available in the Servo iota ventilator. Comparison of two methods for measuring tidal volume in an animal laboratory. Twenty healthy, intubated, sedated, spontaneously breathing pigs. Volume was measured in ten neonatal-sized and ten pediatric-sized pigs ventilated with the Servo iota ventilator using pressure support ventilation and positive end expiratory pressure with and without circuit compliance compensation. We compared volume measured at the airway opening by pneumotachography to volume measured at the expiratory valve of a conventional ventilator. The use of circuit compliance compensation significantly improved the agreement between the two volume methods in neonatal-sized piglets (concordance correlation coefficient: with circuit compliance compensation, 0.97; without, 0.87, p=0.002). In pediatric-sized pigs there was improvement in agreement between the two measurement methods due to circuit compliance compensation (concordance correlation coefficient with circuit compliance compensation, 0.97; without, 0.88, p=0.027). With circuit compliance compensation off there was positive bias: mean difference (bias) 2.97+/-0.12 in neonatal-sized and 3.75+/-0.38 in pediatric-sized pigs. Our results show that volume can be accurately measured at the expiratory valve of a conventional ventilator in neonatal- and pediatric-sized animals.


Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China.
Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. For Chinese chronic hepatitis B patients, ETV is still the most cost-effective strategy over TDF and other nucleos(t)ide analogs, with a threshold of $20,466 USD/QALY gained.


Interactions between antipsychotic and antihypertensive drugs.
To provide a comprehensive review of the pharmacokinetic and pharmacodynamic interactions between antipsychotics and antihypertensive and to provide recommendations for the selection of antihypertensive in patients receiving antipsychotic therapy. A MEDLINE search of the English-language literature was used to identify pertinent human and animal studies, reviews, and case reports. All available sources were reviewed. Background information was obtained from comprehensive reviews. Individual case reports were assimilated, and pertinent data were extracted. Because hypertension is common in patients with psychiatric illness and antihypertensive agents are used for a multiplicity of indications, significant numbers of patients receive concurrent therapy with antihypertensives and antipsychotics. Many antipsychotics may block the antihypertensive efficacy of guanethidine and related drugs. The interaction between clonidine and antipsychotics is defined less clearly. Limited data suggest possible additive hypotensive effects when chlorpromazine and methyldopa are given in combination. Increased plasma concentrations of thioridazine with a resultant increase in adverse effects have been reported when propranolol or pindolol are added to the regimen. A similar increase in chlorpromazine concentrations has been reported when propranolol was added. Although there are no reports documenting an interaction between a calcium-channel antagonist and an antipsychotic, the possible inhibition of oxidative metabolism of antipsychotics, additive calcium-blocking activity, and additive pharmacodynamic effects are theorized. Hypotension and postural syncope were reported in a patient given therapeutic dosages of chlorpromazine and captopril, and in 2 patients when clozapine was added to enalapril therapy. No antipsychotic-antihypertensive combination is absolutely contraindicated, but no combination should be considered to be completely without risk. Antihypertensives with no centrally acting activity, such as diuretics, may be the least likely to result in adverse reactions. The combination of the beta-antagonists propranolol or pindolol with thioridazine or chlorpromazine should be avoided if possible. Scrupulous patient monitoring for attenuated or enhanced activity of either agent is essential whenever antipsychotics and antihypertensives are given concurrently.


A simple method of identifying organophosphate insecticide resistance in adults of the yellow fever mosquito, Aedes aegypti.
A simple filter paper spot test is described for identifying adult Aedes aegypti resistant to malathion as a result of raised esterase levels. The method is compared with established polyacrylamide gel (PAG) electrophoresis techniques for determining esterase-6 activity, and its applicability as a field test is discussed.


Distinct effects of attention and affect on pain perception and somatosensory evoked potentials.
The influence of affect and attention on sensory and affective pain as well as on somatosensory evoked potentials in response to painful and nonpainful electrical stimuli was investigated in a single experimental design. Affect was induced by pictures from the International Affective Picture System; attention was manipulated by asking participants to focus attention either on the pictures or on the electrical stimuli. Sensory and affective pain ratings were generally lower during exposure to positive compared to negative and neutral pictures. Attention modulated only sensory pain ratings with lower ratings with an attention focus on pictures than with an attention focus on sensory pain. The N150 was modulated by picture valence, the P260 by picture arousal. Furthermore, the P260 was modulated by attention with highest amplitudes with an attention focus on the stimulus intensity. This study provides neurophysiological evidence that attention and affect have distinct effects on pain processing.


The vectoring of cactophilic yeasts by Drosophila.
At two locations in the Sonoran Desert, yeasts were sampled from species of Drosophila, the flies' cactus hosts, and other neighboring sources of cactophilic yeasts to determine the relation between the yeasts vectored by the fly and the yeasts found in their breeding sites. D. mojavensis, D. nigrospiracula, and D. mettleri vectored yeast assemblages significantly more similar to the yeast species found on the rot from which the flies were collected than to the yeasts found on other rots from the flies host cactus or other rotting cactus at the same site. Rots with Drosophila had fewer yeast species than those without flies, suggesting that flies were associated with younger rots. Rots with flies and the Drosophila also had more yeast species with the capability to produce ethyl acetate than rots without flies. The results support the contention that cactophilic Drosophila feed on a subset of the yeasts available in an area, and may act to maintain differences among the yeast communities found on different species of cactus.


Hybrid Mesoporous Carbon/Copper Ferrite Electrode for Asymmetric Supercapacitors.
Asymmetric supercapacitors (ASCs) with two dissimilar electrodes are known to exhibit relatively moderate energy and power densities. If electrodes derived from earth-abundant materials or renewable resources such as lignocellulosic biomass (LCB) are used for fabrication, energy storage systems are expected to become less expensive and more sustainable. Hybrid electrode materials have advantages such as higher surface area, better chemical stability, and superior energy density. This study reports on the synthesis of a novel hybrid electrode material containing porous carbon (POC) and copper ferrite, which is designated as POC@Cu-ferrite, and its electrochemical performance in ASC configuration. Corn stover derived hydrochar is utilized for the sol-gel synthesis of POC@Cu-ferrite hybrid material using earth-abundant Cu and Fe-based precursors. This material is characterized using X-ray diffraction (XRD), Raman spectroscopy, Brunauer-Emmett-Teller (BET) surface area analyzer, and scanning and transmission electron microscopy (SEM/TEM). As-synthesized Cu-ferrite is found to contain 89.2% CuFe2O4 and 10.8% Fe2O3, whereas other phases such as Fe3O4, CuFeO2, and CuO are observed for the POC@Cu-ferrite. BET-specific surface area (SSA) and pore volume of POC@Cu-ferrite are observed as 1068 m2/g and 0.72 cm3/g, respectively. POC@Cu-ferrite hybrid electrode is used with POC opposite electrode to fabricate ASC, which is tested using Gamry G-300 potentiostat/galvanostat/ZRA to obtain cyclic voltammetry (CV) profiles and galvanostatic charge-discharge (GCD) plots. ASC is also prepared using Cu-ferrite and POC materials and its specific capacitance and stability are compared with ASCs prepared with POC@Cu-ferrite and POC or graphene nanoplatelets (GNPs) electrodes. POC@Cu-ferrite hybrid electrode is found to be superior with a 2-fold higher capacitance and significant electrochemical stability over 100 GCD cycles as compared to the Cu-ferrite electrode.


Muscle plombage for extensive bronchial necrosis after right lower lobectomy.
Bronchial stump necrosis is a lethal complication after pulmonary resection. We report a patient who had extensive necrosis of the intermediate bronchus after right lower lobectomy. The large bronchial defect was successfully fixed with latissimus dorsi muscle and replaced by bronchial epithelialization.


Unattended sleep study in screening for sleep apnea in the acute phase of ischemic stroke.
We aimed to compare the feasibility of automatically and manually scored cardiorespiratory polygraphy results for sleep apnea screening in the acute phase of ischemic stroke. Prospective study included 204 ischemic stroke patients, who underwent nocturnal unattended portable monitoring with three-channel device during 48 h after onset of stroke symptoms. Sleep apnea diagnosis was determined as a respiratory event index (REI) ≥5/hour. The mean age of the patients was 67.7 years and 62.7% were males. Automatic scoring identified sleep apnea in 148/72.5% and manual scoring in 186/91.2% of patients, showing moderate agreement (Kappa value 0.407). Of the cohort, 39 (19.1%) patients fulfilled the criteria for diagnosis of central sleep apnea (CSA) (>50% of events central) and 165 (80.9%) had obstructive sleep apnea (OSA). Automatic scoring identified poorly the type of events, and missed 18.6% of recordings. Oxygen desaturation 4% index (ODI4), interclass correlation coefficient (ICC) value 0.993, (95% CI 0.990-0.994), lowest saturation (ICC value 0.989, 95% CI 0.985-0.991) and percent of time spent <90% (ICC value 0.987, 95% CI 0.982-0.990) showed excellent agreement. Interclass correlation value for REI was 0.869 (95% CI 0.828 to 0.901) and ICC value 0.848 (95% CI 0.800 to 0.885) for obstructive apnea index, both indicating good agreement. Automatic scoring underestimated the severity of sleep apnea. Both automatically and manually scored results recognized sleep apnea, albeit manual scoring identified more sleep apnea. Sleep apnea diagnosis agreement was moderate. Underestimation of the severity of sleep apnea by automatic scoring may result in undertreatment of sleep apnea. URL:http://www.clinicaltrials.cov. Unique identifier: NCT01861275.


Facile synthesis of Cu(II) impregnated biochar with enhanced adsorption activity for the removal of doxycycline hydrochloride from water.
In this study, the effect factors and mechanisms of doxycycline hydrochloride (DOX) adsorption on copper nitrate modified biochar (Cu-BC) was investigated. Cu-BC absorbent was synthesized through calcination of peanut shells biomass at 450°C and then impregnation with copper nitrate. The Cu-BC has exhibited excellent sorption efficiency about 93.22% of doxycycline hydrochloride from aqueous solution, which was double higher than that of the unmodified biochar. The experimental results suggest that the adsorption efficiency of DOX on the Cu-BC is dominated by the strong complexation, electrostatic interactions between DOX molecules and the Cu-BC samples. Comprehensively considering the cost, efficiency and the application to realistic water, the Cu-BC hold the significant potential for enhancing the effectiveness to remove DOX from water.


Biosynthesis of thiamin. Different biosynthetic routes of the thiazole moiety of thiamin in aerobic organisms and anaerobic organisms.
The nitrogen atom of glycine was incorporated into the thiazole moiety of thiamin in the aerobic microorganisms Bacillus subtilis, Pseudomonas putida, Saccharomyces cerevisiae, Mucor racemosus, Neurospora crassa, and Emericella nidulans. It was not incorporated in the case of the facultative anaerobic microorganisms Escherichia coli and Enterobacter aerogenes, which, however, did incorporate the nitrogen atom of tyrosine. These results show that aerobic microorganisms and facultative anaerobic microorganisms have different biosynthetic pathways for the thiazole moiety of thiamin.


Regulation and management of the biosecurity for synthetic biology.
Synthetic biology (SynBio) is a high-profile interdiscipline combining engineering with science. As a dual-purpose discipline, SynBio is bringing large changes to many fields and providing great benefits to humans. However, due to its characteristic of complexity and uncertainty, SynBio also presents potential biosafety and biosecurity risks. Biosecurity risks refer to unauthorized access, loss, theft, misuse, diversion or intentional release. If a biosecurity accident happens, it would pose a huge threat to humans and nature. Therefore, it is crucial to establish a set of regulations and management practices for the biosecurity risks of SynBio. In this paper, we summarized the sources of the biosecurity risks of SynBio, from its research materials, products, technologies, information to Do-it-yourself synthetic biology. We reviewed and analyzed the current situation of regulation and management of biosecurity for SynBio in the international community and in China. We found that in most countries and regions, SynBio risks commonly follow the regulation and management of Genetically Modified Organisms which has loopholes if applied to the regulation for SynBio without any amendments. Here, we proposed suggestions for the Chinese-featured regulation and management of biosecurity for SynBio, including a top-to-bottom governing framework, a think-tank implementation mechanism, a Synthetic Biology Laboratory Biosecurity Manual safeguarding system, and strengthening biosecurity education on synthetic biology and self-regulation awareness among relevant personnel. Through this work, we aim to improve the standardized process of biosecurity regulation and management for SynBio in China and thereby map out a peaceful, profitable, and practical development path for synthetic biology.


Decoding the Metabolome and Lipidome of Child Malnutrition by Mass Spectrometric Techniques: Present Status and Future Perspectives.
Child malnutrition (CM) is a global public health problem. It contributes to poor health in one in four children under five years worldwide and causes serious health problems in children, including stunted, wasted, and overweight growth. These serious public health issues lead to a higher chance of living in poverty in adulthood. Malnutrition is related with reduced economic productivity and increases the serious national and international burden. Currently, there is no meaningful therapeutic intervention of CM, and the use of different therapeutic foods has shown poor outcomes among supplemented malnourished children. The role of metabolites and lipids has been extensively recognized as early determinants of child health, but their contribution in CM and its pathobiology are poorly understood. This perspective provides a most recent update on these aspects. After briefly introducing the disciplines of metabolomics and lipidomics, we describe a mass spectrometry-based metabolic workflow for analysis of both metabolites and lipids and summarize several recent applications of metabolomics and lipidomics in CM. Finally, we discuss the future directions of the field toward the development of meaningful interventions for CM through metabolomics and lipidomics advances.


Crosstalk between Long Non Coding RNAs, microRNAs and DNA Damage Repair in Prostate Cancer: New Therapeutic Opportunities?
It is increasingly appreciated that transcripts derived from non-coding parts of the human genome, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are key regulators of biological processes both in normal physiology and disease. Their dysregulation during tumourigenesis has attracted significant interest in their exploitation as novel cancer therapeutics. Prostate cancer (PCa), as one of the most diagnosed malignancies and a leading cause of cancer-related death in men, continues to pose a major public health problem. In particular, survival of men with metastatic disease is very poor. Defects in DNA damage response (DDR) pathways culminate in genomic instability in PCa, which is associated with aggressive disease and poor patient outcome. Treatment options for metastatic PCa remain limited. Thus, researchers are increasingly targeting ncRNAs and DDR pathways to develop new biomarkers and therapeutics for PCa. Increasing evidence points to a widespread and biologically-relevant regulatory network of interactions between lncRNAs and miRNAs, with implications for major biological and pathological processes. This review summarises the current state of knowledge surrounding the roles of the lncRNA:miRNA interactions in PCa DDR, and their emerging potential as predictive and diagnostic biomarkers. We also discuss their therapeutic promise for the clinical management of PCa.


Nonlinear kinetics of ferritin adsorption.
The adsorption of ferritin at a methylized quartz surface was measured with off-null ellipsometry and transmission electron microscopy. An initial lag-phase was seen, followed by an accelerating adsorption leading to mass transport limitation of the reaction. The rate of adsorption then decreased at a surface concentration far below monolayer coverage, and a continuously decreasing rate of binding was seen. The slope of the binding rate was linear with the logarithm of time (fractal kinetics). The adsorbed ferritin molecules were distributed in clusters as seen by transmission electron microscopy. Clusters grown during the mass transport limited adsorption had crystalline structure at short range and low fractal dimensions (df = 0.89) over long range. Clusters grown during adsorption with fractal kinetics showed random structure at short range and a high fractal dimension df = 1.86 over all ranges. These findings indicate some new important mechanisms responsible for the complex kinetics of macromolecular reactions at solid-liquid interfaces. The results are discussed in relation to recently developed theories of self-organized criticality.


Structural Alterations in Human Fibroblast Growth Factor Receptors in Carcinogenesis.
Fibroblast growth factor (FGF) plays an important role in human embryogenesis, angiogenesis, cell proliferation, and differentiation. Carcinogenesis is accompanied by aberrant constitutive activation of FGF receptors (FGFRs) resulting from missense mutation in the FGFR1-4 genes, generation of chimeric oncogenes, FGFR1-4 gene amplification, alternative splicing shift toward formation of mesenchymal FGFR isoforms, and FGFR overexpression. Altogether, these alterations contribute to auto- and paracrine stimulation of cancer cells and neoangiogenesis. Certain missense mutations are found at a high rate in urinary bladder cancer and can be used for non-invasive cancer recurrence diagnostics by analyzing urine cell pellet DNA. Chimeric FGFR1/3 and amplified FGFR1/2 genes can predict cell response to the targeted therapy in various oncological diseases. In recent years, high-throughput sequencing has been used to analyze exomes of virtually all human tumors, which allowed to construct phylogenetic trees of clonal cancer evolution with special emphasis on driver mutations in FGFR1-4 genes. At present, FGFR blockers, such as multi-kinase inhibitors, specific FGFR inhibitors, and FGF ligand traps are being tested in clinical trials. In this review, we discuss current data on the functioning of the FGFR family proteins in both normal and cancer cells, mutations in the FGFR1-4 genes, and mechanisms underlying their oncogenic potential, which might be interesting to a broad range of scientists searching for specific tumor markers and targeted anti-cancer drugs.


Quantitation of cytomegalovirus DNA in lung tissue of bone marrow transplant recipients.
Five bone marrow transplant recipients who died of respiratory failure were retrospectively analyzed with polymerase chain reaction (PCR) assay for pulmonary cytomegalovirus (CMV) infection. Two patients had CMV interstitial pneumonitis according to the virus isolation and the histologic and immunofluorescent examinations of the lungs, while the other three patients had non-CMV diseases (ie, idiopathic interstitial pneumonitis, pulmonary aspergillosis, or Streptococcus mitis septicemia). Cytomegalovirus DNA was amplified from the postmortem lung tissue with PCR. The PCR assay showed apparent PCR signals specific to CMV DNA in the two patients with CMV pneumonitis. In contrast, CMV DNA was hardly detectable or undetectable in the three patients without CMV disease. With quantitative PCR assay the initial CMV copy number in the lung tissue of the two patients with CMV pneumonitis was more than 10(4) copies/micrograms DNA and was over 1,000-fold more than that of the three patients without CMV pneumonitis. These results show that quantitative PCR assay could be useful as a diagnostic measure for pulmonary CMV infection.


Ethical cautions in the use of outcomes for resource allocation in the managed care environment of mental health.
Increasingly, resources are being allocated through competitive contracting based on outcome data. This context for outcome research renews ethical concern about the nature of outcome data in the field of mental health. The epistemology of mental illness creates special concerns regarding outcome measurement. Ethical cautions specific to six types of outcome measurement are reviewed: utilization, clinician reports, patient reports, objective measures of diagnostic entities, objective measures of functioning and multifactor research. Brief guidelines are offered for addressing ethical cautions. Also discussed are the difficulty in defining good outcomes and a social obligation to future generations that may be better addressed through process measurements.


Feasibility study on production of a matrix reference material for cyanobacterial toxins.
The worldwide increase in cyanobacterial contamination of freshwater lakes and rivers is of great concern as many cyanobacteria produce potent hepatotoxins and neurotoxins (cyanotoxins). Such toxins pose a threat to aquatic ecosystems, livestock, and drinking water supplies. In addition, dietary supplements prepared from cyanobacteria can pose a risk to consumers if they contain toxins. Analytical monitoring for toxins in the environment and in consumer products is essential for the protection of public health. Reference materials (RMs) are an essential tool for the development and validation of analytical methods and are necessary for ongoing quality control of monitoring operations. Since the availability of appropriate RMs for cyanotoxins has been very limited, the present study was undertaken to examine the feasibility of producing a cyanobacterial matrix RM containing various cyanotoxins. The first step was large-scale culturing of various cyanobacterial cultures that produce anatoxins, microcystins, and cylindrospermopsins. After harvesting, the biomass was lyophilized, blended, homogenized, milled, and bottled. The moisture content and physical characteristics were assessed in order to evaluate the effectiveness of the production process. Toxin levels were measured by liquid chromatography with tandem mass spectrometry and ultraviolet detection. The reference material was found to be homogeneous for toxin content. Stability studies showed no significant degradation of target toxins over a period of 310 days at temperatures up to +40 °C except for the anatoxin-a, which showed some degradation at +40 °C. These results show that a fit-for-purpose matrix RM for cyanotoxins can be prepared using the processes and techniques applied in this work.


Age-related differences in fibrinolytic parameters in patients with acute traumatic brain injury.
Coagulopathy and old age have been associated with poor outcomes in traumatic brain injury (TBI) patients; however, the relationships of coagulopathy and age with the acute phase of TBI remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more severe in older patients in the acute phase of TBI and may explain, in part, their poor outcome. We analyzed the relationship between coagulation/fibrinolytic parameters and age in the acute phase of TBI by retrospectively evaluating 274 patients with initial blood samples obtained no more than 1 hour after injury. Measurement of platelet count, prothrombin time, activated partial thromboplastin time, plasma levels of fibrinogen, and D-dimer was done in the emergency department on arrival as well as 3, 6, and 12 hours following injury. Values were compared between patients aged 16-55 years (group 1) and those aged older than 55 years (group 2) with an Abbreviated Injury Score (AIS)-head of 3-5 to identify any relationship between these parameters and age. When groups 1 and 2 were matched for AIS-head, plasma levels of D-dimer in group 2 were significantly higher than those in group 1 from hospital admission to 12 hours after injury. The Glasgow Outcome Scale scores at 3 months post-injury of group 2 with AIS 4 and 5 were significantly lower than those of group 1 (both P < 0.0001). Fibrinolytic abnormalities are more severe in older acute-phase TBI patients, which may be a factor associated with their poor prognosis.


Associations between community participation and types of places visited among persons living with and without dementia: risks perception and socio-demographic aspects.
Increasingly, literature has focused on community participation in places visited by persons living with and without dementia. Earlier research indicates that multiple factors, including socio-demographic aspects and risk perception may influence community participation. This cross-sectional, explorative study aims to inquire into how places visited, socio-demographic aspects and risks perception are associated with self-rated community participation for persons living with and without dementia (n = 70) in Switzerland. Data was collected through face-to-face interviews with questionnaires (ACT-OUT, MoCA, sociodemographic). First, we investigated whether the number of places visited was correlated with self-rated participation; then we added socio-demographic and risks perception factors with a bivariate analysis; and searched for a model using multinomial logistic regressions. For the group of participants living with dementia, risks of falling (p = .014) and of getting lost (p = .037) were significantly associated with self-rated participation. For the group of participants living without dementia, visiting places outside the home was significantly associated with self-rated participation, especially visiting places in domain D/places for recreational and physical activities (p = .005). The results of exploring multiple factors and searching for a model highlights the complexity of community participation as a construct. Risks and visiting places for recreational and physical activities seem to play a role in self-rated participation. Mobile interviews might be better suited to gain in-depth understanding on community participation for persons living with dementia.


The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis.
The measurement of circulating free light chains (FLC) is of utmost importance in immunoglobulin light chain (AL) amyloidosis, being a fundamental part of the diagnostic workup, prognostic stratification and assessment of response to therapy. Renal failure is a common feature of AL amyloidosis and can considerably affect the concentration of FLC. We assessed the impact of renal failure on the clinical performance of the Freelite assay in 982 consecutive, newly diagnosed patients with AL amyloidosis, 822 with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, and 160 with eGFR <30 mL/min/1.73 m2. The diagnostic sensitivity of the κ/λ FLC ratio was lower for λ amyloidogenic FLC in patients with renal failure (81% vs. 60%, p<0.001) and the FLC concentration had no independent prognostic significance in patients with severe renal dysfunction. However, FLC response to chemotherapy could still discriminate patients with better outcome. Renal failure is a relevant interference factor when using the Freelite assay for the identification of the amyloidogenic light chain and for prognostic assessment in patients with AL amyloidosis and renal failure.


Functional characterisation of the transcriptome from leaf tissue of the fluoroacetate-producing plant, Dichapetalum cymosum, in response to mechanical wounding.
Dichapetalum cymosum produces the toxic fluorinated metabolite, fluoroacetate, presumably as a defence mechanism. Given the rarity of fluorinated metabolites in nature, the biosynthetic origin and function of fluoroacetate have been of particular interest. However, the mechanism for fluorination in D. cymosum was never elucidated. More importantly, there is a severe lack in knowledge on a genetic level for fluorometabolite-producing plants, impeding research on the subject. Here, we report on the first transcriptome for D. cymosum and investigate the wound response for insights into fluorometabolite production. Mechanical wounding studies were performed and libraries of the unwounded (control) and wounded (30 and 60 min post wounding) plant were sequenced using the Illumina HiSeq platform. A combined reference assembly generated 77,845 transcripts. Using the SwissProt, TrEMBL, GO, eggNOG, KEGG, Pfam, EC and PlantTFDB databases, a 69% annotation rate was achieved. Differential expression analysis revealed the regulation of 364 genes in response to wounding. The wound responses in D. cymosum included key mechanisms relating to signalling cascades, phytohormone regulation, transcription factors and defence-related secondary metabolites. However, the role of fluoroacetate in inducible wound responses remains unclear. Bacterial fluorinases were searched against the D. cymosum transcriptome but transcripts with homology were not detected suggesting the presence of a potentially different fluorinating enzyme in plants. Nevertheless, the transcriptome produced in this study significantly increases genetic resources available for D. cymosum and will assist with future research into fluorometabolite-producing plants.


Inotropic changes in ischaemic and non-ischaemic myocardium and arrhythmias within the first 120 minutes of coronary occlusion in pigs.
In 16 anaesthetized open-chest pigs occlusion of the distal third of the LAD was performed. Local myocardial contractility within and outside the ischaemic area, measured using electromagnetic and ultrasonic probes, arrhythmias and plasma catecholamine concentrations were monitored during 180 min before and 120 min after occlusion of the distal LAD. 5 pigs developed ventricular fibrillation (VF) during phase 1 a of arrhythmias (1-6 min post occlusion) and a further 5 pigs during phase 1 b (10-30 min post occlusion). Segment lengthening within the ischaemic area, measured at the beginning of ventricular ejection, started within a few seconds of ischaemia and reached 11-13.5% of end-diastolic length prior to occlusion after 2 min of ischaemia. Between 2 min and 120 min after the onset of occlusion, no further segment lengthening was observed. There were no significant differences in segment lengthening between VF and non-VF pigs. However, within the VF group, mechanical alterations 2 min after the onset of ischaemia were more marked in pigs developing VF within phase 1 a than those with VF in phase 1 b. VES increased markedly after 50 min of occlusion and seemed to occur independently of further mechanical alterations, VF within the first 30 min of ischaemia often occurred without preceding VES.


Complement split products and proinflammatory cytokines in intraoperatively salvaged unwashed blood during hip replacement: comparison between heparin-coated and non-heparin-coated autotransfusion systems.
The aim of the present study was to investigate the quality of shed blood collected in a new intraoperative autotransfusion system (Sangvia, AstraTech, Sweden) and to study whether heparin-coated surfaces in the device reduce the production of inflammatory mediators. The study was randomized and prospective. Twelve total hip arthroplasty patients whose blood was collected with a device having a heparin-coated surface and 12 patients whose blood was collected with a device having a non-heparin-coated surface were included. Venous blood was drawn from the patients preoperatively. Intraoperatively 200 ml salvaged blood was collected and samples were also withdrawn; samples were obtained from the blood bag. Compared to venous blood, elevated concentrations of interleukin 6 (IL-6), IL-8, C3a and polymorphonuclear elastase were found in collected blood. No significant differences in inflammatory mediators were found between the heparin-coated and the non-heparin-coated groups. The median haemoglobin concentration in the salvaged blood was 74 g/l in both groups. Plasma haemoglobin and potassium concentrations were also elevated. There were no significant differences between the groups. The present study indicates that the blood salvaged intraoperatively contains elevated levels of complement split product and proinflammatory cytokines and that heparin-coated surfaces of the salvage device do not significantly influence the formation of inflammatory mediators.


Otomycosis in the north of Iran: common pathogens and resistance to antifungal agents.
Otomycosis as a kind of external otitis can be caused by various species of fungi. To use the appropriate treatment, it is necessary to identify the causal agent of otomycosis. The aim of this study was to determine the pathogens that caused otomycosis and also the efficacy of different antifungal agents. 100 patients with diagnosis of otomycosis/otitis extern were entered in this study. Bacterial culture was performed by eosin methylene blue agar, blood agar; and Sabouraud dextrose agar was used to culture the fungal agents. Minimum inhibitory concentration test also was performed to determine the efficacy of Clotrimazole, Fluconazole, Ketoconazole and Nystatin on the fungal pathogens. Otomycosis was confirmed in 43% of patients by positive culture. The most prevalent fungal pathogen was Aspergillus niger which was sensitive to Clotrimazole, Fluconazole, Ketoconazole. Candida albicans was sensitive to all drugs, in which, the most sensitivity was due to fluconazole. The most frequent fungal pathogen in our otomycosis cases is A. niger, and most of fungi that caused otomycosis are sensitive to clotrimazole.


Burns in Abidjan, Cote d'Ivoire.
Burns are frequent in Côte d'Ivoire with about 700 cases yearly registered in the three Teaching Hospitals of Abidjan (Yopougon, Treichville and Cocody). Unfortunately, no specialized substructure is equipped for treating these patients in the country. The aim of the retrospective study carried out during 1993 in the Burns Care Unit of the Teaching Hospital of Cocody is to illustrate the epidemiology of burns in a poorly developed country in West Africa. Faced with many problems and especially a lack of space, the burns care unit is fighting to become a burns centre, which may become functional in 1995. Regarding studies from other countries, the results from our service are comparable to those obtained in poorly developed countries, they are different from those notified in countries with a higher socioeconomic level where substructures and financial means allow more appropriate care. The Abidjan Burns Centre aims to improve the current preventive activities and to provide burned people with the best possible care.


Plasmakinetic enucleation of the prostate versus transvesical open prostatectomy for benign prostatic hyperplasia >80 mL: 12-month follow-up results of a randomized clinical trial.
To prospectively evaluate perioperative results and 12-month follow-up after plasmakinetic enucleation of the prostate (PKEP) and transvesical open prostatectomy (OP) for benign prostatic hyperplasia (BPH) >80 mL. A total of 83 patients with a prostate >80 mL were randomized to either PKEP or OP. Perioperative and postoperative outcome data were obtained during a 12-month follow-up. No statistical differences were observed in the preoperative data. Both groups resulted in a similar and significant postoperative improvement in International Prostate Symptom Score (IPSS), quality of life (QOL), maximum uroflow rate (Qmax), postvoid residual (PVR) urine volume and prostate specific antigen (PSA), but no significant difference was found between the groups at the 12-month follow-up. Compared to OP, operation time (111.2 ± 27.1 minutes vs 109.6 ± 28.2 minutes, P = .708) were not significantly different between the groups, but blood loss was significantly less (10.2 ± 4.5 g/l vs 15.1 ± 4.3 g/l, P <.001), and bladder irrigation (2.4 ± 1.0 days vs 4.3 ± 1.1 days, P <.001), catheterization time (3.3 ± 1.1 days vs 6.2 ± 1.3 days, P <.001), and hospital stay (5.4 ± 1.2 days vs 9.3 ± 1.1 days, P <.001) were significantly shorter in the PKEP group. Effects on erectile function were similar in both groups, but adverse events were less frequent in the PKEP group. PKEP can be performed safely and is an equally effective procedure for treatment of large BPH with OP, with minimal complications and faster postoperative recovery. The PKEP helps to reduce the morbidity associated with OP and may become the attractive alternative to OP for patients with large BPH.


Data integration for inferring context-specific gene regulatory networks.
Transcriptional regulatory networks control context-specific gene expression patterns and play important roles in normal and disease processes. Advances in genomics are rapidly increasing our ability to measure different components of the regulation machinery at the single-cell and bulk population level. An important challenge is to combine different types of regulatory genomic measurements to construct a more complete picture of gene regulatory networks across different disease, environmental, and developmental contexts. In this review, we focus on recent computational methods that integrate regulatory genomic data sets to infer context specificity and dynamics in regulatory networks.


[Effect of Schistosoma mansoni infection on the immune reactions against heterologous antigens in mice].
Mice (BALB/c or ICR) were infected with Schistosoma mansoni cercariae. After different intervals (mostly eight weeks) the following antigens were injected: a) sheep erythrocytes--b) DNP-thyroglobulin. Afterwards the immune response against these antigens were checked by means of different methods (plaque assay, haemagglutination test, rosette technique). Immune responses to these antigens were depressed in all cases compared to age matched uninfected mice but it was not possible to transfer this immunosuppression with spleen cells to normal or to irradiated recipients.


Fortification with vitamin D: Comparative study in the Saudi Arabian and US markets.
Vitamin D deficiency is common among Saudi Arabian population. To evaluate the current status of vitamin D fortification and calcium content of commonly consumed food items by the Saudi population and to compare it to US data. Cross-sectional market survey at markets of Eastern Province of Saudi Arabia and State of Illinois, USA. A dietary survey was carried out for the content of calcium and vitamin D on the most commonly consumed food products by the Saudi population which are suppose to be fortified by vitamin D. The survey included different brands of fresh milk, yoghurt, powdered milk, cheese, ready-to-eat breakfast cereals and orange juice. Vitamin D content in the products studied from the Saudi marketplace was compared with the suggested vitamin D content in the same products according to US Code of Federal Regulations recommendations. The overall calcium content in the processed dairy products is generally higher than the content in fresh dairy products. Vitamin D content in the fresh dairy products varied from 40 IU/L to 400 IU/L. None of the cereals or orange juice in Saudi Arabia contain vitamin D supplement. The vitamin D content in the food items from the Saudi marketplace is mostly lower than recommended by the US Code of Federal Regulations. Most commonly consumed food products by Saudi population which are suppose to be fortified by vitamin D either not fortified or contain an amount less than recommended by guidelines set for US marketplace.


Characterization of Amyloid Oligomers by Electrospray Ionization-Ion Mobility Spectrometry-Mass Spectrometry (ESI-IMS-MS).
Soluble oligomers formed during the self-assembly of amyloidogenic peptide and protein species are generally thought to be highly toxic. Consequently, thorough characterization of these species is of much interest in the quest for effective therapeutics and for an enhanced understanding of amyloid fibrillation pathways. The structural characterization of oligomeric species, however, is challenging as they are often transiently and lowly populated, and highly heterogeneous. Electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) is a powerful technique which is able to detect individual ion species populated within a complex heterogeneous mixture and characterize them in terms of shape, stoichiometry, ligand binding capability, and relative stability. Herein, we describe the use of ESI-IMS-MS to characterize the size and shape of oligomers of beta-2-microglobulin through use of data calibration and the derivation of models. This enables information about the range of oligomeric species populated en route to amyloid formation and the mode of oligomer growth to be obtained.


Aortic regurgitation caused by cusp bending of aortic valve leaflet.
Pure aortic regurgitation (AR) is caused by primary disease of the aortic leaflet and/or the aortic root. However, there are many patients with AR with unclear etiology and mechanism. The assessment of mechanism is critical to the decision of surgical modality for AR. Echocardiography, particularly a detailed analysis of the aortic leaflets and root by transesophageal echocardiography (TEE), could be an important diagnostic step to assess its mechanism. In this report, we present a case of AR in which the TEE images led to diagnosis of cusp bending of aortic leaflet without specific findings indicating this pathology.