Simple, inexpensive suction electrode system for the student physiology laboratory.
A versatile, inexpensive, easily constructed suction electrode system is described that can be used for routine exercises by the student on, or for demonstrations of, the electrophysiology of frog sciatic nerve and gastrocnemius and sartorius muscles. A disposable plastic syringe and a disposable pipette with Ag-AgCl wire comprise the suction electrode. Six readily manipulable electrodes are installed in the walls of the Plexiglas preparation bath, and an arbitrary number of additional "free" electrodes can be placed where desired. An optional small chamber, formed from a disposable plastic culture dish and Gootch rubber tubing, provides for "barrier" recording within the larger chamber. Interpretations are given of the electrical responses of nerve and muscle in terms of longitudinal currents along the preparation within the suction electrode tubes.


Total arch repair using supra-aortic debranching technique with banding of the ascending aorta for endovascular stent graft fixation.
Endovascular stenting requires a satisfactory landing zone that guarantees fixation and sealing of the proximal part of the endograft. We report total arch repair using supra-aortic debranching technique with banding of the ascending aorta for endovascular graft fixation. An 85-year-old man presented with hoarseness of voice. A fusiform aneurysm with a maximum transverse diameter of 62 mm on the aortic arch was identified by computed tomographic angiography. Supra-aortic arch debranching of the 3 neck vessels using a trifurcated graft and coronary arterial bypass grafting were performed while closely monitoring the regional cerebral oxygen saturation. The ascending aorta was dilated to 41 mm; we successfully reduced this to a mean outer diameter of 36 mm by banding the aorta using an expanded polytetrafluoroethylene surgical membrane. The endovascular procedure was performed 17 days after surgical intervention. The patient was extubated immediately after endovascular stent placement and spent 1 day in intensive care with no signs of transient or permanent neurologic events. A postoperative computed tomographic scan did not reveal any evidence of endoleak. The banding of the ascending aorta for endovascular graft fixation could facilitate endovascular aortic arch repair and provide an alternative treatment for high-risk patients.


Characterization of a stable eukaryotic cell line expressing the Rous sarcoma virus integrase.
The Rous sarcoma virus integration protein (IN) is required for efficient integration of viral DNA into the host genome. IN was expressed in mouse C127 cells using a bovine papillomavirus vector. This system utilizes the mouse metallothionein promoter and the SV40 late polyadenylation signal for efficient expression of IN. A stable cell line derived from a single hygromycin-resistant colony was characterized. The expression of IN increased significantly upon Zn2+ induction of the metallothionein promoter, but did not respond to "superinduction" protocols. Full-length nonphosphorylated IN was the major product of expression. A minor product resulting from initiation of translation at an internal Met codon was also produced. The expressed IN did not exhibit the polypeptide heterogeneity at its COOH-terminus nor phosphorylation as is seen when IN is immunoprecipitated from virions. Using subcellular fractionation and indirect immunofluorescence, IN was primarily localized to nuclei and in some cells appeared to concentrate at discrete loci within the nuclei.


DICOM® integrated EEG data: A first clinical implementation of the new DICOM standard for neurophysiology data.
Demonstrating a pilot implementation of the Digital Imaging and Communication in Medicine (DICOM) neurophysiology standard published in 2020. An automated workflow for converting EEG data from a proprietary vendor EEG format to standardized and interoperable DICOM format was developed and tested. Retrieval of proprietary EEG data, associated videos, annotations and metadata from the vendor EEG archive and their subsequent conversion to DICOM EEG was possible without changes to the departmental workflow. To transfer DICOM EEG data to the central radiology DICOM archive, only minor extensions in the parameterization of the archive's DICOM interfaces were necessary. Linkage with the electronic health record (EHR) and display in a DICOM EEG viewer could be demonstrated. A random sample of 88 DICOM EEG studies was compared to the original vendor files and EEG and video file sizes were comparable. Storing and reviewing EEG data in standardized DICOM format is feasible, facilitated by existing DICOM infrastructure, and therefore allows for vendor independent access to EEG data. We report the first implementation of the DICOM neurophysiology standard, thus promoting standardization in the field of neurophysiology as well as data exchange and access to legacy recordings in an interoperable vendor independent format.


Maintenance of sweat glands by stem cells located in the acral epithelium.
The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1-positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexal epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1-positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes.


Long-term sexual functioning in germ-cell tumor survivors.
Survivors of germ-cell tumors (GCT) may suffer from long-term adverse consequences. Our study was conducted to assess a long-term sexual functioning in GCT survivors. GCT survivors (N = 170) from the National Cancer Institute in Slovakia completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire 9-year median follow up (range 5-32) as a primary exploratory aim. Study groups consisted of 17 survivors (10%) who had active surveillance (AS, controls), and 153 (90%) survivors who received treatment beyond orchiectomy (Tx), including cisplatin-based chemotherapy (CT, N = 132; 78%), radiotherapy to the retroperitoneal lymph nodes (RT, N = 12; 7%) or both (CTRT, N = 9; 5%). In univariate analysis, treatment of any type resulted in difficulty to maintain erection during sexual intercourse compared to patients treated with AS (P = 0.04). Survivors who received CTRT had lower ability to achieve orgasm during sexual activities (P = 0.04) and they reported disappointment with their overall quality of sex life (P = 0.002). The number of attempts to initiate sexual intercourse did not differ. Sexual relationships caused none or mild anxiety and the desire to be sexually active was higher after CTRT (P = 0.05). Multivariable analysis confirmed that orgasmic dysfunction after ≥400 mg/m2 of cisplatin and issues in maintaining erection after Tx were independent of retroperitoneal lymph-node dissection (P = 0.03 and P = 0.04, respectively). Survivors were disappointed with the quality of sex life and had stronger desire to be sexually active independent of age, (P = 0.01 and P = 0.05, respectively). This study identified an impairment in sexual function may represent an issue for long-term GCT survivors. Treatment with chemotherapy plus radiotherapy were associated with disappointment and stronger sexual desire, while a higher cumulative dose of cisplatin may be responsible for orgasmic dysfunction.


Failure of daptomycin monotherapy for endocarditis caused by an Enterococcus faecium strain with vancomycin-resistant and vancomycin-susceptible subpopulations and evidence of in vivo loss of the vanA gene cluster.
A patient with native valve endocarditis caused by a vancomycin "heteroresistant" strain of Enterococcus faecium experienced failure of daptomycin monotherapy without evidence of daptomycin resistance. The infecting organism exhibited in vivo emergence of a vancomycin-susceptible subpopulation lacking vanA. Treatment with a combination of high-dose daptomycin, gentamicin, and high-dose ampicillin cleared the infection.


Devic's neuromyelitis optica: study of nine cases.
Multiple sclerosis (MS) is by far the most popular diagnosis for patients with multifocal neurological disease. Owing to demyelinating inflammatory non-necrotic plaques of the white matter, MS can give remitting symptoms of virtually every part of the central nervous system. Corticosteroids are usually helpful. Devic's neuromyelitis optica (DNMO) is a neurological disease involving only the optic nerves and the spinal cord, where demyelination evolves towards necrosis and atrophy; the prognosis is poor and no satisfactory treatment is known. The objectives of this study are to describe clinical, biological, pathological and radiological data of patients with DNMO and to differentiate DNMO from MS. We studied the files of 14 patients diagnosed with possible DNMO in three French hospitals between 1980 and 1999 and reviewed the literature. Nine patients were included as definite DNMO. Five were excluded because they did not fulfil the diagnostic criteria. For the nine patients with definite DNMO, DNMO was either monophasic or multiphasic. The prognosis was generally poor: two patients died and five others developed severe disability such as blindness, para or quadriplegia or both. Cerebrospinal fluid study and neuroimaging were essential to confirm the diagnosis of DNMO. Various immunosuppressive treatments generally failed to benefit the patients. In the literature (as well as our 14 initial patients) only a few cases of patients described as suffering from DNMO fulfilled the diagnostic criteria. The others showed evidence that another disease like MS was involved. We stress that inclusion and exclusion criteria have to be kept in mind to differentiate clearly DNMO from MS and other central nervous system white matter diseases.


Disturbances in the hypothalamo-pituitary-adrenal and other neuroendocrine axes in bulimia.
Disturbances in the hypothalamo-pituitary-adrenal (HPA) and other endocrine axes were assessed in 24 women with bulimia and healthy controls. Overnight blood samples for measuring nocturnal plasma cortisol, prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were obtained at 30-min intervals. A 1.5 mg dexamethasone suppression test (DST) and a TRH-test were performed. Patients were monitored closely while their nutritional intake was recorded over 21 days. Compared with healthy controls, nocturnal cortisol plasma levels were not elevated in the bulimics. There was a trend toward insufficient cortisol suppression in the DST in patients with bulimia, which was most pronounced in patients with signs of restricted caloric intake. Plasma dexamethasone levels were significantly reduced in bulimics compared with healthy controls. There was a trend for blunted thyrotropin stimulating hormone (TSH) responses to thyrotropin releasing hormone (TRH) in bulimia. The prolactin response to TRH was significantly reduced in bulimics with a history of anorexia nervosa. Plasma LH and plasma FSH were significantly reduced in bulimics with signs of reduced caloric intake [low T3, high levels of beta-hydroxy-butyric acid (BHBA), reduced daily caloric intake, high number of fasting days] as compared with healthy controls. Bulimics with high BHBA levels had significantly reduced nocturnal prolactin plasma levels. Results show that multiple neuroendocrine disturbances exist in bulimia in a milder form than in anorexia nervosa. Evidence for the impact of caloric intake on endocrine functions is presented. Endocrine dysfunctions in our bulimic sample did not show a positive association with the presence of depressive symptoms.


Management of cervical precancers: a global perspective.
Cervical cancer incidence and mortality have decreased dramatically over the past 50 years in countries with access and resources to provide frequent screening, evaluation, and treatment of high-grade cervical cancer precursors. For countries with fewer resources and many competing health concerns, cervical cancer remains one of the most lethal and common cancers among women. With the advent of newer technology, such as low-cost HPV vaccines and self-administered HPV tests, followed by simple well-known techniques such as VIA and cryotherapy, cervical cancer rates may well start to decrease worldwide.


US-assisted catalytic degradation of paraquat using ZnO/Fe3O4 recoverable composite: Performance, toxicity bioassay test and degradation mechanism.
In this study, the ZnO/Fe3O4 catalyst was used as an active catalyst for the oxidation of Paraquat (PQ) herbicide in aqueous solution under ultrasonic (US) waves. FTIR, XRD, FE-SEM, and VSM analyses were performed to characterize the synthesized catalyst. Studies on the effect of radical scavengers were also carried out and the amount of organic matter degradation was determined by measuring the TOC. Under the optimized conditions (catalyst concentration = 0.75 g/L, herbicide concentration = 10 ppm, US power = 70w), the degradation and mineralization rates of the herbicide were acquired as 96.1% and 68% within 60 min, respectively. The quenching tests showed that the hydroxyl (oOH) radical was the most effective oxidant agent in the degradation process of the PQ under ZnO/Fe3O4/US system. The toxicity of treated effluent assayed by Daphnia Magna was decreased from %73.16 in raw samples to %7.2 in the treated samples, during 96 h. Finally, it can be concluded that ZnO/Fe3O4/US process can be successfully performed as an effective process to herbicides in aqueous solutions, due to the high efficiency and excellent catalytic activity.


Vinorelbine and cisplatin in advanced squamous cell carcinoma of the cervix: the South African experience.
This phase II trial was performed to assess the activity and safety of the cisplatin and vinorelbine combination in patients with advanced cervical carcinoma. Forty-two patients with advanced cervical cancer were included in the study to receive vinorelbine at 30 mg/m2 on d 1 and d 8 and cisplatin 100 mg/m2 on day 1 every 4 weeks. Thirty-seven patients were evaluable for response and 40 patients for tolerance. Twenty-four patients (64.8%) achieved objective responses. The median duration of response was 17.5 months (range 2.5-57 months), median time to progression was 13.2 months (range 0.4-57 months) and median survival was 20.6 months (range 0.4-55 months). This regimen was well-tolerated; no WHO grade 4 neutropenia was observed, grade 3 nausea and vomiting occured in 50% of patients and grade 2 peripheral neuropathy in 5% of patients. Vinorelbine-cisplatin is an active and well-tolerated regimen in advanced cervical carcinoma.


No negative effects of boat sound playbacks on olfactory-mediated food finding behaviour of shore crabs in a T-maze.
Anthropogenic noise underwater is increasingly recognized as a pollutant for marine ecology, as marine life often relies on sound for orientation and communication. However, noise may not only interfere with processes mediated through sound, but also have effects across sensory modalities. To understand the mechanisms of the impact of anthropogenic sound to its full extent, we also need to study cross-sensory interference. To study this, we examined the effect of boat sound playbacks on olfactory-mediated food finding behaviour of shore crabs. We utilized opaque T-mazes with a consistent water flow from both ends towards the starting zone, while one end contained a dead food item. In this way, there were no visual or auditory cues and crabs could only find the food based on olfaction. We did not find an overall effect of boat sound on food finding success, foraging duration or walking distance. However, after excluding deviant data from one out of the six different boat stimuli, we found that crabs were faster to reach the food during boat sound playbacks. These results, with and without the deviant data, seem to contradict an earlier field study in which fewer crabs aggregated around a food source during elevated noise levels. We hypothesise that this difference could be explained by a difference in hunger level, with the current T-maze crabs being hungrier than the free-ranging crabs. Hunger level may affect the motivation to find food and the decision to avoid or take risks, but further research is needed to test this. In conclusion, we did not find unequivocal evidence for a negative impact of boat sound on the processing or use of olfactory cues. Nevertheless, the distinct pattern warrants follow up and calls for even larger replicate samples of acoustic stimuli for noise exposure experiments.


Impact of lifestyle and socioeconomic position on use of non-steroidal anti-inflammatory drugs: A population-based cohort study.
Lifestyle and socioeconomic position may confound the link between non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular events, if associated with NSAID use. We examined this association. We conducted a cohort study of all adult first-time responders to the Danish National Health Surveys of 2010, 2013, or 2017 without an NSAID prescription within 3 months before survey completion (n = 407 395). Study exposures were weight, smoking status, alcohol consumption, binge drinking frequency, physical activity level, marital status, highest achieved level of education, income, and employment status. We used a Cox model to compute hazard ratios of time to first redemption of an NSAID prescription and a cumulative odds model to compute odds ratios (ORs) of redeeming one additional NSAID prescription in the year after survey completion. Total follow-up time was 1 931 902 years. The odds of redeeming one additional NSAID prescription in the year after survey completion varied within all categories of lifestyle and socioeconomic position. The largest ORs were observed within categories of weight (1.70, 95% CI: 1.65-1.74 for obesity vs. normal weight), smoking status (1.24, 95% CI: 1.21-1.27 for current vs. never use), and education (1.44, 95% CI: 1.39-1.49 for primary or other vs. university or higher education). The Cox model showed consistent results. Markers of unhealthy lifestyle and low socioeconomic position were associated with initiation and prolonged NSAID use. Consideration of lifestyle and socioeconomic markers as potential confounders in NSAID studies is therefore recommended.


Exploration of Hanshi Zufei prescription for treatment of COVID-19 based on network pharmacology.
Network pharmacology combines drug and disease targets with biological information networks based on the integrity and systematicness of the interactions between drugs and disease targets. This study aims to explore the molecular basis of Hanshi Zufei formula for treatment of COVID-19 based on network pharmacology and molecular docking techniques. Using TCMSP, the chemical constituents and molecular targets of Atractylodis Rhizoma, Citri Reticulatae Pericarpium, Magnoliae Officinalis Cortex, Pogostemonis Herba, Tsaoko Fructus, Ephedrae Herba, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, and Arecae Semen were investigated. The predicted targets of novel coronavirus were screened using the NCBI and GeneCards databases. To further screen the drug-disease core targets network, the corresponding target proteins were queried using multiple databases (Biogrid, DIP, and HPRD), a protein interaction network graph was constructed, and the network topology was analyzed. The molecular docking studies were also performed between the network's top 15 compounds and the coronavirus (SARS-CoV-2) 3CL hydrolytic enzyme and angiotensin conversion enzyme II (ACE2). The herb-active ingredient-target network contained nine drugs, 86 compounds, and 49 drug-disease targets. Gene ontology (GO) enrichment analysis resulted in 1566 GO items (P < 0.05), among which 1438 were biological process items, 35 were cell composition items, and 93 were molecular function items. Fourteen signal pathways were obtained by enrichment screening of the KEGG pathway database (P < 0.05). The molecular docking results showed that the affinity of the core active compounds with the SARS-CoV-2 3CL hydrolase was better than for the other compounds. Several core compounds can regulate multiple signaling pathways by binding with 3CL hydrolase and ACE2, which might contribute to the treatment of COVID-19.


Therapy development for the mucopolysaccharidoses: Updated consensus recommendations for neuropsychological endpoints.
Neurological dysfunction represents a significant clinical component of many of the mucopolysaccharidoses (also known as MPS disorders). The accurate and consistent assessment of neuropsychological function is essential to gain a greater understanding of the precise natural history of these conditions and to design effective clinical trials to evaluate the impact of therapies on the brain. In 2017, an International MPS Consensus Panel published recommendations for best practice in the design and conduct of clinical studies investigating the effects of therapies on cognitive function and adaptive behavior in patients with neuronopathic mucopolysaccharidoses. Based on an International MPS Consensus Conference held in February 2020, this article provides updated consensus recommendations and expands the objectives to include approaches for assessing behavioral and social-emotional state, caregiver burden and quality of life in patients with all mucopolysaccharidoses.


Exceptional oxidation activity with size-controlled supported gold clusters of low atomicity.
The catalytic activity of gold depends on particle size, with the reactivity increasing as the particle diameter decreases. However, investigations into behaviour in the subnanometre regime (where gold exists as small clusters of a few atoms) began only recently with advances in synthesis and characterization techniques. Here we report an easy method to prepare isolated gold atoms supported on functionalized carbon nanotubes and their performance in the oxidation of thiophenol with O2. We show that single gold atoms are not active, but they aggregate under reaction conditions into gold clusters of low atomicity that exhibit a catalytic activity comparable to that of sulfhydryl oxidase enzymes. When clusters grow into larger nanoparticles, catalyst activity drops to zero. Theoretical calculations show that gold clusters are able to activate thiophenol and O2 simultaneously, and larger nanoparticles are passivated by strongly adsorbed thiolates. The combination of both reactants activation and facile product desorption makes gold clusters excellent catalysts.


Myocardial infarction due to coronary thrombosis in a patient with Henoch-Schönlein purpura.
Henoch-Schönlein purpura (HSP) is characterized by vasculitic involvement of small-sized vessels and results in multisystem manifestations. Cardiac involvement is extremely rare and myocardial infarction with coronary thrombus formation in those patients has also rarely been reported. Herein, we report a 33-year-old man with acute myocardial infarction due to coronary thrombus formation and HSP.


The pharmacodynamic basis for the increased antileukaemic efficacy of cytosine arabinoside-based treatment regimens in acute myeloid leukaemia with a high proliferative activity.
The current study was initiated to explore the mechanisms underlying the previously demonstrated association between the proliferative activity of leukaemic blasts and the response to cytosine arabinoside (AraC)-based therapy in de novo acute myeloid leukaemia (AML). The activity of key enzymes of AraC metabolism-deoxycytidine kinase (DCK), cytidine deaminase (DCD) and polymerase alpha (PolyA) were determined in blast cells from 33 patients. In addition, formation and retention of intracellular levels of AraC triphosphate (AraCTP) and DNA incorporation of AraC were measured, as was the proliferative activity of leukaemic blasts by [3H]-TdR incorporation before and after stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte CSF (G-CSF) for 48 h. AraC incorporation into the DNA (median 0.60 pmol/105 cells) was significantly related to the proliferative activity of AML blasts (r = 0.74, P < 0.001). Similarly, priming with GM-CSF or G-CSF increased both the proliferative activity of AML blasts by a median of 1.84- and 1.64-fold, respectively, and the incorporation of AraC into the DNA (1.29- and 1.40-fold respectively). In contrast, no relationship was found between the endogenous proliferative activity (EPA) and enzyme activities regulating AraC activation (DCK; median 4.70 pmol/min/mg protein), inactivation (DCD; median 2.92 pmol/min/mg protein) or inhibitory effects (PolyA; median 1.50 pmol/min/mg protein), nor the formation or retention of AraCTP (median 306.1 ng/107 cell and 1.6 h respectively). When samples were grouped according to EPA (more than or less than the median), slowly proliferating specimens had a higher response to cytokine priming for proliferative activity and incorporation of AraC into DNA. Clinical data of 15 patients were available. Although all eight patients with a high endogenous proliferative activity reached complete remission, only four out of seven patients with a low proliferative activity responded, whereas the other three patients were non-responders (P = 0.077).


Insect-inspired jumping robots: challenges and solutions to jump stability.
Some insects can jump to heights that are several times their body length. At smaller scales, jumping mechanisms are constrained by issues relating to scaling of power generation, which insects have resolved over the course of their evolution. These solutions have inspired the design of small jumping robots. However, the insect' solution for the power constraint came at a price of instability and limited control over jump performance and these drawbacks were inherited by the jumping robots inspired by them. This review focuses on the jumping mechanisms of insects and robots, the challenges it imposes on control and stability and possible solutions. Although jump stability might not be a critical problem for insects, it poses substantial challenges for engineers of small jumping robots, who hope to develop autonomous devices with improved mobility over rough terrain.


Prescription of resistance training for sarcopenic older adults: Does it require specific attention?
Sarcopenia is an age-related neuromuscular disease characterized by substantial muscle atrophy, dynapenia and/or loss of physical function. Sarcopenia progression increases the risk for numerous negative events, including falls, disability, hospitalization, nursing home placement, and death. As such, this condition is recognized as an important topic in gerontology and geriatrics. The best approach to counteract the development and progression of sarcopenia is actively debated. Resistance training (RT) has received special attention in this context, owing to the large number of studies showing its ability to produce significant improvements in sarcopenia-related parameters. Recommendations to guide RT prescription for older adults with different conditions, including people who have traits of sarcopenia, have been published. Some authors have argued that RT guidelines for older adults are similar to one another, which may indicate that the presence of sarcopenia does not require specific physical exercise programs. However, older people with sarcopenia might present with peculiar physical, biomechanical, physiological, and psychosocial characteristics that, in our view, are not taken into adequate consideration in existing exercise guidelines. Here, we present evidence to support the view that RT prescription for older adults with sarcopenia is complex, multifactorial, and still needs more evidence.


Intraosseous infusion for burns resuscitation.
Two examples of resuscitation of a scalded child by intraosseous infusion, following failed peripheral venous cannulation, are presented. The technique of intraosseous infusion is reviewed and it is concluded that this technique provides a valuable second-line technique for establishing emergency venous access in children. It is quick, reliable and enables the rapid infusion of intravenous fluids and drugs into the systemic venous system. Complications are rare but can be serious and close observation of the infusion site is advisable.


Production of three plasminogen activators and an inhibitor in keratinocyte cultures.
Keratinocyte function in extracellular proteolysis was investigated. Keratinocytes derived from rat tongue ventral epithelium were maintained and serially propagated under conditions which support continuous expansion of epithelial colonies but are restrictive to fibroblast proliferation (30-32 degrees C and pH 6.8-7.0). These cultures, and cultures of an established, terminally differentiating keratinocyte line, also derived from the ventral epithelium of the rat tongue, released substantial plasminogen activator activity as visualized by the fibrin-agar overlay technique. In addition, keratinocytes grown directly on 3H-labeled fibrin lysed this substrate in a plasmin-assisted process. The presence of serum modulated the kinetics of the reaction in a manner which suggests that a constant inhibitor tonus serves to contain the proteolytic reaction in the tissues and to prevent a chain reaction. Electrophoretic resolution of keratinocyte secretory proteins and of cell lysates revealed three distinct activators migrating at molecular weights of 48 000, 66 000 and 95 000. The keratinocytes also manufactured inhibitor(s) of the fibrinolytic reaction mainly directed against the activation step. The inhibitory activity was present in serum-free culture harvest media in quantities sufficient to completely annihilate the endogenous activators.


Effect of dynamic display and speed of display movement on reading Chinese text presented on a small screen.
Automatic dynamic displays, e.g., scrolling displays, are frequently used to present text information on small screens. This study examined the effects of three dynamic displays [leading, scrolling, and rapid serial visual presentation (RSVP)] and three presentations speeds [171, 250, and 305 wpm (words per minute)] on subjects' reading comprehension for different types of small screens for laptops, personal digital assistants (PDAs), and mobile phones. 12 college students who were native speakers of Chinese (4 men and 8 women between the ages of 19 and 36 years) participated. Scores for reading comprehension indicated (1) for laptops, both leading displays and RSVP, at speeds of about 250 wpm, comprehension was highest; (2) for PDAs and mobile phones, scrolling displays and RSVP, speeds of about 305 wpm were more suitable for presenting information in Chinese text; (3) consequently, RSVP appeared to be the most viable dynamic display on small screens and led to the highest reading comprehension for these Chinese readers.


The presence of disulfide bonds reveals an evolutionarily conserved mechanism involved in mitochondrial protein translocase assembly.
Disulfide bond formation is crucial for the biogenesis and structure of many proteins that are localized in the intermembrane space of mitochondria. The importance of disulfide bond formation within mitochondrial proteins was extended beyond soluble intermembrane space proteins. Tim22, a membrane protein and core component of the mitochondrial translocase TIM22, forms an intramolecular disulfide bond in yeast. Tim22 belongs to the Tim17/Tim22/Tim23 family of protein translocases. Here, we present evidence of the high evolutionary conservation of disulfide bond formation in Tim17 and Tim22 among fungi and metazoa. Topological models are proposed that include the location of disulfide bonds relative to the predicted transmembrane regions. Yeast and human Tim22 variants that are not oxidized do not properly integrate into the membrane complex. Moreover, the lack of Tim17 oxidation disrupts the TIM23 translocase complex. This underlines the importance of disulfide bond formation for mature translocase assembly through membrane stabilization of weak transmembrane domains.


Exposure and response prevention with or without parent management training for children with obsessive-compulsive disorder complicated by disruptive behavior: a multiple-baseline across-responses design study.
Comorbidity with disruptive behavior disorders may have important implications for exposure-based cognitive behavioral treatments of children with OCD. Child noncompliance and parent-child conflict may interfere with performance of exposure activities and completion of therapeutic homework assignments, thus diminishing response to treatment. We investigated whether response to exposure and response prevention (ERP) can be enhanced if disruptive behavior is treated first with parent management training (PMT). A multiple-baseline across-responses design was used to investigate the effects of ERP with or without PMT in six children (age range 9-14 years) with OCD and disruptive behavior. Weekly ratings of OCD were conducted for four weeks to establish baseline. After that, children were randomly assigned to receive six weekly sessions of PMT and then twelve weekly sessions of ERP (ERP-plus-PMT condition) or to receive ERP after a six week waiting period (ERP-only condition). The outcome assessments were conducted weekly using the Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) administered by an experienced clinician, who was blind to treatment assignment. Three subjects in the ERP-plus-PMT condition evidenced a 39 percent reduction in the CY-BOCS score versus a 10 percent reduction in three subjects in the ERP-only condition. The results of our single-subject study suggest the feasibility and positive effects of combining ERP with PMT for children with OCD complicated by disruptive behavior.


[Splenic rupture: conservative treatment with sonographic control of its course].
The spleen is the abdominal organ most frequently damaged in blunt abdominal trauma. Because of the high incidence of fatal sepsis after splenectomy, conservative treatment is getting increasingly important. Besides CT and radionuclide scanning, sonography has become an increasingly important tool in diagnosis and follow-up.


Lack of research-based standards for accessible housing: problematization and exemplification of consequences.
To increase the understanding of how definitions of standards for housing design influence the proportion of dwellings not meeting the standards and the proportion of individuals defined as having accessibility problems. The sample included old people and their dwellings in three European countries (N = 1,150). Frequencies and percentages were reported and empirical distribution functions were used. Depending on the functional profile and standards in question, the magnitude of influence of the standards differs in extent, e.g., the existing standard for door openings at the entrance (defined ≥75 cm) implied that the proportion of dwellings not meeting it was 11.3% compared to 64.4%, if the standard was set to ≥83 cm. The proportion of individuals defined as having accessibility problems for profiles not using mobility devices was 4-5, 57% for profiles using them and 1-3% for the total sample if the standard was set to 90 cm. Research-based standard definitions for housing design are necessary to ensure that they actually lead to enhanced accessibility, which is a prerequisite for the independence and health of persons with functional limitations.


[Allergic rhinitis--does the radioallergosorbent test improve the diagnosis? (author's transl)].
A comparison between the skin test and radioallergosorbent test RAST) in 127 patients with allergic rhinitis reveals no advantage of RAST. This contrasts with the results obtained in other allergic diseases. However, the determination of a single pollen allergen allows the in vitro diagnosis of allergic rhinitis, which, obviously, is due to cross reactivity of pollen allergens. This makes the RAST a useful procedure in routine diagnosis, especially in the case of patients living far away from an allergy centre. In these cases RAST can easily be used as a screening test.


Can Thyroid Nodules be Managed with Radiofrequency Ablation?
Radiofrequency ablation (RFA) is an established and growing minimally-invasive technique with an impressive safety profile used to manage thyroid nodules. Beyond shorter operative and recovery times, the main advantages of RFA include the lack of an incisional scar as well as maximizing the potential for maintenance of normal thyroid function. RFA can significantly reduce nodular volume, achieving rates of 60% to 95% in a breadth of thyroid disease, including benign nodules, primary carcinomas, and recurrent malignancies. Thorough patient counselling is imperative for RFA candidates, including a discussant of complications, nodule regrowth, and the potential for a subsequent ablation session.


Engineering microRNA responsiveness to decrease virus pathogenicity.
The cellular tropisms of eukaryotic viruses are shaped by their need for entry receptors and intracellular transcription factors. Here we show that viral tropisms can also be regulated by tissue-specific microRNAs (miRNAs). Target sequences complementary to muscle-specific miRNAs were inserted into the 3' untranslated region (UTR) of an oncolytic picornavirus that causes lethal myositis in tumor-bearing mice. The recombinant virus still propagated in subcutaneous tumors, causing total regression and sustained viremia, but could not replicate in cells expressing complementary miRNAs and therefore did not cause myositis. This altered tropism was not due to insertional attenuation, as a control virus containing a 3' UTR insert with a disrupted miRNA target sequence fully retained its lethal myotropism. Tissue-specific destabilization of viral genomes by miRNA target insertion provides a potentially versatile new mechanism for controlling the tropism of replicating viruses for therapy and may serve as a new modality for attenuating viruses for vaccine purposes.


Biomimetic amphiphilic chitosan nanoparticles: Synthesis, characterization and antimicrobial activity.
Naturally derived antimicrobial peptides (AMPs) are an attractive source of new antimicrobial agents. However, clinical application of AMPs is associated with poor bioavailability and toxicity. In this study, we address these limitations by designing a new series of chitosan derivatives to mimic the amphiphilic topology of AMPs. The synthesized chitosan derivatives were found to self-assemble into nanoparticles in the aqueous environment. Among the compounds, a chitosan derivative grafted with arginine and oleic acid (CH-Arg-OA) exhibited the most potent antimicrobial activity, especially against Gram-negative bacteria. It also caused minimal cell death when tested in HEK293 and HepG2 cell lines, thus confirming the role of cationicity and lipophilicity for selective bacteria targeting. CH-Arg-OA exhibited its antimicrobial activity by disrupting bacterial membranes and causing the leakage of cytoplasmic contents. Thus, amphiphilic chitosan nanoparticles offer a great promise as a new class of AMPs mimics that is effective against Gram-negative bacteria.


An insight into the pharmacophores of phosphodiesterase-5 inhibitors from synthetic and crystal structural studies.
Selective inhibitors of cyclic nucleotide phosphodiesterase-5 (PDE5) have been used as drugs for treatment of male erectile dysfunction and pulmonary hypertension. An insight into the pharmacophores of PDE5 inhibitors is essential for development of second generation of PDE5 inhibitors, but has not been completely illustrated. Here we report the synthesis of a new class of the sildenafil derivatives and a crystal structure of the PDE5 catalytic domain in complex with 5-(2-ethoxy-5-(sulfamoyl)-3-thienyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (12). Inhibitor 12 induces conformational change of the H-loop (residues 660-683), which is different from any of the known PDE5 structures. The pyrazolopyrimidinone groups of 12 and sildenafil are well superimposed, but their sulfonamide groups show a positional difference of as much as 1.5A. The structure-activity analysis suggests that a small hydrophobic pocket and the H-loop of PDE5 are important for the inhibitor affinity, in addition to two common elements for binding of almost all the PDE inhibitors: the stack against the phenylalanine and the hydrogen bond with the invariant glutamine. However, the PDE5-12 structure does not provide a full explanation to affinity changes of the inhibitors. Thus alternatives such as conformational change of the M-loop are open and further structural study is required.


A cost-effective combination of Rose Bengal and off-the-shelf cationic polystyrene for the photodynamic inactivation of Pseudomonas aeruginosa.
Two new photoactive materials have been prepared, characterized and tested against Pseudomonas aeruginosa bacteria (planktonic suspension). The synthesis of the polymeric photosensitizers can be made at a multigram scale, in few minutes, starting from inexpensive and readily available materials, such as Rose Bengal (photosensitizer) and ion exchange resins Amberlite® IRA 900 (macroporous) or IRA 400 (gel-type) as cationic polystyrene supports. The most notable feature of these systems is their notable bactericidal activity in the dark (4-5 log10 CFU/mL reduction of the population of P. aeruginosa) which becomes enhanced upon irradiation with visible light (to reach a total reduction of 8 log10 CFU/mL for the macroporous polymer at a fluence of 120 J/cm2 using green light of 515 nm).


Fast two-dimensional grid and transmission X-ray microscopy scanning methods for visualizing and characterizing protein crystals.
A fast continuous grid scan protocol has been incorporated into the Swiss Light Source (SLS) data acquisition and analysis software suite on the macromolecular crystallography (MX) beamlines. Its combination with fast readout single-photon counting hybrid pixel array detectors (PILATUS and EIGER) allows for diffraction-based identification of crystal diffraction hotspots and the location and centering of membrane protein microcrystals in the lipid cubic phase (LCP) in in meso in situ serial crystallography plates and silicon nitride supports. Diffraction-based continuous grid scans with both still and oscillation images are supported. Examples that include a grid scan of a large (50 nl) LCP bolus and analysis of the resulting diffraction images are presented. Scanning transmission X-ray microscopy (STXM) complements and benefits from fast grid scanning. STXM has been demonstrated at the SLS beamline X06SA for near-zero-dose detection of protein crystals mounted on different types of sample supports at room and cryogenic temperatures. Flash-cooled crystals in nylon loops were successfully identified in differential and integrated phase images. Crystals of just 10 µm thickness were visible in integrated phase images using data collected with the EIGER detector. STXM offers a truly low-dose method for locating crystals on solid supports prior to diffraction data collection at both synchrotron microfocusing and free-electron laser X-ray facilities.


Users evaluation of a Spanish eHealth pediatric website.
Parents use the Internet to take decisions about their children's health, but few resources have focused on eHealth technology evaluations from their point of view. The main aim of this research was to evaluate a Spanish eHealth pediatric website for parents. A previously validated web questionnaire was used to evaluate five domains: usability, utility, trust and confidence, well-child section and accessibility of the website. Univariate, bivariate and multiple linear regression analyses were performed. 516 users participated in the research and rated the website as usable, useful, trustworthy and accessible. Higher scores were given by the participants who relied most on the Internet for taking decisions about health; by the participants who used a smartphone to access the pediatric website; by the participants who knew the website the longest; and by the participants who had accessed it more times. No differences in the evaluations of the website were found regarding age, education level or household income of the participants. eHealth pediatric websites, written by a pediatrician in an easy to understand language, can be perceived as usable, trustworthy, useful and accessible by their users and consequently help them with their decisions making. Some characteristics of the users are associated with a better perception of these websites.


Aspirin dosage for infants and children.
The labeled dosage schedule that has long been on pediatric aspirin preparations is at variance with the recommendation in authoritative medical references, studies demonstrating antipyretic effectiveness in children, and the prescribing habits of pediatricians as revealed by a poll conducted by the authors. Aspirin pharmacokinetics are influenced by a number of physiologic factors, as well as by dosage, and complicate the problem of assuring safe and effective pediatric use. Basic pharmacokinetic considerations indicate that the increase in size of individual doses needed to assure therapeutic salicyate blood levels, thereby removing the temptation of parents to administer the drug too often, is made permissible (i.e., safe while effective) by expanding the interdose interval to four hours instead of three. A revised pediatric aspirin disage schedule is presented that better meets the practices of the pediatric community and the needs of consumers.


Role of prostaglandin E and interferon in secretion of colony-stimulating factor by murine macrophages after in vitro treatment with biological response modifiers.
We have evaluated the possible role of biological response modifiers (BRMs) in myelopoiesis by investigating BRM modulated secretion of hematopoietic growth factors and inhibitors. Here, we report the evidence of augmented secretion of granulocyte and/or macrophage colony stimulating factors (CSF) by murine resident peritoneal macrophages after in vitro incubation with murine interferons (alpha, beta-mIFN; beta-mIFN; gamma-mIFN), poly ICLC (polyriboinosinic-polycytidylic acid poly-L-lysine), BM 41.332 (2-cyano-1-[(2-methoxy-6-methyl-pyridin-3yl)-methyl]-aziridine) and lipopolysaccharide (LPS). The secretion of CSF appears to be independent of the ability of the BRMs to induce IFN, as shown by the use of neutralizing antibodies against mIFN. The antiproliferative effects of IFN also did not block the BRM induced effects of CSF. The combination of alpha, beta-mIFN and poly ICLC or LPS and poly ICLC at suboptimal concentrations resulted in additive, but not synergistic effects on CSF secretion by macrophages. Histological examination of the colonies induced indicated the presence of two types of CSF, namely CSF1 and CSF3, which give rise to pure macrophage and granulocyte colonies respectively. In parallel to their effect on CSF secretion, these BRMs also caused a considerable increase in secretion of prostaglandins of the E series (PGE) by macrophages. However, the production of PGE did not interfere or influence CSF secretion, since the inhibition of the enzyme cyclooxygenase with indomethacin (10(-7) molar) 3 h before stimulation with poly ICLC, alpha, beta-mIFN, or LPS, inhibited the secretion of PGE by macrophages without affecting the secretion of CSF. Macrophages, stimulated by one of the active BRMs for 24 h, could not be restimulated by any of these agents to again secrete significant amounts of CSF or PGE, even after a 2 day resting phase. Other drugs tested (diethyldithiocarbamate, maleic anhydride divinyl ether, azimexone) failed to stimulate the in vitro secretion of significant amounts of CSF and PGE. The results presented here indicate that several BRMs can be utilized to stimulate macrophages to secrete the myelopoietic growth factor CSF, thus supporting the concept that these BRMs might be of value in reconstituting or promoting impaired granulocyte and monocyte/macrophage function.


Sense codons are found in specific contexts.
The sequence environment of codons in structural genes has been investigated statistically, using computer methods. A set of Escherichia coli genes with abundant products was compared with a set having low gene product levels, in order to detect potential differences associated with expression. The results show striking non-randomness in the nucleotides occurring near codons. These effects are, unexpectedly, very much larger and more homogeneous among the genes with rare products. The intensity of effects in weakly expressed genes suggests that such non-random sequence environments decrease expression. In the weakly expressed set of genes, the 5' neighbor of a codon, and all positions of the 3' neighbor codon are biased. In the highly expressed genes, the first nucleotide of the next codon is a uniquely affected site. The distribution of non-randomness in weakly expressed genes suggests that sequence bias is primarily due to a constraint acting directly on the secondary or tertiary structure of the codon/anticodon. In highly expressed genes, the observed bias suggests an interaction between the codon/anticodon and a site outside the codon/anticodon. Much of the tendency to non-random near-neighbor sequences in weakly expressed genes can be ascribed to a correlation between nearby nucleotides and the wobble nucleotide of the codon, despite the fact that selection of such correlations will alter the amino acid sequence. The favored pattern, in genes expressed at low level, is R YYR or Y RRY. R indicates purine, Y indicates pyrimidine; the space is the boundary between codons. It seems likely that this preference for nearby sequences is the physical basis of the genetic context effect. Under this assumption such sequence biases will affect expression. On this basis, we predict new sites for contextual mutations which decrease expression, and suggest strategy for the design of messages having optimal translational activity.


Effect of prior stress on interleukin-1β and HPA axis responses to acute stress.
Interleukin-1β (IL-1β) level is modulated during multiple stress reactions both in brain structures involved in hypothalamic-pituitary-adrenal (HPA) axis regulation and peripheral systems. Multiple distinct stressors induce different IL-1β and HPA axis responses. The purpose of the present study was to determine if the effect of prior repeated restraint stress on IL-1β levels in prefrontal cortex, hippocampus, hypothalamus and plasma may have an impact on alterations induced in HPA axis responses. Experiments were performed on male Wistar rats which were exposed to 10 min restraint stress twice a day for 3 days. Twenty four hours after the last stress period rats were restrained for 10 min and decapitated at 0, 1, 2 or 3 h after cessation of stress. Control rats were injected ip with saline and some of experimental groups with IL-1β receptor antagonist (IL-1ra). After rapid decapitation, trunk blood was collected and prefrontal cortex, hippocampus and hypothalamus were excised and frozen. Interleukin-1β, adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined in plasma using commercially available kits and IL-1β levels in brain structures samples were analyzed by western blot procedure. Repeated restraint for 3 days alone did not alter resting plasma levels of IL-1β, and moderately augmented plasma ACTH and CORT levels and IL-1β content in brain structures 24 h after the last restraint. IL-1β antagonist abolished the increase in plasma levels of IL-1β, ACTH and CORT as well as IL-1β in brain structures in response to repeated stress and also reduced these changes induced by 10 min stress. This suggests the selectivity of IL-1β receptors in central and peripheral mechanisms modulating the stress-induced HPA axis responses. These results indicate that repeated stress markedly increases IL-1β production in brain structures involved in HPA axis regulation. The present results support the role of brain and peripheral IL-1β in adaptation of HPA response during prolonged stress.


Annular geometry in patients with chronic ischemic mitral regurgitation: three-dimensional magnetic resonance imaging study.
Although animal studies showed that annular remodeling may be related to the pathogenesis of chronic ischemic mitral regurgitation (CIMR), little was known in humans. A better understanding of the precise 3D geometry of the mitral valvular-ventricular complex in CIMR is needed to devise a better surgical technique. The purpose of the study was to elucidate mitral annular geometry in patients with CIMR using cardiac MRI. Thirty-eight patients with previous inferior or posterior myocardial infarction were studied. With the 3D reconstruction of the mitral annulus and subvalvular apparatus from a series of longitudinal cine MRIs, end-systolic mitral annulus dimensions and 3D geometry were calculated. Patients were grouped by mitral regurgitation grade using echocardiography (> or =2+, n=15 versus < or =1+, n=23). Both septal-lateral and commissure-commissure mitral annular diameters were significantly greater in CIMR(+) patients (35+/-5 versus 30+/-4 mm, P=0.005; 46+/-6 versus 39+/-4 mm, P<0.001, respectively). The length of the fibrous annulus was significantly larger in CIMR(+) patients (28+/-3 versus 24+/-3 mm; P<0.001). The height of the annular "saddle horn" above a best-fit plane was lower in CIMR(+) patients (4.2+/-1.2 versus 6.0+/-1.8 mm; P=0.002), and the annular height to commissural width ratio was significantly lower in CIMR(+) patients (12+/-3 versus 21+/-5%; P<0.001). Patients with CIMR had greater septal-lateral and commissure-commissure mitral annular dimension, larger intertrigonal distance, and flattened saddle shape of mitral annulus. These associated geometric alterations may be important in the pathogenesis of CIMR.


Chromosomal mutations responsible for fluoroquinolone resistance in Ureaplasma species in the United States.
We sequenced the full lengths of the gyrA, gyrB, parC, and parE genes in 13 fluoroquinolone-resistant Ureaplasma isolates (levofloxacin MICs, 4 to 32 μg/ml) and 10 susceptible isolates (MICs ≤ 2 μg/ml). Mutations were detected in all resistant isolates but in none of the susceptible isolates. The most prevalent mutation was the S83L substitution in the ParC protein. No plasmid-mediated fluoroquinolone resistance genes were detected.


Binding interaction of a ring-hydroxylating dioxygenase with fluoranthene in Pseudomonas aeruginosa DN1.
Pseudomonas aeruginosa DN1 can efficiently utilize fluoranthene as its sole carbon source, and the initial reaction in the biodegradation process is catalyzed by a ring-hydroxylating dioxygenase (RHD). To clarify the binding interaction of RHD with fluoranthene in the strain DN1, the genes encoding alpha subunit (RS30940) and beta subunit (RS05115) of RHD were functionally characterized through multi-technique combination such as gene knockout and homology modeling as well as molecular docking analysis. The results showed that the mutants lacking the characteristic alpha subunit and/or beta subunit failed to degrade fluoranthene effectively. Based on the translated protein sequence and Ramachandran plot, 96.5% of the primary amino-acid sequences of the alpha subunit in the modeled structure of the RHD were in the permitted region, 2.3% in the allowed region, but 1.2% in the disallowed area. The catalytic mechanism mediated by key residues was proposed by the simulations of molecular docking, wherein the active site of alpha subunit constituted a triangle structure of the mononuclear iron atom and the two oxygen atoms coupled with the predicted catalytic ternary of His217-His222-Asp372 for the dihydroxylation reaction with fluoranthene. Those amino acid residues adjacent to fluoranthene were nonpolar groups, and the C7-C8 positions on the fluoranthene ring were estimated to be the best oxidation sites. The distance of C7-O and C8-O was 3.77 Å and 3.04 Å respectively, and both of them were parallel. The results of synchronous fluorescence and site-directed mutagenesis confirmed the roles of the predicted residues during catalysis. This binding interaction could enhance our understanding of the catalytic mechanism of RHDs and provide a solid foundation for further enzymatic modification.


Natural compounds: A new perspective on targeting polarization and infiltration of tumor-associated macrophages in lung cancer.
With the development in tumor immunology, people are gradually understanding the complexity and diversity of the tumor microenvironment immune status and its important effect on tumors. Tumor-associated macrophages (TAMs), an important part of the tumor immune microenvironment, have a double effect on tumor growth and metastasis. Many studies have focused on lung cancer, especially non-small cell lung cancer and other "hot tumors" with typical inflammatory characteristics. The polarization and infiltration of TAMs is an important mechanism in the occurrence and development of malignant tumors, such as lung cancer, and in the tumor immune microenvironment. Therapeutic drugs designed for these reasons are key to targeting TAMs in the treatment of lung cancer. A large number of reports have suggested that natural compounds have a strong potential of affecting immunity by targeting the polarization and infiltration of TAMs to improve the immune microenvironment of lung cancer and exert a natural antitumor effect. This paper discusses the infiltration and polarization effects of natural compounds on lung cancer TAMs, provides a detailed classification and systematic review of natural compounds, and summarizes the bias of different kinds of natural compounds by affecting their antitumor mechanism of TAMs, with the aim of providing new perspectives and potential therapeutic drugs for targeted macrophages in the treatment of lung cancer.


Social inequalities in childhood are predictors of unemployment in early adulthood.
The aim of the present study was to establish if social inequalities in early childhood, particularly living in a socially and economically deprived neighbourhood, are predictive of later unemployment. A cohort was established in 1987. It consists of 8-9 year-old children living in a socially deprived suburb who were followed in national registers for all categories of welfare benefits. The follow-up covered the period when participants were 21-27 years of age. A control group with the same age and gender distribution who were living in a neighbouring, relatively privileged middle class district were also followed for the purpose of comparison. The annual unemployment rate during the seven years of follow-up was significantly higher in the deprived neighbourhood group than in the middle class neighbourhood group, whereas long-term unemployment lasting more than two years did not differ significantly between the groups. Childhood background including a mother receiving social benefit was an independent factor associated with increased risk of later unemployment, whereas gender and single parenthood were not. The present findings suggest that socioeconomic disadvantage during childhood substantially increases the risk of unemployment in early adulthood, even during a follow-up period in the first decade of the 21st century when employment opportunities in Denmark were excellent. not relevant. not relevant.


Chronic relapsing experimental allergic encephalomyelitis in the Lewis rat.
Chronic relapsing experimental allergic encephalomyelitis (CR-EAE) was induced in rats with an emulsion of guinea-pig spinal cord tissue (GPSC) in complete Freund's adjuvant (CFA) enriched with Mycobacterium tuberculosis H37RA (Tbc). 78% of the sensitized rats developed a CR-EAE showing 2 to 3 clinical relapses during the first 40 days. After 60-80 days, approximately half of the rats with CR-EAE had a further relapse which was followed by complete recovery in only 35% of the cases. The remaining 65% of these animals showed a progressive state of the disease, characterized by paralysis or severe motor deficit, eventually leading to death. CR-EAE in rats showed some similarities to multiple sclerosis in man (MS) and it may be a useful model for the study of this disease.


Aloe gel glucomannan induced colon cancer cell death via mitochondrial damage-driven PINK1/Parkin mitophagy pathway.
Mitophagy can selectively remove damaged mitochondria, which is critical in regulating mitochondrial homeostasis in diseases, such as cancer. Herein, we found that Aloe gel glucomannan (AGP) significantly inhibited the proliferation of colon cancer cells. RNA-seq analysis revealed that AGP upregulated autophagy, lysosome and mitochondrial fission signal pathways in colon cancer cell line CT26. Notably, AGP induced the accumulation of impaired and reactive oxygen species (ROS)-generating mitochondria, which triggered excessive mitophagy. Interestingly, the mitophagy activator enhanced AGP-induced mitophagy and cytotoxicity, whereas the mitophagy inhibitor reversed the influence of AGP. Furthermore, activation of PINK1/Parkin mitophagy pathway and transcription factor EB (TFEB) signaling was dependent on ROS overproduction. Taken together, these results indicated that AGP induced cytotoxic mitophagy through ROS-related PINK1/Parkin pathway and TFEB activation in CT26 cells. The research would provide theoretical basis for the development of AGP as a promising anticancer agent.


Endobronchial fibrous histiocytoma.
Fibrous histiocytomas are uncommon pulmonary tumors. They generally involve only the lung parenchyma. Endobronchial involvement is extremely rare. Usually, surgical resection of the mass is required for definitive diagnosis and therapy. We report a case of benign atypical fibrous histiocytoma visualized during fiberoptic bronchoscopy and review the clinical findings and pathologic features of this tumor.


The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against Salmonella.
Salmonella enterica serovar Enteritidis (SE) is the most frequently-detected Salmonella in foodborne outbreaks in the European Union. Among such outbreaks, egg and egg products were identified as the most common vehicles of infection. Possibly, the major antibacterial property of egg white is iron restriction, which results from the presence of the iron-binding protein, ovotransferrin. To circumvent iron restriction, SE synthesise catecholate siderophores (i.e. enterobactin and salmochelin) that can chelate iron from host iron-binding proteins. Here, we highlight the role of lipocalin-like proteins found in egg white that could enhance egg-white iron restriction through sequestration of certain siderophores, including enterobactin. Indeed, it is now apparent that the egg-white lipocalin, Ex-FABP, can inhibit bacterial growth via its siderophore-binding capacity in vitro. However, it remains unclear whether Ex-FABP performs such a function in egg white or during bird infection. Regarding the two other lipocalins of egg white (Cal-γ and α-1-glycoprotein), there is currently no evidence to indicate that they sequester siderophores.


Protein kinase inhibitors reduce GABA but not glutamate release in the nucleus accumbens.
We investigated the role of endogenous protein kinase activity on synaptic transmission in the rat nucleus accumbens slice. The isoquinolinesulfonamide H-7 (50muM), a non-selective serine/threonine protein kinase inhibitor, had no effect on pharmacologically isolated glutamatergic EPSCs. However, it reduced GABA release in a dose-dependent manner. This effect of H-7 was not mimicked by the selective cAMP-dependent protein kinase inhibitor H-89, the PKC inhibitor Bisindolylmaleimide-1, or the cGMP-dependent protein kinase inhibitor KT5823. However, bath application of the myosin light chain kinase (MLCK) inhibitor, ML-7, significantly reduced IPSC amplitudes and partially occluded the reduction in IPSCs observed following bath application of H-7. These results suggest that endogenous protein kinase activity, specifically MLCK activity, regulates GABA, but not glutamate release, onto medium spiny neurons in the nucleus accumbens.


Optimal Clinical Target Volume of Radiotherapy Based on Microscopic Extension around the Primary Gross Tumor in Non-Small-Cell Lung Cancer: A Systematic Review.
A crucial issue in radical radiation therapy for non-small-cell lung cancer is how to define the clinical target volume (CTV). Although the scope of microscopic extension (ME) and microscopic proximal bronchial extension (PBE) from a primary tumor should be considered when defining the CTV, there has been limited research on ME and PBE. Therefore, we conducted this systematic review. The PubMed, ICHUSHI (Japanese database), and Cochrane Library databases were searched, and 816 articles were initially retrieved. After primary and secondary screenings, eight articles were ultimately selected. The results of this systematic review suggest the importance of a 0 mm margin in stereotactic radiotherapy for early-stage cancer and a 5-8 mm margin in curative irradiation for locally advanced cancer. Regarding PBE, this review yielded the conclusion that it is appropriate to consider the addition of an approximately 15 mm margin from the bronchial vasculature. Although there were few articles with a high level of evidence, this systematic review enabled us to collate results from previous studies and to provide recommendations, to some extent, regarding the CTV margin in the current clinical environment, where high-precision radiation therapy, such as image-guided radiotherapy and intensity-modulated radiotherapy, is predominant.


Determination of voriconazole in human plasma and saliva using high-performance liquid chromatography with fluorescence detection.
Voriconazole is a widely used triazole antifungal agent with a broad spectrum including Aspergillus species. A simple, sensitive and selective high-performance liquid chromatography method for the determination of voriconazole in human plasma and saliva was developed. Drug and internal standard (UK-115 794) were extracted from alkaline plasma and saliva with n-hexane-ethyl acetate (3:1, v/v) and analyzed on a Luna C 18 column with fluorimetric detection set at excitation and emission wavelengths of 254 and 372 nm, respectively. The calibration curve was linear through the range of 0.1-10 microg/ml using a 0.3 ml sample volume. The intra- and inter-day precisions were all below 6.1% for plasma and below 9.1% for saliva. Accuracies ranged from 94 to 109% for both matrices. Mean recovery was 86+/-4% for voriconazole. The method showed acceptable values for precision, recovery and sensitivity and is well suited for routine analysis work and for pharmacokinetic studies.


Efficacy of Laminoplasty in Improving Sensory Disturbances in Patients with Cervical Spondylotic Myelopathy: A Prospective Study.
Upper extremity sensory disturbances are primary symptoms that affect the quality of life (QOL) of patients with cervical spondylotic myelopathy. Although laminoplasty is 1 of the surgical options, its effects on sensory disturbances have remained unclear. We aimed to determine whether surgical intervention would improve the sensory disturbances of patients with cervical spondylotic myelopathy. We conducted a prospective clinical trial of 101 patients who had undergone open door laminoplasty. For an objective sensory assessment, we measured the current perception thresholds (CPTs) in the patients' forearms and palms using PainVision PS-2100. For a subjective sensory assessment, numbness in the upper extremities was rated using a visual analog scale (VAS). Using the VAS scores, the patients were divided into those with improvement and without improvement. Their self-reported 36-item short-form health survey and Japanese Orthopaedic Association cervical myelopathy evaluation questionnaire scores were compared. The postoperative CPTs in relationship to the preoperative CPTs at 3, 6, and 12 months was 99.3%, 98.1%, and 93.8% in the forearm and 93.6%, 90.6%, and 87.8% in the palm, respectively. The corresponding postoperative numbness VAS scores were 63.8%, 50.5%, and 48.0%. At 12 months postoperatively, the 36-item short-form health survey physical and role component summary scores, cervical spine function effectiveness rates, upper and lower extremity function, and QOL items in the Japanese Orthopaedic Association cervical myelopathy evaluation questionnaire were significantly higher in the improvement group. Our findings have indicated that improvement in postoperative subjective sensory disturbances will occur relatively earlier and will be significantly greater than the improvement in objective sensory disturbances. Furthermore, improvement in the subjective sensory disturbances contributes to functional spinal cord recovery and patients' health-related QOL.


Amplification of the chromosome 20q region is associated with expression of HPV-16 E7 in human airway and anogenital epithelial cells.
To study the role of human papillomavirus (HPV) infection in the development of genetic instability, we transduced normal human airway and anogenital epithelial cells with various combinations of HPV-16 E6, E7, and the reverse transcriptase component of telomerase (hTERT). Cell lines generated by co-expression of E7 with E6 and/or hTERT (i.e., E6/E7, E7/hTERT, and E6/E7/hTERT) exhibited extra copies of chromosome 20 and specific amplification of the 20q12-ter region, whereas those generated without E7 (i.e., hTERT alone or E6/hTERT) did not. Co-expression of hTERT and a dominant-negative version of cdk4 that has been shown to inactivate the retinoblastoma (pRb) pathway also resulted in 20q amplification. Interestingly, extra copies of chromosome 20 were observed in early passage keratinocytes that expressed E7 alone, and microarray expression analysis revealed that genes in the 20q region and on chromosome 5 were specifically upregulated in these cells. Our results indicate that chromosome 20q amplification is an early event that may be specifically caused by expression of E7 through inactivation of the pRb pathway in human epithelial cells.


Identification of a novel HLA-A allele, A*24:128 in a Chinese individual.
The novel HLA-A*24:128 shows one nucleotide change from HLA-A*24:02:01:01 in exon 2 at position 155 from A to G.


A new turn on coumarin-based fluorescence probe for Ga(3+) detection in aqueous solution.
The probe CT was synthesized and investigated as a novel label-free chemosensor for Ga(3+) detection in water. Probe CT showed remarkable selectivity and sensitivity for Ga(3+) in Tris-HCl aqueous buffer solution (pH7.0). The chemosensor responded rapidly to Ga(3+) with a 1:1 stoichiometry. Meanwhile, the unapparent changes of fluorescence lifetime decays suggest the turn-on process of probe CT by Ga(3+) which appears to be a static mechanism.


Bedtime-to-Morning Glucose Difference and iGlarLixi in Type 2 Diabetes: Post Hoc Analysis of LixiLan-L.
A difference of ≥ 50-55 mg/dL between bedtime and morning glucose (BeAM) values in patients with type 2 diabetes (T2D) on basal insulin is an indicator of poor postprandial glucose control. This analysis compared the effect of treatment with a fixed-ratio combination of insulin glargine/lixisenatide (iGlarLixi) vs insulin glargine (iGlar) on BeAM values, and evaluated the impact of BeAM values on glycemic and safety endpoints. In this post hoc analysis of 517 participants from the LixiLan-L trial, change in BeAM values and composite efficacy and safety endpoints stratified by BeAM value < 55 mg/dL or ≥ 55 mg/dL were evaluated in patients with T2D uncontrolled on basal insulin randomized to iGlarLixi or iGlar over 30 weeks (LixiLan-L). Greater reductions in BeAM values were seen with iGlarLixi vs iGlar, and a higher proportion of patients reached a BeAM value < 55 mg/dL in the iGlarLixi arm. A BeAM value < 55 mg/dL was associated with improved glycemic control, lower risk of hypoglycemia, and a greater proportion of patients achieving glycemic targets without hypoglycemia or weight gain. Greater reductions in BeAM values were seen with iGlarLixi vs iGlar, irrespective of stratification by glycated hemoglobin A1c or glycemic endpoints. Greater reductions in bedtime-to-morning glucose differential, or BeAM, were observed with iGlarLixi vs iGlar in patients with T2D uncontrolled on basal insulin, reflecting better overall control of both fasting and prandial glucose and more appropriate matching of therapy to physiologic needs. ClinicalTrials.gov Identifier NCT02058160. Sanofi US, Inc.


Introducing the Language of "Relativity" for New Scaffold Categorization.
Research related with scaffold engineering tends to be cross-domain and miscellaneous. Several realms may need to be focused simultaneously, including biomedicine for cell culture and 3D scaffold, physics for dynamics, manufacturing for technologies like 3D printing, chemistry for material composition, as well as architecture for scaffold's geometric control. As a result, researchers with different backgrounds sometimes could have different understanding towards the product described as 'Scaffold'. After reviewing the literature, numerous studies termed their developed scaffold as 'novel', compared with scaffolds previously designed by others using comparing criterion like 'research time', 'manufacturing method', 'geometry', and so on. While it may have been convenient a decade ago to, for example, categorize scaffold with 'Dualistic Thinking' logic into 'simple-complicated' or 'traditional-novel', this method for categorizing 'novelty' and distinguishing scaffold is insufficiently persuasive and precise when it comes to modern or future scaffold. From this departure of philosophical language, namely the language of 'relativity', it is important to distinguish between different scaffolds. Other than attempting to avoid ambiguity in perceiving scaffold, this language also provides clarity regarding the 'evolution stage' where the focused scaffolds currently stand, where they have been developed, and where in future they could possibly evolve.


Concerted evolution of ribosomal DNA: Somatic peace amid germinal strife: Intranuclear and cellular selection maintain the quality of rRNA.
Most eukaryotes possess many copies of rDNA. Organismal selection alone cannot maintain rRNA function because the effects of mutations in one rDNA are diluted by the presence of many other rDNAs. rRNA quality is maintained by processes that increase homogeneity of rRNA within, and heterogeneity among, germ cells thereby increasing the effectiveness of cellular selection on ribosomal function. A successful rDNA repeat will possess adaptations for spreading within tandem arrays by intranuclear selection. These adaptations reside in the non-coding regions of rDNA. Single-copy genes are predicted to manage processes of intranuclear and cellular selection in the germline to maintain the quality of rRNA expressed in somatic cells of future generations.


On the effects of thiamphenicol and chloramphenicol on nucleic acid and protein synthesis in rabbit bone marrow cells in vivo and in vitro.
Besides the in vivo effects of thiamphenicol (TAP), this study shows the in vitro effects of TAP and D- and L-threo-chloramphenicol (CAP) on the synthesis of DNA, RNA, protein and hemoglobin in marrow cells and reticulocytes. The experiments make it likely that TAP exerts its action on a stem cell in a proliferating phase.


Bradykinin and cysteinyl leukotriene concentrations in cell-salvaged blood before and after passage through negatively charged filters during clinical use in cancer patients: a pilot study.
It has been suggested that giving cell-salvaged blood through a leucocyte depletion filter can cause hypotension due to bradykinin released when factor XII and platelets are activated by the negatively charged surface of the filter. We measured the concentration of bradykinin and cysteinyl leukotrienes in cell-salvaged blood sampled before and after passage through a negatively charged leucodepletion filter in 24 consecutive patients with gynaecological or bowel cancer undergoing elective surgery with cell salvage. In no case was an increase in bradykinin concentration observed after passage through the filter; in 23 patients the post-filtration bradykinin concentration was zero (p = 0.007). The change in the concentration of cysteinyl leukotrienes detected during passage across the filter was not statistically significant (p = 0.1). Our findings do not support the suggestion that either bradykinin or cysteinyl leukotrienes are generated in cell-salvaged blood during passage through leucodepletion filters.


Characterization and mapping of dipolar interactions within macromolecules in tissues using a combination of DQF, MT and UTE MRI.
This study shows that by combining a double-quantum filtered magnetization transfer (DQF-MT) with an ultra-short TE (UTE) MRI that it is possible to obtain contrast between tissue compartments based on the following characteristics: (a) the residual dipolar coupling interaction within the biomacromolecules, which depends on their structure, (b) residual dipolar interactions within water molecules, and (c) the magnetization exchange rate between biomacromolecules and water. The technique is demonstrated in rat-tail specimens, where the collagenous tissue such as tendons and the annulus pulposus of the disc are highlighted in these images, and their macromolecular properties along with those of bones and muscles can be characterized. DQF-MT UTE MRI also holds promise because collagenous tissues that are typically invisible in conventional MRI experiments produce significant signal intensities using this approach.


Osmotically regulated asymmetric capsular systems for simultaneous sustained delivery of anti-tubercular drugs.
Sustained release asymmetric membrane capsular systems were developed for simultaneous oral delivery of rifampicin and isoniazid sodium in order to reduce the problems associated with the multi drug therapy of tuberculosis. Dense semipermeable membrane coating capsules were also prepared for the delivery of these drugs by adopting two different filling approaches. In vitro release studies were carried out for both types of systems and the results were compared. Asymmetric membrane capsules provided sustained release of rifampicin associated with initial burst release, where isoniazid release rates were comparatively high due to higher aqueous solubility. Dense semipermeable membrane systems provided controlled release of both drugs but were devoid of initial burst release of isoniazid. To overcome these drawbacks, a modified asymmetric system was developed by adding appropriate amount of hydrophilic polymer mixture with isoniazid. The system provided satisfactory sustained release of rifampicin and isoniazid with initial burst release may be sufficient to achieve minimum effective concentration in blood. In vitro dissolution kinetics of the systems followed first order kinetics and statistical analysis of release rate data proved that modified asymmetric system was better amongst the developed systems.


Social stigma and compounded losses: quality-of-life issues for multiple-birth families.
To determine the quality-of-life domains most impacted by multiple births. Focus groups, qualitative research. Human volunteers in a medical research environment.Forty-three mothers, 29 raising multiple-birth children, 13 raising singletons, identified from random and convenience samples. None. Maternal self-reports of the psychosocial sequelae of multiple or singleton births, based on qualitative data analysis of transcribed group discussions. The quality-of-life domains that were most impacted by raising multiple birth children were social stigma, pregnancy loss, marital satisfaction, children's health, unmet family needs, parenting stress, maternal depression, and the infertility experience. Qualitative methods identified two novel quality-of-life domains in iatrogenic multiple birth families: social stigma and compounded losses. An unexpected finding was the potential for increased marital solidification as parents coped with the inordinate stresses of multiple births. As anticipated, children's health, unmet family needs, maternal depression, and parental stress were key areas of concern. In addition, the infertility experience had a lasting impact. These findings are significant, given that at least 38% of all assisted conceptions result in a multiple birth. This study lays the groundwork for further research on the impact of iatrogenic multiple births.


Acute myocarditis with transient eosinophilia and serum hyper-IgE-emia in a patient with atopic dermatitis.
A 14-year-old girl with acute myocarditis, transient eosinophilia, and hyper-IgE-emia associated with atopic dermatitis is described. The patient was admitted because of severe heart failure and shock, and severe atopic dermatitis was seen. Blood examinations showed moderate eosinophilia (1917/mm3) and hyper-IgE-emia (830IU/ml). The response to treatment with dopamine was excellent, and the congestive heart failure was gradually ameliorated, followed by improvement in her atopic dermatitis. In addition, rapid improvement in eosinophilia and hyper-IgE-emia was observed. Histopathological examination of the right ventricular myocardium obtained by endomyocardial biopsy showed mild interstitial fibrosis and mild infiltrations of inflammatory cells, indicating myocarditis. We speculated that the transient eosinophilia and hyper-IgE-emia in the present case indicated that an allergen induced strong allergic reactions, including type 1 allergy, and caused both acute myocarditis and deterioration of the atopic dermatitis; specifically noteworthy is that the patient's disease rapidly improved without corticosteroid treatment.


Involvement of caspase in patulin-induced hepatotoxicity in vitro and in vivo.
Patulin (PAT) a kind of mycotoxin, is a widely disseminated mycotoxin found in agricultural products and could cause liver damage. However, evidence on the underlying mechanisms of patulin is still lacking. In the present study, Human liver cancer cells (HepG2) together with a mouse model were used to explore the possible effect and mechanism. The results demonstrated that PAT treatment inhibited cell proliferation and caused liver toxicity in mice. In vitro, PAT inhibited the growth of HepG2 cells in a dose-dependent manner and a time-dependent manner; lipid peroxidation, malondialdehyde (MDA) production increased and the level of SOD and GSH in cells changed significantly. In vivo, Kunming mice were treated with PAT(2.5-15 μM), We indicated that liver damage are observed. The activity of serum alanine transaminase (ALT) and aspartate transaminase (AST) were increased significantly, the hepatocyte nucleus stained with Hematoxylin and Eosin (HE) was blurred and deformed. we also explored the lipid peroxidation and enzymes related to redox and found that the activities of SOD in animals do not change significantly, not like that in cells, while GSHpx played a major role. In addition, we measured the caspase activity of cells and the expression of caspase in mice. PAT-induced the caspase cascade was confirmed with the elevation of the activity and expression of caspase. These data suggest that PAT treatment altered both the redox systems in cells and animals. involvement of caspase in patulin-induced hepatotoxicity.


Association between EFHD2 gene polymorphisms and schizophrenia among the Han population in northern China.
Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. The gene encoding EF-hand domain-containing protein D2 (EFHD2) may be a genetic risk locus for schizophrenia. We genotyped four EFHD2 single-nucleotide polymorphisms (281 schizophrenia cases [SCZ], 321 controls) from northern Chinese Han individuals using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis. Differences existed in genotype, allele, and haplotype frequency distributions between SCZ and control groups. The rs2473357 genotype and allele frequency distributions differed between SCZ and controls; however, this difference disappeared after Bonferroni correction. Differences in rs2473357 genotype and allele frequency distributions between SCZ and controls were more pronounced in men than in women. The G allele increased schizophrenia risk (odds ratio = 1.807, 95% confidence interval = 1.164-2.803). Among six haplotypes (G-, A-, G-insC, A-C, G-C, and G-T), the G- haplotype frequency distribution differed between SCZ and controls in women; the A-C and G-C haplotype frequency distributions differed between SCZ and controls in men. EFHD2 may be involved in schizophrenia. Sex differences in EFHD2 genotype and allele frequency distributions existed among schizophrenia patients. Further research is needed to determine the role of EFHD2 in schizophrenia.


Elective Neck Dissection Versus Observation in Squamous Cell Carcinoma of Oral Cavity With Clinically N0 Neck: A Systematic Review and Meta-Analysis of Prospective Studies.
To assess the possible benefits of elective neck dissection (END) in patients with squamous cell carcinoma (SCC) of the oral cavity and clinically N0 neck. Medline, Embase, the China National Knowledge Infrastructure, and the Wan Fang Database were systematically searched. A meta-analysis was performed to evaluate the possible benefits of END to such patients. Six prospective studies involving 865 patients fulfilled the inclusion criteria. Meta-analysis of all included studies showed that END substantially lowered the risk of regional recurrences (risk ratio [RR] = 0.27; 95% confidence interval [CI], 0.21-0.36) in the fixed-effect model compared with observation only. Three of the 6 included studies showed that the specific death rate related to regional recurrences was lower in the END group than in the observation group in the fixed-effect model (RR = 0.35; 95% CI, 0.19-0.65). The mean metastasis rate of occult cervical lymph node was 30.27% (standard deviation, 9.42%). When the fixed-effect model was applied, 4 of the 6 included studies showed less recurrence in the END group compared with the observation group (RR = 0.53; 95% CI, 0.44-0.64). END substantially decreases recurrences and deaths related to regional recurrences in early-stage SCC of the oral cavity with clinically N0 neck, especially SCC of the oral tongue and floor of the mouth, which is necessary for such patients.


Inhibition of ATP synthesis by fenbufen and its conjugated metabolites in rat liver mitochondria.
Fenbufen is an arylpropionic acid derivative belonging to the group of non-steroidal anti-inflammatory drugs (NSAIDs). Even though fenbufen is considered a safe drug, some adverse reactions including hepatic events have been reported. To investigate whether mitochondrial damage could be involved in the drug induced liver injury (DILI) by fenbufen, the inhibitory effect of fenbufen and its conjugated metabolites on oxidative phosphorylation (ATP synthesis) in rat liver mitochondria was investigated. Fenbufen glucuronide (F-GlcA), fenbufen-N-acetyl cysteine-thioester (F-NAC) and fenbufen-S-glutathione thioester (F-SG) were found to be more potent inhibitors compared to parent fenbufen (F), whereas fenbufen-O-carnitine (F-carn), fenbufen-glycine (F-gly) and fenbufen-N-acetyl lysine amide (F-NAL) were less potent compared to fenbufen. Fenbufen-CoA thioester (F-CoA) was equally potent as fenbufen in inhibiting ATP synthesis. Fenbufen showed time and concentration dependent inhibition of ATP synthesis with Kinact of 4.4 min(-1) and KI of 0.88 μM and Kinact/KI ratio of 5.01 min(-1) μM(-1). Data show that fenbufen did not act through opening MPT pore, nor did incubation of mitochondria with reduced GSH and fenbufen show any protective effect on fenbufen mediated inhibition of oxidative phosphorylation. Inclusion of NADPH in mitochondrial preparations with fenbufen did not modulate the inhibitory effects, suggesting no role of CYP mediated oxidative metabolites on the ATP synthesis in isolated mitochondria. The results from the present experiments provide evidence that fenbufen and its metabolites could be involved in mitochondrial toxicity through inhibition of ATP synthesis.


A trypsin-resistant heme peptide from cardiac cytochrome c1.
A tryptic resistant heme peptide has been prepared and purified from cardiac cytochrome c1. This purified peptide is not further hydrolyzed by reactions of other proteolytic enzymes, such as pronase. The peptide contains 2 residues each of serine, cysteine and valine, and 1 residue each of alanine, methionine, tyrosine, histidine, arginine, proline, glutamic acid (glutamine) and aspartic acid. The intensity of the absorption spectrum of the peptide has been found to be dependent upon, but the positions of the absorption maxima do not vary with, concentration. The heme peptide does not show multiple splitting of absorption peaks at liquid N2 temperatures as does the intact cytochrome C1. However, cyanide rapidly reacts with the peptide and causes significant spectral changes. CD spectra of the peptide exhibit a typical profile of a non-structured heme peptide with positive CD bands in the Soret region and around 250 nm, and a broad negative extreme of 320-360 nm. The similarities and differences between the tryptic resistant heme peptides from cytochromes c1 and c have been compared.


Evaluation of shelf-life, antioxidant activity and nutritional quality attributes in carnauba wax coated eggplant genotypes.
Eggplant genotypes of white, green and violet are very popular in the specific regions of sub-tropics and tropics. These possess enormous health benefits as having high antioxidant activity. Due to limited shelf life i.e. 3 days at ambient storage, wholesalers and retailers apply many unhygienic practices. They use petroleum based oil to make the fruit surface shiny and attractive. In the present study, Eggplant genotypes, viz. violet, green and white, were assessed after carnauba wax (CW) emulsion containing additives such as 2.5% polyethylene glycol (PEG) and 0.5% sodium alginate (SA) as T1, 0.5% SA as T2, 2.5% PEG as T3 and non-coated eggplant fruits as control fruits (T4) for shelf life extension and retention of nutritional quality attributes at ambient condition (20 ± 2 °C and RH 52-54%) for 7 days. The additives mixed CW coatings were effective in extending the shelf life and retaining the nutritional quality attributes than control genotypes. Sodium alginate (SA) mixed CW coating resulted in maximum shelf life extension of white eggplant genotypes by 7 days as compared to 3-4 days in control eggplant genotypes at ambient storage. However, 6.9%, 1.83% and 6.04% decrease in physiological loss in weight was obtained in 0.5% SA based CW coating after 5 days of ambient storage of violet, green and white eggplant genotypes, respectively in comparison to fully control eggplant genotype. The firmness level of eggplant genotypes in 0.5% SA based CW coating was more (85.1%, 50% and 45%) after 7 days of ambient storage of violet, green and white genotypes, respectively in comparison to fully control eggplant genotype. Similarly, total phenol content was also increased (26.1%, 37.5% and 180.9%) in 0.5% SA based CW coated eggplant genotypes of violet, green and white, respectively after 7 days of ambient storage in comparison to fully control eggplant genotype. Initially there had been increase in antioxidant activity in white genotype up to 5 days of storage which thereafter decreased on 7 days of storage in all the treatments. However, violet and green genotypes had not followed any trend during storage.


Postural abnormalities in Asian and Caucasian Parkinson's disease patients: A multicenter study.
Postural abnormalities (PA) are disabling features of Parkinson's disease (PD). Indirect analyses suggested a higher prevalence of PA among Asian patients compared to Caucasian ones, but no direct comparisons have been performed so far. An international, multicenter, cross-sectional study was performed in 6 European and Asian movement disorders centers with the aim to clarify differences and similarities of prevalence and characteristics of PA in Asian vs. Caucasian PD patients. Axial PA, encompassing antecollis (AC), camptocormia (CC), and Pisa syndrome (PS), and appendicular PA (appPA) were systematically searched and analysed in consecutive patients. 88 (27%) of 326 PD patients had PA (29.1% in Asians and 24.3% in Caucasians, p: 0.331). Prevalence of axial PA was 23.6% in Asians and 24.3% in Caucasians (p = 0.886), in spite of a longer disease duration among Caucasians, but a longer PA duration among Asians. No differences in prevalence between AC, CC, and PS were found between the two ethnicities. The prevalence of appPA was higher in Asians (p = 0.036), but the regression analysis did not confirm a significant difference related to ethnicity. Considering the whole population, male gender (OR, 4.036; 95% CI, 1.926-8.456; p < 0.005), a longer disease duration (OR, 2.61; 95% CI, 1.024-6.653; p = 0.044), and a higher axial score (OR, 1.242; 95% CI, 1.122-1.375; p < 0.0005) were the factors associated with axial PA. The prevalence of axial PA in PD patients is not influenced by ethnicity. However, Asian PD patients tend to develop PA earlier in the disease course, particularly AC.


Inactivation of transcription by UV irradiation of T. brucei provides evidence for a multicistronic transcription unit including a VSG gene.
We have used inactivation of transcription by UV irradiation to map transcription units in trypanosomes. The relative inactivation rate of the transcription of mini-exon, 5S, and rRNA genes was inversely proportional to the previously estimated lengths of these transcription units. The telomeric transcription unit containing the gene for variant-specific surface glycoprotein (VSG) 221 was inactivated as a single unit of 60 kb. This long transcription unit comprises at least one other protein-coding gene and yields seven other stable mRNAs. These data thus provide evidence for a multicistronic transcription unit for cellular genes in a eukaryote.


Long Term Dietary Supplementation with Omega-3 Fatty Acids in Charolais Beef Cattle Reared in Italian Intensive Systems: Nutritional Profile and Fatty Acids Composition of Longissimus lumborum Muscle.
Recently, the quality of beef has received great attention, and health concerns have been focused on fatty acid composition in relation to dietary requirements. The present work aims to evaluate the effect of omega-3 fatty acids (FA) lipid supplement in beef diet on the nutritional characteristics of Longissimus lumborum (LL) muscle. One hundred and eighty Charolais beef were divided in two groups: the control group (CON) received a basal diet and the second one (TR) an isoenergetic diet containing the omega-3 supplement. Dietary treatment did not affect (p > 0.05) growth performances, carcass characteristics and LL colour indices. Cholesterol content resulted lower (p < 0.001) in LL muscle from TR group than CON. The omega-3 FA and conjugated linoleic acid content were higher (p < 0.001) in LL muscle from TR than CON. As expected, LL muscle from TR group showed an increased value of malondialdehyde than CON during refrigerated storage, anyway, remaining within the threshold value of 1 mg/kg meat. In conclusion, the lipid supplement, rich in omega-3 FA improves the fatty acid profile and decreases cholesterol content of LL muscle. This feeding practice is suggested to enhance the nutritional value of meat from beef reared in intensive condition, improving the consumer's health.


Severe aplastic anaemia in children: Impact of histopathology profile and treatment on very long-term outcomes.
To assess very long-term outcomes of children with severe aplastic anaemia (SAA) and impact of histopathology and of different treatments over time. We conducted a retrospective study of 57 consecutive patients with SAA during 1973-2019. According to period, treatment consisted of androgens, immunosuppressive treatment (IST) and haematopoietic cell transplantation (HCT) in 14, 31 and 13 patients, respectively. Histopathology immune profiles were studied on bone marrow (BM). Response rate (RR) to androgens was 35%, with long-term survivorship in 4 of 5 responders. RR and 10-year overall survival (OS) after IST was 65% and 80%, respectively. RR was higher in girls (92% vs 43% in boys, P = .02). Mean baseline BM values of CD34 + and of B-lymphocytes in responders vs non-responders were 1.3% vs 0 (P = .08) and 14.1% vs 9.7% (P = .07), respectively. After IST, BM cellularity gradually increased and cytotoxic T-lymphocytes decreased (time variation P = .003 and 0.07, respectively). Outcome did not differ between patients with IST or frontline HCT. Ten-year OS improved over time, increasing from 35.3% to 77.1% and 77% during 1973-1985, 1986-2003 and 2004-2019, respectively. Histopathology may refine response prediction to IST. The course of SAA in children, a previously fatal disease, was altered in recent times.


Resonance Assisted Chalcogen Bonding as a New Synthon in the Design of Dyes.
Intramolecular chalcogen bonding in arylhydrazones of sulfamethizole is strengthened by conjugation in the π-system of a noncovalent five-membered ring. The S⋅⋅⋅O distance in the sulfamethizole moiety of these compounds ranges from 2.698(3) to 2.806(15) Å, which indicates its strong dependence on the attached arylhydrazone fragments. Information on the nature of the intramolecular chalcogen bond was afforded by DFT calculations.