Myocardial Protection in Minimally Invasive Mitral Valve Surgery: Retrograde Cardioplegia Alone Using Endovascular Coronary Sinus Catheter Compared With Combined Antegrade and Retrograde Cardioplegia.
To compare myocardial protection with retrograde cardioplegia alone with antegrade and retrograde cardioplegia in minimally invasive mitral valve surgery (MIMS). Retrospective study. Tertiary care university hospital. The authors studied 97 MIMS patients using retrograde cardioplegia alone and 118 MIMS patients using antegrade and retrograde cardioplegia. The data from patients admitted for MIMS using retrograde cardioplegia (MIMS retro) between 2009 to 2012 were compared with the data from patients undergoing MIMS with antegrade and retrograde cardioplegia (MIMS ante-retro) between 2006 and 2010 (control group). Cardioplegia in the MIMS retro group was delivered solely through an endovascular coronary sinus (CS) catheter positioned under echographic and fluoroscopic guidance. Antegrade and retrograde cardioplegia was used in the MIMS ante-retro group. Data regarding myocardial infarction (MI; creatine kinase Mb, troponin T, electrocardiogram), myocardial function, and hemodynamic stability were collected for comparison. Adequate cardioplegia administration (CS pressure >30 mmHg and asystole) was attained in 74.2% of the patients with retrograde cardioplegia alone. In 23.7% of the patients, the addition of an antegrade cardioplegia was necessary. No difference was observed in the incidence of MI (0 MIMS retro v 1 for MIMS ante-retro, p = 0.3623), difficult separation from cardiopulmonary bypass, and postoperative malignant arrhythmia. No difference was found for maximal creatine kinase Mb (39.1 [28.0-49.1] v 37.9 [28.6-50.9]; p = 0.8299) and for maximal troponin T levels (0.39 [0.27-0.70] v 0.47 [0.32-0.79]; p = 0.1231) for MIMS retro and MIMS ante-retro, respectively. However, lactate levels in the MIMS retro group were significantly lower than in the MIMS ante-retro group (2.1 [1.4-3.05] v 2.4 [1.8-3.3], respectively; p = 0.0453). No difference was observed in duration of intensive care unit stay and death. MIMS retro patients had a shorter hospital stay (7.0 [6.0-8.0] v 8.0 [7.0-9.0] days; p = 0.0003). Retrograde cardioplegia administration alone provided comparable myocardial protection to antegrade and retrograde cardioplegia during MIMS, but was not sufficient to achieve asystole in one-fifth of patients.


Exploring bioactive properties of marine cyanobacteria isolated from the Portuguese coast: high potential as a source of anticancer compounds.
The oceans remain a major source of natural compounds with potential in pharmacology. In particular, during the last few decades, marine cyanobacteria have been in focus as producers of interesting bioactive compounds, especially for the treatment of cancer. In this study, the anticancer potential of extracts from twenty eight marine cyanobacteria strains, belonging to the underexplored picoplanktonic genera, Cyanobium, Synechocystis and Synechococcus, and the filamentous genera, Nodosilinea, Leptolyngbya, Pseudanabaena and Romeria, were assessed in eight human tumor cell lines. First, a crude extract was obtained by dichloromethane:methanol extraction, and from it, three fractions were separated in a Si column chromatography. The crude extract and fractions were tested in eight human cancer cell lines for cell viability/toxicity, accessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactic dehydrogenase release (LDH) assays. Eight point nine percent of the strains revealed strong cytotoxicity; 17.8% showed moderate cytotoxicity, and 14.3% assays showed low toxicity. The results obtained revealed that the studied genera of marine cyanobacteria are a promising source of novel compounds with potential anticancer activity and highlight the interest in also exploring the smaller filamentous and picoplanktonic genera of cyanobacteria.


Reconstitution Inflammatory Syndrome Like Reactive Hemophagocytic Syndrome Associated with Disseminated Histoplasmosis in a HIV Patient.
We describe an unusual clinical association of disseminated histoplasmosis with reactive hemophagocytic syndrome. We report the case of a new HIV-positive patient with reconstitution inflammatory syndrome like reactive hemophagocytic syndrome associated with disseminated histoplasmosis. We describe the clinical case, the procedures performed, the treatment provided and the patient's evolution. A figure of liver biopsy Grocott's silver methenamine stain that shows lots of uniform ovoid yeasts in portal spaces' macrophages that supports the diagnosis of disseminated histoplasmosis in our case.


Whose genome project?
The human genome project is a multinational project aimed at obtaining a detailed map and a complete DNA sequence of the human genome. It will have many scientific, medical, economic, ethical, legal, and social implications. A fundamental question to ask is "Whose genome project is it?" We can answer this question from different perspectives, and this aids our thinking about the issues that arise from the project. We can think of who proposed the idea, who should fund the research, who should perform the research, whose genome is mapped and sequenced, who should own the data, who should benefit from the results, and who should make these decisions. We can also compare the answers to these ethical questions with what is occurring in practice.


Entropic bounds between two thermal equilibrium states.
The positivity conditions of the relative entropy between two thermal equilibrium states ρ[over ̂]_{1} and ρ[over ̂]_{2} are used to obtain upper and lower bounds for the subtraction of their entropies, the Helmholtz potential and the Gibbs potential of the two systems. These limits are expressed in terms of the mean values of the Hamiltonians, number operator, and temperature of the different systems. In particular, we discuss these limits for molecules that can be represented in terms of the Franck-Condon coefficients. We emphasize the case where the Hamiltonians belong to the same system at two different times t and t^{'}. Finally, these bounds are obtained for a general qubit system and for the harmonic oscillator with a time-dependent frequency at two different times.


Modulation of agrin binding and activity by the CT and related carbohydrate antigens.
Agrin is a nerve-derived signal that is essential for the proper organization of postsynaptic acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction. It is likely that carbohydrates play a significant role in regulating agrin activity, as agrin binds multiple glycan structures and is itself a highly glycosylated protein. Here we provide support for this contention by showing that agrin can be modified with the CT antigen, a carbohydrate structure expressed at the neuromuscular junction, and by describing the resulting changes in agrin binding to neoglycoconjugates and cultured myotubes, as well as changes in agrin-dependent AChR clustering. Glycosylation of agrin with the CT antigen required the mucin domain and the dystroglycan/heparin-binding domain. The presence of the mucin domain lowered agrin binding to several N-acetyllactosaminyl-containing saccharides and C2 myotubes and lowered agrin activity in AChR clustering. Glycosylation of agrin with the CT antigen, by contrast, increased agrin binding to myotubes and potentiated its AChR clustering activity at subsaturating concentrations. Last, sialylated and nonsialylated variants of N-acetyllactosamine differentially modulated AChR clustering and agrin activity, and these changes correlated with the ability of MuSK, an agrin-stimulated kinase, to bind to these structures. These experiments demonstrate that the glycosylation state of agrin affects its activity and suggest a role for the CT antigen in modulating agrin function.


Generation of specific cytotoxic T cells with a fragment of the Epstein-Barr virus-encoded p63/latent membrane protein.
Human B lymphocytes, transformed by the herpesvirus Epstein-Barr virus, are known to express a characteristic antigen(s) recognized by the cellular immune response. This structure has been termed lymphocyte-determined membrane antigen. Because of the significance of this structure in controlling Epstein-Barr virus infection in vivo, the molecular nature of lymphocyte-determined membrane antigen has been long sought. In this paper, we show that a sequence of 10 amino acids (residues 43-53) from the Epstein-Barr virus-encoded membrane protein p63/latent membrane protein can induce Epstein-Barr virus-specific cytotoxic T cells and, therefore, bears at least one of the lymphocyte-determined membrane antigenic determinants.


RANIBIZUMAB FOR RETINAL VEIN OCCLUSION: Predictive Factors and Long-Term Outcomes in Real-Life Data.
The purpose of the study was to evaluate the long-term anatomical and functional outcomes in patients with retinal vein occlusion (RVO), either central retinal vein occlusion or branch retinal vein occlusion, treated with intravitreal ranibizumab and to determine the predictive factors of the final visual outcome. This retrospective study included 54 treatment-naive patients with macular edema due to RVO (25 with central retinal vein occlusion and 29 with branch retinal vein occlusion), who were treated with intravitreal ranibizumab (3 monthly injections and pro re nata). Predictive factors for visual outcome were assessed. In addition, the best-corrected visual acuity change and the percentage of patients with edema resolution were evaluated. The mean follow-up time was 47.4 ± 11.1 months. At the end of the follow-up, patients with central retinal vein occlusion gained +6.9 letters (∼1 Snellen line), whereas patients with branch retinal vein occlusion gained +15.1 letters (3 Snellen lines). Forty-eight percent of patients in central retinal vein occlusion group and 69.0% in branch retinal vein occlusion group presented resolution of macular edema. Negative predictive factors for the final visual outcome were found to be increasing age, increasing macular thickness, the presence of intraretinal fluid, the duration of RVO >3 months, the ischemic type of RVO, the cystoid type of edema, and the external limiting membrane and ellipsoid zone disruption. The various predictive factors that determine the visual outcome and possibly define the patients' prognosis after ranibizumab treatment in RVO have been studied. The long follow-up period showed that ranibizumab seems to be safe and effective in the treatment of the disease.


A simple and inexpensive apparatus for measuring fish metabolism.
A simple, noninvasive, and economical home-made respirometer has been used to determine the standard metabolism of goldfish. The apparatus has been tested on several fishes and has proved its accuracy in determining a mass effect on standard metabolism. The apparatus can be made easily by middle school, high school, and undergraduate students and can be used to introduce them to basic concepts in animal physiology and in biological statistics.


Controlled release of chlorhexidine from UDMA-TEGDMA resin.
Chlorhexidine salts are available in various formulations for dental applications. This study tested the hypothesis that the release of chlorhexidine from a urethane dimethacrylate and triethylene glycol dimethacrylate resin system can be effectively controlled by the chlorhexidine diacetate content and pH. The filler concentrations were 9.1, 23.1, or 33.3 wt%, and the filled resins were exposed to pH 4 and pH 6 acetate buffers. The results showed that Fickian diffusion was the dominant release mechanism. The rates of release were significantly higher in pH 4 buffer, which was attributed to the increase of chlorhexidine diacetate solubility at lower pH. The higher level of filler loading reduced the degree of polymerization, leading to a greater loss of organic components and higher chlorhexidine release rates.


Teaching behaviours of clinical instructors: an audit instrument.
This article describes the development and initial psychometric testing of an instrument that permits the observation and recording of teaching behaviours exhibited by clinical instructors while supervising nursing students. Observations of Nursing Teachers in Clinical Settings (ONTICS) consists of 44 items grouped into nine categories of desirable and undesirable teaching behaviours: questioning method; responding style; method of giving feedback; teaching skill; method of demonstration; interaction with patient/family; interactions with health team; undesirable teaching behaviours; undesirable questioning/responding method. The instrument was refined on several occasions based on input from expert judges. Construction validity, internal consistency reliability and test-retest reliability were found to be acceptable. ONTICS appears to capture an aspect of clinical teaching not readily identified by other, more subjective, instruments.


TFE3 controls lipid metabolism in adipose tissue of male mice by suppressing lipolysis and thermogenesis.
Transcription factor E3 (TFE3) is a transcription factor that binds to E-box motifs and promotes energy metabolism-related genes. We previously reported that TFE3 directly binds to the insulin receptor substrate-2 promoter in the liver, resulting in increased insulin response. However, the role of TFE3 in other tissues remains unclear. In this study, we generated adipose-specific TFE3 transgenic (aP2-TFE3 Tg) mice. These mice had a higher weight of white adipose tissue (WAT) and brown adipose tissue than wild-type (WT) mice under fasting conditions. Lipase activity in the WAT in these mice was lower than that in the WT mice. The mRNA level of adipose triglyceride lipase (ATGL), the rate-limiting enzyme for adipocyte lipolysis, was significantly decreased in aP2-TFE3 Tg mice. The expression of Foxo1, which directly activates ATGL expression, was also suppressed in transgenic mice. Promoter analysis confirmed that TFE3 suppressed promoter activities of the ATGL gene. In contrast, G0S2 and Perilipin1, which attenuate ATGL activity, were higher in transgenic mice than in WT mice. These results indicated that the decrease in lipase activity in adipose tissues was due to a decrease in ATGL expression and suppression of ATGL activity. We also showed that thermogenesis was suppressed in aP2-TFE3 Tg mice. The decrease in lipolysis in WAT of aP2-TFE3 Tg mice inhibited the supply of fatty acids to brown adipose tissue, resulting in the inhibition of the expression of thermogenesis-related genes such as UCP1. Our data provide new evidence that TFE3 regulates lipid metabolism by controlling the gene expression related to lipolysis and thermogenesis in adipose tissue.


Rapid Response of Eastern Mediterranean Deep Sea Microbial Communities to Oil.
Deep marine oil spills like the Deepwater Horizon (DWH) in the Gulf of Mexico have the potential to drastically impact marine systems. Crude oil contamination in marine systems remains a concern, especially for countries around the Mediterranean Sea with off shore oil production. The goal of this study was to investigate the response of indigenous microbial communities to crude oil in the deep Eastern Mediterranean Sea (E. Med.) water column and to minimize potential bias associated with storage and shifts in microbial community structure from sample storage. 16S rRNA amplicon sequencing was combined with GeoChip metagenomic analysis to monitor the microbial community changes to the crude oil and dispersant in on-ship microcosms set up immediately after water collection. After 3 days of incubation at 14 °C, the microbial communities from two different water depths: 824 m and 1210 m became dominated by well-known oil degrading bacteria. The archaeal population and the overall microbial community diversity drastically decreased. Similarly, GeoChip metagenomic analysis revealed a tremendous enrichment of genes related to oil biodegradation, which was consistent with the results from the DWH oil spill. These results highlight a rapid microbial adaption to oil contamination in the deep E. Med., and indicate strong oil biodegradation potential.


Prevalence of irritable bowel syndrome (IBS) and variability of diagnostic criteria.
The main objectives of this study were to assess whether the use of different definitions of irritable bowel syndrome (IBS) could influence measurements of its prevalence and characterize the patient population fulfilling these different diagnostic criteria. A telephone survey was carried out by contacting 8,221 subjects aged >or=18 Years representative of the French population. A "screening" questionnaire based on three algorithms of IBS classification (Manning, with or without a notion of a minimal duration of symptoms, Rome I and Rome II) was used by specialised inquirers. Twenty three percent of the subjects interviewed stated that they had suffered from abdominal pain during the previous 12 Months. The prevalence of IBS considerably varied, depending on the diagnostic criteria used: 12% based on Manning criteria without reference to the duration of symptoms; 2.5% if the notion of duration of symptoms was added to the Manning criteria, and 2.1% and 1.1% based on the Rome I and Rome II criteria, respectively (the latter including the same notion of duration). In total, 212 subjects (2.6%) met at least one of the criteria including a minimal duration of symptoms, with a predominance for women (sex-ratio close to 2). The prevalence of IBS is strongly dependent on the classification algorithm employed. The requirement of a minimum duration of symptoms eliminates IBS in a large number of subjects complaining of abdominal disorders. Once these methodological variations were taken into account, the prevalence of IBS in France was found to be comparable to that published in international literature.


Large Mammary Paget Disease without Underlying Breast Carcinoma.
Mammary Paget disease is an uncommon type of breast cancer. Redness, scaling, and thickness involving the nipple and areola are common clinical symptoms. Invasive breast cancer was found in nearly 90% of these patients. Only a few cases of mammary Paget disease with no underlying cancer have been described, with a better prognosis. Treatment options include wide excision or mastectomy. However, if the lesion is very extensive, breast reconstruction may be required. We reported a rare case of extensive Paget disease in a 65-year-old woman who had a 7-year history of a 14 × 19 cm progressively enlarging erythematous scaling lesion that covered her entire left breast. No evidence of related malignancy or metastatic lesion was seen. A left mastectomy with sentinel lymph node biopsy and immediate pedicled transverse rectus abdominis myocutaneous flap reconstruction was chosen. There is uncertainty about axillary node metastasis since multiple enlarged and palpable left axillary lymph nodes were seen. She had axillary lymph node dissection instead. A histological examination confirmed the diagnosis of Paget disease of the nipple in the absence of underlying breast cancer and there was no evidence of axillary lymph node metastasis. This article emphasizes the need to pay close attention to diagnosis, progression, and treatment of the disease.


Bronchogenic adenocarcinoma presenting as a synchronous solitary lytic skull lesion with ischaemic stroke--case report and literature review.
The authors describe a rare case of metastatic bronchogenic adenocarcinoma in a 55-year-old man presenting with concomittant solitary lytic skull lesion and ischaemic stroke. Metastatic bronchogenic carcinoma is known to present as lytic skull lesions. Primary brain tumours are also known to cause ischaemic brain injury. An underlying stroke risk may be exagerated by cranial tumour surgery. Patients with brain tumours are well known to be predisposed to an increased risk of developing thromboembolic disease. It is unusual to see metastatic bronchogenic adenocarcinoma presenting as ischaemic stroke with a background of concomittant cerebral metastasis. The aetio-pathogenesis of this rare occurrence is discussed with a review of literature.


A rare reaction to synthetic mono-filament sutures: a report of two cases.
Due to their clinical advantages, synthetic mono-filament sutures are dominantly used for postoperative wound closures. We present two patients who suffered rare skin reactions to either poliglecaprone 25 or glyconate sutures, following breast cancer lumpectomy. This report aims to make perioperative practitioners and clinicians aware of reactions to sutures and possible management options.


Serologic evidence of Chlamydia pneumoniae infection as a long-term predictor of cardiovascular death in renal transplant recipients.
Cardiovascular disease is the main cause of death with a functioning graft in renal transplant recipients. Elevated levels of C-reactive protein (CRP) and evidence of chronic Chlamydia pneumoniae infection have been linked to cardiovascular disease and survival in patients with normal renal function and patients with end-stage renal disease on dialysis. So far, no such data have been available in renal transplant recipients. CRP, immunoglobulin (Ig)G and IgA antibodies to C. pneumoniae, and classic risk factors were compiled in 143 patients who underwent renal transplantation between January 1989 and April 1991. Samples were collected at transplantation, 1 year later, and at study end. Cardiovascular disease, death, and graft loss were documented during follow-up. A total of 44 patients died during a mean follow-up of 10 years. Cardiac events were responsible for 37% of deaths. Age, gender, number of antihypertensive drugs, and seropositivity for IgG and IgA antibodies to C. pneumoniae, but not CRP levels, were significantly associated with cardiac death. C. pneumoniae serology and CRP levels, however, did not influence graft survival. Age, presence of diabetes, calcium phosphorus ion product, number of antihypertensive drugs, serum creatinine at 1 year, and presence of chronic rejection were all negatively correlated with graft survival. Serologic evidence of chronic C. pneumoniae infection is associated with mortality as the result of cardiovascular disease in renal transplant recipients. CRP serum levels do not predict cardiac death in renal transplant recipients, in contrast with patients with normal renal function and patients on dialysis.


Transduction of reducing power across the plasma membrane by reduced glutathione. A 1H-NMR spin-echo study of intact human erythrocytes.
The NMR signal of reduced glutathione (GSH) was monitored in intact human erythrocytes by the 1H spin-echo Carr-Purcell-Meiboom-Gill pulse sequence. Addition of GSH, which was unable to cross the erythrocyte membrane, produced an approximate twofold increase of the GSH signal in glucose-depleted cells. Addition of oxidised glutathione (GSSG), did not affect the signal, and addition of GSH to hemolysates gave a much smaller increase. Reduction of internal GSSG by NADPH-dependent enzymes was excluded by experiments with glucose-supplied or glucose-6-phosphate dehydrogenase deficient cells. Involvement of external thiol groups of the erythrocyte membrane was shown by the lack of effect in cells treated with an impermeable thiol-blocking compound. Involvement of spectrin was indicated by the proportional loss of the effect in erythrocytes with variable genetic deficiency of spectrin. Protein-glutathione mixed disulfides appeared to be the source of the NMR response since an increase of their content, by diamide treatment or aging procedures, produced a higher GSH signal, while their reduction by permeable reductants gave the opposite effect. It is concluded that GSH can transduce its reducing power by a thiol/disulfide exchange mechanism that sequentially involves sulfur-rich proteins spanning across the erythrocyte membrane.


Acid and NaCl limits to growth of Listeria monocytogenes and influence of sequence of inimical acid and NaCl levels on inactivation kinetics.
Variability in growth limits of Listeria monocytogenes in response to low pH (adjusted with HCl) or high salinity (NaCl) was evaluated for 127 strains in brain heart infusion broth at 25 degrees C. Over 95% of strains habituated at pH 5.0 grew subsequently at pH 4.2, while 25% were able to grow at pH 4.1. More than 85% of strains preadapted to growth at 8.5% NaCl (wt/vol) subsequently grew in the presence of 11.3% NaCl, while 25% were able to grow at 13% NaCl, and 4.7% grew in the presence of 13.9% NaCl. The results extend the generally accepted growth limits for L. monocytogenes in response to these hurdles. Two strains, one of which was relatively tolerant of both hurdles, and another that was less tolerant of both hurdles, were subjected to different sequences of lethal acid (pH 3.5) and NaCl (14%, wt/vol) stresses to determine whether survival was affected by growth limits, or by sequence of application of treatment. There was no significant difference in the inactivation kinetics of the two strains, but inactivation rates were affected by different treatments. For both strains, the inactivation rates, from fastest to slowest, resulted from: (i) lethal pH and then by lethal water activity, or lethal water activity and then by lethal pH; (ii) lethal pH and water activity applied simultaneously; (iii) lethal pH; and (iv) lethal water activity. The results demonstrated that the sequence of lethal stress application strongly influences L. monocytogenes inactivation, and that L. monocytogenes growth limits are not good predictors of survival in inimical environments.


Theoretical calculations of infrared absorption, vibrational circular dichroism, and two-dimensional vibrational spectra of acetylproline in liquids water and chloroform.
Infrared absorption, vibrational circular dichroism, and two-dimensional infrared pump-probe and photon echo spectra of acetylproline solutions are theoretically calculated and directly compared with experiments. In order to quantitatively determine interpeptide interaction-induced amide I mode frequency shifts, high-level quantum chemistry calculations were performed. The solvatochromic amide I mode frequency shift and fluctuation were taken into account by carrying out molecular dynamics simulations of acetylproline dissolved in liquids water and chloroform and by using the extrapolation method developed recently. We first studied correlation time scales of the two amide I vibrational frequency fluctuations, cross correlation between the two fluctuating local mode frequencies, ensemble averaged conformations of the acetylproline molecule in liquids water and chloroform. The corresponding conformations of the acetylproline in liquids water and chloroform are close to the ideal 3(10) helix and the C(7) structure, respectively. A few methods proposed to determine the angle between the two transition dipoles associated with the amide I vibrations were tested and their limitations are discussed.


Surgical fixation of fractures of the distal radius within 2 weeks reduces postoperative finger stiffness.
Locked anterior plating remains the most common form of surgical fixation for displaced fractures of the distal radius. We hypothesized that delayed surgical fixation later than 2 weeks after injury contributes to poorer patient outcomes for patients with displaced or intra-articular fractures of the distal radius. We conducted a retrospective cohort study of 158 patients who underwent locked anterior plating for an intra-articular or displaced fracture of the distal radius using multiple regression analysis to identify any relationship between patient, injury or treatment factors with the patient-rated wrist and hand evaluation score or finger and wrist stiffness. There was no significant correlation between timing of surgery and functional scores. A delay in time to surgery of more than 2 weeks did correlate significantly with increased finger and thumb stiffness. However, this relationship was not seen for wrist stiffness. Our study supports the consensus that early recovery and function is facilitated by surgical fixation within 2 weeks and that delayed fixation beyond this may contribute to protracted finger stiffness.Level of evidence: IV.


Single photon emission computed tomography scanning in the diagnosis of knee pathology.
To evaluate the role of single photon emission computed tomography (SPECT) bone scan for the diagnosis of knee lesions in routine clinical practice. 40 consecutive case records were examined in patients who underwent a SPECT scan prior to knee arthroscopy in routine clinical practice. The accuracy of clinical examination, SPECT scan results, and arthroscopic findings (as the gold standard) in diagnosing knee lesions were compared. The sensitivity of SPECT scans in detecting medial meniscal, lateral meniscal, anterior cruciate ligament lesions, osteochondral defects, and chondromalacia patellae was 77%, 14%, 33%, 50%, and 74%, respectively. The specificities for the same structural lesions were high at 89%, 94%, 97%, 94%, and 69%, respectively. SPECT bone scan appears to be useful in the diagnosis of knee pathology in routine practice and in selecting patients for arthroscopy, especially most useful for the diagnosis of medial meniscal tears.


Do public neighborhood centers have the capacity to be instruments of change in human services?
This article examines the capacity of public neighborhood centers to be instruments of change in human services. The authors focus specifically on the centers' ability to perform critical leadership functions in social planning and locality development. Data presented in the article were gathered through an independent study of 45 public neighborhood centers in Central Florida. Study findings indicate that public neighborhood centers tend to reflect the characteristics of static rather than dynamic organizations. Major adjustments in their goals, funding, technology, decision making, and performance will be needed before public officials can count on them to lead innovations in social planning and locality development.


Apoptosis and epithelial injury in the lungs.
Epithelial injury is a critical event in the development of acute lung injury, but the mechanisms that cause death of the alveolar epithelium are not completely understood. Epithelial death occurs by necrosis and apoptosis; more information is needed about the balance between these two types of cell death in the lungs. Direct epithelial necrosis probably occurs in response to bacterial exotoxins and over-distension of alveolar units by mechanical ventilation. Apoptosis is a regulated form of cell death that is mediated by membrane death receptors and direct mitochondrial injury. Apoptosis pathways are activated in the lungs of patients with acute lung injury, in part by activation of the membrane Fas death receptor by soluble Fas ligand (sFasL), which accumulates in biologically active form at the onset of lung injury. Accumulating evidence in humans and experimental models links sFasL and Fas pathway with lung epithelial injury and fibrosis. New strategies to inhibit Fas-mediated epithelial apoptosis need to be developed in order to develop new ways to preserve epithelial function in patients who develop acute lung injury.


Leupeptin protects sensory hair cells from acoustic trauma.
Calpains, a family of calcium activated proteases, promote the breakdown of cellular proteins, kinases, phosphatases and transcription factors. Calpain inhibitors attenuate some neurodegenerative processes in certain cell types. Here we show that leupeptin, a potent calpain inhibitor, protects the sensory hair cells in the inner ear from acoustic overstimulation (48 h, 100 or 105 dB SPL, octave band noise at 4 kHz). Acoustic overstimulation caused a significant increase in calpain immunolabeling in the sensory epithelium suggesting a possible role in noise-induced cochlear degeneration. Infusion of leupeptin into the inner ear significantly reduced the amount of sensory cell loss from acoustic overstimulation. However, leupeptin did not protect against hair cell loss from the ototoxic drug, carboplatin.


Influence of surface chemical properties on the toxicity of engineered zinc oxide nanoparticles to embryonic zebrafish.
Zinc oxide nanoparticles (ZnO NPs) are widely used in a variety of products, thus understanding their health and environmental impacts is necessary to appropriately manage their risks. To keep pace with the rapid increase in products utilizing engineered ZnO NPs, rapid in silico toxicity test methods based on knowledge of comprehensive in vivo and in vitro toxic responses are beneficial in determining potential nanoparticle impacts. To achieve or enhance their desired function, chemical modifications are often performed on the NPs surface; however, the roles of these alterations play in determining the toxicity of ZnO NPs are still not well understood. As such, we investigated the toxicity of 17 diverse ZnO NPs varying in both size and surface chemistry to developing zebrafish (exposure concentrations ranging from 0.016 to 250 mg/L). Despite assessing a suite of 19 different developmental, behavioural and morphological endpoints in addition to mortality in this study, mortality was the most common endpoint observed for all of the ZnO NP types tested. ZnO NPs with surface chemical modification, regardless of the type, resulted in mortality at 24 hours post-fertilization (hpf) while uncoated particles did not induce significant mortality until 120 hpf. Using eight intrinsic chemical properties that relate to the outermost surface chemistry of the engineered ZnO nanoparticles, the highly dimensional toxicity data were converted to a 2-dimensional data set through principal component analysis (PCA). Euclidean distance was used to partition different NPs into several groups based on converted data (score) which were directly related to changes in the outermost surface chemistry. Kriging estimations were then used to develop a contour map based on mortality data as a response. This study illustrates how the intrinsic properties of NPs, including surface chemical modifications and capping agents, are useful to separate and identify ZnO NP toxicity to zebrafish (Danio rerio).


A model to estimate the oestrogen receptor mediated effects from exposure to soy isoflavones in food.
The advantages that regular consumption of a diet containing soy may have on human health have been enshrined in a major health claim that has been approved by the Food and Drug Administration in the USA, regarding potential protection from heart disease by soy. This could have a major influence on the dietary consumption patterns of soy for consumers and lead to the development of soy enriched foods to enable consumers to achieve the benefits thought to be associated with increased soy consumption in a Western diet. If an increase in soy consumption is beneficial to particular disease conditions, there is always the possibility that there will be effects other than those that are desirable. For soy-containing foods there has been concern that the phytoestrogen content of soy, which is composed of several isoflavones, could be a separate health issue, due to the oestrogen-like activity of isoflavones. To address this, a method has been developed to estimate, relative to 17-beta oestradiol, the activity of the common isoflavones present in soy phytoestrogens, based on their binding to and transcriptional activation of the major oestrogen receptor sub-types alpha and beta. Using this approach, the additional oestrogen-like activity that would be expected from inclusion of soy supplemented foodstuffs in a Western diet, can be determined for different sub-populations, who may have different susceptibilities to the potential for the unwanted biological effects occurring with consumption of soy enriched foods. Because of the theoretical nature of this model, and the controversy over the nature of whether some of the oestrogen-like effects of phytoestrogens are adverse, the biological effects of soy isoflavones and their potential for adverse effects in man, is also reviewed. The question that is critical to the long term safe use of foods enriched in soy is, which observed biological effects in animal studies are likely to also occur in man and whether these would have an adverse effect on human health.


Crohn's Colitis: Development of a multiplex gene expression assay comparing mRNA levels of susceptibility genes.
Crohn's disease (CD) is a multifactorial immunologically mediated disease. In this study we explored, for the first time, the efficacy of the Multiplex Gene Assay technology for detecting mRNA expression profile of 24 selected CD related genes in endoscopic biopsies and surgical specimens from CD patients with colonic localization of the disease. The polymorphisms of genes most frequently associated with CD were also analysed in DNA samples from the same patients. The analysis of endoscopic samples showed increased expression of 7 genes in inflamed mucosa compared to non-inflamed mucosa and suggests the activation of the autophagy process and of a Th17 adaptive response. The analysis of surgical specimens showed increased expression of 16 genes in inflamed tissue compared to non-inflamed internal controls and revealed the activation of immune-adaptive Th17 response in association with a Th1 response. Furthermore, an increased expression of genes involved in ionic transport and signal transduction was found in inflamed mucosa compared to non-inflamed internal controls. This study confirms the activation of Th17 and Th1 adaptive-immune response also in colonic CD. It should be stressed that these responses have been disclosed in biopsy tissue, while only Th17 differentiation is revealed in endoscopic tissue. Interestingly, the polymorphisms analysis revealed that a homozygous genotype is associated to a more complicated clinical course.


Evaluation of the clinical course of dry eye syndrome.
To assess subjective symptoms, tear function factors, and ocular surface morphology in the clinical course of patients with dry eye syndrome under treatment within an observation period of up to 8 years. In 97 patients (78 women and 19 men) with ocular discomfort, a clinical diagnosis of dry eye syndrome was made based on typical symptoms and a reduced tear film breakup time of less than 10 seconds. Subsequent evaluations revealed a diagnosis of aqueous tear deficiency in 9 patients, meibomian gland dysfunction in 32 patients, and aqueous tear deficiency combined with meibomian gland dysfunction in 30 patients, aqueous tear deficiency associated with Sjögren syndrome in 12 patients, and aqueous tear deficiency and meibomian gland dysfunction associated with Sjögren syndrome in 14 patients. Follow-up assessments were performed 12 to 94 months (mean follow-up, 40 months) after the initial diagnosis. In different subgroups of dry eye tear film breakup time, Schirmer test without local anesthesia (Schirmer I), fluorescein and rose bengal staining, impression cytology, as well as subjective dry eye symptoms and frequency of tear substitute application were compared at baseline and after a follow-up of 1 to 8 years (mean, 3.3 years). At baseline, tear film function and ocular surface test results found more pathologic abnormalities and more severe subjective symptoms in patients with aqueous tear deficiency associated with Sjögren syndrome and aqueous tear deficiency and meibomian gland dysfunction associated with Sjögren syndrome compared with the other groups who had dry eye syndrome. No differences in frequency of tear substitute application were observed. At follow-up, tear breakup time, Schirmer I test results, and corneal fluorescein staining improved compared with baseline values, whereas rose bengal staining and impression cytology of the conjunctival surface remained almost unchanged. Subjective symptoms and frequency of artificial tear application were reduced. Within the observation period of up to 8 years, the dry eye syndrome improved or stabilized under appropriate treatment. Although no patient was completely cured, subjective reports as well as frequency of artificial tear application were reduced.


TRIM21 Aggravates Herpes Simplex Virus Epithelial Keratitis by Attenuating STING-IRF3-Mediated Type I Interferon Signaling.
Herpes simplex virus-1 (HSV-1) is the leading cause of infectious blindness in the developed world. HSV-1 infection can occur anywhere in the eye, and the most common presentation is epithelial keratitis. In the HSV epithelial keratitis mice model, we detected the expression of TRIM21 and then investigated the clinical relationship between TRIM21 and HSV epithelial keratitis by silencing TRIM21. Through the clinical scores and histopathology examination, we found that TRIM21 can effectively reduce the severity of HSV epithelial keratitis. Furthermore, silencing TRIM21 significantly controlled the virus particle release at 1, 3, and 5 days post-HSV-1 infection. Notably, the production of IFN-β was enhanced, and the secretion of pro-inflammatory cytokines (IL-6 and TNF-a) was inhibited. Next, human corneal epithelial cells were pretreated with lentivirus or siRNA, respectively, so that TRIM21 expression was overexpressed or silenced. We focused on the regulation of STING-IRF3 and type I interferon signaling after infected with HSV-1. In conclusion, our results have identified that TRIM21 is abnormally high expressed in HSV epithelial keratitis. TRIM21 enhances the replication of HSV-1 in corneal epithelial cells via suppressing the production of type I IFN by inhibiting STING/IRF3 signaling. It also promotes the secretion of IL-6 and TNF-a, thereby aggravating the severity of HSV epithelial keratitis.


Correlation of elastase production by some strains of Aspergillus fumigatus with ability to cause pulmonary invasive aspergillosis in mice.
Seventy-five strains of Aspergillus fumigatus were screened for production of elastase in liquid and agar media containing elastin in yeast carbon base buffered with 0.05 M borate, pH 7.6. Of 71 strains which cleared elastin in agar plates, 33 produced elastase in liquid medium, as measured spectrophotometrically with elastin-Congo red. Six strains producing elastase and four nonproducers were tested for ability to cause invasive aspergillosis in immunocompromised mice (six mice per strain). All 36 mice exposed to elastase-producing strains died within 48 to 96 h. Lung tissue from dead mice showed hyphae and necrosis of the alveoli. Lungs of mice exposed to spores of strains not producing elastase showed few germinated spores and no destruction of alveoli. These results indicate that elastase may be significant in the invasion process.


Antidiabetic activity of perylenequinonoid-rich extract from Shiraia bambusicola in KK-Ay mice with spontaneous type 2 diabetes mellitus.
Bitter and cold traditional Chinese medicines (TCMs) have been long used to treat diabetes mellitus (DM) based on unique medical theory system since ancient China. As one of bitter and cold TCMs, the stromatas of Shiraia bambusicola have been used for the treatment of DM and exerted clinical effects to a certain extent. However, the corresponding active principles and antidiabetic mechanism of the TCM still remain unknown. Therefore, the aim of the present investigation was to evaluate the potential antidiabetic effect of the active Shiraia bambusicola EtOAc extract (SB-EtOAc) in vitro and in vivo, and elucidate its probable antidiabetic mechanism. A LC-PDA-ESIMS protocol was developed to determine the chemical principles of the active EtOAc extract rapidly and unambiguously. The effect of SB-EtOAc on the glucose transporter type 4 (GLUT4) translocation and glucose uptake in L6 cells was examined. SB-EtOAc was orally administration at the dose of 30, 60 and 120mg/kg/d in KK-Ay mice, for 21 days. Body weight, plasma glucose, oral glucose tolerance test, fasted blood glucose levels, oral glucose tolerance test and insulin tolerance test, serum insulin and blood-lipid indexes were measured. GLUT4 on L6 cells membrane and phosphorylation of the AMP-activated protein kinase (p-AMPK) expression in L6 cells were measured. The GLUT4 and p-AMPK expression in KK-Ay mice skeletal muscle were measured. Phosphorylation of the acetyl-CoA carboxylase (p-ACC) and p-AMPK were measured. In vitro, SB-EtOAc exhibited a strong effect of stimulation on GLUT4 translocation by 3.2 fold in L6 cells compared with basal group, however, the selective AMPK inhibitor compound C can completely inhibit the AMPK pathway and prevent the GLUT4 translocation caused by SB-EtOAc. The further western blotting experiments showed that SB-EtOAc can stimulate AMPK phosphorylation in L6 cells and improve the expression of GLUT4. In vivo, SB-EtOAc can improve the KK-Ay mice insulin resistant and oral glucose tolerance to a certain extent. And the body weight, blood glucose levels and the serum TC, TG, FFA, AST, ALT and LDL-C were significantly reduced and HDL-C were increased after 3 weeks treatment. Mechanistically, phosphorylation of the AMPK and ACC had been improved obviously and the levels of AMPK phosphorylation and GLUT4 had been also enhanced. In vitro, SB-EtOAc exhibited a strong effect of stimulation on GLUT4 translocation and improved significantly the glucose uptake. In vivo, SB-EtOAc significantly improved oral glucose tolerance and the insulin resistant as well as glucolipid metabolism. In this study, SB-EtOAc displayed promising positive antidiabetic activity in vitro and in vivo, partly by modulating AMPK-GLUT4 and AMPK-ACC signaling pathways.


Relationship Between Human Meibum Lipid Composition and the Severity of Meibomian Gland Dysfunction: A Spectroscopic Analysis.
Information on the relationship between meibum lipid composition and severity of meibomian gland dysfunction (MGD) is limited. The purpose of this study was to analyze the molecular components of meibum collected from individuals with no MGD, mild-to-moderate MGD, and severe MGD. Adults with and without MGD were enrolled in a prospective, multicenter, exploratory clinical trial (ClinicalTrials.gov Identifier: NCT01979887). Molar ratios of cholesteryl ester to wax ester (RCE/WE) and aldehyde to wax ester (Rald/WE) in meibum samples were measured with 1H-NMR spectroscopy. Results were evaluated for participants grouped by MGD disease status and severity (non-MGD, mild-to-moderate MGD, and severe MGD), as defined by maximum meibum quality scores, Schirmer test results, and Subject Ocular Symptom Questionnaire responses. Sixty-nine meibum samples from 69 individuals were included in the analysis: 24 non-MGD, 24 mild-to-moderate MGD, and 21 severe MGD. Mean RCE/WE was 0.29 in non-MGD, 0.14 in mild-to-moderate MGD (P = 0.038 vs. non-MGD, 51% lower), and 0.07 in severe MGD (P = 0.16 vs. mild-to-moderate MGD, 52% lower; P = 0.002 vs. non-MGD, 76% lower). Mean Rald/WE was 0.00022 in non-MGD, 0.00083 in mild-to-moderate MGD (P = 0.07 vs. non-MGD, 277% higher), and 0.0024 in severe MGD (P = 0.003 vs. mild-to-moderate MGD, 190% higher; P < 0.001 vs. non-MGD, 992% higher). RCE/WE was lowest and Rald/WE was highest in the severe MGD cohort, suggesting that these meibum constituent molar ratios may result from the pathophysiology associated with MGD and can impact ocular surface lipid and tear film homeostasis. These findings may potentially help identify targets for MGD treatment.


Effect of Paclobutrazol Application on Enhancing the Efficacy of Nitenpyram against the Brown Planthopper, Nilaparvata lugens.
The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive rice pests in Asia. It has already developed a high level of resistance to many commonly used insecticides including nitenpyram (NIT), which is a main synthetic insecticide that is used to control BPH with a much shorter persistence compared to other neonicotinoid insecticides. Recently, we found that an exogenous supplement of paclobutrazol (PZ) could significantly enhance the efficacy of NIT against BPH, and the molecular mechanism underlying this synergistic effect was explored. The results showed that the addition of a range of 150-300 mg/L PZ increased the toxicity of NIT against BPH with the highest mortalities of 78.0-87.0% on the 16th day after treatments, and PZ could also significantly prolong the persistence of the NIT efficacies. Further investigation suggested that PZ directly increased the content of flavonoids and H2O2 in rice and increased the activity of polyphenol oxidase, which might be involved in the constitutive defense of rice in advance. Additionally, there was an interaction between PZ and BPH infestation, indicating that PZ might activate the host defense responses. Therefore, PZ increased the efficacy of NIT against the brown planthoppers by enhancing the constitutive and inducible defense responses of rice. Our study showed for the first time that PZ could contribute to improving the control effects of insecticides via inducing the defense responses in rice plants against BPH, which provided an important theoretical basis for developing novel pest management strategies in the field.


Global azimuthal anisotropy in the transition zone.
Surface wave dispersion measurements for Love wave overtones carry evidence of azimuthal anisotropy in the transition zone of Earth's mantle (400 to 660 kilometers deep). A Backus-Gilbert inversion of anisotropic phase velocity maps, with resolution kernels mainly sensitive to the transition zone, shows a robust long-wavelength azimuthally anisotropic velocity structure. This observation puts new constraints on the mineralogy and dynamics of the transition zone because this anisotropy may result from aligned minerals, tilted laminated structures, or even organized pockets of fluid inclusions.


Muscular strength and jumping performance after handball training versus physical education program for pre-adolescent children.
The purpose was to compare a 6-mo. specific handball training program and a typical physical education program on various strength and jumping skills. The participants (M age= 13.7 yr., SD= 1.5) were divided into the Handball Group (n=51) and the Physical Education Group (n=70). The latter performed 3 sessions/ week (60 min.) including ball-handling drills, horizontal and vertical jump shots, fast break, and several defensive skills. The former performed the program provided by the Ministry of Education including track and field and other team sport drills. Analyses of covariance showed that the handball group displayed greater improvement in explosive strength of upper limbs, jumping performance, maximum isometric force of right grip, and 10-m running velocity. Handball training can significantly improve pre-adolescent performance with upper and lower limbs. Inclusion of specific handball drills in the physical education program is recommended.


Clinical Characteristics and Prognosis of Small Cell Carcinoma in the Nasopharynx: A Population-Based Study.
Nasopharyngeal small cell carcinoma (SmCC) is a rare histological type of nasopharyngeal cancer, and its prognosis remains poor. This study aimed to determine the clinical characteristics and survival prognostic factors of nasopharyngeal SmCC. Detailed clinicopathologic and therapeutic characteristics of a patient diagnosed with nasopharyngeal SmCC were determined. Nasopharyngeal SmCC cases reported previously were reviewed and summarized. Furthermore, a retrospective analysis was performed on data from the Surveillance, Epidemiology, and End Results (SEER) Program database. Kaplan-Meier analysis was conducted to compare survival within groups. Univariate and multivariate analyses were performed to investigate prognostic factors. A nasopharyngeal SmCC patient treated with chemoradiotherapy who achieved 46 months long-term survival was reported. In reviewing 16 reported cases with epidemiologic and therapeutic details, we found most of nasopharyngeal SmCC patients were diagnosed with advanced grades and received chemoradiotherapy. In total, 13,993 cases of nasopharyngeal cancer were extracted from the SEER database, from which 57 nasopharyngeal SmCC cases were eventually screened out. The mean age of the patients was 55.70 years, and 64.9% of these cases were either grade III or IV; the median overall survival (OS) was 18 months. Statistically significant differences were observed in the OS values of groups categorized by age (P = .025) or radiotherapy (P = .037). Age (<70 years) and radiotherapy were identified as independent survival and prognostic factors. Patients with nasopharyngeal SmCC are usually diagnosed with advanced grades and have poor prognoses; nevertheless, they can benefit from radiotherapy with prolonged overall survival.


Molecular Design toward Heavy-Atom-free Photosensitizers Based on the C═S Bond and their Dual Functions in Hypoxia Photodynamic Cancer Therapy and ClO- Detection.
In this article, we designed and synthesized the thionated NpImidazole derivatives BS and NS, new heavy-atom-free photosensitizers, which efficiently generate a triplet excited state with high singlet oxygen quantum yield. The introduction of the C═S bond to the NpImidazole core is essential for increasing spin-orbit coupling (SOC). The fluorescence emission of BS and NS was quenched at standard ambient temperature, accompanied with the increase in the ISC process from the singlet states to triplet excited states via thionation. BS and NS showed negligible dark cytotoxicity against HeLa cells in working concentration. In contrast, BS and NS rapidly induced cell death under blue light irradiation both under normoxia and hypoxia conditions. Our current study demonstrates that the C═S group can play an important role in type I ROS generation of PSs, which are unprecedented in the previous reports. Finally, the photophysical changes were assigned to the oxidative desulfurization of the C═S group of BS and NS to the C═O group of the corresponding BO and NO via hypochlorite. The combined results demonstrated the dual function of BS and NS as a fluorescent imaging agent for ClO- and an anti-cancer therapeutic by PDT that showed the potential strategy for "one-for-all" and multifunctional agents.


Time course of diastolic and systolic function improvement after pulmonary valve replacement in adult patients with tetralogy of Fallot.
The aim of this research was to assess right ventricular diastolic and systolic function before and after pulmonary valve replacement (PVR) in adult patients after repair of tetralogy of Fallot. Pulmonary valve replacement (PVR) in adult patients late after repair of tetralogy of Fallot leads to rapid improvement of right ventricular (RV) systolic function. A total of 16 patients and 8 healthy subjects were included. Median age at initial repair was 4.9 (0.9 to 13.1) years, and mean age at PVR was 28.7 (19.5 to 45.6) years. Cardiac magnetic resonance imaging was performed before and 8 and 22 months after PVR. Right ventricular volumes and function as well as RV in- and outflow patterns were assessed. The volume of the early filling of the RV (Evol) increased from 49.8 +/- 14.7 ml to 53.8 +/- 19.3 ml (not significant) and 62.0 +/- 18.9 ml, respectively (p < 0.05), whereas the volume of the atrial contraction (Avol) remained unchanged. Consequently, the Evol/Avol ratio increased from 1.4 +/- 0.7 before PVR to 1.6 +/- 0.7 at 8 months (not significant) and 2.3 +/- 1.2 at 22 months (p < 0.01). The Evol/Avol ratio was not significantly different from the healthy subjects at 22 months, indicating late recovery of diastolic function. Systolic function improved rapidly after PVR; the indexed RV end-systolic volume decreased from 93.7 +/- 33.0 ml/m2 to 60.9 +/- 18.4 ml/m2 (p < 0.01) and 54.8 +/- 21.0 ml/m2 (p < 0.01). In adult patients late after total repair of Fallot, PVR leads to late improvement of diastolic function. We speculate that the rapid volume unloading after PVR increases systolic performance, whereas improvement in diastolic function requires long-term remodeling.


Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells.
The nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 are mammalian cytosolic pattern recognition receptors sensing bacterial peptidoglycan fragments in order to initiate cytokine expression and pathogen host defense. Since endothelial cells are relevant cells for pathogen recognition at the blood/tissue interface, we here analyzed the role of NOD1- and NOD2-dependently expressed microRNAs (miRNAs, miR) for cytokine regulation in murine pulmonary endothelial cells. The induction of inflammatory cytokines in response to NOD1 and NOD2 was confirmed by increased expression of tumour necrosis factor (Tnf)-α and interleukin (Il)-6. MiRNA expression profiling revealed NOD1- and NOD2-dependently regulated miRNA candidates, of which miR-147-3p, miR-200a-3p, and miR-298-5p were subsequently validated in pulmonary endothelial cells isolated from Nod1/2-deficient mice. Analysis of the two down-regulated candidates miR-147-3p and miR-298-5p revealed predicted binding sites in the 3' untranslated region (UTR) of the murine Tnf-α and Il-6 mRNA. Consequently, transfection of endothelial cells with miRNA mimics decreased Tnf-α and Il-6 mRNA levels. Finally, a novel direct interaction of miR-298-5p with the 3' UTR of the Il-6 mRNA was uncovered by luciferase reporter assays. We here identified a mechanism of miRNA-down-regulation by NOD stimulation thereby enabling the induction of inflammatory gene expression in endothelial cells.


A syndrome differentiation model of TCM based on multi-label deep forest using biomedical text mining.
Syndrome differentiation and treatment is the basic principle of traditional Chinese medicine (TCM) to recognize and treat diseases. Accurate syndrome differentiation can provide a reliable basis for treatment, therefore, establishing a scientific intelligent syndrome differentiation method is of great significance to the modernization of TCM. With the development of biomdical text mining technology, TCM has entered the era of intelligence that based on data, and model training increasingly relies on the large-scale labeled data. However, it is difficult to form a large standard data set in the field of TCM due to the low degree of standardization of TCM data collection and the privacy protection of patients' medical records. To solve the above problem, a multi-label deep forest model based on an improved multi-label ReliefF feature selection algorithm, ML-PRDF, is proposed to enhance the representativeness of features within the model, express the original information with fewer features, and achieve optimal classification accuracy, while alleviating the problem of high data processing cost of deep forest models and achieving effective TCM discriminative analysis under small samples. The results show that the proposed model finally outperforms other multi-label classification models in terms of multi-label evaluation criteria, and has higher accuracy in the TCM syndrome differentiation problem compared with the traditional multi-label deep forest, and the comparative study shows that the use of PCC-MLRF algorithm for feature selection can better select representative features.


Thoracolumbar epidural anaesthesia with 0.5% bupivacaine with or without methadone in goats.
Epidural anaesthesia is one of the most commonly used locoregional techniques in ruminants. The lumbosacral epidural technique is reasonably easy to perform and requires low volumes of local anaesthetic drug to allow procedures caudal to the umbilicus. However, surgical procedures in the flank of the animal would require an increased volume of drugs. The anaesthetized area provided by thoracic epidural technique is larger than the lumbosacral technique; however the former is rather challenging to perform. Therefore, access through lumbosacral area to introduce a catheter into the thoracolumbar space is a potential alternative to thoracic access. Epidural anaesthesia is achieved with local anaesthetics; opioids can be added to improve analgesia. This study aimed to evaluate the effects of 0.5% bupivacaine with or without methadone, administered through an epidural catheter inserted through the lumbosacral access and advanced to the thoracolumbar space, on thoracolumbar epidural anaesthesia in goats. Six animals received two treatments each in a randomized crossover study: BUP treatment consisted of 0.5% bupivacaine (1 mL per each 10 cm of spine column; 1 ± 0.2 mg/kg BW) and BMT treatment was the same; however 1 mL of bupivacaine was replaced by 1 mL (0.22 ± 0.03 mg/kg BW) of methadone (10 mg/mL). The treatments were administered near to T11-T12 through an epidural catheter. Motor blockade and analgesia were evaluated by electrical stimulation. Heart rate, respiratory rate, ruminal motility and rectal temperature were evaluated before and after the treatment. Motor blockade was observed on both treatments, up to 6 h post-treatment. Analgesia was observed on BUP up to 4 h and on BMT up to 6 h post-treatment. Physiological values did not change at any moment. Bupivacaine-methadone combination promoted longer-lasting analgesia in goats compared to bupivacaine alone when administered through an epidural catheter into the thoracolumbar space.


Learning-rate-dependent clustering and self-development in a network of coupled phase oscillators.
We investigate the role of the learning rate in a Kuramoto Model of coupled phase oscillators in which the coupling coefficients dynamically vary according to a Hebbian learning rule. According to the Hebbian theory, a synapse between two neurons is strengthened if they are simultaneously coactive. Two stable synchronized clusters in antiphase emerge when the learning rate is larger than a critical value. In such a fast learning scenario, the network eventually constructs itself into an all-to-all coupled structure, regardless of initial conditions in connectivity. In contrast, when learning is slower than this critical value, only a single synchronized cluster can develop. Extending our analysis, we explore whether self-development of neuronal networks can be achieved through an interaction between spontaneous neural synchronization and Hebbian learning. We find that self-development of such neural systems is impossible if learning is too slow. Finally, we demonstrate that similar to the acquisition and consolidation of long-term memory, this network is capable of generating and remembering stable patterns.


Brief report: Emotional processing in high-functioning autism--physiological reactivity and affective report.
This study examined physiological response and affective report in 10 adult individuals with autism and 10 typically developing controls. An emotion induction paradigm using stimuli from the International Affective Picture System was applied. Blood pressure, heart and self-ratings of experienced valence (pleasure), arousal and dominance (control) were assessed during the experiment. Physiological response profiles correlated low to significantly negative between groups. Individuals with autism experienced less arousal when viewing sad pictures but higher arousal while processing neutral stimuli. In addition, they reported more control than the normative group when viewing fearful and sad stimuli. Findings indicate altered physiological reactivity and affective report in autism, which may be related to more general impairments in socio-emotional functioning.


Inflammatory cytokine release in patients with unstable angina after coronary angioplasty.
The aim of the present study was to investigate inflammatory cytokine release and the interaction with platelets in patients with unstable angina (UA) after coronary angioplasty. In 50 patients with stable angina (SA) and 58 patients with UA, serial venous blood samples were obtained immediately before, and 30 minutes, 4, 12, 24, 48 and 72 hours, and 7 days after coronary angioplasty. Plasma concentrations of IL-8 and vWF were determined by immunoassay, while the expression of CD11 b/CD18 on monocytes and the expression of CD41 on platelets were assessed by flow cytometry. Differences in the baseline plasma concentrations of IL-8, vWF and CD11b/CD18, CD41 were found in the UA and SA groups before angioplasty (101.1 +/- 31.28 pg/mL to 55.8 +/- 17.24 pg/mL, 137.67 +/- 38.14% to 107.40 +/- 28.67% and 318.67 +/- 36.85 MFI to 240.72 +/- 28.43 MFI, 147.5 +/- 23.18 MFI to 104.43 +/- 26.68 MFI all p < 0.05). The peak plasma levels of IL-8 (172.24 +/- 37.82 pg/mL at 12 hours) and vWF (256 +/- 42.32% at 4 hours) significantly increased after coronary angioplasty (both p < 0.01), and were associated with significant time course increases in surface expression of CD11b/CD18 (p < 0.01) and CD41 (p < 0.01). The levels of plasma IL-8 and vWF were significantly higher pre- and post-procedure in UA patients with lesion type C compared to types A or B (p < 0.05), but there were no differences for pre-procedure in the SA group patients with different lesion types (p > 0.05). There were significant correlations between plasma IL-8 and monocyte CD11b/CD18, vWF and CD41 in the UA group (r = 0.5248, r = 0.6240 both p < 0.01, respectively). The findings demonstrate increases in plasma IL-8 and CD11b/CD18 as inflammatory mediators, vWF and CD41 as the abnormal coagulation activity may therefore yield a rationale for pharmacological anticytokines in patients with UA after coronary angioplasty.


Beaklike SnO2 nanorods with strong photoluminescent and field-emission properties.
Beaklike SnO2 nanorods were synthesized by a vapor-liquid-solid approach using Au as a catalyst. The nanorods grow along the [10 1] direction and the beak is formed by switching the growth direction to [1 12] through controlling the growth conditions at the end of the synthesis. The photoluminescence (PL) spectrum of the nanorods exhibits visible light emission with a peak at 602 nm. The field-emission (FE) properties of the nanorods have been measured to exhibit a turn-on field of 5.8 V microm(-1). A comparative study of FE measurements between SnO2 nanorods with uniform diameters and these beaklike nanorods suggests that the shape and curved tips are important factors in determining the FE properties.


Social and emotional loneliness in Korsakoff's syndrome.
Loneliness is the subjective negative evaluation of social participation and isolation. Emotional loneliness reflects the absence of close relationships, and social loneliness the absence of a social network. Although loneliness is a growing problem in modern society, studies about loneliness in patients with Korsakoff's syndrome (KS) in need of chronic care are currently missing. Sixty-three KS patients in long-term care and their primary caregivers reported loneliness of the patients on the De Jong Gierveld Loneliness Scale. A majority of KS patients reliably reported to feel lonely on both a social and emotional level of loneliness. The caregiving professionals rated loneliness of the patients even higher. Patients that had stayed in the clinic for a longer time tended to report less social loneliness, while caregivers reported less emotional loneliness in those patients. The KS-specific neuropsychiatric symptom of confabulations and a lack of social visits had a negative impact on social loneliness as perceived by the caregivers. Loneliness is a large problem in patients with KS that live in a long term care facility. Social loneliness can be positively influenced by creating possibilities to interact with other people, although the severity of the neuropsychiatric aspects of KS could compromise the presence of those interactions.


Phosphorylation of Dynamin-Related Protein 1 (DRP1) Regulates Mitochondrial Dynamics and Skeletal Muscle Wasting in Cancer Cachexia.
Cancer-associated cachexia (CAC) is a syndrome characterized by skeletal muscle atrophy, and the underlying mechanisms are still unclear. Recent research studies have shed light on a noteworthy link between mitochondrial dynamics and muscle physiology. In the present study, we investigate the role of dynamin-related protein 1 (DRP1), a pivotal factor of mitochondrial dynamics, in myotube atrophy during cancer-associated cachexia. Seventy-six surgical patients, including gastrointestinal tumor and benign disease, were enrolled in the study and divided to three groups: control, non-cachexia, and cancer-associated cachexia. Demographic data were collected. Their rectus abdominis samples were acquired intraoperatively. Muscle fiber size, markers of ubiquitin proteasome system (UPS), mitochondrial ultrastructure, and markers of mitochondrial function and dynamics were assayed. A cachexia model in vitro was established via coculturing a C2C12 myotube with media from C26 colon cancer cells. A specific DRP1 inhibitor, Mdivi-1, and a lentivirus of DRP1 knockdown/overexpression were used to regulate the expression of DRP1. Muscle diameter, mitochondrial morphology, mass, reactive oxygen species (ROS), membrane potential, and markers of UPS, mitochondrial function, and dynamics were determined. Patients of cachexia suffered from a conspicuous worsened nutrition status and muscle loss compared to patients of other groups. Severe mitochondrial swelling and enlarged area were observed, and partial alterations in mitochondrial function were found in muscle. Analysis of mitochondrial dynamics indicated an upregulation of phosphorylated DRP1 at the ser616 site. In vitro, cancer media resulted in the atrophy of myotube. This was accompanied with a prominent unbalance of mitochondrial dynamics, as well as enhanced mitochondrial ROS and decreased mitochondrial function and membrane potential. However, certain concentrations of Mdivi-1 and DRP1 knockdown rebalanced the mitochondrial dynamics, mitigating this negative phenotype caused by cachexia. Moreover, overexpression of DRP1 aggravated these phenomena. In clinical patients, cachexia induces abnormal mitochondrial changes and possible fission activation for the atrophied muscle. Our cachexia model in vitro further demonstrates that unbalanced mitochondrial dynamics contributes to this atrophy and mitochondrial impairment, and rebuilding the balance by regulating of DRP1 could ameliorate these alterations.


Functional magnetic resonance imaging in zebra finch discerns the neural substrate involved in segregation of conspecific song from background noise.
Recently, fMRI was introduced in a well-documented animal model for vocal learning, the songbird. Using fMRI and conspecific signals mixed with different levels of broadband noise, we now demonstrate auditory-induced activation representing discriminatory properties of auditory forebrain regions in anesthetized male zebra finches (Taeniopygia guttata). Earlier behavioral tests showed comparable calling responses to the original conspecific song stimulus heard outside and inside the magnet. A significant fMRI response was elicited by conspecific song in the primary auditory thalamo-recipient subfield L2a; in neighboring subareas L2b, L3, and L; and in the rostral part of the higher-order auditory area NCM (caudomedial nidopallium). Temporal BOLD response clustering revealed rostral and caudal clusters that we defined as "cluster Field L" and "cluster NCM", respectively. However, because the actual border between caudal Field L subregions and NCM cannot be seen in the structural MR image and is not precisely reported elsewhere, the cluster NCM might also contain subregion L and the medial extremes of the subregions L2b and L3. Our results show that whereas in cluster Field L the response was not reduced by added noise, in cluster NCM the response was reduced and finally disappeared with increasing levels of noise added to the song stimulus. The activation in cluster NCM was significant for only two experimental stimuli that showed significantly more behavioral responses than the more degraded stimuli, suggesting that the first area within the auditory system where the ability to discern song from masking noise emerges is located in cluster NCM.


Rehabilitation effects of land and water-based aerobic exercise on lung function, dyspnea, and exercise capacity in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.
We sought to synthesize the evidence about aerobic exercise intervention during pulmonary rehabilitation, and to further explore the difference in rehabilitation effects between water and land-based aerobic exercise. This review's purpose is to provide a basis by which practitioners and therapists can select and create appropriate therapeutic programs. Data of randomized and quasi-randomized controlled trials comparing training group (TG, aerobic exercise in water or land) and control group (CG, usual care) in chronic obstructive pulmonary disease (COPD) patients (January 1, 2000-December 28, 2019) were obtained from the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases. Two researchers independently reviewed the literature, extracted the data, and evaluated the quality of the literature. Review Manager software (Rev Man 5.3; Cochrane, London, UK) was used for meta-analysis. The rehabilitation effect of water- or land based aerobic exercise was evaluated by subgroup analysis. The proposed systematic review details were registered in PROSPERO (CRD 42020168331). Eighteen studies (1311 cases of COPD) were included. Meta-analysis results show that compared with the control group, the dyspnea level and functional and endurance exercise capacity in COPD patients were significantly improved after aerobic exercise (P < .05), but there was no significant change in lung function (P > .05). Compared with land-based aerobic exercise, water-based aerobic exercise significantly improved the endurance exercise capacity in COPD patients (mean difference [MD]: 270.18, 95% CI: 74.61-465.75). Medium to high-quality evidence shows that aerobic exercise can effectively improve dyspnea and exercise capacity in COPD patients. Compared with land-based aerobic exercise, water-based aerobic exercise had a significant additional effect in improving the endurance exercise capacity of COPD patients.


Minimum area thresholds for rattlesnakes and colubrid snakes on islands in the Gulf of California, Mexico.
We expand a framework for estimating minimum area thresholds to elaborate biogeographic patterns between two groups of snakes (rattlesnakes and colubrid snakes) on islands in the western Gulf of California, Mexico. The minimum area thresholds for supporting single species versus coexistence of two or more species relate to hypotheses of the relative importance of energetic efficiency and competitive interactions within groups, respectively. We used ordinal logistic regression probability functions to estimate minimum area thresholds after evaluating the influence of island area, isolation, and age on rattlesnake and colubrid occupancy patterns across 83 islands. Minimum area thresholds for islands supporting one species were nearly identical for rattlesnakes and colubrids (~1.7 km2), suggesting that selective tradeoffs for distinctive life history traits between rattlesnakes and colubrids did not result in any clear advantage of one life history strategy over the other on islands. However, the minimum area threshold for supporting two or more species of rattlesnakes (37.1 km2) was over five times greater than it was for supporting two or more species of colubrids (6.7 km2). The great differences between rattlesnakes and colubrids in minimum area required to support more than one species imply that for islands in the Gulf of California relative extinction risks are higher for coexistence of multiple species of rattlesnakes and that competition within and between species of rattlesnakes is likely much more intense than it is within and between species of colubrids.


RNA Trans-Splicing Targeting Endogenous β-Globin Pre-Messenger RNA in Human Erythroid Cells.
Sickle cell disease results from a point mutation in exon 1 of the β-globin gene (total 3 exons). Replacing sickle β-globin exon 1 (and exon 2) with a normal sequence by trans-splicing is a potential therapeutic strategy. Therefore, this study sought to develop trans-splicing targeting β-globin pre-messenger RNA among human erythroid cells. Binding domains from random β-globin sequences were comprehensively screened. Six candidates had optimal binding, and all targeted intron 2. Next, lentiviral vectors encoding RNA trans-splicing molecules were constructed incorporating a unique binding domain from these candidates, artificial 5' splice site, and γ-globin cDNA, and trans-splicing was evaluated in CD34+ cell-derived erythroid cells from healthy individuals. Lentiviral transduction was efficient, with vector copy numbers of 9.7 to 15.3. The intended trans-spliced RNA product, including exon 3 of endogenous β-globin and γ-globin, was detected at the molecular level. Trans-splicing efficiency was improved to 0.07-0.09% by longer binding domains, including the 5' splice site of intron 2. In summary, screening was performed to select efficient binding domains for trans-splicing. Detectable levels of trans-splicing were obtained for endogenous β-globin RNA in human erythroid cells. These methods provide the basis for future trans-splicing directed gene therapy.


All records of rodents (Mammalia, Rodentia) and hares (Mammalia, Lagomorpha) in Georgia from 1855 through to 2022.
In Georgia, there are 40 species from 21 genera and nine families of rodents, along with one species from a single genus and a family of hares. The dataset, which includes 3146 records, provides information regarding the presence of these species within 1559 locations. Of the total of 3146 records, 285 records from 281 locations belong to hares, while 2864 records from 1394 locations are associated with rodents. The dataset incorporates data sourced from various institutions, including the Collection of the Institute of Zoology of Ilia State University, the Georgian National Museum, the Collection of the Zoological Institute of Russian Academy of Sciences, the Zoological Museum of Moscow State University, as well as data extracted from literature and our own field data. The method for establishing the dataset included data compilation from all the above-mentioned sources. The dataset includes records from 1855 through to 2022. In this publication, out of 3146 records, 14.9% are our new unpublished data. The unpublished data were collected from 2004 through to 2022. In total, 26% of all records are literature data, 50% are museum data and 24% are data collected by us. The dataset includes data obtained from literature sources, museum collections and the field observations. It includes occurrences of species found in the same locality, but within different years, resulting in separate records for each location. The dataset provided has the potential to significantly contribute to our understanding of the distribution of rodents and hares in Georgia.


Nutrition and the neurosurgical patient.
There has been a rapid expansion of knowledge in the field of nutrition and metabolism with regard to the general surgical patient. However, only recently has there been greater appreciation of the benefits of adequate nutrition and appropriate metabolic care of the neurosurgical patient. In this review, the authors attempt to outline 1) the metabolic response to stress in general, and how it applies to the neurosurgical patient; 2) how best to provide adequate nutritional support for the neurosurgical patient; 3) the effects of nutrition on neurotransmitters; and 4) the effect of diet and nutrition on patients with malignant brain tumors.


Comparative assessment of the stability of nonfouling poly(2-methyl-2-oxazoline) and poly(ethylene glycol) surface films: an in vitro cell culture study.
Poly(ethylene glycol) (PEG) has been the most frequently reported and commercially used polymer for surface coatings to convey nonfouling properties. PEGylated surfaces are known to exhibit limited chemical stability, particularly due to oxidative degradation, which limits long-term applications. In view of excellent anti-adhesive properties in the brush conformation and resistance to oxidative degradation, poly(2-methyl-2-oxazoline) (PMOXA) has been proposed recently as an alternative to PEG. In this study, the authors systematically compare the (bio)chemical stability of PEG- and PMOXA-based polymer brush monolayer thin films when exposed to cultures of human umbilical vein endothelial cells (HUVECs) and human foreskin fibroblasts (HFFs). To this end, the authors used cell-adhesive protein micropatterns in a background of the nonfouling PEG and PMOXA brushes, respectively, and monitored the outgrowth of HUVECs and HFFs for up to 21 days and 1.5 months. Our results demonstrate that cellular micropatterns spaced by PMOXA brushes are significantly more stable under serum containing cell culture conditions in terms of confinement of cells to the adhesive patterns, when compared to corresponding micropatterns generated by PEG brushes. Moreover, homogeneous PEG and PMOXA-based brush monolayers on Nb2O5 surfaces were investigated after immersion in endothelial cell medium using ellipsometry and x-ray photoelectron spectroscopy.


Central venous oxygenation: when physiology explains apparent discrepancies.
Central venous oxygen saturation (ScvO2) >70% or mixed venous oxygen saturation (SvO2) >65% is recommended for both septic and non-septic patients. Although it is the task of experts to suggest clear and simple guidelines, there is a risk of reducing critical care to these simple recommendations. This article reviews the basic physiological and pathological features as well as the metrological issues that provide clear evidence that SvO2 and ScvO2 are adaptative variables with large inter-patient variability. This variability is exemplified in a modeled population of 1,000 standard ICU patients and in a real population of 100 patients including 15,860 measurements. In these populations, it can be seen how optimizing one to three of the four S(c)vO2 components homogenized the patients and yields a clear dependency with the fourth one. This explains the discordant results observed in large studies where cardiac output was increased up to predetermined S(c)vO2 thresholds following arterial oxygen hemoglobin saturation, total body oxygen consumption needs and hemoglobin optimization. Although a systematic S(c)vO2 goal-oriented protocol can be statistically profitable before ICU admission, appropriate intensive care mandates determination of the best compromise between S(c)vO2 and its four components, taking into account the specific constraints of each individual patient.


Drying technology strategies for colon-targeted oral delivery of biopharmaceuticals.
In chronic intestinal diseases like inflammatory bowel disease, parenteral administration of biopharmaceuticals is associated with numerous disadvantages including immune reactions, infections, low patient compliance, and toxicity caused by high systemic bioavailability. One alternative that can potentially overcome these limitations is oral administration of biopharmaceuticals, where the local delivery will reduce the systemic exposure and furthermore the manufacturing costs will be lower. However, the development of oral dosage forms that deliver the biologically active form to the intestines is one of the greatest challenges for pharmaceutical technologists due to the sensitive nature of biopharmaceuticals. The present article discusses the various drug delivery technologies used to produce orally administered solid dosage forms of biopharmaceuticals with an emphasis on colon-targeted delivery. Solid oral dosage compositions containing different types of colon-targeting biopharmaceuticals are compiled followed by a review of currently applied and emerging drying technologies for biopharmaceuticals. The different drying technologies are compared in terms of their advantages, limitations, costs and their effect on product stability.


Pancreatic mass leading to left-sided portal hypertension, causing bleeding from isolated gastric varices.
Mucinous cystic neoplasms (MCN) are an uncommon form of exocrine neoplasms of the pancreas. Symptoms are most often vague and this makes the diagnosis more difficult. The current case is one of three cases yet reported where the MCN caused left-sided portal hypertension leading to the formation of isolated gastric varices and subsequent bleeding from the varices. In the previously reported cases the main symptom was hematemesis. However in the current case the patient experienced no hematemesis, only isolated incidents of dark coloured diarrhea, but the main symptoms were those of iron-deficiency anemia. We present the case report of a 34-year-old woman who presented with dizziness and lethargy and was found to have 12 cm MCN in the pancreas.


Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase.
Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1beta release from a human monocyte cell line. The ability of Aspergillus hyphae to activate the NLRP3 inflammasome in the monocytes requires K(+) efflux and ROS production. In addition, our data show that NLRP3 inflammasome activation as well as pro-IL-1beta expression relies on the Syk tyrosine kinase, which is downstream from the pathogen recognition receptor Dectin-1, reinforcing the importance of Dectin-1 in the innate immune response against fungal infection. Furthermore, we show that treatment of monocytes with corticosteroids inhibits transcription of the gene encoding IL-1beta. Thus, our data demonstrate that the innate immune response against A. fumigatus infection involves a two step activation process, with a first signal promoting expression and synthesis of pro-IL-1beta; and a second signal, involving Syk-induced activation of the NLRP3 inflammasome and caspase-1, allowing processing and secretion of the mature cytokine.


Expression of the gene encoding blood coagulation factor VIII without domain B in E. coli bacterial expression system.
In this article, we have demonstrated the feasibility of generating an active form of recombinant blood coagulation factor VIII using an E. coli bacterial expression system as a potential treatment for hemophilia type A. Factor VIII (FVIII), an essential blood coagulation protein, is a key component of the fluid phase blood coagulation system. So far, all available recombinant FVIII formulations have been produced using eukaryotic expression systems. Mammalian cells can produce catalytically active proteins with all the necessary posttranslational modifications. However, cultivating such cells is time-consuming and highly expensive, and the amount of the obtained product is usually low. In contrast to eukaryotic cells, bacterial culture is inexpensive and allows the acquisition of large quantities of recombinant proteins in a short time. With this study, we aimed to obtain recombinant blood coagulation factor VIII using the E. coli bacterial expression system, a method not previously explored for this purpose. Our research encompasses the synthesis of blood coagulation factor VIII and its expression in a prokaryotic system. To achieve this, we constructed a prokaryotic expression vector containing a synthetic factor VIII gene, which was then used for the transformation of an E. coli bacterial strain. The protein expression was confirmed by mass spectrometry, and we assessed the stability of the gene construct while determining the optimal growth conditions. The production of blood coagulation factor VIII by the E. coli bacterial strain was carried out on a quarter-technical scale. We established the conditions for isolation, denaturation, and renaturation of the protein, and subsequently confirmed the activity of FVIII.


MicroRNA-15b participates in the development of peripheral arterial disease by modulating the growth of vascular smooth muscle cells.
As an atherosclerotic disease, the process of peripheral arterial disease (PAD) is complicated and includes the abnormal proliferation of vascular smooth muscle. The current study aimed to determine the role of microRNA-15b (miR-15b) in the development of PAD and its associated mechanisms. Human vascular smooth muscle cells (hVSMCs) were used in the current study. To assess the effects of miR-15b on hVSMCs, miR-15b was up- or downregulated in hVSMCs using miR-15b mimics or miR-15b inhibitors respectively. Cell viability, migration and apoptosis were then determined via MTT, transwell and flow cytometry assays, respectively. TargetScan bioinformatics software was utilized to predict the targets of miR-15b, and the binding sites between insulin growth factor 1 receptor (IGF1R) and miR-15b were confirmed by dual-luciferase reporter assay. The results reveled that the miR-15b mimic significantly reduced hVSMC cell viability and migration, and promoted cell apoptosis. However, the opposite effect was observed following miR-15b inhibitor transfection. It was also determined that miR-15b directly targeted IGF1R and negatively regulated its expression in hVSMCs. Additionally, the results demonstrated that the miR-15b mimic inhibited the PI3K/AKT signaling pathway in hVSMCs, whereas the miR-15b inhibitor promoted it. Furthermore, the results indicated that the effect of the miR-15b mimic on hVSMCs was reversed by IGF1R overexpression. In conclusion, the data indicated that miR-15b participated in the occurrence and development of PAD by modulating hVSMC proliferation, apoptosis and migration via the regulation of IGF1R expression.


[Retrospective assessment of the effectiveness of BCG vaccination by multiple puncture method (Kuchiki's needle) in childhood tuberculosis].
The retrospective assessment of the effectiveness of BCG vaccination by multiple puncture method (Kuchiki's needle) was examined in childhood tuberculosis patients treated at our hospital. They were 137 children aged 0 month to 15 years. Seventy-nine of them were vaccinated with BCG and 58 of them were not vaccinated. Forty-seven patients had been vaccinated at 3 to 4 months after birth, and excluding 2 cases who were revaccinated thereafter the remaining 45 patients were compared with unvaccinated 58 patients. Following results were obtained. 1. Vaccinated 45 patients. 1) Within 3 months after the vaccination, 6 children showed breakdown of tuberculosis. Two of them were miliary tuberculosis. Three patients were positive bacteriologic findings. They were supposed to be infected before BCG vaccination or before the appearance of immunity by BCG vaccination. 2) From 4 months to 2 years after the vaccination, 12 children showed breakdown of tuberculosis, but they were all mild type and all of them were negative bacteriologic findings. 3) After 2 years or more from the vaccination, 27 children showed breakdown of tuberculosis. Three of them were positive bacteriologic findings. 2. Unvaccinated 58 patients. 1) Thirty-seven patients, aged 0 month to 2 years and 4 months, showed breakdown of tuberculosis. Seventeen patients were positive bacteriologic findings. Three cases of tuberculous meningitis (2 of them died) and 2 cases of miliary tuberculosis were observed. Paratracheal lymph node swelling was recognized in 5 cases, and bronchial stenosis due to compression was seen in 4 cases (one of them died). 2) Twenty-one patients were more than 2 years and 5 months old. Eight of them were positive bacteriologic findings.(ABSTRACT TRUNCATED AT 250 WORDS)


Structuring successful interventions in employee health programs.
This literature review explored common characteristics of successful health promotion interventions that have produced positive outcomes for the diverse populations studied. Health education interventions delivered in structured environments with quarterly monitoring produced the most positive outcomes. Interventions delivered to employees in a "team" format were as successful as interventions delivered one on one. Single disease- or health behavior-focused interventions were more successful than multifocused interventions. Review findings indicate that academic or consultant researchers may lend expertise to research methods and informed consent as employers create health promotion programs they wish to evaluate. Employers may find benefits in conducting health-related studies developed through partnerships or collaborations with academic researchers.


Structure of NADP(+)-dependent glutamate dehydrogenase from Escherichia coli--reflections on the basis of coenzyme specificity in the family of glutamate dehydrogenases.
Glutamate dehydrogenases (GDHs; EC 188.8.131.52-4) catalyse the oxidative deamination of L-glutamate to α-ketoglutarate, using NAD(+) and/or NADP(+) as a cofactor. Subunits of homo-hexameric bacterial enzymes comprise a substrate-binding domain I followed by a nucleotide-binding domain II. The reaction occurs in a catalytic cleft between the two domains. Although conserved residues in the nucleotide-binding domains of various dehydrogenases have been linked to cofactor preferences, the structural basis for specificity in the GDH family remains poorly understood. Here, the refined crystal structure of Escherichia coli GDH in the absence of reactants is described at 2.5-Å resolution. Modelling of NADP(+) in domain II reveals the potential contribution of positively charged residues from a neighbouring α-helical hairpin to phosphate recognition. In addition, a serine that follows the P7 aspartate is presumed to form a hydrogen bond with the 2'-phosphate. Mutagenesis and kinetic analysis confirms the importance of these residues in NADP(+) recognition. Surprisingly, one of the positively charged residues is conserved in all sequences of NAD(+)-dependent enzymes, but the conformations adopted by the corresponding regions in proteins whose structure has been solved preclude their contribution to the coordination of the 2'-ribose phosphate of NADP(+). These studies clarify the sequence-structure relationships in bacterial GDHs, revealing that identical residues may specify different coenzyme preferences, depending on the structural context. Primary sequence alone is therefore not a reliable guide for predicting coenzyme specificity. We also consider how it is possible for a single sequence to accommodate both coenzymes in the dual-specificity GDHs of animals.


[Cataract surgery and the "Blue Miracle"].
Continuous circular capsulorhexis enabling safe phacoemulsification and implantation of the PC-IOL in the bag is extremely difficult to perform in the absence of red reflex. Staining of the anterior capsule with a vital dye (Vision blue(R); DORC, The Netherlands) allows easy capsulorhexis under such conditions. Because of missing or poor red reflex Vision blue(R) was applied to allow capsulorhexis in 26 eyes of 25 patients (aged 24 - 86 years). Sixteen patients had mature cataracts, two patients had dense vitreous opacities and 8 patients had pronounced anterior subcapsular opacifications. Continuos circular capsulorhexis was easy to perform in 22/26 eyes after staining the anterior capsule with Vision blue(R). Due to increased intracapsular pressure two eyes developed an uncontrolled tearing of the anterior capsule towards the periphery, and in two eyes capsulotomy had to be completed with high-frequency capsulotomy or scissors. Ten of sixteen eyes with mature cataracts had extremely hard nuclei requiring extended phacoemulsification time (more than 90 seconds calculated for 100 % power). There was no rupture of the posterior capsule nor vitreous loss. All PC-IOL's (23 x Acrysof(R); Alcon; 3 x 6.5 mm PMMA) were implanted into the capsular bag. Preoperatively 19/26 eyes had visual acuity of handmotions or less, postoperatively 18/26 eyes achieved 20/30 or better visual acuity. In the absence of red reflex staining of the anterior capsule with Vision blue(R) allows continuous circular capsulorhexis and implantation of the PC-IOL in the bag. An extremely hard nucleus requiring extended phacoemulsification time must be expected in elderly patients with mature cataracts.