Bronchoalveolar glutathione and nitrite/nitrate in idiopathic pulmonary fibrosis and sarcoidosis.
Bronchoalveolar lavage (BAL) is useful in diagnosis and management of interstitial lung diseases. Glutathione (GSH) represents an important defence molecule against reactive oxygen species produced during inflammation, which underlies both idiopathic pulmonary fibrosis (IPF) and sarcoidosis. Nitric oxide has been suggested as a marker of airway inflammation. The aim of this study was to examine the content of GSH and NO stable metabolites, nitrite/nitrate, in the BAL of a group of patients with IPF and sarcoidosis. BAL was performed in 13 patients with newly diagnosed IPF, 13 patients with sarcoidosis and 4 controls. Total GSH and nitrite/nitrate were measured. BAL was repeated, in 5 patients with IPF, after 6 and 12 months and GSH was measured again. IPF patients had significantly lower levels of total GSH compared to sarcoidosis patients or controls (129 +/- 22 vs. 324 +/- 40 and 383 +/- 23 mM; p < 0.001) in the epithelial lining fluid (ELF). In patients with IPF (n = 5), total GSH levels in the ELF increased after 6 and 12 months (T0 = 98 +/- 19; T6 = 219 +/- 22; T12 = 301 +/- 34 microM; p < 0.05) following therapy with immunosuppressive drugs such as corticosteroids, methotrexate, cyclosporin A. Levels of nitrite/nitrate were found significantly elevated in IPF (n = 8) and sarcoidosis (n = 10) patients compared to controls (230 +/- 37 and 216 +/- 36 vs. 86 +/- 11 microM; p < 0.05). These observations support the role of inflammation and antioxidant defences in interstitial lung diseases and may provide insights into the pathogenesis of oxidant-induced interstitial disease and their therapy.


Non-invasive bedside assessment of central venous pressure: scanning into the future.
Noninvasive evaluation of central venous pressure (CVP) can be achieved by assessing the Jugular Venous Pressure (JVP), Peripheral Venous Collapse (PVC), and ultrasound visualization of the inferior vena cava. The relative accuracy of these techniques compared to one another and their application by trainees of varying experience remains uncertain. We compare the application and utility of the JVP, PVC, and handheld Mini Echo amongst trainees of varying experience including a medical student, internal medicine resident, and cardiology fellow. We also introduce and validate a new physical exam technique to assess central venous pressures, the Anthem sign. Patients presenting for their regularly scheduled echocardiograms at the hospital echo department had clinical evaluations of their CVP using these non-invasive bedside techniques. The examiners were blinded to the echo results, each other's assessments, and patient history; their CVP estimates were compared to the gold standard level 3 echo-cardiographer's estimates at the completion of the study. 325 patients combined were examined (mean age 65, s.d. 16 years). When compared to the gold standard of central venous pressure by a level 3 echocardiographer, the JVP was the most sensitive at 86%, improving with clinical experience (p<0.01). The classic PVC technique and Anthem sign had better specificity compared to the JVP. Mini Echo estimates were comparable to physical exam assessments. JVP evaluation is the most sensitive physical examination technique in CVP assessments. The PVC techniques along with the newly described Anthem sign may be of value for the early learner who still has not mastered the art of JVP assessment and in obese patients in whom JVP evaluation is problematic. Mini Echo estimates of CVPs are comparable to physical examination by trained clinicians and require less instruction. The use of Mini Echo in medical training should be further evaluated and encouraged.


Efficacy of early bundle therapy on moderate to severe aspiration pneumonia after cervical esophagogastrostomy for esophageal cancer.
The aim of this paper was to investigate the methodology and clinical efficacy of early bundle therapy for complicated moderate to severe aspiration pneumonia after cervical esophagogastrostomy for esophageal cancer. A prospective study was conducted to analyze the clinical data from 49 patients who developed complicated moderate to severe aspiration pneumonia after cervical esophagogastrostomy for esophageal cancer. Among them, 27 patients underwent a bundle therapy-tracheostomy followed by ventilator-assisted breathing with reverse trendelenburg position, early goal-directed hemodynamic support, enteral nutrition by nasointestinal tube, effective antibiotic usage and large doses of expectorants in addition to the conventional treatments. The remaining 22 patients underwent conventional treatment (controls). The hospital fatality rates, incidence of serious complications, mechanical ventilation time and ICU length of stay of the two groups were compared. Patients in the bundle therapy group had higher cure rate of pneumonia than the control group (P=0.041), significantly lower fatality rate than the controls (P=0.005), lower incidence of complications than the controls (P<0.05), shorter ICU length of stay than the control group (P=0.017), significantly shorter mechanical ventilation time (P=0.032), lower Acute Physiology and Chronic Health Evaluation II Score (P=0.036) and lower Clinical Pulmonary Infection Score (P=0.047). Early bundle therapy can effectively improve the treatment efficacy for moderate to severe aspiration pneumonia after cervical esophagogastrostomy for esophageal cancer.


Robustifying Experimental Tracer Design for13C-Metabolic Flux Analysis.
13C metabolic flux analysis (MFA) has become an indispensable tool to measure metabolic reaction rates (fluxes) in living organisms, having an increasingly diverse range of applications. Here, the choice of the13C labeled tracer composition makes the difference between an information-rich experiment and an experiment with only limited insights. To improve the chances for an informative labeling experiment, optimal experimental design approaches have been devised for13C-MFA, all relying on some a priori knowledge about the actual fluxes. If such prior knowledge is unavailable, e.g., for research organisms and producer strains, existing methods are left with a chicken-and-egg problem. In this work, we present a general computational method, termed robustified experimental design (R-ED), to guide the decision making about suitable tracer choices when prior knowledge about the fluxes is lacking. Instead of focusing on one mixture, optimal for specific flux values, we pursue a sampling based approach and introduce a new design criterion, which characterizes the extent to which mixtures are informative in view of all possible flux values. The R-ED workflow enables the exploration of suitable tracer mixtures and provides full flexibility to trade off information and cost metrics. The potential of the R-ED workflow is showcased by applying the approach to the industrially relevant antibiotic producer Streptomyces clavuligerus, where we suggest informative, yet economic labeling strategies.


Cost and outcome of treatment of adults with acute myeloid leukemia at the National Cancer Institute-Egypt.
Despite important advances in the therapy of acute myeloid leukemia (AML), the majority of patients die of their disease, unless bone marrow transplantation (BMT) is done. Infection and hemorrhage are still the major causes of mortality in AML patients. Progress in therapy and supportive care has led to gradual improvement in the overall results, but further improvements are still needed. The aim of this study is to identify the outcome and costs of adult AML patients treated with conventional chemotherapy (CCT) at the National Cancer Institute (NCI), Cairo University during the time period from April 1999 to January 2002. Clinical, laboratory characteristics were all recorded. Data regarding different types of therapies given for these patients including response, outcome and costs were also collected. The median age of 82 identified AML patients was 34 years. The complete remission (CR) rate after induction with CCT was 52% (42/82 patients) with a median CR duration of 9 months. Twenty-eight percent of patients who achieved CR subsequently relapsed. By January 2003, fifty-eight patients were dead (70.7%). Infections were the major mortality cause, followed by disease progression then bleeding (65% , 28% and 7% respectively). The median treatment cost per patient was 33158 Egyptian Pounds (LE). It was higher for patients who achieved CR compared to those who relapsed and/or died. Drugs contributed by 78 % to the total treatment cost, while hospitalization, investigations and blood-component therapy contributed by 6%, 7% and 8% respectively. Outcome of patients with AML treated at NCI- Cairo University can be enhanced by improvement of supportive therapy; mainly infection control and expanding BMT programs to accommodate all eligible patients.


Acute effects of aldosterone on the epithelial Na channel in rat kidney.
The acute effects of aldosterone administration on epithelial Na channels (ENaC) in rat kidney were examined using electrophysiology and immunodetection. Animals received a single injection of aldosterone (20 μg/kg body wt), which reduced Na excretion over the next 3 h. Channel activity was assessed in principal cells of cortical collecting ducts as amiloride-sensitive whole cell clamp current (INa). INa averaged 100 pA/cell, 20-30% of that reported for the same preparation under conditions of chronic stimulation. INa was negligible in control animals that did not receive hormone. The acute physiological response correlated with changes in ENaC processing and trafficking. These effects included increases in the cleaved forms of α-ENaC and γ-ENaC, assessed by Western blot, and increases in the surface expression of β-ENaC and γ-ENaC measured after surface protein biotinylation. These changes were qualitatively and quantitatively similar to those of chronic stimulation. This suggests that altered trafficking to or from the apical membrane is an early response to the hormone and that later increases in channel activity require stimulation of channels residing at the surface.


Effect of restriction of working memory on reported paranormal belief.
56 college students completed Tobacyk's 1988 Revised Paranormal Belief Scale and Watson, Clark, and Tellegen's 1988 Positive and Negative Affect Scale. Experimental group participants, but not control group participants, rehearsed a five-digit number while completing the Paranormal Belief Scale. Analysis showed higher reported paranormal belief for experimental group participants but no differences on the Positive and Negative Affect Scale. Results are discussed in terms of the effect of restriction in working memory on the critical evaluation of paranormal phenomena.


Disease course and outcome of acute disseminated encephalomyelitis is more severe in adults than in children.
Acute disseminated encephalomyelitis (ADEM) affects children more frequently than adults. Current studies investigating ADEM in different age groups are difficult to compare. To investigate whether the clinical presentation, outcome and disease course of ADEM differ between adults and children. Disease characteristics of 25 adults and 92 children suffering from ADEM between 1988 and 2008 were compared. The most common presenting symptoms of ADEM in both groups were pyramidal signs and encephalopathy. Ataxia occurred more frequently in children (p = 0.002). In general, MRI showed ill-defined and large white matter lesions in both groups, whereas periventricular lesions were more prevalent in adults (p = 0.001). In adults, duration of hospitalization was longer (p = 0.002) and intensive care unit (ICU) admission was more frequently required (p = 0.043). Three adults (12%) and one child (1%) died (p = 0.030). Fewer adults had complete motor recovery after their first clinical event (p < 0.001). In 73 patients follow-up time was ≥ 2 years and most of these patients remained monophasic. Although relapses after ADEM can occur, only one adult (5%) and five children (6%) converted to MS. The clinical presentations in children and adults share similarities, but the disease course and outcome of ADEM is more severe in adults with respect to hospitalization, ICU admission, recovery and mortality.


Tolerance in organ transplantation: from conventional immunosuppression to extracellular vesicles.
Organ transplantation is often the unique solution for organ failure. However, rejection is still an unsolved problem. Although acute rejection is well controlled, the chronic use of immunosuppressive drugs for allograft acceptance causes numerous side effects in the recipient and do not prevent chronic allograft dysfunction. Different alternative therapies have been proposed to replace the classical treatment for allograft rejection. The alternative therapies are mainly based in pre-infusions of different types of regulatory cells, including DCs, MSCs, and Tregs. Nevertheless, these approaches lack full efficiency and have many problems related to availability and applicability. In this context, the use of extracellular vesicles, and in particular exosomes, may represent a cell-free alternative approach in inducing transplant tolerance and survival. Preliminary approaches in vitro and in vivo have demonstrated the efficient alloantigen presentation and immunomodulation abilities of exosomes, leading to alloantigen-specific tolerance and allograft acceptance in rodent models. Donor exosomes have been used alone, processed by recipient antigen-presenting cells, or administered together with suboptimal doses of immunosuppressive drugs, achieving specific allograft tolerance and infinite transplant survival. In this review, we gathered the latest exosome-based strategies for graft acceptance and discuss the tolerance mechanisms involved in organ tolerance mediated by the administration of exosomes. We will also deal with the feasibility and difficulties that arise from the application of this strategy into the clinic.


Association between serum 25-hydroxyvitamin D level and type of coccidioidal infection.
The clinical manifestations of coccidioidomycosis vary depending upon the extent of exposure and immune status of the host. Recent studies have demonstrated an essential role for vitamin D in both innate and acquired immunity and serum levels strongly correlate with the development of upper respiratory tract infections, including tuberculosis. Despite similar pathophysiologic processes at play in the control of tuberculosis and invasive fungal infections, a possible association of low serum 25(OH) vitamin D levels had not previously been assessed in the latter patient group. Therefore, we performed a case-control study examining serum 25(OH) vitamin D levels in three distinct groups of patients with coccidioidomycosis as compared to healthy uninfected controls. Of the 89 patients included in this study, there were 26 negative controls, 23 who were immune, 22 with primary coccidioidal pneumonia, and 18 who had disseminated/meningeal infection. Serum 25(OH) vitamin D levels varied between groups with lowest levels seen in the group with disseminated/meningeal coccidioidomycosis (P= 0.14). In this evaluation of a diverse group of patients with varying forms of coccidioidomycosis we found no association of vitamin D with the acquisition or resolution of this infection. Vitamin D does not play a significant role in host susceptibility to coccidioidomycosis.


Virus-like particles presenting interleukin-33 molecules: immunization characteristics and potentials of blockingIL-33/ST2 pathway in allergic airway inflammation.
We sought to develop an IL-33 vaccine and evaluate its efficacy in a mouse model of asthma. The full-length molecules of putative mature IL-33 were inserted into the immunodominant epitope region of hepatitis B core antigen using gene recombination techniques. The expressed chimeric protein presented as virus-like particles (VLPs) under observation using an electron microscopy. To investigate immunization characteristics of the VLPs, mice were immunized by using different doses, adjuvants, and routes. The VLPs induced sustained and high titers of IL-33-specific IgG and IgA even without the use of a conventional adjuvant, and the lowered ratio of IgG1/IgG2a in vaccinated mice indicated a shift from Th2 to Th1-like responses. To assess the vaccine effects on blocking the signaling of IL-33/ST2 pathway, mice receiving 3 vaccinations subjected to intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). Control animals received carrier or PBS in place of the vaccine. Immunization with the VLPs significantly suppressed inflammatory cell number and IL-33 level in BALF. OVA -induced goblet cell hyperplasia and lung tissue inflammatory cell infiltration were significantly suppressed in vaccinated mice. Our data indicate that IL-33 molecule-based vaccine, which may block IL-33/ST2 signaling pathway on a persistent basis, holds potential for treatment of asthma and, by extension, other diseases where overexpressed IL-33 plays a pivotal role in pathogenesis.


Targeting Notch-Activated M1 Macrophages Attenuates Joint Tissue Damage in a Mouse Model of Inflammatory Arthritis.
Expression levels of Notch signaling molecules are increased in synovium from patients with rheumatoid arthritis (RA). However, it is not known which cell type(s) in RA synovium have Notch activation or if they play a pathogenetic role in RA. Here, we used Hes1-GFP/TNF-transgenic (TNF-Tg) mice to investigate the role of cells with active Notch signaling (GFP+) in RA. The number of GFP+ cells was significantly increased in synovium in Hes1-GFP/TNF-Tg mice and about 60% of them were F4/80+ macrophages expressing the inflammatory macrophage (M1) marker. TNF-Tg mice transplanted with Hes1-GFP/TNF-Tg bone marrow (BM) had significantly more GFP+ cells in their synovium than in BM. Intraarticular injection of Hes1-GFP/TNF-Tg or Hes1-GFP+ BM macrophages into WT and TNF-Tg mice showed the highest synovial GFP+ cells in the TNF-Tg mice that received Hes1-GFP/TNF-Tg cells. Thapsigargin (THAP), a Notch inhibitor, decreased TNF-induced M1 and increased M2 numbers and reduced joint lesion, synovial M1s, and GFP+ cells in Hes1-GFP/TNF-Tg mice. THAP did not affect M1s from mice carrying a constitutively active Notch1. Thus, the main cells with activated Notch signaling in the inflamed synovium of TNF-Tg mice are M1s derived from BM and targeting them may represent a new therapeutic approach for patients with inflammatory arthritis. © 2017 American Society for Bone and Mineral Research.


Changes in abdominal wounds following treatment with sirolimus and steroids in a rat model.
Wound healing complications have been observed in patients receiving sirolimus (SLR). This study examined the degree and duration of delayed healing in various protocols using SLR. Sprague-Dawley rats underwent a standard midline abdominal incision and wound closure. Groups of 6 rats each were randomized to receive different doses of SLR (2 and 5 mg/kg) with or without loading dose (10 mg/kg x3 days), and with or without steroids (20 mg/kg x3 days followed by 5 mg/kg for 2 weeks). Rats were humanely killed on postoperative days 5, 10, or 15. Wound breaking force was measured using the EHMI BIAX-II instrument and tensile strength was calculated. Wounds in control animals had gradual increase in tensile strength during the 15-day observation. In contrast, high and loading doses of SLR caused reduction in wound strength until day 10, but the wounds' tensile strength became equivalent to control by day 15. The addition of steroids prolonged wound recovery with low doses of SLR until day 15 and had very profound effects on healing in high-dose SLR-treated animals (>50% reduction) that continued beyond the 2 weeks of observation. Low doses of SLR in non-steroid-treated animals had a short-term (5-day) impact on wound healing; high dose and loading doses delayed healing for 10 to 15 days. The addition of steroids had a synergistic effect on delayed wound healing, particularly in animals receiving high-dose SLR, which demonstrated prolonged wound weakness. These results may provide practical guidelines for postoperative introduction of SLR in the context of various clinical protocols.


Using SWMM for emergency response planning: A case study evaluating biological agent transport under various rainfall scenarios and urban surfaces.
To assist in emergency preparedness for a biological agent terrorist attack or accidental pathogen release, potential contaminant levels and migration pathways of spores spread by urban stormwater were evaluated using a Storm Water Management Model (SWMM) of U.S. Coast Guard Base Elizabeth City, North Carolina. The high temporal-spatial resolution SWMM model was built using spore concentrations in stormwater runoff from asphalt, grass, and concrete collected from a point-scale field study. The subsequent modeled contamination scenarios included a notional plume release and point releases mimicking the field study under three rainfall conditions. The rainfall scenarios included a 6-hour natural rainfall event on Dec. 8, 2021 and two design storms (2-year and 100-year events). The observed spore concentrations from asphalt and concrete from the actual field experiment were applied to calibrate the washoff parameters in the SWMM model, using an exponential washoff function. The calibrated washoff coefficient (c1) and exponent (c2) were 0.01 and 1.00 for asphalt, 0.05 and 1.45 for grass, and 2.45 and 1.00 for concrete, respectively. The calibrated SWMM model simulated spore concentrations in runoff at times and magnitudes similar to the field study data. In the point release modeled scenario, the concrete surface generated 55.6% higher average spore concentrations than asphalt. Similarly, in the field experiment, a 175% (p < 0.05) higher average spore concentration in surface runoff was observed from concrete than from asphalt. This study demonstrates how SWMM may be used to evaluate spore washoff from urban surfaces under different precipitation amounts, intensities, and durations, and how visualized spatial migration pathways in stormwater runoff may be used for emergency planning and remediation.


Functional receptors for atrial natriuretic peptide in the rat mammary gland during lactation.
The present study was undertaken: 1) to localize and characterize atrial natriuretic peptide (ANP) receptors in the rat mammary gland; and 2) to elucidate ANP-induced cellular formation of cyclic GMP (cGMP) and alterations in alveolar morphology during both early and late lactation. Receptor autoradiography, employing rat-specific [125I]ANP as radioligand, demonstrated binding sites in the secretory tissue and larger blood vessels of the mammary gland. Binding of [125I]rANP to membrane fractions was completely displaced by unlabeled ANP and brain natriuretic peptide. C-type natriuretic peptide and cANP(4-23) revealed limited competition with radiolabeled ANP only during early lactation, indicating a more heterogeneous receptor population at that time. Systemically administered ANP induced cGMP formation in the alveolar epithelium, as shown with immunohistochemistry, and increased mammary tissue cGMP concentrations in vivo throughout the lactation period. Image analysis revealed enlargement of alveolar (but not epithelial) cell area after ANP stimulation in late lactation, suggesting altered alveolar filling or myoepithelial cell relaxation. These results indicate that ANP induces biological effects in the rat mammary gland through specific ANP-A receptor interaction with subsequent intracellular cGMP formation. ANP may therefore play a regulatory role in the control of mammary gland blood supply and secretory function.


A non-proteolytic function of ubiquitin in transcription repression.
Regulation of transcription is vitally important for maintaining normal cellular homeostasis and is also the basis for cellular differentiation, morphogenesis and the adaptability of any organism. Transcription activators, which orchestrate time and locus-specific assembly of complex transcription machinery, act as key players in these processes. One way in which these activators are controlled is by the covalent attachment of the conserved protein, ubiquitin (Ub), which can serve as either a proteolytic or non-proteolytic signal. For a subset of the activators, polyubiquitination-dependent degradation of the activator controls its abundance. In these cases transcription activation can require protein synthesis as well as internal or external stimulus. In contrast, other activators have been reported to undergo mono- or oligoubiquitination that does not lead to protein degradation. The mechanisms by which monoubiquitination of transcription activators affect their activities have been poorly understood. In a recent study, we demonstrated that monoubiquitination of some transcription activators can inhibit transcription by recruiting the AAA+ ATPase Cdc48 (also known in metazoan organisms as p97 or valosin-contain protein, VCP), which then extracts the ubiquitinated activator from DNA.


Spermatogonial behavior in rats during radiation-induced arrest and recovery after hormone suppression.
Ionizing radiation has been shown to arrest spermatogenesis despite the presence of surviving stem spermatogonia, by blocking their differentiation. This block is a result of damage to the somatic environment and is reversed when gonadotropins and testosterone are suppressed, but the mechanisms are still unknown. We examined spermatogonial differentiation and Sertoli cell factors that regulate spermatogonia after irradiation, during hormone suppression, and after hormone suppression combined with Leydig cell elimination with ethane dimethane sulfonate. These results showed that the numbers and cytoplasmic structure of Sertoli cells are unaffected by irradiation, only a few type A undifferentiated (Aund) spermatogonia and even fewer type A1 spermatogonia remained, and immunohistochemical analysis showed that Sertoli cells still produced KIT ligand (KITLG) and glial cell line-derived neurotrophic factor (GDNF). Some of these cells expressed KIT receptor, demonstrating that the failure of differentiation was not a result of the absence of the KIT system. Hormone suppression resulted in an increase in Aund spermatogonia within 3 days, a gradual increase in KIT-positive spermatogonia, and differentiation mainly to A3 spermatogonia after 2 weeks. KITL (KITLG) protein expression did not change after hormone suppression, indicating that it is not a factor in the stimulation. However, GDNF increased steadily after hormone suppression, which was unexpected since GDNF is supposed to promote stem spermatogonial self-renewal and not differentiation. We conclude that the primary cause of the block in spermatogonial development is not due to Sertoli cell factors such (KITL\GDNF) or the KIT receptor. As elimination of Leydig cells in addition to hormone suppression resulted in differentiation to the A3 stage within 1 week, Leydig cell factors were not necessary for spermatogonial differentiation.


Azygos continuation of the inferior vena cava: demonstration by NMR imaging.
Azygos continuation of the inferior vena cava was diagnosed by magnetic resonance (MR) imaging in a patient with a right tracheobronchial angle mass. The characteristic findings included a dilated azygos vein and absence of the hepatic segment of the inferior vena cava. Advantages of MR imaging in evaluation of anomalies of the cava are discussed.


PRPCalc2: An App for Platelet-Rich Plasma Preparation.
Platelet-rich plasma (PRP), an inexpensive yet powerful treatment modality, is widely used but poorly understood. Three areas of unmet need are the ability to compare results using differing centrifuges and methods; translating a study result into a specific practice; and estimating yield and dosage without the benefit of an in-office hematology analyzer. PRPCalc2 is a set of software tools that facilitates these goals. The app consists of software tools that (1) calculate the appropriate radius for centrifugation, (2) calculate the correct revolutions per minute (RPM) for the centrifuge, (3) calculate the mean yield for the method and its confidence interval, and (4) calculate platelet dosage. Using these tools, a practitioner with any centrifuge can create and validate their own PRP preparation method and then use it to create a standardized PRP.


1H NMR-Based Metabolomics to Assess the Impact of Soil Type on the Chemical Composition of Nero d'Avola Red Wines.
In this study, the soil effect on the micro-component composition of Nero d'Avola wines obtained from different locations was investigated through 1H NMR-based metabolomics. Two different approaches were applied: the targeted (TA) and the non-targeted one (NTA). The former differentiated the wines by profiling (i.e., by identifying and quantifying) a number of different metabolites. The latter provided wine fingerprinting by processing the entire spectra with multivariate statistical analysis. NTA also allowed investigation of the hydrogen bond network inside wines via the analysis of 1H NMR chemical shift dispersions. Results showed that the differences among wines were due not only to the concentrations of various analytes but also to the characteristics of the H-bond network where different solutes were involved. The H-bond network affects both gustatory and olfactory perceptions by modulating the way how solutes interact with the human sensorial receptors. Moreover, the aforementioned H-bond network is also related to the soil properties from which the grapes were taken. Therefore, the present study can be considered a good attempt to investigate terroir, i.e., the relationship between wine quality and soil characteristics.


Hematological and Histological Changes in Prussian Carp Carassius gibelio Infected with Cyprinid Herpesvirus 2.
Outbreaks of cyprinid herpesvirus 2 (CyHV-2) disease, also known as herpesviral hematopoietic necrosis, among cultured Prussian Carp Carassius gibelio has occurred each year in Jiangsu province, China, since 2009. In autumn 2014, hematological, blood biochemical, and histological changes in naturally infected moribund Prussian Carp were investigated after CyHV-2 was confirmed as the sole etiologic agent by etiological analyses. Total erythrocyte count, total leukocyte count, hemoglobin concentration, and thrombocyte count were significantly reduced (P < 0.01), whereas erythrocyte osmotic brittleness was significantly increased (P < 0.01) in infected fish compared with control fish. In addition, monocyte count was higher (P < 0.01) and lymphocyte count was lower (P < 0.01) in diseased fish than in control fish. The blood biochemical analyses indicated significant increases (P < 0.01) in the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase as well as in the levels of total protein, globulin, total bilirubin, creatinine, and urea along with significant decreases (P < 0.01) in glucose and albumin in the diseased group. Histopathological examinations indicated that the kidneys and spleens of moribund Prussian Carp were the most severely lesioned organs, followed by the gills and hearts. Hypertrophied nuclei with marginated chromatin also appeared in the hearts and renal tubular epithelia from diseased fish. Pathological analysis of blood cells showed that approximately 78% of erythrocytes and 94% of leukocytes were lesioned with different levels of degeneration and necrosis in the diseased group. These previously unreported observations may be useful in the diagnosis of CyHV-2 disease. Received May 11, 2015; accepted March 24, 2016.


Pathological vascular invasion and tumor differentiation predict cancer recurrence in stage IA non-small-cell lung cancer after complete surgical resection.
The appropriate therapeutic strategy and postoperative management for patients with stage IA non-small-cell lung cancer (NSCLC) still remain a matter of debate because of the prognostic heterogeneity of this population, including the risk of cancer recurrence. The objective of the current study was to identify the clinicopathological factors that affect overall prognosis and cancer recurrence of stage IA NSCLC. We reviewed the data of 532 patients in whom complete resection of stage IA NSCLC had been performed. Overall survival and recurrence-free proportion (RFP) were estimated using the Kaplan-Meier method. RFP was estimated from the date of the primary tumor resection to the date of the first recurrence or last follow-up. We performed univariate and multivariate analyses to determine the independent prognostic factors. On multivariate analyses, three variables were shown to be independently significant recurrence risk factors: histological differentiation (hazard ratio [HR] = 1.925), blood-vessel invasion (HR = 1.712), and lymph-vessel invasion (HR = 1.751). On subgroup analyses combining these risk factors, the 5-year RFP was 91.3% for patients with no risk factors, 79.5% for those with either poorly differentiated carcinoma or vascular invasion, (p < 0.001 for both), and 62.9% for those with both poorly differentiated carcinoma and vascular invasion (p = 0.068). These results indicated that vascular invasion and tumor differentiation have a significant impact on the prediction of cancer recurrence in patients with stage IA NSCLC. Patients with these predictive factors of recurrence may be good candidates for adjuvant chemotherapy.


Pathophysiology and principles of management of the many faces of the acute vaso-occlusive crisis in patients with sickle cell disease.
Effective management of sickle cell pain entails a thorough understanding of its pathophysiology and the pharmacogenomics of the opioids used to manage it. In recent years, there has been significant progress along these two lines. At the pathophysiologic level, there is evidence that the severity and frequency of painful stimuli modulate their transmission at the level of the dorsal horn of the spinal cord. This modulation is achieved via two channels: the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors. Initially, the AMPA channel controls the transmission of stimuli of mild-moderate severity. Once the AMPA channel reaches its limit of membrane depolarization, the NMDA channel is activated and facilitates the transmission of painful stimuli in a progressive fashion leading to central sensitization and glial activation. At the level of pharmacogenomics, the metabolism of each opioid is patient-specific. Glucuronidation is unique for the metabolism of morphine, hydromorphone, and oxymorphone. The metabolism of all other opioids requires specific Cytochrome P450 (CYP) isoenzymes. The activity of each isoenzyme and the activity of the metabolites of each opioid vary among patients depending on their genetic makeup and coexistent environmental factors such as the use of other medications that may enhance or inhibit the CYP isoenzyme activity.


Hyperimmunoglobulin E syndrome: Genetics, immunopathogenesis, clinical findings, and treatment modalities.
The hyperimmunoglobulin E syndromes (HIESs) are very rare immunodeficiency syndromes with multisystem involvement, including immune system, skeleton, connective tissue, and dentition. HIES are characterized by the classic triad of high serum levels of immunoglobulin E (IgE), recurrent staphylococcal cold skin abscess, and recurrent pneumonia with pneumatocele formation. Most cases of HIES are sporadic although can be inherited as autosomal dominant and autosomal recessive traits. A fundamental immunologic defect in HIES is not clearly elucidated but abnormal neutrophil chemotaxis due to decreased production or secretion of interferon γ has main role in the immunopathogenesis of syndrome, also distorted Th1/Th2 cytokine profile toward a Th2 bias contributes to the impaired cellular immunity and a specific pattern of infection susceptibility as well as atopic-allergic constitution of syndrome. The ophthalmic manifestations of this disorder include conjunctivitis, keratitis, spontaneous corneal perforation, recurrent giant chalazia, extensive xanthelasma, tumors of the eyelid, strabismus, and bilateral keratoconus. The diagnosis of HIES is inconclusive, dependent on the evolution of a constellation of complex multisystemic symptoms and signs which develop over the years. Until time, no treatment modality is curative for basic defect in HIES, in terms of cytokines/chemokines derangement. Of note, bone marrow transplant and a monoclonal anti-IgE (omalizumab) are hoped to be successful treatment in future.


A role for the medial preoptic area in CGRP-induced suppression of pulsatile LH secretion in the female rat.
Calcitonin gene-related peptide (CGRP) is involved in a variety of stress responses and plays a pivotal role in stress-induced suppression of the GnRH pulse generator in the rat. Intracerebroventricular administration of CGRP suppresses luteinizing hormone (LH) pulses and increases Fos expression within the medial preoptic area (mPOA) and paraventricular nucleus (PVN). The aims of the present study were to investigate whether the mPOA or PVN are sites of action for CGRP-induced suppression of LH pulses and whether lipopolysaccharide (LPS), restraint or insulin-induced hypoglycaemia, stressors known to suppress LH pulses, affect mRNA expression for CGRP and its receptor subunits (calcitonin receptor-like receptor (CL) and RAMP-1) in the mPOA and PVN. Micro-infusion of CGRP (50, 250 or 500 pmol) into the mPOA, but not the PVN, dose-dependently suppressed LH pulse frequency. LPS, restraint and hypoglycaemia suppressed RAMP-1 mRNA, but not CL or CGRP mRNA expression in the mPOA. In the PVN, all three stressors suppressed CL mRNA expression, but only LPS or restraint suppressed RAMP-1 mRNA, and CGRP mRNA was unaffected. These results provide evidence that, unlike the PVN, the mPOA might play an important role in the inhibitory effect of CGRP on pulsatile LH secretion. Additionally, CGRP receptor function may be involved in this brain region in stress-induced suppression of the GnRH pulse generator.


Effect of partial whey protein depletion during membrane filtration on thermal stability of milk concentrates.
Membrane filtration technologies are widespread unit operations in the dairy industry, often employed to obtain ingredients with tailored processing functionalities. The objective of this work was to better understand the effect of partial removal of whey proteins by microfiltration (MF) on the heat stability of the fresh concentrates. The micellar casein concentrates were compared with control concentrates obtained using ultrafiltration (UF). Pasteurized milk was microfiltered (80 kDa polysulfone membrane) or ultrafiltered (30 kDa cellulose membrane) without diafiltration (i.e., no addition of water) to 2× and 4× concentration, based on volume reduction. The final concentrates showed no differences in pH, casein micelle size, or mineral concentration in the serum phase. The micellar casein retentates (obtained by MF) showed a 20 and 40% decrease in whey protein concentration compared with the corresponding UF milk protein concentrates for 2× and 4× concentration, respectively. The heat coagulation time decreased with increasing protein concentration, regardless of the treatment; however, MF retentates showed a higher thermal stability than the corresponding UF controls. The average diameter for casein micelles increased after heating in UF but not MF concentrates. The turbidity (measured by light scattering) increased after heating, but to a higher extent for UF retentates than for MF retentates at the same protein concentration. It was concluded that the reduced amount of whey protein in the MF retentates caused a significant increase in the heat stability compared with the corresponding UF retentates. This difference was not due to ionic composition differences or pH, but to the type and amount of complexes formed in the serum phase.


The molecular biology of soft-tissue sarcomas and current trends in therapy.
Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.


Preperitoneal tunneling-a novel technique in peritoneal dialysis catheter insertion.
This study describes a new preperitoneal tunneling (PPT) method for inserting a peritoneal dialysis catheter (PDC), thereby lessening surgical complications and increasing the catheter's survival. This new technique was used in 23 cases from December 2005 to January 2007 and followed up until March 2011 (63 months). The procedure was performed laparoscopically under local (16 cases) or general (7 cases) anesthesia by one surgeon. Catheter survival is reported by Kaplan-Meyer analysis. The catheters were mechanically obstructed in 2/23 cases (8.7%); and were withdrawn due to a peritonitis in 2 cases and inadequacy of peritoneal dialysis in 1 case. Ten patients received kidney transplantation and six died before completing this follow-up period. The patients still reaped the benefits of the PDC until receiving a kidney transplant or death. The 5-year survival rate of the catheter was 89%. No incidence of catheter migration, omental wrapping, herniation or leakage was noticed. Preperitoneal tunneling is a simple and safe method for insertion of PDC, and can effectively prevent catheter migration, dislocation and omental wrapping.


Tactile Stimuli Increase Effects of Modality Compatibility in Task Switching.
Modality compatibility refers to the similarity of stimulus modality and modality of response-related sensory consequences. Previous dual-task studies found increased switch costs for modality incompatible tasks (auditory-manual/visual-vocal) compared to modality compatible tasks (auditory-vocal/visual-manual). The present task-switching study further examined modality compatibility and investigated vibrotactile stimulation as a novel alternative to visual stimulation. Interestingly, a stronger modality compatibility effect on switch costs was revealed for the group with tactile-auditory stimulation compared to the visual-auditory stimulation group. We suggest that the modality compatibility effect is based on crosstalk of central processing codes due to ideomotor "backward" linkages between the anticipated response effects and the stimuli indicating this response. This crosstalk is increased in the tactile-auditory stimulus group compared to the visual-auditory stimulus group due to a higher degree of ideomotor-compatibility in the tactile-manual tasks. Since crosstalk arises between tasks, performance is only affected in task switching and not in single tasks.


Maternal thyroid hormones during pregnancy, childhood adiposity and cardiovascular risk factors: the Generation R Study.
Variation in maternal thyroid function during early pregnancy may permanently affect childhood growth and cardiovascular development. We examined the associations of early pregnancy maternal TSH and free T4 (FT4) levels with childhood growth, body composition and cardiovascular characteristics. We performed a population-based prospective cohort study among 5646 mothers and their children. Maternal thyroid parameters were assessed in early pregnancy (median: 13·2 weeks; 95% range: 9·7-17·6 weeks). Childhood growth was repeatedly measured from birth to 6 years. At the age of 6 years, childhood body mass index (BMI), total body and abdominal fat distribution, blood pressure and left ventricular mass were measured. Maternal thyroid parameters were not consistently associated with childhood length and weight growth characteristics. Lower maternal TSH levels were associated with lower childhood BMI, total fat mass, abdominal subcutaneous fat mass area and diastolic blood pressure (P-values <0·05), but not with preperitoneal abdominal fat mass area, systolic blood pressure or left ventricular mass. Higher maternal FT4 levels were associated with lower childhood BMI, abdominal subcutaneous and preperitoneal fat mass area (P for trends <0·05), but not with other cardiovascular characteristics. Clinically maternal hypothyroid or hyperthyroid statuses were not associated with childhood growth, body fat or cardiovascular outcomes. Maternal thyroid function during early pregnancy may influence childhood body composition and cardiovascular development. Further studies are needed to replicate these findings and to examine the influence of maternal thyroid hormone levels during pregnancy on long-term growth and cardiovascular development in the offspring.


Mixing particle softness in a two-dimensional hopper: Particle rigidity and friction enable variable arch geometry to cause clogging.
Understanding the clogging of mixtures of soft and rigid particles flowing through hoppers becomes important as soft particle usage increases in consumer products. We investigate this clogging under varying particle size and rigid fraction by quantifying various properties of arches formed in the neck of a quasi-two-dimensional hopper. As more soft particles are added to the mixture, the arch tends to become both narrower and more curved. This effect arises from the fact that soft particles have less ability to sustain a clog than rigid particles. The clogging probability is seen to have a linear correlation with the span (width) of the arch. The angles between the arch particles are shown to have higher values as rigid fraction increases. The arch occasionally shows a partially convex shape at high rigid fractions when rigid particles are sitting next to each other, while soft particles can form angles of less than 180^{∘} only. The relation between the span and aspect ratio (width to height) of the arch is theoretically formulated for three-particle arches and extended to arches of more than three particles, using an asymptotic parameter that represents the width of a flat arch. Finally, it is concluded that clogging probability closely correlates with both the arch span and the variation of other geometric arch properties.


Investigation of the presence and role of calmodulin and other mitogens in human burn blister fluid.
It is unclear whether burn blister fluid is beneficial or deleterious to the healing of the underlying wound. We investigated the calcium binding protein calmodulin in human burn blister fluid and its role in the mitogenicity of this fluid in the culture of human keratinocytes, fibroblasts, and mouse 3T3 fibroblasts. Calmodulin levels in blister fluid were three times greater than in serum (p < 0.005), whereas epidermal growth factor and platelet-derived growth factor concentrations were significantly lower (p < 0.001). Calmodulin in blister fluid was biochemically identified after affinity chromatography, Western blotting, and immunostaining with a monoclonal antibody. Inhibiting calmodulin with either an antagonist or antibody to calmodulin reduced the mitogenic activity of blister fluid in three cell types by 26% to 80%. These in vitro studies suggest that burn blister fluid may promote wound healing, and locally released calmodulin contributes to this effect. In appropriate cases it may be beneficial to leave burn blisters intact.


Dual electrode stimulation using the nucleus CI24RE cochlear implant: electrode impedance and pitch ranking studies.
The first aim of the study was to determine the reduction in electrode impedances using dual electrode stimulation compared with single electrode stimulation in the new Nucleus CI24RE receiver-stimulator. The CI24RE is connected to the Nucleus 22-electrode intracochlear array. Dual electrode stimulation is produced by electrically coupling two adjacent single electrodes. The second aim was to determine whether dual electrode stimulation produced pitch percepts that were intermediate to the pitch of the two adjacent single electrodes. Eight postlingually hearing-impaired adults with severe to profound loss, implanted with the CI24RE, participated in the study. Electrode impedances were measured by using the standard telemetry function of the system. A pitch ranking task was used to measure pitch for dual and single electrodes. Seven sets of three electrodes along the electrode array were tested. Each set of electrodes consisted of a dual electrode and the two adjacent single electrodes. Pitch ranking was measured using a two-alternative forced choice procedure, with the three electrodes in each set paired with each other as AB and BA pairs. The subject indicated which of the two stimuli had the higher pitch. Random variation in current level was used to remove any loudness cues. The average electrode impedance was 38.6% lower for dual electrodes compared with single electrodes. Three subjects were able to successfully rank the three electrodes in each set in the expected tonotopic order for all seven sets of electrodes along the array. Three other subjects were able to rank sets of electrodes in the tonotopic order for most of the tested positions on the array. The remaining two subjects gave more variable pitch ranking across positions along the array, although successful tonotopic ranking was demonstrated for several sets of electrodes. Dual electrode stimulation with the CI24RE receiver-stimulator produced systematically lower electrode impedances and was capable of producing pitch percepts that were intermediate to those produced by the corresponding adjacent single electrodes. This makes available up to 43 channels of stimulation from 22 single electrodes.


admixr-R package for reproducible analyses using ADMIXTOOLS.
We present a new R package admixr, which provides a convenient interface for performing reproducible population genetic analyses (f3, D, f4, f4-ratio, qpWave and qpAdm), as implemented by command-line programs in the ADMIXTOOLS software suite. In a traditional ADMIXTOOLS workflow, the user must first generate a set of text configuration files tailored to each individual analysis, often using a combination of shell scripting and manual text editing. The non-tabular output files then need to be parsed to extract values of interest prior to further analyses. Our package simplifies this process by automating all low-level configuration and parsing steps, making analyses as simple as running a single R command. Furthermore, we provide a set of R functions for processing, filtering and manipulating datasets in the EIGENSTRAT format. By unifying all steps of the workflow under a single R framework, this package enables the automation of analytic pipelines, significantly improving the reproducibility of population genetic studies. The source code of the R package is available under the MIT license. Installation instructions, reference manual and a tutorial can be found on the package website at https://bioinf.eva.mpg.de/admixr. Supplementary data are available at Bioinformatics online.


Nanoparticle assembly modulated by polymer chain conformation in composite materials.
Mixing nanoparticles into a strategically selected polymer matrix yields nanocomposites with well-controlled microstructures and unique properties and functions. The modulation of nanoparticle assembly by polymer chain conformation can play a dominant role in determining nanocomposite structures, yet such a physical mechanism remains largely unexplored. We hypothesize that highly ordered microdomains of rigid linear polymers provide a template for nanoparticle assembly into open fractal structures. We conducted mesoscopic computer simulations and physical experiments to elucidate how polymer chain conformation regulates the dynamic evolution of nanoparticle structures during the drying processing of polymer nanocomposite films. The evaporation of polymer-nanoparticle mixtures with varying chain stiffnesses was simulated using dissipative particle dynamics. The formation of distinguished nanoparticle assemblies as a result of matrix selection was further corroborated by probing nanoparticle aggregation in different polymer nanocomposite coatings. The results show that polymer conformation not only influences the dispersion states of individual particles (dispersed vs. aggregated), but also modulates the morphologies of large-scale assembly (globular vs. fractal). The emergence of nematically ordered polymer clusters when the chain rigidity is increased creates local solvent-rich "voids" that promote anisotropic particle aggregates, which then percolate into open fractal structures upon solvent evaporation. The nanoparticle dynamics also exhibits an intriguing non-monotonic behavior attributed to the transitions between the coupling and decoupling with polymer dynamics. The nanoparticle assembly morphologies obtained in simulations match well with the electron microscopy images taken in physical experiments.


Human keratinocyte migration on type IV collagen. Roles of heparin-binding site and alpha 2 beta 1 integrin.
The migration of human keratinocytes is an early and important event in the re-epithelialization of cutaneous wounds. Type IV collagen, a ubiquitous basement membrane component, promotes keratinocyte migration. In this study, we sought to identify specific sites within the type IV collagen molecule that induce keratinocyte locomotion and to characterize the cell surface receptors involved. We first examined purified fragments of the type IV collagen molecule as substrates for keratinocytes in a phagokinetic migration assay. We then tested several synthetic peptides derived from the triple-helical region of type IV collagen, as well as antibodies against specific integrin subunits, for their ability to either support or inhibit keratinocyte migration on matrices of both type IV collagen and relevant peptide derivatives. Keratinocytes migrated on the triple-helical fragment to the same extent as they did on the native type IV collagen. The amino-terminal 7S and the carboxy-terminal NC1 regions of type IV collagen failed to support keratinocyte migration. In addition, Hep III peptide was active both in inhibiting keratinocyte migration on type IV collagen and in serving as a substrate matrix for migration. Peptide containing the amino acid sequence RGD did not influence cell migration on type IV collagen. A specific monoclonal antibody against the alpha 2 beta 1 integrin receptor significantly inhibited keratinocyte migration on matrices of both type IV collagen and Hep III peptide. Keratinocyte migration on type IV collagen involves the interaction of the alpha 2 beta 1 receptor with the Hep III region of the type IV collagen molecule.


Molecular cytogenetic analysis of genome structure in Lupinus angustifolius and Lupinus cosentinii.
Molecular cytogenetic analysis of Lupinus angustifolius and Lupinus cosentinii was performed using flow cytometry, fluorescence in situ hybridisation (FISH) and differential chromosome staining. Genome size was determined as 2.07 pg for L. angustifolius and 1.54 pg for L. cosentinii. Analysis of nuclear DNA amount in cells during plant development has shown endopolyploidisation in different organs. The highest level of endopolyploidy was in cotyledons and reached 32C in L. angustifolius and 64C in L. cosentinii. Both of the investigated Lupinus species belong to the polysomatic type of plants. Double FISH with rDNA probes provided chromosomal landmarks for 10 out of 40 chromosomes for L. angustifolius and 8 out of 32 chromosomes for L. cosentinii. In L. angustifolius, the number and localisation of 25S rDNA hybridisation signals precisely corresponded to the chromomycin A3 (CMA(+)) bands, while in L. cosentinii both 25S and 5S rDNA loci overlapped with CMA(+) bands. Silver staining revealed that only 45S rRNA genes located in secondary constriction regions were transcriptionally active. FISH with Arabidopsis-type telomeric arrays revealed the presence of signals at termini of all chromosomes. Despite the application of different DNA probes for FISH and different chromosome staining, a relatively small proportion of chromosomes in the Lupinus karyotypes can be distinguished. Identification of all chromosomes requires the use of more chromosome-specific markers.


[Hearing damage caused by workplace noise among patients given audiometry tests in general practice].
The objective of the present study was to identify the prevalence of hearing damage caused by workplace noise among patients presenting hearing loss and among those given audiometry tests at primary health care centres in the Management Area no. 5 Costa del Ponent. The study is descriptive and synchronic. The study was carried out at primary health care level, at the audiometry test services in the Management Area no. 5 Costa del Ponent. 2,366 audiometry tests were carried out over a period of three months. A study was performed of 1,152 patients presenting the conditions necessary for inclusion in the study: age over 16 years and presenting a hearing loss greater than 30 dB over any frequencies. All the participants were given a questionnaire investigating the risk factors involved in their hearing difficulty, in particular those relating to the workplace. FIGURES AND PRINCIPAL RESULTS: 269 (23.4%) of those in the study present hearing curves compatible with hearing loss due to noise. 501 participants declared themselves to be subject to work' place noise, and of those 247 (49.3%) present hearing curves compatible with hearing loss due to noise. The results of the study suggests that the health system should pay attention to workplace pathology and points out the need to develop action programmes which may permit an adequate response to the problem: specific systems should be established for detection of and information about workplace diseases, together with sufficient support at different levels of attendance to make such systems effective; training programmes should be set up for health workers in the area of workplace health for health workers.


Glomerular cells and macrophages in the progression of experimental focal and segmental glomerulosclerosis.
To determine the characteristics of glomerular cell involvement in experimental focal and segmental glomerulosclerosis (FGS) in rats induced by repeated injections of aminonucleoside of puromycin (PAN) and protamine sulfate (PS), glomeruli were isolated and grown in tissue culture. When compared with saline controls the FGS rats had decreased rates of glomerular attachment and significantly reduced outgrowths of type 1 (epithelial) and type II (mesangial) cells. However, the FGS rats had greater numbers of type III cells (macrophages) present in the outgrowths than controls. The production of interleukin-1 (IL-1) in the glomerular culture supernatant, measured by thymocyte stimulating activity, was determined at various stages throughout the evolution of FGS and in saline controls. The FGS glomeruli early in the disease course (day 10) had higher levels of IL-1 activity than glomerular outgrowths from control rats but significantly lower levels of IL-1 were produced late in the disease (day 80). Glomerular macrophages were present throughout the evolution of the disease but in greater numbers early (day 10). In this experimental model of FGS, IL-1 production, has been demonstrated early in the disease process, could originate from macrophages and/or mesangial cells, and could be involved in the progressive glomerulosclerosis.


Controlling rabies through a multidisciplinary, public health system in Trujillo, La Libertad, Peru.
Rabies remains endemic in Peru. In 1983, Latin America and the Caribbean promised to eliminate canine-transmitted rabies from the continent. This led to Peru introducing a multidisciplinary public health system for controlling and managing rabies across the country. The system consists of mass canine vaccination campaigns, post exposure prophylaxis and monitoring aggressor animals for signs of rabies. The Peruvian city of Trujillo, La Libertad, is an urban area where dogs are the principal reservoir for rabies. The disease burden of rabies in Trujillo, La Libertad is currently minimal, with no rabies cases in humans for over 10 years, and only three canine cases. No human deaths due to rabies have occurred for several decades. From this it can be inferred that antirabies systems such as this do have real effects in reducing cases of human rabies at a grass roots level.


Impact of the COVID-19 Pandemic on Surgical Education and Training: A Resident Survey in a Developing Country.
Background The COVID-19 pandemic has adversely affected medical education and training programs worldwide. Early investigations have shown that surgical residents face a lot of challenges in these unprecedented times. This study aims to assess the impact of the COVID-19 pandemic on surgical education and training in a developing country. Methods This cross-sectional study was conducted in Allied Hospitals of Rawalpindi Medical University, Rawalpindi, Pakistan from June 2021 to July 2021. A structured questionnaire designed by the researchers was distributed to all surgery departments, and surgical residents who consented to participate in this study were included. Results A total of 152 residents participated in this study, of which 53 (34.9%) were in general surgery and 99 (65.1%) in various surgical allied specialties. Of the residents, 14.5% reported full transfer from the parent unit to the COVID-19 unit. An increase in emergency surgical procedures was reported by 52.8% of general surgery residents as compared to surgical allied specialties (P = 0.037). Of the residents, 90.1% reported increased stress and anxiety levels, with the number of allied residents significantly higher than general surgery residents (P = 0.031). A total of 125 (82.2%) respondents claimed that fear of contracting the virus affected proper patient evaluation. Conclusion The COVID-19 pandemic has severely impacted the training and psychological well-being of surgical residents.


Calorie restriction and glucose regulation.
Ketogenic diets (KDs) are effective treatments for epilepsy. The mechanisms of action are poorly understood. In some experimental seizure models, calorie restriction and hypoglycemia may augment the antiseizure effects of KDs. In addition, inhibiting glycolysis or diverting glucose from the glycolytic pathway inhibits seizures and possibly epileptogenesis, suggesting an interaction between energy regulation and the anticonvulsant actions of these interventions. Children on KDs frequently exhibit poor weight gain and have lower blood glucose levels compared to children on standard, balanced diets. Young rodents on a KD also exhibit slow weight gain, lower blood glucose and insulin levels, and elevated leptin levels. This review considers the possibility that calorie restriction, low serum glucose, and KDs share common cell signaling pathways to alter brain excitability. AMP-activated protein kinase (AMPK) is an attractive candidate signaling protein that could link energy balance to gene expression in such a way so as to reduce brain excitability.


Auxological and biochemical assessment of short stature.
Measurements of height and calculation of height velocity are highly accurate and sensitive to changes in a child's health. Definition of normality must be based on height velocity, and it is not acceptable to label a child as short and normal purely on the basis of a biochemical test unless this is substantiated with the demonstration of a normal height velocity. Response to therapy is dependent on the child's pretreatment growth rate and also on the amount of GH administered and the frequency of administration.


The impact of psychiatric diagnosis on length of stay in a university medical center in the managed care era.
Inpatient use data were examined for fiscal years 1999-2001. Patients with and without psychiatric diagnoses were compared for length of hospital stay and complexity of illness. Patients with psychiatric disorders represented 33%-35% of total cases. Substance use (9,824 cases), mood disorders (2,524 cases), and cognitive disorders (2,362 cases) were the most common psychiatric illnesses. Patients with substance use disorders or no psychiatric diagnosis had the shortest adjusted length of stay, whereas the small number with adjustment disorders (N=147) had the longest. Other psychiatric patients had lengths of stay between these extremes. Excepting substance use disorders, increased lengths of stay with psychiatric comorbidity have persisted into the managed care era.


[ABDOMINAL WALL BLOCKS FOR POST CESAREAN DELIVERY ANALGESIA].
Intrathecal morphine administration at the time of neuraxial anesthesia performance is the gold standard for post-cesarean delivery (CD) analgesia. When intrathecal morphine administration is inappropriate or contraindicated, the use of systemic analgesic options increase side effects and risks to both the parturient and the breastfeeding neonate. Moreover, systemic analgesia is often inadequate. The increased clinical use of ultrasound has made way for regional analgesia techniques, mostly in the form of local anesthesia injected between muscular planes. The transversus abdominis plane (TAP) block is the most well-known and the most commonly used for Cesarean delivery. It has been shown to be effective in the absence of intrathecal morphine administration. It has however, not been shown to be beneficial when intrathecal morphine has been administered. Other, newer techniques are being increasingly used and investigated. Some may prove to be superior to the TAP block. These techniques include: ilioinguinal/ilio-hypogastric nerve blocks (II-IH), the quadratus lumborum (QL) blocks and the erector spinae plane (ESP) block. In this review, we will discuss and assess these techniques regarding analgesia following CD.


The efficient persistence and migration of Cupriavidus gilardii T1 contribute to the removal of MCPA in laboratory and field soils.
The application of exogenous biodegradation strains in pesticide-polluted soils encounters the challenges of migration and persistence of inoculants. In this study, the degradation characteristics, vertical migration capacity, and microbial ecological risk assessment of an enhanced green fluorescent protein (EGFP)-tagged 2-Methyl-4-chlorophenoxyacetic acid (MCPA)-degrading strain Cupriavidus gilardii T1 (EGFP) were investigated in the laboratory and field soils. The optimum remediation conditions for T1 (EGFP) was characterized in soils. Meanwhile, leaching experiments showed that T1 (EGFP) migrated vertically downwards in soil and contribute to the degradation of MCPA at different depths. After inoculation with T1 (EGFP), a high expression levels of EGFP gene was observed at 28 d in the laboratory soil and at 45 d in the field soil. The degradation rates of MCPA were ≥ 60% in the laboratory soil and ≥ 48% in the field soil, indicating that T1 (EGFP) can efficiently and continuously remove MCPA in both laboratory and field conditions. In addition, the inoculation of T1 (EGFP) not only showed no significant impact on the soil microbial community structure but also can alleviate the negative effects induced by MCPA to some extent. Overall, our findings suggested that T1 (EGFP) strain is an ecologically safe resource for the in situ bioremediation of MCPA-contaminated soils.


Mechanical properties of cellulose fibres and wood. Orientational aspects in situ investigated with synchrotron radiation.
Highly oriented native cellulose fibres (flax) and softwood (pine) have been investigated by means of X-ray diffraction. Local structural information was obtained by using X-ray microbeams. Tensile tests were performed in situ, revealing a change of orientation of cellulose microfibrils in materials with tensile strain. In flax fibres, the microfibrils rotate during the first percent of stretching, into a more parallel orientation with respect to the fibre axis. For wood, a decrease of orientation with the onset of strain hardening is found for the first time.


[Ultrasound diagnosis of the liver and gallbladder (author's transl)].
Ultrasound echography has proved a non-invasive, reproducible, harmless and, for the patient, not burdensome technique for the diagnosis of diseases of the liver and bile ducts in the right upper abdomen. Diffuse changes of the organs and disease of the bile ducts as well as cystic or tumorous solid changes in the upper abdomen are the main spheres of sonography. The use of "grey value" techniques has increased the efficiency of compound ultrasound examinations. We can expect further improvements with digital computerised evaluation of signals.


Fast growth conditions uncouple the final stages of chromosome segregation and cell division in Escherichia coli.
Homologous recombination between the circular chromosomes of bacteria can generate chromosome dimers. They are resolved by a recombination event at a specific site in the replication terminus of chromosomes, dif, by dedicated tyrosine recombinases. The reaction is under the control of a cell division protein, FtsK, which assembles into active DNA pumps at mid-cell during septum formation. Previous studies suggested that activation of Xer recombination at dif was restricted to chromosome dimers in Escherichia coli but not in Vibrio cholerae, suggesting that FtsK mainly acted on chromosome dimers in E. coli but frequently processed monomeric chromosomes in V. cholerae. However, recent microscopic studies suggested that E. coli FtsK served to release the MatP-mediated cohesion and/or cell division apparatus-interaction of sister copies of the dif region independently of chromosome dimer formation. Here, we show that these apparently paradoxical observations are not linked to any difference in the dimer resolution machineries of E. coli and V. cholerae but to differences in the timing of segregation of their chromosomes. V. cholerae harbours two circular chromosomes, chr1 and chr2. We found that whatever the growth conditions, sister copies of the V. cholerae chr1 dif region remain together at mid-cell until the onset of constriction, which permits their processing by FtsK and the activation of dif-recombination. Likewise, sister copies of the dif region of the E. coli chromosome only separate after the onset of constriction in slow growth conditions. However, under fast growth conditions the dif sites separate before constriction, which restricts XerCD-dif activity to resolving chromosome dimers.


Endoscopically harvested stem cells: a putative method in future autotransplantation.
The discovery of stem cells in the adult human brain and developing stem cell technology open a possible future scenario of autotransplantation, where stem cells are harvested from the patient and propagated in vitro before they are used as transplants. The objectives of this study were: 1) to investigate the feasibility of harvesting tissue containing neural stem cells by endoscopy; 2) to study the possibility of propagating and multiplying stem cells from this tissue efficiently in vitro; and 3) to examine whether the stem cells differentiate into functional neurons. In 13 patients with hydrocephalus undergoing routine neurosurgical procedures, we used an endoscope and a 3-mm biopsy forceps (Medtronic) to harvest the small piece of the ventricular wall that is detached by the introduction of the endoscope. Cells were cultured as neurospheres, and after induced differentiation, they were investigated with immunocytochemistry and whole-cell patch-clamp recordings. All cells characterized were propagated under strict clonal conditions. We found it uncomplicated to harvest the part of the lateral ventricular wall that compares with the inner lumen of the endoscope. Single cells, isolated and cultivated in vitro, multiplied to form neurospheres in a serum-free environment. A single stem cell had the potential to give rise to approximately 9 x 10(5) new cells after two passages. The total number of cells produced from a single biopsy was already, after the second passage, far beyond the number required in, for instance, Parkinson's disease. Within 1 week of induced differentiation, cells expressing markers for neurons (beta-III-tubulin or NeuN), oligodendrocytes (RIP or O4), and astrocytes (glial fibrillary acidic protein) appeared. After 3 weeks, cells with a neuronal phenotype showed a firing pattern distinctive of mature neurons, including repetitive, short-lasting, and overshooting action potentials that were blocked by inhibiting voltage-dependent Na+-channels with tetrodotoxin. These results indicate that it may be feasible to produce neural tissue for autotransplantation from endoscopically harvested stem cells, but further work is needed in refining culture protocols to control phenotype fate.


Design of dispersant structures for preparing highly concentrated one-dimensional inorganic molecular chains from V2Se9 crystals.
We studied dispersants for exfoliating bulk V2Se9 into one dimensional chain units. V2Se9, with a negative zeta potential of -30.1 mV, was acidic and strongly anchored with the amine head of octadecylamine by charge transfer reaction. The steric hindrance by the octadecyl tail promoted the dispersion of V2Se9 to the nano level.


An injectable and tumor-specific responsive hydrogel with tissue-adhesive and nanomedicine-releasing abilities for precise locoregional chemotherapy.
Locoregional chemotherapy, especially using implantable hydrogel depots to sustainably deliver chemotherapeutics at tumor site, has shown great potential for improving antitumor efficacy and reducing systemic toxicity. However, the hydrogel applications are limited by some intrinsic constraints, especially the contradiction between increasing drug penetration and accumulation in tumor and decreasing random drug diffusion into surrounding normal tissues. Herein, we report a unique "Jekyll and Hyde" nanoparticle-hydrogel (NP-gel) hybrid platform, which can keep dormant in adjacent normal tissues but be activated by mildly acidic and hyaluronidase-rich microenvironment in malignant tumor tissues to unidirectionally release tumor-targeting and penetrative doxorubicin (DOX)-loaded NPs. Apart from tumor-specific recognition, penetration, internalization and release, NP-gel features: shear-thinning behavior for injection, tissue-adhesiveness for continuous on-site activation, and full biodegradability for safe use. Precise delivery was clearly demonstrated in both tumor-grafted and tumor-resected mice. A single peritumoral injection of DOX-loaded NP-gel exhibited a significantly higher drug accumulation in tumor for 3 weeks than in nontarget organs and thus long-term tumor remission. More importantly, significant inhibition in tumor recurrence without detectable toxicity to healthy organs was demonstrated when applied after tumor resection. The designed system displayed long-acting and precise anticancer efficacy, paving the way toward effective tumor locoregional treatment. STATEMENT OF SIGNIFICANCE: Injectable hydrogels, allowing sustained drug delivery directly at tumor site, has shown great potential for locoregional chemotherapy. However, how to achieve tumor-specific drug accumulation but meanwhile impede the random drug diffusion into surrounding normal tissues remains an insurmountable challenge, especially considering high drug concentration gradient, higher interstitial fluid pressure and denser extracellular matrix in tumor than adjacent normal tissue. Herein, a 'Jekyll and Hyde' nanoparticle-hydrogel hybrid formulation was designed to keep dormant in adjacent normal tissues but be activated by mildly acidic and hyaluronidase-rich microenvironment in malignant tumor tissues to unidirectionally release tumor-targeting and penetrative DOX-loaded nanoparticles, leading to a significant tumor inhibition and antirecurrence efficiency without detectable toxicity to healthy organs, thus presenting great potential for precise locoregional chemotherapy.


[Estimation of pH-dependence of calcium binding with calmodulin].
A methodical approach to estimating calmodulin Ca(2+)-binding properties based on its interaction with highly porous watman and consequent 45Ca2+ binding was proposed. At changing pH from 6.5 until 7.5 the affinity of Ca2+ to calmodulin increases in 4.3-fold. The article displays a model of mechanism for Ca(2+)-binding with calmodulin where the dissociation of H+ from Ca(2+)-binding sites is a limited stage of the process.


Haematological parameters of laying hens under different group size.
The relevance of this study lies in its potential implications for poultry farming practices and animal welfare. Understanding the impact of group size on the blood parameters of hens can provide valuable insights for optimising their health and well-being in farming environments. The aim of the study was an analysis of haematological parameters of laying hens under the influence group size with the same stoking density in analogous cages by design. Hens were kept for 34 weeks in cages of multilevel batteries at different group sizes: I group-93 birds, II group-52 birds, III group-17 birds and IV group-9 birds. The study analysed blood samples from laying hens at 18 and 52 weeks of age. Results showed that reducing the group size from 93 to 52 birds led to a haematological status within the physiological norm, characterized by increased heterophils and decreased monocyte levels. Whereas, the decrease in group size to 17 birds was accompanied by a decrease in the hens' blood content of thrombocytes, an increase of heterophile, a decrease of monocytes and lymphocytes within the physiological norm, as well as an increase in the heterophiles to lymphocytes ratio.


Arabidopsis peroxisomes possess functionally redundant membrane and matrix isoforms of monodehydroascorbate reductase.
The H2O2 byproduct of fatty acid catabolism in plant peroxisomes is removed in part by a membrane-associated antioxidant system that involves both an ascorbate peroxidase and a monodehydroascorbate reductase (MDAR). Despite descriptions of 32-kDa MDAR polypeptides in pea and castor peroxisomal membranes and cDNA sequences for several 'cytosolic' MDARs, the genetic and protein factors responsible for peroxisomal MDAR function have yet to be elucidated. Of the six MDAR polypeptides in the Arabidopsis proteome, named AtMDAR1 to AtMDAR6 in this study, 47-kDa AtMDAR1 and 54-kDa AtMDAR4 possess amino acid sequences that resemble matrix (PTS1) and membrane peroxisomal targeting signals, respectively. Epitope-tagged versions of these two MDARs and a pea 47-kDa MDAR (PsMDAR) sorted in vivo directly from the cytosol to peroxisomes in Arabidopsis and BY-2 suspension cells, whereas AtMDAR2 and AtMDAR3 accumulated in the cytosol. The PTS1-dependent sorting of AtMDAR1 and PsMDAR to peroxisomes was incomplete (inefficient?), but was improved for PsMDAR after changing its PTS1 sequence from -SKI to the canonical tripeptide -SKL. A C-terminal transmembrane domain and basic cluster of AtMDAR4 were necessary and sufficient for targeting directly to peroxisomes. MDAR activity in isolated Arabidopsis peroxisomes was distributed among both water-soluble matrix and KCl-insoluble membrane subfractions that contained respectively 47- and 54-kDa MDAR polypeptides. Notably, a 32-kDa MDAR was not identified. Combined with membrane association and topological orientation findings, these results indicate that ascorbate recycling in Arabidopsis (and probably other plant) peroxisomes is coordinated through functionally redundant MDARs that reside in the membrane and the matrix of the organelle.


Reliability of a new ultrasonic cardiac output monitor in recipients of living donor liver transplantation.
The ultrasonic cardiac output monitor (USCOM) is a new Doppler device for noninvasive hemodynamic monitoring. The aim of this prospective nonrandomized study was to test the feasibility, perioperative reliability, and clinical applicability of using USCOM as an alternative to pulmonary artery catheterization in recipients of living donor liver transplantation. Thirteen patients scheduled to receive living donor liver transplants were initially recruited. Three were subsequently excluded prior to the commencement of surgery because of technical difficulties in obtaining diagnostic-quality images with USCOM. Ten patients proceeded to be studied. Cardiac output measurements by thermodilution and USCOM were compared at 30-minute intervals throughout the procedure and at 10 specific procedural reference points during the surgery when hemodynamic changes were most likely to be observed. The data were analyzed with Lin's concordance coefficient and Bland-Altman analysis. Two hundred ninety paired cardiac output values were obtained from the 10 patients. The concordance between both methods was excellent in 8 patients and satisfactory in 2. Bland-Altman analysis of all data produced a mean bias of - 0.02 L/minute for USCOM, and the 95% limits of agreement were -1.06 to +1.10 L/minute. Further analysis of the 10 reference time points showed minimal bias and high levels of agreement between the methods. We conclude that USCOM provides an accurate and noninvasive method for cardiac output measurement during liver transplantation. It may therefore represent an alternative to pulmonary artery catheter placement with consequent reduction in patient's risk and morbidity associated with catheterization. Liver Transpl 14:1029-1037, 2008. (c) 2008 AASLD.


Phylogenetic evidence for the existence of novel thermophilic bacteria in hot spring sulfur-turf microbial mats in Japan.
So-called sulfur-turf microbial mats, which are macroscopic white filaments or bundles consisting of large sausage-shaped bacteria and elemental sulfur particles, occur in sulfide-containing hot springs in Japan. However, no thermophiles from sulfur-turf mats have yet been isolated as cultivable strains. This study was undertaken to determine the phylogenetic positions of the sausage-shaped bacteria in sulfur-turf mats by direct cloning and sequencing of 16S rRNA genes amplified from the bulk DNAs of the mats. Common clones with 16S rDNA sequences with similarity levels of 94.8 to 99% were isolated from sulfur-turf mat samples from two geographically remote hot springs. Phylogenetic analysis showed that the phylotypes of the common clones formed a major cluster with members of the Aquifex-Hydrogenobacter complex, which represents the most deeply branching lineage of the domain bacteria. Furthermore, the bacteria of the sulfur-turf mat phylotypes formed a clade distinguishable from that of other members of the Aquifex-Hydrogenobacter complex at the order or subclass level. In situ hybridization with clone-specific probes for 16S rRNA revealed that the common phylotype of sulfur-turf mat bacteria is that of the predominant sausage-shaped bacteria.


Leave-taking experiences in the lives of abused women.
The World Health Organization identifies domestic violence as a major health crisis confronting women across the globe. The addition of women's voices about their abusive experiences increases understandings of domestic violence. In this phenomenological investigation of the coping strategies of abused women, 17 women provided meaningful insights into how, why, and when they left abusive relationships. Timing, selection of support systems, and intuition add new descriptions about abused women's leave-taking experiences. Implications for nursing practice include the use of helpful questioning and employment of the advocacy role. Based on thefindings of this study, more research is called for that allows abused women to demonstrate the variety of their experiences with the leave-taking process.


An updated review on the role of prescribed exercise in the management of Amyotrophic lateral sclerosis.
Introduction: Amyotrophic Lateral Sclerosis is a group of sporadic or familial disorders, characterized by upper and lower motor neuron involvement, with variable progression.Areas covered: The authors present the role of exercise in counteracting muscle disuse, particularly on limb weakness, that might antagonize denervation. The persistence of inactivity can affect many systems and the patient can develop deconditioning, muscle joint tightness, which causes contractures and pain. The main area of the review is the evaluation of the studies done on ALS exercise rehabilitation protocols, this was done by the evaluation of outcome function and patient independence exerting a positive psychological impact on both patients and caregivers. A second target is underlying differences between endurance and resistance exercise protocols, which may throw light on the biological mechanism of skeletal muscle repair, functional performance, and metabolism. The authors present not only exercise trials but also molecular biomarkers that might help define changes induced by physical rehabilitation. Our findings might help to achieve the best rehabilitation program. A standardized rehabilitation protocol is important: the instructed patients may continue therapy at home or be followed by telemedicine.Expert opinion: This review evaluates exercise rehabilitation, a controversial issue, evidence is weak and non-conclusive but represents the art status.


Artificial intelligence and placental DNA methylation: newborn prediction and molecular mechanisms of autism in preterm children.
Autism Spectrum Disorder (ASD) represents a heterogeneous group of disorders with a complex genetic and epigenomic etiology. DNA methylation is the most extensively studied epigenomic mechanism and correlates with altered gene expression. Artificial intelligence (AI) is a powerful tool for group segregation and for handling the large volume of data generated in omics experiments. We performed genome-wide methylation analysis for differential methylation of cytosine nucleotide (CpG) was performed in 20 postpartum placental tissue samples from preterm births. Ten newborns went on to develop autism (Autistic Disorder subtype) and there were 10 unaffected controls. AI including Deep Learning (AI-DL) platforms were used to identify and rank cytosine methylation markers for ASD detection. Ingenuity Pathway Analysis (IPA) to identify genes and molecular pathways that were dysregulated in autism. We identified 4870 CpG loci comprising 2868 genes that were significantly differentially methylated in ASD compared to controls. Of these 431 CpGs met the stringent EWAS threshold (p-value <5 × 10-8) along with ≥10% methylation difference between CpGs in cases and controls. DL accurately predicted autism with an AUC (95% CI) of 1.00 (1-1) and sensitivity and specificity of 100% using a combination of 5 CpGs [cg13858611 (NRN1), cg09228833 (ZNF217), cg06179765 (GPNMB), cg08814105 (NKX2-5), cg27092191 (ZNF267)] CpG markers. IPA identified five prenatally dysregulated molecular pathways linked to ASD. The present study provides substantial evidence that epigenetic differences in placental tissue are associated with autism development and raises the prospect of early and accurate detection of the disorder.


Resolving the Rules of Robustness and Resilience in Biology Across Scales.
Why do some biological systems and communities persist while others fail? Robustness, a system's stability, and resilience, the ability to return to a stable state, are key concepts that span multiple disciplines within and outside the biological sciences. Discovering and applying common rules that govern the robustness and resilience of biological systems is a critical step toward creating solutions for species survival in the face of climate change, as well as the for the ever-increasing need for food, health, and energy for human populations. We propose that network theory provides a framework for universal scalable mathematical models to describe robustness and resilience and the relationship between them, and hypothesize that resilience at lower organization levels contribute to robust systems. Insightful models of biological systems can be generated by quantifying the mechanisms of redundancy, diversity, and connectivity of networks, from biochemical processes to ecosystems. These models provide pathways towards understanding how evolvability can both contribute to and result from robustness and resilience under dynamic conditions. We now have an abundance of data from model and non-model systems and the technological and computational advances for studying complex systems. Several conceptual and policy advances will allow the research community to elucidate the rules of robustness and resilience. Conceptually, a common language and data structure that can be applied across levels of biological organization needs to be developed. Policy advances such as cross-disciplinary funding mechanisms, access to affordable computational capacity, and the integration of network theory and computer science within the standard biological science curriculum will provide the needed research environments. This new understanding of biological systems will allow us to derive ever more useful forecasts of biological behaviors and revolutionize the engineering of biological systems that can survive changing environments or disease, navigate the deepest oceans, or sustain life throughout the solar system.


Metoprolol, a beta-1 selective blocker, can be used safely in coronary artery disease patients with chronic obstructive pulmonary disease.
The coexistence of coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD) is frequent because of common etiological factors. Beta-blockers remain underutilized in patients with CAD who also have COPD. This study was performed to evaluate the safety of beta-1 selective blocker agents in CAD patients with COPD. Fifty patients (aged 57.3 +/- 10.1 years) were enrolled in this study; 27 patients received metoprolol CR (controlled release), and 23 received metoprolol (conventional). The patients were stratified according to the severity of COPD (21 severe, 21 moderate, and 8 mild), started on metoprolol CR or conventional metoprolol, and titrated up to the maximum tolerated dose. The clinical controls were done during the first week and then at the first and third month. Patients received a mean total daily dose of 92.5 +/- 18 mg of metoprolol CR or 189 +/- 36.7 mg of metoprolol. Seven patients could not receive the maximum dose. There was no significant decrease in forced expiratory volume in 1 s (FEV(1)) in either group (basal vs last FEV(1): 54.5% +/- 13.4% vs 54.3% +/- 13% in the metoprolol CR group and 49.6% +/- 14.5% vs 53.2% +/- 12.8% in the metoprolol group). No adverse event was experienced. Metoprolol, a beta-1 selective blocker, can be used safely at the maximum dose in CAD patients with COPD.


Nimesulide inhibits tumor growth in mice implanted hepatoma: overexpression of Bax over Bcl-2.
To investigate whether nimesulide could suppress tumor growth and induce apoptosis in implanted hepatoma mice and to explore the molecular mechanisms. Male mice received nimesulide 10 mg/kg, 20 mg/kg, and 40 mg/kg ig daily for 21 d. Electron microscopy (EM), flow cytometry (FCM), DNA ladder, radioimmunoassay (RIA), and Western blot analysis were employed to investigate effect of nimesulide on mice hepatoma and the related molecular mechanisms. Nimesulide inhibited the growth of hepatoma (from 14 % to 62 %) and elicited typical apoptotic morphologic changes. The DNA ladder of high dose nimesulide was more clearly observed and apoptotic rate was 51.3 %+/-1.5 %. Nimesulide also decreased cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and Bcl-2 expression, while increased the level of Bax protein. Nimesulide suppresses tumor growth and induces apoptosis by inhibiting COX-2 and PGE2 expression, which may be related to overexpression of Bax over Bcl-2.


Comparative study between standard and inside-out vein graft techniques on sciatic nerve repair of rats. Muscular and functional analysis.
To compare the functional result of standart vein grafts and inside-out vein graft technique on sciatic nerve repair. We used 24 male Wistar rats divided into 4 groups: control group (CG), standard vein graft group (SVG), Inside-out vein graft group (IOVG) and denervated Group (DG). SVG, IOVG and DG underwent total section of the sciatic nerve, SVG and IOVG however underwent nerve repair surgery using a graft with normal jugular vein and inside-out jugular vein, respectively. Histological analysis of the soleus and Extensor Digitorum Longus (EDL), and Sciatic Functional Index were used to compare the results after 6 weeks. Both grafts acted favorably in muscle recovery and improved functionality; They were similar in all parameters, however, in more points SVG achieved similar to the CG, in the other hand IOVG more times was similar to DG. Fact that makes the graft with normal vein the most viable option between the two options. Both types of grafts acted beneficially wherein the graft normal vein has proved to be the best option.


Recurrent anterior shoulder instability: Review of the literature and current concepts.
The purpose of this review article is to discuss the clinical spectrum of recurrent traumatic anterior shoulder instability with the current concepts and controversies at the scientific level. Because of increasing participation of people from any age group of the population in sports activities, health care professionals dealing with the care of trauma patients must have a thorough understanding of the anatomy, patho-physiology, risk factors, and management of anterior shoulder instability. The risk factors for recurrent shoulder dislocation are young age, participation in high demand contact sports activities, presence of Hill-Sachs or osseous Bankart lesion, previous history of ipsilateral traumatic dislocation, ipsilateral rotator cuff or deltoid muscle insufficiency, and underlying ligamentous laxity. Achieving the best result for any particular patient depends on the procedure that allows observation of the joint surfaces, provides the anatomical repair, maintains range of motion, and also can be applied with low rates of complications and recurrence. Although various surgical techniques have been described, a consensus does not exist and thus, orthopedic surgeons should follow and try to improve the current evidence-based treatment modalities for the patients.


Molecular identification of Trichinella spiralis nudix hydrolase and its induced protective immunity against trichinellosis in BALB/c mice.
Nudix hydrolases (Nd) is a widespread superfamily, which is found in all classes of organism, hydrolyse a wide range of organic pyrophosphates and has a 'housecleaning' function. The previous study showed that Trichinella spiralis Nd (TsNd) bound to intestinal epithelial cells (IECs), and the vaccination of mice with T7 phage-displayed TsNd polypeptides produced protective immunity. The aim of this study was to clone, express and identify the full-length TsNd and to investigate its immune protection against T. spiralis infection. The full-length cDNA sequence of TsNd gene encoding a 46 kDa protein from T. spiralis intestinal infective larvae (IIL) was cloned and identified. The antigenicity of rTsNd was analyzed by Western blot. Transcription and expression of TsNd at T. spiralis different stages were observed by RT-PCR and IFT. The levels of the specific total IgG, IgG1 and IgG2a antibodies to rTsNd were determined by ELISA. The immune protection of rTsNd against T. spiralis infection was investigated. Sequence and phylogenetic analysis revealed that TsNd had a nudix motif located at 226-244aa, which had high homology and the closest evolutionary status with T. pseudospiralis. The rTsNd was obtained after expression and purification. Western blot analysis showed that anti-rTsNd serum recognized the native TsNd protein in crude antigens of muscle larvae (ML), IIL, adult worms (AW) and newborn larvae (NBL), and ES antigens of ML. Transcription and expression of TsNd gene was observed in all developmental stages of T. spiralis (ML, IIL, AW and NBL), with high level expression in IIL. An immunolocalization analysis identified TsNd in the cuticle, stichocytes and reproductive organs of the parasite. Following immunization, anti-rTsNd IgG levels were increased, and the levels of IgG1 were more significantly higher than that of IgG2a. After a challenge infection with T. spiralis, mice immunized with the rTsNd displayed a 57.7% reduction in adult worms and a 56.9% reduction in muscle larval burden. TsNd induced a partial protective immunity in mice and could be considered as a novel candidate vaccine antigen against trichinellosis.


[The central vein catheterization. 2. Procedure, step by step].
Several approaches exist for central vein catheterization. Mastery of the various steps of this procedure and understanding of the basics of asepsis are critical to prevent any complication. They also built the basis for an exhaustive communication with the patient, to obtain an informed consent. This article can in addition be used to develop a checklist in order to (self-)assess competence in procedural skills.