KLF4 overexpression decreases the viability, invasion and migration of papillary thyroid cancer cells.
Kruppel-like factor 4 (KLF4) has been implicated in a number of different types of cancer; however, the role of KLF4 in papillary thyroid cancer remains elusive. The present study aimed to investigate the role of KLF4 in papillary thyroid cancer and its potential underlying molecular mechanisms. The expression of KLF4 in thyroid tumor tissue and adjacent non-cancerous tissues were detected via immunohistochemistry and western blotting. The papillary thyroid cancer cell line, KTC1, was transfected with viruses carrying KLF4 overexpression vectors. The relative expression of KLF4, E-cadherin, N-cadherin, Vimentin, matrix metalloproteinase (MMP)2, MMP9 and collagen was detected via quantitative-PCR. The viability of KTC1 cells was detected using a cell counting kit-8 assay at 24, 48 and 72 h. Cell invasion was examined via a transwell invasion assay. Cell migration was examined via a scratch migration assay at 0 and 24 h. Compared with adjacent non-cancerous tissues, the expression of KLF4 was significantly lower in thyroid tumor tissues. The expression of KLF4 in KTC1 cells were significantly increased compared with the blank or negative control groups. The expression of N-cadherin, MMP2, MMP9 and collagen was significantly decreased in the KLF4 overexpression group. The viability of KTC1 cells was markedly decreased in KLF4 overexpression group at 24, 48 and 72 h when compared with the blank or negative control groups. The invasion of KTC1 cells in the KLF4 overexpression group was markedly decreased. Compared with the negative control group, the KTC1 cell migration in the KLF4 overexpression group was markedly decreased at 24 h. The expression of KLF4 was also significantly lower in thyroid tumor tissues. The cell viability, tumor invasion and migration ability and expression levels of N-cadherin, MMP2, MMP9 and collagen in papillary thyroid cancer cells were markedly decreased with KLF4 overexpression.


Sepsis causes right ventricular myocardial inflammation independent of pulmonary hypertension in a porcine sepsis model.
Right ventricular (RV) myocardial dysfunction is a common feature in septic shock. It can worsen outcome, but the etiology is poorly understood. Pulmonary artery hypertension (PAH) plays a part in the pathogenesis of the right heart dysfunction in sepsis but its importance is unknown. In pigs, PAH in sepsis is substantial and the translational value of porcine sepsis models therefore questioned. We hypothesized that porcine sepsis causes a myocardial inflammatory response which leads to myocardial dysfunction independent of PAH. Sepsis was induced by Escherichia coli-infusion in 10 pigs resulting in PAH and increased right ventricular pressure (RVP). The same degree of RVP was achieved by external pulmonary artery banding (PAB) in a consecutive series of 6 animals. Sepsis, but not PAB, led to increase in endothelial damage marker PAI-1 and cytokines TNF and IL-6 (all p<0.05) in plasma. In myocardium, TNF and IL-6 were significantly elevated in sepsis, TNF in both ventricles and IL-6 mostly in RV, while IL-1β, IL-18 and C5a were significantly higher in RV compared to LV after PAB (all p<0.05). Myocardial mRNA levels of IL-1β, IL-6, IL-18, IP-10, E-selectin and PAI-1 were significantly elevated in RV and LV during sepsis compared to PAB, while Caspase-1 was decreased in septic compared to PAB animals (all p<0.05). Cathepsin L activity was increased in RV by PAB, while sepsis inhibited this response. Escherichia coli-induced sepsis caused myocardial inflammation independent of PAH. Prominent PAH should therefore not exclude porcine sepsis models to further our understanding of human sepsis.


Total Spinal Anesthesia Following an Interscalene Block Treated with Intravenous Lipid Emulsion.
Total spinal anesthesia following interscalene block is a rare and life-threatening complication of regional anesthesia. A 56-year-old woman underwent an uncomplicated left shoulder bone spur removal under general anesthesia with an interscalene nerve block at an outpatient surgical center. Subsequently, she developed bilateral mydriasis, paralysis of all extremities, and respiratory arrest. She was intubated and transferred to the emergency department (ED) where she was given intravenous lipid emulsion (ILE) with complete recovery of neurological function. ILE therapy may be considered as a rescue treatment in addition to supportive therapy for total spinal anesthesia.


Time independent description of rapidly oscillating potentials.
The classical and quantum dynamics in a high frequency field are found to be described by an effective time independent Hamiltonian. It is calculated in a systematic expansion in the inverse of the frequency (omega) to order omega(-4). The work is an extension of the classical result for the Kapitza pendulum, which was calculated in the past to order omega(-2). The analysis makes use of an implementation of the method of separation of time scales and of a quantum gauge transformation in the framework of Floquet theory. The effective time independent Hamiltonian enables one to explore the dynamics in the presence of rapidly oscillating fields, in the framework of theories that were developed for systems with time independent Hamiltonians. The results are relevant, in particular, for exploring the dynamics of cold atoms.


[The expression of TfR1 mRNA and IRP1 mRNA in the placenta from different maternal iron status].
To investigate the mRNA expression of transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) in the full-term placenta from different maternal iron status, and explore the mechanism of placental iron transport and regulation. The mRNA level of TfR1 and IRP1 in full-term placentae was detected by reverse transcription polymerase chain reaction (RT-PCR) in normal group (N), iron deficiency group (ID) and iron deficiency anemia group (IDA). (1) The expression of TfR1 mRNA in N group was 0.4813 +/- 0.1891, in ID group was 0. 6647 +/- 0.2788, and in IDA group was 0.9767 +/- 0.2858. There was significant difference between IDA group and N group or ID group (t = 0.002, P < 0.01 or t = 0.028, P < 0.05), and was no difference between ID group and N group (t = 0.117, P > 0.05). (2) The expression of IRP1 mRNA in N group was 0.2616 +/- 0.0785, in ID group was 0.3696 +/- 0.1801, and in IDA group was 0.3971 +/- 0.0902 and was no difference among the three groups (F = 1.845, P = 0.179). The expression of TfR1 mRNA is increased when maternal iron deficiency progressed while there is no change in the expression of IRP1 mRNA in the placentae of TfR1 mRNA indicated that IRP1 takes part in the regulation of placenta iron transport.


Detailed diffraction imaging of x-ray optics crystals with synchrotron radiation.
Rocking curve topography at the Advanced Photon Source's beamline 1-BM measures the x-ray reflection from large (many cm2) flat crystals on a sub-mm scale with microradian angular resolution. The (011̄1) reflection at 8 keV is uniform across the crystal and close to theory for three thick quartz wafers well-polished with increasingly finer grit. However, the reflection is non-uniform for some ∼0.1 mm thin, bendable crystals that are made flat by optical contact with a flat substrate. These thin crystals are bent to serve in certain x-ray diagnostics of plasmas, and similar non-uniformities could then occur in bent crystals as well. The same detail in x-ray reflection in bent crystals is unachievable with the existing topography setup: One way to get the desired resolution is with a standard microfocusing approach.


Non-targeted effects of virus-induced gene silencing vectors on host endogenous gene expression.
Virus-induced gene silencing (VIGS) uses recombinant viruses to study gene function; however, the effect of the virus vector itself on the gene expression of the host is not always considered. In our work, we investigated non-targeted gene expression changes of the host in order to see how often these changes appear. Effects of various VIGS vector infections were analysed by monitoring gene expression levels of housekeeping genes by Northern blot analysis in four different hosts. We found that non-targeted changes happens very often. More importantly, these non-targeted effects can cause drastic changes in the gene-expression pattern of host genes that are usually used as references in these studies. We have also found that in a tobacco rattle virus (TRV)-based VIGS, the presence of foreign sequences in the cloning site of the vector can also have a non-targeted effect, and even the use of an internal control can lead to unpredicted changes. Our results show that although VIGS is a very powerful technique, the VIGS vector, as a pathogen of the host, can cause unwanted changes in its gene-expression pattern, highlighting the importance of careful selection of both the genes to be tested and those to be used as references in the planned experiments.


Phytochemical Screening and Antibacterial Activities of Aqueous and Alcoholic Extracts of Averrhoa bilimbi Leaf against Bacteria Isolated from Oral Cavity.
Medicinal herbs have been used as traditional treatments for many pathogens and extracted bioactive compounds from medicinal plants with a suitable therapeutic index for the production of new drugs. Moreover, they are utilized to evaluate different concentrations of aqueous and alcoholic extracts of Averrhoa bilimbi leaves and antibiotics against bacteria isolated from the oral cavity. This study was conducted simultaneously at the Departments of Botany and Biology, Shatrah Hospital, Thi-Qar, Iraq, during March and August 2021. A. bilimbi leaf extracts were utilized in the plant component examination and the assessment of the antibacterial activity. The bacterial strain of Escherichia coli and Klebsiella pneumoniae was isolated from the oral cavity. To test the antibacterial impact of the extracts on bacteria, the agar well diffusion method was used. The phytochemical screening indicated the presence of Alkaloids, Flavonoids, Sapiens, Steroids, Tannins, Glycosides, and Carbohydrates, followed by the absence of Tannins in aqueous extract. Due to the A. bilimbi leaf aqueous and methanol extract against E. coli, areas of inhibition were found (0.20 cm and 0.19 cm) at the concentration of 100 mg/ml, respectively. However, there were no regions of inhibition of the K. pneumoniae trend for both extracts. The sensitivity of bacterial isolates of E. coli and K. pneumonia to antibiotics was also tested through Gentamicin, Amoxycillin, Azithromycin, Ciprofloxacin, Penicillin, and Polymyxin B, and the regions of inhibition appeared against E. coli (0.5cm, 0 cm, 0.34 cm, 0.45 cm, 0 cm, and 0.12 cm, respectively). Furthermore, the regions of inhibition appeared against K. pneumoniae (3 cm, 0.3 cm, 0.4 cm, 0.55 cm, 0 cm, 0.66 cm, respectively). The antibiotics showed a higher inhibition zone, compared to the aqueous and alcoholic extracts; however, further studies are required to be conducted to validate its reliability.


Peto's Paradox: how has evolution solved the problem of cancer prevention?
The risk of developing cancer should theoretically increase with both the number of cells and the lifespan of an organism. However, gigantic animals do not get more cancer than humans, suggesting that super-human cancer suppression has evolved numerous times across the tree of life. This is the essence and promise of Peto's Paradox. We discuss what is known about Peto's Paradox and provide hints of what is yet to be discovered.


Air-dispersed aquatic microorganisms show establishment and growth preferences in different freshwater colonisation habitats.
We attempted to mimic aeolian ecosystems to examine how filters posed by regional characteristics can influence the establishment and growth of airborne microcolonisers of a common air source. Using a natural single source of aerosols we applied a combined microscopy and high-throughput sequencing approach to examine the diversity, settling and growth potential of air-dispersed microbes in water containers representing newly formed aquatic colonisation habitats of different trophic states and salinity. Heterotrophic microeukaryotes were favoured as initial settlers when nutrients were low, while autotrophs rapidly proliferated in the high-nutrient containers, possibly due to favourable germinating conditions for their preferred mode of dispersal with resting spores. Following settling of colonisers, we investigated two contrasting hypotheses: if the different water colonisation habitats harboured the same microbial communities after establishment and growth periods, this would point towards a selection of best-fit cosmopolitan colonisers, regardless of habitat-specific characteristics. Alternatively, community dissimilarities after the growth period would suggest a selection of settlers due to bottom-up controls combined with priority effects. Both analyses suggested that the structure of the microbial communities in the different colonisation habitats were driven by nutrient content and salinity, showing clustering to similar bottom-up forces and dissimilarities in significantly different colonisation habitats.


Outcomes of cementless fixation in medial unicompartmental knee arthroplasty: review of recent literature.
Medial unicompartmental knee arthroplasty (UKA) is considered the most effective treatment for anteromedial knee osteoarthritis. Cementless fixation of UKA was developed to reduce aseptic loosening. We performed a review of the recent literature to assess the latest outcomes of cementless UKA. A review of English literature was performed on Medline through Pubmed. Retrospective or prospective studies with at least 2 years of follow-up (FU) and at least 20 patients were included. The PRISMA 2009 flowchart and checklist were considered to edit the review. Survival rate, revision rate, time for revision, incidence of radiolucent lines and reasons for revision (such as aseptic loosening, osteoarthritis progression, bearing dislocation or periprosthetic fracture) were extrapolated from the papers. Nineteen articles were included in the review, only 2 with a level of evidence of I. A total of 3432 UKA with a FU range of 24-132 months were analyzed. The studies showed good clinical and functional outcomes. In 12 studies, survival rate were more than 90%. Revision rate for aseptic loosening were lower than 2% for 15 studies. Cementless UKA represents a surgical option allowing low revision rate. Further high-quality long-term studies would better clarify complications, clinical and radiological results of this promising fixation method.


Early Aggressive Hydration Hastens Clinical Improvement in Mild Acute Pancreatitis.
Early aggressive intravenous hydration is recommended for acute pancreatitis treatment although randomized trials have not documented benefit. We performed a randomized trial of aggressive vs. standard hydration in the initial management of mild acute pancreatitis. Sixty patients with acute pancreatitis without systemic inflammatory response syndrome (SIRS) or organ failure were randomized within 4 h of diagnosis to aggressive (20 ml/kg bolus followed by 3 ml/kg/h) vs. standard (10 ml/kg bolus followed by 1.5 mg/kg/h) hydration with Lactated Ringer's solution. Patients were assessed at 12-h intervals. At each interval, in both groups, if hematocrit, blood urea nitrogen (BUN), or creatinine was increased, a bolus of 20 ml/kg followed by 3 ml/kg/h was given; if labs were decreased and epigastric pain was decreased (measured on 0-10 visual analog scale), hydration was then given at 1.5 ml/kg/h and clear liquid diet was started. The primary endpoint, clinical improvement within 36 h, was defined as the combination of decreased hematocrit, BUN, and creatinine; improved pain; and tolerance of oral diet. The mean age of the patients was 45 years and only 14 (23%) had comorbidities. A higher proportion of patients treated with aggressive vs. standard hydration showed clinical improvement at 36 h: 70 vs. 42% (P=0.03). The rate of clinical improvement was greater with aggressive vs. standard hydration by Cox regression analysis: adjusted hazard ratio=2.32, 95% confidence interval 1.21-4.45. Persistent SIRS occurred less commonly with aggressive hydration (7.4 vs. 21.1%; adjusted odds ratio (OR)=0.12, 0.02-0.94) as did hemoconcentration (11.1 vs. 36.4%, adjusted OR=0.08, 0.01-0.49). No patients developed signs of volume overload. Early aggressive intravenous hydration with Lactated Ringer's solution hastens clinical improvement in patients with mild acute pancreatitis.


Hemodynamic effects of inosine in combination with positive and negative inotropic drugs: studies on rats in vivo.
Inosine applied as a continuous i.v. infusion of 400 mg/kg/h for 20 min had a negative chronotropic and inotropic effect in closed-chest, anesthetized rats. In the presence of adenosine deaminase (ADA, 133 U/kg/h), the reduction in heart rate was abolished indicating that adenosine is responsible for that effect. However, the negative inotropic effect persisted. It was characterized by a 38 and 56% decrease in left ventricular systolic pressure (LVSP) and diastolic aortic pressure, respectively, a 24% decline in LV dp/dtmax and a 16% fall in cardiac output. Total peripheral resistance was diminished by 38%. Inosine in combination with ADA antagonized the noradrenaline-induced positive inotropic effect and the increase in cardiac output. On the other hand, i.v. bolus injection of noradrenaline in rats pretreated with inosine and ADA did not increase blood pressure and total peripheral resistance. Inosine administered in animals pretreated with the beta-receptor blocker metoprolol or with the calcium antagonist verapamil aggravated the negative inotropic effect. Inosine in combination with ADA caused a decline in cardiac output in metoprolol-pretreated rats that was more pronounced than that induced by inosine alone. However, in rats pretreated with verapamil, inosine did not cause a reduction in cardiac output.


Acute Itch Induces Attentional Avoidance of Itch-related Information.
Attention is known to modulate itch intensity. In contrast, the reverse relationship, i.e. the degree to which the presence of an acute itch affects attention, is currently not well understood. The aims of this study were to investigate whether acute itch induces an attentional bias towards or away from visual itch-related stimuli, and if so, whether it occurs in the early or later stages of processing. A volunteer sample of 60 healthy individuals were subjected to a skin prick (either histamine or placebo), followed by completion of a spatial cueing paradigm using itch-related and neutral words as cues, in order to obtain reaction time estimates of attentional bias. The results suggest that experience of acute itch induces attentional avoidance of visual itch threats. This attentional avoidance occurs at a later processing stage in the form of facilitated disengagement of attention from itch and/or delayed disengagement from neutral information.


Advancing CH4/H2 separation with covalent organic frameworks by combining molecular simulations and machine learning.
A high-throughput computational screening approach combined with machine learning (ML) was introduced to unlock the potential of both synthesized and hypothetical COFs (hypoCOFs) for adsorption-based CH4/H2 separation. We studied 597 synthesized COFs for adsorption of a CH4/H2 mixture using Grand Canonical Monte Carlo (GCMC) simulations under pressure-swing adsorption (PSA) and vacuum-swing adsorption (VSA) conditions. Based on the simulation results, the CH4/H2 selectivities, CH4 working capacities, adsorbent performance scores, and regenerabilities of the synthesized COFs were assessed and the structural properties of the top-performing COFs were identified. The hypoCOF database composed of 69 840 materials was then filtered to identify 7737 hypothetical materials having similar structural properties to the top synthesized COFs. These hypothetical COFs were then examined for CH4/H2 separation using molecular simulations and the results showed that the top hypoCOFs have CH4 selectivities and working capacities in the ranges of 21.9-28.7 (64.7-128.6) and 5.8-7.6 (1.3-3.1) mol kg-1 under PSA (VSA) conditions, respectively, outperforming the synthesized COFs and metal-organic frameworks (MOFs). ML models were then developed based on the hypoCOF simulation results to accurately predict the CH4/H2 mixture adsorption properties of all remaining hypothetical materials when their structural and chemical properties are fed into the models. These models accurately assessed the CH4/H2 mixture separation performances of any hypoCOF within seconds without performing computationally demanding molecular simulations. The computational approach that we have proposed in this study will provide an accurate and efficient assessment of COF materials for CH4/H2 separation and significantly accelerate the experimental efforts towards the design and discovery of new high-performing COF adsorbents.


[Right ventricular myxoma in a child: an uncommon presentation].
The right ventricle is an uncommon location for cardiac myxoma. Its most common complications are pulmonary embolism and obstruction due to pulmonary valve tumor. We report the case of a 11-year old child with repetitive syncopes admitted to Cardiology ward. Echocardiography showed a right ventricular myxoma of 2cm obstructing the pulmonary orifice. Emergency surgical excision was performed under cardiopulmonary bypasss with favorable postoperative course. Anatomo-pathological examination of the surgical specimen confirmed the diagnosis of myxoma. At 18 months follow-up, there was no evidence of tumor recurrence.


Aptasensors: employing molecular probes for precise medical diagnostics and drug monitoring.
Accurate detection and monitoring of therapeutic drug levels are vital for effective patient care and treatment management. Aptamers, composed of single-stranded DNA or RNA molecules, are integral components of biosensors designed for both qualitative and quantitative detection of biological samples. Aptasensors play crucial roles in target identification, validation, detection of drug-target interactions and screening potential of drug candidates. This review focuses on the pivotal role of aptasensors in early disease detection, particularly in identifying biomarkers associated with various diseases such as cancer, infectious diseases and cardiovascular disorders. Aptasensors have demonstrated exceptional potential in enhancing disease diagnostics and monitoring therapeutic drug levels. Aptamer-based biosensors represent a transformative technology in the field of healthcare, enabling precise diagnostics, drug monitoring and disease detection.


Media exposure predicts children's reactions to crime and terrorism.
In this study we examined reactions to 3 news events (September 11 terrorist attacks, Summer 2002 kidnappings, and Fall 2002 sniper shootings) in a national, representative sample of children aged 2 to 17. Media exposure was related to increased worry and changes in activities, with September 11 creating the most concern and shootings the least. More signs of stress were apparent among 10- to 13-year-olds, minority children and those of low socioeconomic status, children with prior adversities, and children who lived in close geographical proximity. Girls aged 10 to 17 had more reaction to the kidnappings, suggesting that other features of target similarity may heighten a sense of risk. The results support moderating exposure for both younger and older youth.


On the discovery of cementum.
Though cementum of the tooth root is critical for periodontal structure and tooth attachment and function, this tissue was not discovered and characterized on human teeth until a full century later than enamel and dentin. Early observations from the seventeenth to the nineteenth centuries by Marcello Malpighi, Antonie van Leeuwenhoek, Robert Blake, Jacques Tenon and Georges Cuvier founded a confusing and conflicting nomenclature that obscured the nature of cementum, often conflating it with bone. Advances in microscopy and histological procedures yielded the first detailed descriptions of human cementum in the 1830s by Jan Purkinje and Anders Retzius, who identified for the first time acellular and cellular types of cementum, and the resident cementocytes embedded in the latter. Comparative anatomy studies by Richard Owen and others over the latter half of the nineteenth century identified coronal and radicular cementum varieties across the Reptilia and Mammalia. The functional importance of cementum was not appreciated until detailed anatomical studies of the periodontium were performed by G.V. Black and others in the late nineteenth and early twentieth centuries. These early studies on cementum laid the foundation for more advanced understanding of cementum ultrastructure, composition, development, physiology, disease, genetics, repair and regeneration throughout the twentieth and into the twenty-first century.


Modulation of Cortisol Responses to an Acute Stressor in Zebrafish Visually Exposed to Heterospecific Fish During Development.
Studies regarding predator-prey relationships have often focused on prey assessment and the responses to predation risk, but few have verified the relationship in the presence or absence of visual contact with a predator (e.g., tiger oscar, Astronotus ocellatus) or a nonpredator (e.g., goldfish, Carassius auratus) during the developmental phase, which could alter several physiological and neuroendocrine mechanisms in adulthood. Herein, we determined responses to physical (chasing with a net) and biological stressors (visualization to predator) in adult zebrafish raised in visual contact with a predator or nonpredator fish. We demonstrated that adult naive zebrafish show a more intense cortisol stress response than fish housed in visual contact with the stimulus fish (predator or nonpredator) when larvae, and that this alteration is related with movement specificity of the stimulus fish.


Effect of abiotic factors on the unique glitter-like iridescence of Cellulophaga lytica.
Iridescence is a property of structural color that has been poorly documented in the prokaryotic kingdom. We recently isolated a Cellulophaga lytica strain that exhibits, on solid media, a unique intense glitter-like iridescence in reflection. Iridescence of C. lytica CECT 8139 was optically and physically characterized but physiological significance of the phenomenon was not. In the present work, we investigated the effect of key abiotic factors on C. lytica's growth and iridescence. Special attention was paid to conditions that mimic rocky shore ecosystem, the natural biotope of C. lytica. We found that C. lytica's iridescence required the presence of seawater. The phenomenon was not influenced by light exposure or plate orientation during growth. Cellulophaga lytica's iridescence occurred under a wide range of culture conditions notably under psychrophilic, halophilic, and hydric stress conditions. Changes in colonies' colors (blue, violet, red, yellow, and green) were linked to cell density. These data indicate that iridescence is induced under conditions that mimic the natural biotope of C. lytica.


Does subanesthetic isoflurane affect the ventilatory response to acute isocapnic hypoxia in healthy volunteers?
Differences in results studying the effects of subanesthetic concentrations of volatile agents on the hypoxic ventilatory response may be related to the conditions under which the subjects were tested. In this study we investigated the effects of 0.1 minimum alveolar concentration (MAC) of isoflurane on the hypoxic ventilatory response without and with audiovisual stimulation. Step decreases in arterial hemoglobin oxygen saturation from normoxia into hypoxia (arterial hemoglobin oxygen saturation 80% +/- 2%; duration of hypoxia 5 min) were performed in ten healthy subjects. We obtained four responses per subject: one without isoflurane in a darkened, quiet room; one without isoflurane with audiovisual input (music videos); one in a darkened room at 0.1 MAC isoflurane; and one at 0.1 MAC isoflurane with audiovisual input (subjects were addressed to keep their eyes open). Experiments were performed against a background of isocapnia (end-tidal carbon dioxide tension 1-1.4 mmHg above initial resting values). The hypoxic responses averaged 0.54 +/- 0.09 1.min-1.%-1 (without isoflurane in a darkened, quiet room), 0.27 +/- 0.06 l-min-1.%-1 (in a darkened room at 0.1 MAC isoflurane; P < 0.01), 0.56 +/- 0.131.min-1.%-1 (without isoflurane with audiovisual input), and 0.47 +/- 0.13 l.min-1.%-1 (at 0.1 MAC isoflurane with audiovisual input). Values are means +/- SE. During 0.1 MAC isoflurane administration, all subjects showed a depressed hypoxic response when not stimulated, while with stimulation two subjects had an increased response, four a decreased response and four an unchanged response compared to control. We observed an important effect of the study conditions on the effects that 0.1 MAC isoflurane has on the hypoxic ventilatory response. A depressant effect of subanesthetic isoflurane was found only when external stimuli to the subjects were absent. With extraneous audiovisual stimuli the effect of isoflurane on the response to hypoxia was more variable. On the average, however, the response then was not depressed by isoflurane.


Anthrax lethal toxin and tumor necrosis factor-α synergize on intestinal epithelia to induce mouse death.
Bacillus anthracis (B. anthracis) lethal toxin (LT) is a determinant of lethal anthrax. Its function in myeloid cells is required for bacterial dissemination, and LT itself can directly trigger dysfunction of the cardiovascular system. The interplay between LT and the host responses is important in the pathogenesis, but our knowledge on this interplay remains limited. Tumor necrosis factor-α (TNF) is a pleiotropic pro-inflammatory cytokine induced by bacterial infections. Since LT accumulates and cytokines, predominantly TNF, amass during B. anthracis infection, co-treatment of TNF+LT in mice was used to mimic in vivo conditions for LT to function in inflamed hosts. Bone marrow transplantation and genetically engineered mice showed unexpectedly that the death of intestinal epithelial cells (IECs) rather than that of hematopoietic cells led to LT+TNF-induced lethality. Inhibition of p38α mitogen-activated protein kinase (MAPK) signaling by LT in IECs promoted TNF-induced apoptosis and necroptosis of IECs, leading to intestinal damage and mouse death. Consistently, p38α inhibition by LT enhanced TNF-mediated cell death in human colon epithelial HT-29 cells. As intestinal damage is one of the leading causes of lethality in anthrax patients, the IEC damage caused by LT+TNF would most likely be a mechanism underneath this clinical manifestation and could be a target for interventions.


Bipedality in chimpanzee (Pan troglodytes) and bonobo (Pan paniscus): testing hypotheses on the evolution of bipedalism.
A host of ecological, anatomical, and physiological selective pressures are hypothesized to have played a role in the evolution of hominid bipedalism. A referential model, based on the chimpanzee (Pan troglodytes) and bonobo (Pan paniscus), was used to test through experimental manipulation four hypotheses on the evolution of hominid bipedalism. The introduction of food piles (Carry hypothesis) increased locomotor bipedality in both species. Neither the introduction of branches (Display hypothesis) nor the construction of visual barriers (Vigilance hypothesis) altered bipedality in either species. Introduction of raised foraging structures (Forage hypothesis) increased postural bipedality in chimpanzees. These experimental manipulations provided support for carrying of portable objects and foraging on elevated food-items as plausible mechanisms that shaped bipedalism in hominids.


Expression of Ki67, BCL-2, and COX-2 in canine cutaneous mast cell tumors: association with grading and prognosis.
The expression of Ki67, BCL-2, and COX-2 was investigated in 53 canine cutaneous mast cell tumors (MCTs) by immunohistochemistry and quantitative real time polymerase chain reaction (qPCR) to evaluate their prognostic significance and the association with the histologic grading and the mitotic index (MI). MCTs were graded according to the Patnaik grading system and the novel 2-tier grading system proposed by Kiupel. The numbers of mitotic figures/10 high-power fields (MI) were counted. Both grading systems were significantly associated with prognosis. The Patnaik grading was of limited prognostic value for grade 2 MCTs, with 23% being associated with mortality. The concordance among pathologists was strongly improved by the application of the 2-tier grading system, and 71% of high-grade MCTs were associated with a high mortality rate. MI and Ki67 protein expression were significantly associated with grading and survival. No significant association between BCL-2 protein expression and either grading system or health status was observed. BCL-2 mRNA expression was significantly higher in grade 2 than in grade 1 MCTs, while no statistically significant differences were detected between low- and high-grade MCTs. The increased BCL-2 mRNA level was significantly associated with increased mortality rate. The COX-2 protein expression was detected in 78% of the MCTs investigated. However, neither association with the tumor grade nor with the health status was observed. COX-2 mRNA was significantly up-regulated in MCTs compared to surgical margins and control skin tissue, but it was neither associated with tumor grade nor with survival.


[The classification of aneurysms of the cerebral arteries].
Brain aneurysms are generally subdivided into so-called congenital and acquired (atherosclerotic, embolic and others). This classification does not reflect the reality as more than twenty brain aneurysms of different origin are already known. The classification suggested by the author is grounded on two interconnected features--etiology and pathogenesis--and uses also the term "bifurcation-hemodynamic aneurysms" (instead of so-called congenital aneurysms). This term reflects current understanding of aneurysm etiology and allows one to overcome the psychological barrier which prevented to create a rational classification.


Macrocycle peptides delineate locked-open inhibition mechanism for microorganism phosphoglycerate mutases.
Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode iPGM to select and enrich lariat-like ligands from an mRNA-display macrocyclic peptide library containing >1012 members. Functional analysis of the ligands, named ipglycermides, demonstrates sub-nanomolar inhibition of iPGM with complete selectivity over dPGM. The crystal structure of an iPGM macrocyclic peptide complex illuminated an allosteric, locked-open inhibition mechanism placing the cyclic peptide at the bi-domain interface. This binding mode aligns the pendant lariat cysteine thiolate for coordination with the iPGM transition metal ion cluster. The extended charged, hydrophilic binding surface interaction rationalizes the persistent challenges these enzymes have presented to small-molecule screening efforts highlighting the important roles of macrocyclic peptides in expanding chemical diversity for ligand discovery.


Expression of a cDNA encoding the wheat CM16 protein in Escherichia coli.
The wheat kernel CM16 protein, a subunit of the heterotetrameric insect alpha-amylase inhibitor that has been involved in the technological quality of wheat-products, was produced in Escherichia coli. Cloning of the cDNA part encoding the mature protein in a pET expression plasmid, under the control of a promoter for the bacteriophage T7 RNA polymerase, allows the synthesis of large amounts of the CM16 protein in the bacteria. Upon induction with isopropyl thiogalactopyranoside the recombinant protein accumulates in insoluble inclusion bodies. Solubilization with 6 M urea containing 0.5 mM dithiothreitol, followed by slow elimination of the denaturing agents by step dialysis, results in a significant recovery of the recombinant protein in a soluble, monomeric form. Characterization of the protein was done by automated Edman degradation and total amino acid determination. The recombinant protein in comparison with the one isolated from wheat exhibits a Met extension at the N-terminus that was introduced in the construction for translation initiation. The CM16 protein produced in this manner has the advantage over wheat purified protein of not being contaminated with other proteins from the same family and constitutes adequate material for further analysis of the technological properties of the protein in wheat-derived products.


Long-term treatment of chronic schizophrenics with clopenthixol decanoate.
A study was carried out in 68 chronic schizophrenic out-patients to assess the therapeutic effectiveness and tolerance of long-term maintenance treatment with a depot preparation of clopenthixol decanoate. Patients received 200 mg to 600 mg doses by intramuscular injection every 2 to 3 weeks for a mean treatment period of 20.3 months. Clinical symptomatology was assessed at regular intervals using the Brief Psychiatric Rating Scale (BPRS) and any adverse effects were recorded against a standard check-list. The results showed that there was a significant reduction in total and factor composition BPRS scores after treatment in all patients, the improvement becoming generally evident by the sixth month of treatment. Few autonomic and neurological side-effects were reported.


Experiences of intimate partner violence and related injuries among women in Yokohama, Japan.
We estimated rates of intimate partner violence and related injuries in a sample of 1371 women aged 18 to 49 years in Yokohama, Japan. By the age of 30 years, 14.3% of women who had ever had a partner had experienced violence from that partner, and 3.3% had suffered injuries related to such violence. By the time women had reached the age of 49 years, these percentages were 19% and 4%, respectively. In addition to the need for increased prevention efforts, our findings indicate the need for an expanded legal definition of intimate partner violence in Japan given that the current definition excludes premarital violence.


Atypical angioma serpiginosum.
Angioma serpiginosum is an uncommon, acquired vascular nevoid disorder with capillary dilation and proliferation in the papillary dermis. The eruptions are asymptomatic and characterized by grouped, erythematous to violaceous, serpiginous and punctate macules. The condition usually appears in females during adolescence on unilateral lower extremities and the buttocks. We report a rare case with a late onset and atypical distribution of lesions in a 48-year-old female patient who had groups of punctate lesions on her left foot for four to five years. Histopathological examination showed hyperkeratosis and multiple dilated and proliferated capillaries in the papillary dermis. Inflammation and extravasation of red blood cells were not found. According to the clinical and pathological findings, we established a diagnosis of angioma serpiginosum. She was treated with a pulsed dye laser, and the angiomatous lesions subsequently improved.


A randomized trial of the effectiveness of the neutropenic diet versus food safety guidelines on infection rate in pediatric oncology patients.
The neutropenic diet (ND) is prescribed to avoid introduction of bacteria into a host's gastrointestinal tract and reduce infection. Due to a lack of evidence to support the ND, there continues to be debate among pediatric oncologists regarding its usefulness. This prospective randomized controlled trial evaluated the difference in neutropenic infection rates in pediatric oncology patients randomized to Food and Drug Administration approved food safety guidelines (FSGs) versus the ND plus FSGs during one cycle of chemotherapy. Pediatric patients receiving cancer treatment with myelosuppressive chemotherapy were eligible. Neutropenic infection was the primary outcome and defined as (i) fever with neutropenia or (ii) hospital admission and treatment for clinical infection and neutropenia. The rate of neutropenic infection was compared with Student's t-test for independent samples. Documented infections were identified by comprehensive chart review and compared between groups using a χ2 test. One hundred fifty patients were randomly assigned to FSGs (n = 73) or ND + FSGs (n = 77). The most common diagnoses were acute lymphoblastic leukemia (32%) and sarcoma (32%). There was no significant difference between the groups in the percentage of patients who developed neutropenic infection: FSGs 33% versus ND + FSGs 35% (P = 0.78). Patients randomized to ND + FSGs reported that following the diet required more effort than those on FSGs alone. The ND offers no benefit over FSGs in the prevention of infection in pediatric oncology patients undergoing myelosuppressive chemotherapy and adherence requires more effort for patients and families. Institutions caring for children with cancer should consider replacing ND guidelines with FSGs.


Angular remodeling in single stent-assisted coiling displaces and attenuates the flow impingement zone at the neck of intracranial bifurcation aneurysms.
Self-expanding intracranial stent-assisted coiling of bifurcation aneurysms has recently been shown to straighten target cerebral vessels, a phenomenon with unknown hemodynamic effect. To investigate the impact of angular remodeling in aneurysms treated with single stent-assisted coiling with the use of computational fluid dynamic techniques. Fourteen patients (7 women, mean age 55) who underwent stent coiling of 14 wide-necked bifurcation aneurysms were included based on the availability of high-resolution 3-dimensional rotational angiography. Pretreatment data sets underwent virtual aneurysm removal to isolate the effect of stenting. Wall shear stress and pressure profiles obtained from constant flow input computational fluid dynamic analysis were analyzed for apical hemodynamic changes. Stenting increased the bifurcation angle with significant straightening immediately after treatment and at follow-up (107.3° vs. 144.9°, P < .001). The increased stented angle at follow-up led to decreased pressure drop at the bifurcation apex (12.2 vs. 9.9 Pa, P < .003) and migration of the flow impingement zone (FIZ) toward the contralateral nonstented daughter branch by a mean of 1.48 ± 0.2 mm. Stent-induced angular remodeling decreased FIZ width separating peak apical wall shear stress (3.4 vs. 2.5 mm, P < .004). Analysis of FIZ distance measured from the parent vessel centerline showed it to be linearly (r = .58, P < .002) and FIZ width inversely correlated (r = .46, P < .02) to vessel bifurcation angle. Stent-induced angular remodeling significantly altered bifurcation apex hemodynamics in a favorable direction by blunting apical pressure and inducing the narrowing and migration of the FIZ, a novel response to intracranial stenting that should be added to intimal hyperplasia and flow diversion.


Bilateral posterior dislocation of the crystalline lens after a head injury sustained during a seizure.
This article presents a case of bilateral posterior dislocations of the crystalline lens in a patient with epilepsy who presented with reduced vision and anisocoria 2 weeks after having sustained head injuries during a seizure. The possibility of lens dislocation was raised only at this time, and subsequently confirmed on computed tomography. Such patients may require prompt referral to the ophthalmologist to treat complications such as functional aphakia, uveitis and more seriously pupillary block glaucoma. This case highlights the importance of ocular examination of head injuries to rule out possible ophthalmological pathology.


Continuous-flow pump model study: the effect on pump performance of pump characteristics and cardiovascular conditions.
This model study evaluates the effect of pump characteristics and cardiovascular data on hemodynamics in atrio-aortic VAD assistance. The model includes a computational circulatory sub-model and an electrical sub-model representing two rotary blood pumps through their pressure-flow characteristics. The first is close to a pressure generator-PG (average flow sensitivity to pressure variations, -0.047 l mmHg(-1)); the second is closer to a flow generator-FG (average flow sensitivity to pressure variations, -0.0097 l mmHg(-1)). Interaction with VAD was achieved by means of two interfaces, behaving as impedance transformers. The model was verified by use of literature data and VAD onset conditions were used as a control for the experiments. Tests compared the two pumps, at constant pump speed, in different ventricular and circulatory conditions: maximum ventricular elastance (0.44-0.9 mmHg cm(-3)), systemic peripheral resistance (781-1200 g cm(-4) s(-1)), ventricular diastolic compliance C p (5-10-50 cm(3) mmHg(-1)), systemic arterial compliance (0.9-1.8 cm(3) mmHg(-1)). Analyzed variables were: arterial and venous pressures, flows, ventricular volume, external work, and surplus hemodynamic energy (SHE). The PG pump generated the highest SHE under almost all conditions, in particular for higher C p (+50 %). PG pump flow is also the most sensitive to E max and C p changes (-26 and -33 %, respectively). The FG pump generally guarantees higher external work reduction (54 %) and flow less dependent on circulatory and ventricular conditions. The results are evidence of the importance of pump speed regulation with changing ventricular conditions. The computational sub-model will be part of a hydro-numerical model, including autonomic controls, designed to test different VADs.


[Present state of guidelines for perioperative management of deep vein thrombosis and pulmonary embolism in Japan].
To clarify the present state of local institutional guideline for perioperative deep thrombosis and pulmonary embolism in individual hospitals, a questionnaire was sent to anesthesia departments in Japan. According to the replies, 82 hospitals have original guidelines. Forty of them reported the contents of their guidelines. However, 37 hospitals have some problems regarding their guidelines. Cost for these perioperative managements and application of spinal or epidural anesthesia for heparinized patients appears to be commonly recognized as pending questions in their guideline. It seems to be difficult to make a stereotyped standard guideline in Japan because each local guideline has a specific strategy according to their situations. However, it is needless to say that a further nationwide survey and collaboration, and governmental support for these diseases would be required.


Randomized controlled trial of endostar combined with cisplatin/ pemetrexed chemotherapy for elderly patients with advanced malignant pleural effusion of lung adenocarcinoma.
To evaluate the clinical efficacy and safety of endostar combined with cisplatin/pemetrexed (CP) chemotherapy for elderly patients with advanced malignant pleural effusion (MPE) of lung adenocarcinoma. A total of 128 lung adenocarcinoma patients with MPE were randomly divided into two groups. Patients in the treatment group were treated with pemetrexed 500 mg/m2, i.v., d 1, cisplatin intracavitary administration with a total dose of 75 mg/m2, d 2, 5 and 8, and endostar intracavitary administration 45 mg, d 1, 4 and 7. Patients in the control group were treated with chemotherapy alone (pemetrexed and cisplatin and mode of administration were the same as for the treatment group. The effective rates (ER) of the treatment group and control group were 81.82 and 64.52%, respectively (x2=4.906, p=0.027). The MPE control rates (DCRs) were 93.94 and 79.03%, respectively (x2=6.168, p=0.013). The control rate of the treatment group was higher compared with the control group (p<0.05), especially during the first period when it was 54.55% (p=0.019); in addition, the recurrence rate was lower (9.68 vs 30.61%, p=0.005). Dyspnea, mood and overall health improved significantly in the treatment group patients. No statistically significant differences in side effects between the groups were noticed. Intracavity endostar combined with intracavitary and i.v. pemetrexed and cisplatin had a significant effect on advanced MPE of lung adenocarcinoma. In addition, the quality of life (QoL) was significantly improved and the side effects were tolerable.


Artificial matrix barriers: a diffusion study utilizing dextrans and microspheres.
Eight artificial matrices (AMs) were evaluated for the ability to restrict the passage of diffusion probes. Three AMs were composed exclusively of interstitial type I collagen (Col I) and differed from each other in thickness only. Four AMs consisted of reconstituted basement membrane (RBM) -coated polycarbonate filters (containing 10 microns diameter pores) and also only differed in thickness. One AM consisted of an uncoated 10 microns pore polycarbonate filter. The diffusion probes were uncharged fluorescein isothiocyanate-labeled dextrans, having molecular weights of 17,900, 42,000, 71,200, and 148,900 and negatively charged latex microspheres, having diameters of 0.08, 0.30, and 0.95 microns. Probes were applied to the AMs, incubated for 72 hr at 37 degrees C, and then analyzed spectrophotometrically. Dextran passage was increasingly restricted for Col I matrices as either molecular weight or collagen thickness increased (range 7% to 0.7%). Thin RBM-coated filters were more permeable to dextrans (range 100% to 30%) than Col I matrices. The diffusion rate of microspheres for Col I matrices (range 3.5% to 0) was similar to both thick and thin RBM-coated filters (range 4% to 0). The uncoated filter permitted the most diffusion for both dextrans and microspheres (range 100% to 7%). These data demonstrate that the AMs presented in this study will allow direct observation of the degradative and migratory potential of cells in vitro as they interact with various extracellular matrices.


Pharmacological potentials of Syzygium cumini: a review.
In the last few years there has been an exponential growth in the field of herbal medicine, and these drugs are gaining popularity in both developing and developed countries because of their natural origin and lesser side effects. Syzygium cumini (syn. Eugenia jambolana, Syzygium jambolana, Eugenia cumini, Syzygium jambos), commonly known as jamun in India, is an evergreen tree distributed throughout the Indian subcontinent, Southeast Asia and East Africa. It is mainly utilised as a fruit producer and for its timber. Medicinally, the fruit is reported to have antidiabetic, antihyperlipidaemic, antioxidant, antiulcer, hepatoprotective, antiallergic, antiarthritic, antimicrobial, anti-inflammatory, antifertility, antipyretic, antiplaque, radioprotective, neuropsychopharmacological, nephroprotective and antidiarrhoeal activities. Among these beneficial physiological effects, the antidiabetic property of S. cumini has the most promising nutraceutical value. The health-beneficial effects of S. cumini are mainly attributed to various phytoconstituents such as tannins, alkaloids, steroids, flavonoids, terpenoids, fatty acids, phenols, minerals, carbohydrates and vitamins present in the fruit. This review paper presents an overview of experimental evidence for the pharmacological potential of S. cumini.


Alloreactivity: the Janus-face of hematopoietic stem cell transplantation.
Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus-face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, while preserving antitumor alloreactivity. We analyzed retrospectively a predefined cohort of 32 838 such patients and compared it to 59 692 patients with autologous HSCT as reference group. We found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival (Spearman correlation coefficients of cumulative excess event rates at 5 years 0.964; P<0.00; respectively 0.976; P<0.00). We observed this systematic stepwise effect in all main disease and disease-stage categories. The results suggest that detrimental effects of alloreactivity are additive with each step of mismatching; the beneficial effects remain preserved. Hence, if there is a choice, the best match should be donor of choice. The data support an intensified search for predictive genomic and environmental factors of 'no-graft-versus-host disease'.


Top Ten Tips Palliative Care Clinicians Should Know About the Psychological Aspects of Palliative Care Encounters.
Palliative care clinicians enhance the illness experiences of patients and their families through building therapeutic relationships. Many psychological concepts underlie a clinician's approach to a specific patient. Through high-yield tips, this article highlights ten selected psychological elements that palliative care clinicians often use to support patients. As we all (both clinicians and patients) bring our own histories and unique biographies to the work of palliative care, a more explicit focus on the psychological aspects of this work can enhance our own experience and efficacy as providers. With a thoughtful focus on the psychological aspects of how we engage with patients, palliative care clinicians can offer a more meaningful therapeutic encounter.


[Spontaneous pneumothorax].
Spontaneous pneumothorax comprises app. 0.1-2 % of surgical diseases. There are four subtypes; primary, secondary, catamenial and neonatal. Aetiology of primary pneumothorax is not exactly known since there is no direct relation to any basic lung disease. Nevertheless, in most patients (80-85 %), it develops due to the rupture of an emphysematous bulla or a subpleural air bubble, i.e. blebs. On the other hand, secondary pneumothorax is a result or a complication of a verified localized or general lung disorder. Catamenial pneumothorax is a recurrent lung collapse in women at the time of menstruation. Neonatal pneumothorax is found typically in immature or premature newborns, often in association with congenital lung disorders. From the pathological point of view, it is an acute disorder of distribution of blood gasses in lungs with subsequent hypoxemia, which can be identified as an acute thoracic event. The clinical picture of pulmonary collapse is characterised by a triad of symptoms++dyspnoea, pleuritic pain and dry and non-productive cough. The diagnosis is usually determined on the base of history and after a careful clinical examination. It is then verified on lung X-ray. The objective of therapy of spontaneous pneumothorax is to restore permanent lung expansion to the original extent. Conservative treatment is chosen in the first episodes of pneumothorax with small extent and without further complications or symptoms. In the rest of cases, the surgical treatment is necessary, which includes puncture of the pleural cavity, drainage and surgical revision using videothoracoscopy or thoracotomy. In general, in case of the first episode of pulmonary collapse it is recommended to perform less radical procedure, i.e. drainage of the pleural cavity. Recurrences of the disease are indicated for surgical treatment; primarily miniinvasive procedures, in which the site of air leaking from lung parenchyma is closed and also an artificial pleural symphysis is created to prevent recurrence of the collapse. This type of procedure provides best results; recurrence is not exceeding 3%.


Clinical Scoring Systems in Predicting the Outcome of Acute Upper Gastrointestinal Bleeding; a Narrative Review.
Prediction of the outcome and severity of acute upper gastrointestinal bleeding (UGIB) has significant importance in patient care, disposition, and determining the need for emergent endoscopy. Recent international recommendations endorse using scoring systems for management of non-variceal UGIB patients. To date, different scoring systems have been developed for predicting the risk of 30-day mortality and re-bleeding. We have discussed the screening performance characteristics of Baylor bleeding score, the Rockall risk scoring score, Cedars-Sinai Medical Center predictive index, Glasgow Blatchford score, T-score, and AIMS65 systems, in the present review. Based on the results of this survey, there are only 3 clinical decision rules that can predict the outcome of UGIB patients, independent from endoscopy. Among these, only Glasgow Blatchford score was highly sensitive for predicting the risk of 30-day mortality and re-bleeding, simultaneously.


Statistical rate theory determination of water properties below the triple point.
We report a new method for determining the saturation vapor pressure, Ps(T), of water at conditions below its triple point. Ps(T) appears as a parameter in the statistical rate theory (SRT) expression for the net evaporation flux. We use measurements of the interfacial conditions during steady-state evaporation and condensation experiments and SRT to determine the values of Ps(T) from 50 different experiments over a range of interfacial conditions. From these values of Ps(T), we develop an analytical expression and from it calculate the liquid-vapor latent heat, Llv(T), and the constant pressure specific heat, cp(L)(T). The calculated values of these properties are compared with those obtained from independent measurements. This comparison indicates the SRT expressions for Llv(T) and cp(L)(T) are consistent with the measurements over a range of temperatures.


A particular phenotype in a girl with aldosterone synthase deficiency.
Aldosterone synthase deficiency (ASD) usually presents in infancy as a life-threatening electrolyte imbalance. A 4-wk-old child of unrelated parents was examined for failure to thrive and salt-wasting. Notable laboratory findings were hyperkalemia, high plasma renin, and low-normal aldosterone levels. Urinary metabolite ratios of corticosterone/18-hydroxycorticosterone and 18-hydroxycorticosterone/aldosterone were intermediate between ASD type I and type II. Sequence analysis of CYP11B2, the gene encoding aldosterone synthase (P450c11AS), revealed that the patient was a compound heterozygote carrying a previously described mutation located in exon 4 causing a premature stop codon (E255X) and a further, novel mutation in exon 5 that also causes a premature stop codon (Q272X). The patient's unaffected father was a heterozygous carrier of the E255X mutation, whereas the unaffected mother was a heterozygous carrier of the Q272X mutation. Therefore, the patient's CYP11B2 encodes two truncated forms of aldosterone synthase predicted to be inactive because they lack critical active site residues as well as the heme-binding site. This case of ASD is of particular interest because despite the apparent lack of aldosterone synthase activity, the patient displays low-normal aldosterone levels, thus raising the question of its source.


[Chronic stress model in New Zealand white rabbit with hyperlipidemia].
Objective: To establish and evaluate chronic stress model in New Zealand white rabbit with hyperlipidemia. Methods: A total of 45 clearing grade male New Zealand white rabbits were divided into four groups with random number table method: control (CON), normal diet combined with chronic stress for 8 weeks (CON+ CS), high fat diet (HFD) and high fat diet for 4 weeks combined with chronic stress for 8 weeks (HFD+ CS). Both social stress and physical stress methods were adopted.One-way ANOVA was used for comparison among groups. Results: (1) Chronic stress model assessments: ①body weight, the weight gain of stress groups was significantly reduced; ②behavioral assessment, rabbits exposed to stress in CON+ CS and HFD+ CS group [54%±7%, 55%±5%] exhibited more inactivity behavior than CON and HFD group [27%±5.28%, 34%±6%, P<0.01, P<0.05]; ③serum indexes: after stress regime for 4 weeks, cortisol of HFD+ CS was higher than HFD group [(60±5) ng/ml vs (38±4) ng/ml, P=0.001]. After 8 weeks, the serum levels of hs-CRP and IL-6 also elevated. (2) The effect of hyperlipidemia on chronic stress: compared with CON+ CS, HFD+ CS group showed more inactivity behavior and rising levels of cortisol, hs-CRP and IL-6. (3) Blood lipids: chronic stress induced raised serum total cholesterol. Conclusions: (1)Chronic stress model in rabbit with hyperlipidemia could be successfully established with 4-week high lipid feed followed by social stress combined with physical stress for 8 weeks.(2) Hyperlipidemia and chronic stress influences each other.


Effect of various compounds on the reaction of tris-(2-chloroethyl)amine with ribonucleic acid in vitro and on its toxicity in mice.
The effect of tris-(2-chloroethyl)-amine (HN-3) on RNA and DNA was investigated spectrophotometrically. The shift in the absorbance spectrum caused by the addition of HN-3 was used to test a variety of compounds for their ability to inhibit RNA alkylation. The effect of HN-3 on the activity of several enzymes was also investigated. The activities of ribonuclease A, desoxyribonuclease I, acetylcholinesterase, diaphorase, glutathione reductase, adenosine desaminase, glyoxalase I, 3-hydroxyacyl-CoA-dehydrogenase, xanthine oxidase, glucose-6-phosphate dehydrogenase, hexokinase and the microsomal N-oxygenation of aniline were not changed by HN-3, whereas the activity of cytochrome-c-reductase exhibited a dose dependent diminution in the presence HN-3. Of 105 compounds tested only 14, namely, sodium thiosulfate, dithioxanthine, thiosalicylic acid, 1,2,4-triazole-5-thiol, 2-thiocytosine, 2-thiohistadine, 2,3-dithiosuccinic acid, thioglycolic acid, 3-mercapto-D-valine,6-amino-2-thiouracil, thionicotine amide, dithiothreitol, sodium sulfite, and ergothioneine prevented the alkylation of RNA. All of them also reacted with HN-3 in absence of RNA. No correlation was found between the reaction constant of the reaction compound:HN-3 in the absence of RNA and the concentration of the compound which inhibited RNA alkylation by 50%. The compounds which were effective in vitro were also tested in mice for their ability to reduce HN-3 toxicity in vivo. Only sodium thiosulfate, d-penicillamine, and dithiosuccinic acid were effective. A 3.9fold increase in the LD50 of HN-3 was achieved in mice treated with sodium thiosulfate 3330 mg/kg i.p., a 1.7fold with 2125 mg dithiosuccinic acid/kg, and a 2fold increase with 2500 mg/kg d-penicillamine. The compound tested was injected i.p. 0.5 to 1 min after the s.c. injection of HN-3.


Integration of light- and brassinosteroid-signaling pathways by a GATA transcription factor in Arabidopsis.
Light and brassinosteroid (BR) antagonistically regulate the developmental switch from etiolation in the dark to photomorphogenesis in the light in plants. Here, we identify GATA2 as a key transcriptional regulator that mediates the crosstalk between BR- and light-signaling pathways. Overexpression of GATA2 causes constitutive photomorphogenesis in the dark, whereas suppression of GATA2 reduces photomorphogenesis caused by light, BR deficiency, or the constitutive photomorphogenesis mutant cop1. Genome profiling and chromatin immunoprecipitation experiments show that GATA2 directly regulates genes that respond to both light and BR. BR represses GATA2 transcription through the BR-activated transcription factor BZR1, whereas light causes accumulation of GATA2 protein and feedback inhibition of GATA2 transcription. Dark-induced proteasomal degradation of GATA2 is dependent on the COP1 E3 ubiquitin ligase, and COP1 can ubiquitinate GATA2 in vitro. This study illustrates a molecular framework for antagonistic regulation of gene expression and seedling photomorphogenesis by BR and light.


An international otology database.
There are many reports in the literature on the outcome of ear surgery. However, it is difficult to make comparisons from these reports because of a lack of uniformity in the way in which outcomes are reported. At the same time, the general public expects doctors to provide them with information regarding the benefits and risks of surgery. Many ear surgeons will not be able to provide this information because few have an up-to-date database. A group of otologists in Europe has attempted to establish a common otology database. The aim is to create a framework whereby surgeons in Europe can contribute to a common ear database using a web-based system. The proposed methodology involves two levels of data entry. Level 1 is a minimal database where the main outcomes are included. Level 2 is a comprehensive database where detailed information on pathologies, risk factors, and surgical procedures is also recorded. As both databases share the same core data, clinicians using database 1 can still compare their outcomes with those using database 2. Clinicians will be able to input and retrieve ear data onto or from the web-based database. There has already been an international consensus on the content of the common ear database. The website address is www.ear-audit.net. The international project has now been in operation for more than 6 months, and Ear UK has already given its endorsement. The founder members include 27 otologists from 12 European countries. The cumulative outcome from this group of surgeons will be used as the benchmark for the purpose of comparative audit. These benchmark sites will be subjected to regular external validation. The web-based system is interactive and gives instant feedback to individual surgeons who wish to compare their results to the benchmark. Therefore, it can be a good learning tool for trainees or less experienced surgeons. The common data entry system also provides an opportunity for clinicians to collaborate in clinical research.


The Multinational New Ventures on Corporate Performance Under the Work Environment and Innovation Behavior.
To cope with economic globalization and improve the competitiveness of transnational start-ups, the impact of the work environment and innovation behavior on corporate performance of multinational new ventures is analyzed. First, a model of the interaction among environment, innovation behavior, and enterprise performance is proposed. Then, 296 transnational start-ups in coastal areas are surveyed, and the model results are analyzed. Finally, a series of results are obtained. The results show that from the perspective of psychology, work dynamic organizational learning environment has a positive impact on enterprise performance (standardized path coefficient 0.436, p < 0.01), and resource environment has a significant positive impact on enterprise performance (standardized path coefficient 0.425, p < 0.01). Strategic environment also positively affects enterprise performance (standardized path coefficient 0.474, p < 0.01). Therefore, the working environment of multinational new ventures has a positive impact on firm performance, and the mediating function between the working environment and firm performance is firm innovation behavior. With the research to achieve enterprise innovation of multinational new ventures by improving their response to the dynamic environment, the corporate performance has been greatly promoted, and finally, the new ventures would participate in the international market competition.


Anti-αFR CAR-engineered NK-92 Cells Display Potent Cytotoxicity Against αFR-positive Ovarian Cancer.
Folate receptor alpha (αFR) is overexpressed in 90% of ovarian cancers, one of the most lethal gynecologic cancers. Recent studies have suggested that natural killer (NK) cells may be better chimeric antigen receptor (CAR) drivers because of their favorable innate characteristics, such as directly recognizing and killing tumor cells. However, the therapeutic effects of CAR-engineered NK cells targeting αFR in ovarian cancer have not been reported. In this research, 3 generations of anti-αFR CAR were constructed, namely αFR-ζ (first generation), αFR-28ζ (second generation), and αFR-28BBζ (third generation), and were highly expressed on the surface of NK-92 cells by lentivirus gene transfection. Three anti-αFR CAR-engineered NK-92 cells can specifically kill αFR-positive tumor cells in vitro, especially ovarian cancer cells with high αFR expression. Compared with NK-92 cells expressing αFR-ζ or αFR-28ζ, NK-92 cells expressing αFR-28BBζ showed not only higher antigen-specific cytotoxicity and proliferation but also lower antigen-induced apoptosis. Moreover, stronger degranulation and cytokine secretion were detected in NK-92 cells expressing αFR-28BBζ cocultured with αFR-positive tumor cells. Real-time cell analysis and live cell imaging recorded the process of NK-92 cells expressing αFR-28BBζ killing ovarian cancer cells in vitro. Furthermore, NK-92 cells expressing αFR-28BBζ can effectively eliminate cancer cells in a mouse xenograft model of ovarian cancer and significantly prolong the survival of tumor-bearing mice. These results demonstrate that the anti-αFR CARs redirect NK-92 cells with specific antitumor activity, and the third-generation anti-αFR CAR-engineered NK-92 cells display more potent cytotoxicity against αFR-positive ovarian cancer, laying the foundation for future clinical research.


Dissection of quantitative and durable leaf rust resistance in Swiss winter wheat reveals a major resistance QTL in the Lr34 chromosomal region.
The Swiss winter bread wheat cv. 'Forno' has a highly effective, durable and quantitative leaf rust ( Puccinia triticina Eriks.) resistance which is associated with leaf tip necrosis (LTN). We studied 240 single seed descent lines of an 'ArinaxForno' F(5:7 )population to identify and map quantitative trait loci (QTLs) for leaf rust resistance and LTN. Percentage of infected leaf area (%) and the response to infection (RI) were evaluated in seven field trials and were transformed to the area under the disease progress curves (AUDPC). Using composite interval mapping and LOD >4.4, we identified eight chromosomal regions specifically associated with resistance. The largest and most consistent leaf rust resistance locus was identified on the short arm of chromosome 7D (32.6% of variance explained for AUDPC_% and 42.6% for AUDPC_RI) together with the major QTL for LTN ( R(2)=55.6%) in the same chromosomal region as Lr34 ( Xgwm295). A second major leaf rust resistance QTL ( R(2)=28% and 31.5%, respectively) was located on chromosome arm 1BS close to Xgwm604 and was not associated with LTN. Additional minor QTLs for LTN (2DL, 3DL, 4BS and 5AL) and leaf rust resistance were identified. These latter QTLs might correspond to the leaf rust resistance genes Lr2 or Lr22 (2DS) and Lr14a (7BL).


Pathogenic potential and genetic diversity of environmental and clinical isolates of Pseudomonas aeruginosa.
The aim of this study was to investigate the occurrence of virulence genes among clinical and environmental isolates of Pseudomonas aeruginosa and to establish their genetic relationships by Enterobacterial Repetitive Intergenic Consensus PCR (ERIC-PCR). A total of 60 P. aeruginosa isolates from environmental and clinical sources were studied. Of these, 20 bacterial isolates were from soil, 20 from water, and 20 from patients with cystic fibrosis. Analysis of ERIC-PCR demonstrated that the isolates of P. aeruginosa showed a considerable genetic variability, regardless of their habitat. Numerous virulence genes were detected in both clinical and environmental isolates, reinforcing the possible pathogenic potential of soil and water isolates. The results showed that the environmental P. aeruginosa has all the apparatus needed to cause disease in humans and animals.


Mental disorders and atopic dermatitis in children and adolescents.
Some authors point to a relationship between mental disorders (MD) and atopic dermatitis (AD), but few determine which MD these are, and none of them evaluate the impact of AD on their healthy siblings. To determine which MD affect children and adolescents with AD and compare it with the risk of their healthy siblings. This is a cross-sectional, prospective study with the application of a risk assessment instrument for Mental Disorders in paediatric patients with AD and their siblings from September 2016 to June 2018. The evaluation instrument used to assess the risk of MD was the Child Behaviour Checklist (CBCL). The Wilcoxon-Mann-Whitney, Pearson's χ2 test with Yates correction and Fisher's exact test were used, considering a significance level of 5%. The risk of MD in participants with AD was 63.0%, and in the healthy siblings, 36.0% (p < 0.01). The risk was higher in participants with AD when compared to their siblings for the syndromes "Sleep Problems", "Thought Problems" and "Somatic Complaints". Parental concerns on socialization/bullying were also more frequent for participants with AD when compared to siblings. Children and adolescents with AD present a high risk of MD, and their healthy siblings also present impairment in their mental health. In both cases, this impairment is higher than the one expected in the Brazilian general paediatric population (24.6%) and global paediatric population (22.4%).


Stem cell transplantation-harnessing of graft-versus-malignancy.
Allogeneic transplantation can cure a number of hematologic malignancies; however, the cost in morbidity and mortality is high. Much of the toxicity is a direct consequence of the intensity of the conditioning regimen. It has gradually been recognized that the conditioning regimen is important but not critical for the success of transplantation, particularly in the less aggressive hematologic malignancies. The graft-versus-malignancy effect, that is, the recognition of residual cancer cells by the T cells of the donor, is a critical component of the transplantation process. This effect has been emphasized over high-dose therapy by using less intensive, and therefore less toxic conditioning regimens, thus allowing the graft-versus-malignancy effect to predominate. Reduced-intensity conditioning regimens have allowed the application of transplantation to older patients and to patients with underlying medical problems that preclude full-dose transplantation. Although the long-term results of this type of approach have not yet been defined, it appears to be effective in diseases such as chronic myelogenous leukemia, chronic lymphocytic leukemia, and low-grade lymphomas that are not intrinsically very aggressive. Although the therapy appears to be valuable, concerns about delayed immune reconstitution and graft-versus-host disease remain.


Optimal timing of same-admission orthotopic heart transplantation after left ventricular assist device implantation.
To investigate the impact of timing of same-admission orthotopic heart transplant (OHT) after left ventricular assist device (LVAD) implantation on in-hospital mortality and post-transplant length of stay. Using data from the Nationwide Inpatient Sample from 1998 to 2011, we identified patients 18 years of age or older who underwent implantation of a LVAD and for whom the procedure date was available. We calculated in-hospital mortality for those patients who underwent OHT during the same admission as a function of time from LVAD to OHT, adjusting for age, sex, race, household income, and number of comorbid diagnoses. Finally, we analyzed the effect of time to OHT after LVAD implantation on the length of hospital stay post-transplant. Two thousand and two hundred patients underwent implantation of a LVAD in this cohort. One hundred and sixty-four (7.5%) patients also underwent OHT during the same admission, which occurred on average 32 d (IQR 7.75-66 d) after LVAD implantation. Of patients who underwent OHT, patients who underwent transplantation within 7 d of LVAD implantation ("early") experienced increased in-hospital mortality (26.8% vs 12.2%, P = 0.0483) compared to patients who underwent transplant after 8 d ("late"). There was no statistically significant difference in age, sex, race, household income, or number of comorbid diagnoses between the early and late groups. Post-transplant length of stay after LVAD implantation was also not significantly different between patients who underwent early vs late OHT. In this cohort of patients who received LVADs, the rate of in-hospital mortality after OHT was lower for patients who underwent late OHT (at least 8 d after LVAD implantation) compared to patients who underwent early OHT. Delayed timing of OHT after LVAD implantation did not correlate with longer hospital stays post-transplant.


Study on Bacterial Strains Causing Blood and Urinary Tract Infections in the Neonatal Intensive Care Unit and Determination of Their Antibiotic Resistance Pattern.
Infections are considered as one of the main factors of neonatal mortality, especially in developing countries. Blood and urine infections are one of the most prevalent infectious factors among the infants. On the other hand, resistance against antimicrobial factors is one of the major problems in the world, and it is important to be informed about antibiotic resistance pattern of microorganisms for treatment of infections. The aim of this study was to examine the bacterial strains causing blood and urinary tract infections in Neonatal Intensive Care Unit (NICU) and determine their antibiotic resistance pattern. In this study, the microorganisms of 150 blood and urine samples of infants hospitalized in NICUs of Imam Hussein Hospital, Children Hospital Center and Bahrami Hospital in Tehran, Iran, were collected during seven months, and the antimicrobial resistance patterns of the isolates were studied by the Kirby-Bauer test. During the seven-month study on 105 samples, including 85 (81%) urine samples and 20 (19%) blood samples, 81 samples (77.1%) were Gram-negative and 24 (22.9%) were Gram-positive organisms. Klebsiella pneumoniae (30.5%) was the most common Gram-negative microorganisms and Staphylococcus epidermidis (11.4%) was the most prevalent Gram-positive microorganisms. The most antimicrobial susceptibility in Gram-negative microorganisms was shown to ciprofloxacin (84.2%) and in Gram- positive ones was shown to vancomycin (83.3%). This results of the study show that the most contamination in NICUs is from Gram-negative bacteria and ciprofloxacin is the most effective antibiotic for treatment. Thus, the control of infections in NICUs in hospitals is very important.


Intracellular glycosylation and active efflux as mechanisms for resistance to oleandomycin in Streptomyces antibioticus, the producer organism.
Resistance to macrolides in producing organisms can be achieved by target site modification, intracellular inactivation of the antibiotic or active efflux mechanisms for the excretion of the antibiotic. The oleandomycin producer, Streptomyces antibioticus, possesses oleandomycin-sensitive ribosomes all along the cell cycle. However, it contains an intracellular glycosyltransferase capable of inactivating oleandomycin in the presence of UDP-glucose as cofactor. The correspondent gene (oleD) has been cloned and sequenced and the glycosyltransferase purified. Two other genes (oleB and oleC) that confer oleandomycin resistance have been cloned and characterized and both encode ABC (ATP-Binding Cassette) transporters. These may constitute the excretion mechanism throughout which the glycosylated oleandomycin is excreted. A second enzyme activity has been purified from culture supernatants of the oleandomycin producer that releases the glucose from the inactive glycosylated oleandomycin generating active antibiotic. This enzyme would probably catalyse the last step in the biosynthesis of oleandomycin.


A descriptive profile of elite U.S. women's collegiate field hockey players.
The purposes of this study were to develop a descriptive profile and examine the relationships between grip strength, power and sport specific test performance in 37 elite, female collegiate field hockey players (N=8 backs, N=13 forwards, N=4 goalkeepers, N=8 midfield players, N=4 wings). The tests included circumference and limb lengths, %body fat, Margaria-Kalamen stair test, 50-yard dash test, Queen's College step test, grip strength, Illinois agility test, field hockey specific skills tests, and a coordination test. Mean (+/-SD) height, weight, percent body fat, and predicted oxygen consumption were 164.26 (+/-5.17) cm, 63.06 (+/-8.60) kg, 17.29 (+/-3.79)% and 42.87 (+/-9.08) ml x kg(-1) x min(-1), respectively. Although the goalkeepers were significantly (p<0.05) heavier and had a higher %body fat, there were no significant differences (p>0.05) between any of the player positions in height, limb length, 50-yard dash time, predicted VO(2max), grip strength, agility, or in the field hockey specific tests. There were no significant (p>0.05) correlations (r=0.03 to -0.13) between right and left grip strength and sport-specific test scores but significant (p<0.05) relationships were found between power and pushing accuracy, as well as between the 50 yard dash and coordination test, pushing power and pushing accuracy. In profiling a sample of elite collegiate field hockey players in the Unites States, the results of this study indicate that there are similarities amongst the defensive and offensive players with international level field hockey players, and that measures of power and sport specific tests are significantly correlated.


Diagnostic Accuracy of Periapical Radiography and Cone-beam Computed Tomography in Identifying Root Canal Configuration of Human Premolars.
The aim of this study was to assess the diagnostic accuracy of periapical radiography (PR) and cone-beam computed tomographic (CBCT) imaging in the detection of the root canal configuration (RCC) of human premolars. PR and CBCT imaging of 114 extracted human premolars were evaluated by 2 oral radiologists. RCC was recorded according to Vertucci's classification. Micro-computed tomographic imaging served as the gold standard to determine RCC. Accuracy, sensitivity, specificity, and predictive values were calculated. The Friedman test compared both PR and CBCT imaging with the gold standard. CBCT imaging showed higher values for all diagnostic tests compared with PR. Accuracy was 0.55 and 0.89 for PR and CBCT imaging, respectively. There was no difference between CBCT imaging and the gold standard, whereas PR differed from both CBCT and micro-computed tomographic imaging (P < .0001). CBCT imaging was more accurate than PR for evaluating different types of RCC individually. Canal configuration types III, VII, and "other" were poorly identified on CBCT imaging with a detection accuracy of 50%, 0%, and 43%, respectively. With PR, all canal configurations except type I were poorly visible. PR presented low performance in the detection of RCC in premolars, whereas CBCT imaging showed no difference compared with the gold standard. Canals with complex configurations were less identifiable using both imaging methods, especially PR.


Perinatal assessment.
The role of the nurse in early recognition of risk factors in the perinatal period is very important. The author suggests that obstetrical units use a perinatal nursing team whose role would include the careful assessment of mother and infant for risk factors during the prenatal, intrapartal, and immediate neonatal periods. The perinatal assessment guide accompanying the text offers a comprehensive compilation of data to assist in the identification of perinatal risk factors. This guide will be useful for nurses working in obstetrical units and for nursing instructors teaching student nurses maternal-newborn nursing assessment.


Current challenges for the early clinical development of anticancer drugs in the era of molecularly targeted agents.
The emergence of molecularly targeted agents in oncology has not only revolutionized the care of cancer patients, but also changed the daily practice of medical oncologists. Molecularly targeted agents indeed often differ from traditional cytotoxic agents by their administration schedules and routes, their toxicity profiles, and/or the assessment of their antitumor activity. In addition, the observation that molecularly targeted agents sometimes have limited antitumor activity as single agents has led clinical investigators to combine molecularly targeted agents together or with cytotoxic agents. We review here the current challenges for the early clinical development of anticancer agents in the era of molecularly targeted agents. We focus on the choice of end points in phase I oncology clinical trials, as well as on the choice of dose escalation methods with an emphasis on available dose escalation methods for molecularly targeted agents and for combination trials.


Complications of microvascular head and neck surgery in the elderly.
To evaluate the complications of head and neck reconstruction using microvascular free tissue transfers (MFTTs) performed in an elderly population and to determine whether these complications are more common than in a younger population. Tertiary referral center. Retrospective, consecutive chart review of patients older than 70 years who underwent MFTT in the past 5 years (group 1). The complications in this population were compared with those in a second group (group 2) of consecutive patients younger than 70 years who were matched according to the site of the primary tumor. Surgical and medical complications. The median age for group 1 was 74 years and for group 2, 55 years. The overall complication rate for group 1 was 48%, compared with 57% for group 2. In group 1, surgical morbidity was less common and medical morbidity was more common than in group 2. Mortality rate was 6% for group 1 and 0% for group 2. The types of complications were similar for both groups. There was no difference in complication rates when complications were classified by site of the defect, patient status determined by American Society of Anesthesiologists classification, or use of preoperative radiation. The overall success rate of MFTT was 100% for group 1 and 94% for group 2. Microvascular free tissue transfers for head and neck reconstruction can be safely performed in the elderly. An age older than 70 years does not increase the rate of surgical complications following head and neck reconstruction with MFTT. Medical complications, however, are more common and are equally divided between bronchopulmonary and cardiovascular effects.


Role of platelets in myocardial ischemia-reperfusion injury in dogs.
We investigated the involvement of circulating platelets in myocardial ischemia-reperfusion injury in canine autoperfused heart-lung preparations using filters to deplete platelets and/or leukocytes. The left anterior descending (LAD) coronary artery was occluded for 40 min, followed by 40 min reperfusion, in 3 groups: a leukocyte-platelet-depleted (LPD) group, in which both leukocytes and platelets were depleted; a leukocyte-depleted (LD) group, in which leukocytes alone were depleted; and a control group. There were no differences in hemodynamics or arrhythmias among groups before or during coronary occlusion. After reperfusion, the maximum rate of change in left ventricular pressure during systole and diastole was significantly higher in the LPD group than in the control and LD groups. The LPD group also showed gradual recovery of regional myocardial function and a decrease in the frequency of premature ventricular contractions. The LD group showed a slight improvement in cardiac function and arrhythmias compared with the control group. Although there was no significant difference in the pulmonary arterial plasma level of thromboxane B2 at any stage among groups, the control group showed an increase after reperfusion. These results suggest that platelets are important in reperfusion injury and that the depletion of both leukocytes and platelets effectively protects against reperfusion injury.


Pharmacologic and genetic inhibition of cholesterol esterification enzymes reduces tumour burden: A systematic review and meta-analysis of preclinical models.
Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p < 0.0001). Pharmacological or genetic inhibition of SOAT was associated with significantly smaller tumours of all types (p ≤ 0.002). SOAT inhibition increased tumour apoptosis (p = 0.007), CD8 + lymphocyte infiltration and cytotoxicity (p ≤ 0.05), and reduced proliferation (p = 0.0003) and metastasis (p < 0.0001). Significant risk of publication bias was found and may have contributed to a 32% overestimation of the meta-analysed effect size. Avasimibe, the most frequently used SOAT inhibitor, was effective at doses equivalent to those previously reported to be safe and tolerable in humans. This work indicates that SOAT inhibition should be explored in clinical trials as an adjunct to existing anti-neoplastic agents.


Injection Drug Users' Perceived Barriers to Using Self-Initiated Harm Reduction Strategies.
Increasing the frequency with which injecting drug users (IDUs) engage in self-initiated harm reduction strategies could improve their health, but few investigations have examined IDUs' perceived barriers to engaging in these behaviors. We interviewed 90 IDUs recruited from needle exchanges to assess: a) perceived obstacles to their use of two specific harm reduction strategies (i.e., test shots and pre-injection skin cleaning) designed to reduce two unhealthy outcomes (i.e., overdose and bacterial infections, respectively) and b) their use of other risk-reduction practices. The most frequently cited barrier for both test shots and skin cleaning was being in a rush to inject one's drugs. Other, less commonly cited barriers were strategy-specific (e.g., buying drugs from a known dealer as a reason not to do a test shot; not having access to cleaning supplies as a reason not to clean skin). Regarding other risk reduction practices, participants' most frequently reported using new or clean injecting supplies and avoiding sharing needles and injecting supplies. Some, but not all, of the barriers generated by participants in our study were similar to those frequently reported in other investigations, perhaps due to differences in the type of sample recruited or in the harm reduction behaviors investigated.


Probing the plasma near high power wave launchers in fusion devices for static and dynamic electric fields (invited).
An exploratory study was carried out in the long-pulse tokamak Tore Supra, to determine if electric fields in the plasma around high-power, RF wave launchers could be measured with non-intrusive, passive, optical emission spectroscopy. The focus was in particular on the use of the external electric field Stark effect. The feasibility was found to be strongly dependent on the spatial extent of the electric fields and overlap between regions of strong (>∼1 kV/cm) electric fields and regions of plasma particle recycling and plasma-induced, spectral line emission. Most amenable to the measurement was the RF electric field in edge plasma, in front of a lower hybrid heating and current drive launcher. Electric field strengths and direction, derived from fitting the acquired spectra to a model including time-dependent Stark effect and the tokamak-range magnetic field Zeeman-effect, were found to be in good agreement with full-wave modeling of the observed launcher.


[Humoral factors in the regulation of cell proliferation in haematopoiesis. I. Granulopoiesis and lymphopoiesis (author's transl)].
Humoral Factors obviously play an important role in the maintenance of the steady state in haematopoiesis. There has been work on stimulators and inhibitors for several years. Colony-stimulating factor is the best characterized chemically and biologically. Interest in more or less cell-line-specific stimulators and inhibitors of lymphopoiesis is now growing. Various tissue extracts and cell culture supernatants have been partially purified and characterized biologically and chemically. Monocytes, producing stimulators and inhibitors, have a central function in the regulation of cell proliferation in haematopoiesis. Experiments performed in vitro can help better to understand data so far difficult to explain regarding patients with disturbed haematopoiesis. The in vivo relevance of these experiments, however, remains unclear.


Ileal Pouch-Anal Anastomosis for Dysplasia or Cancer Complicating Inflammatory Bowel Disease: Is Total Mesorectal Excision Always Mandatory? An Analysis of 36 Consecutive Patients.
The extent of lymph node harvesting during surgery for colorectal neoplasm [dysplasia and/or cancer] complicating inflammatory bowel disease [IBD] is a matter of debate. This study aimed to assess the risk of invasive rectal cancer in patients undergoing ileal pouch-anal anastomosis [IPAA] for colonic neoplasm complicating IBD, and thus to clarify whether a systematic total mesorectal excision [TME] should be systematically performed, or not, in those patients. From 1998 to 2015, all patients who underwent IPAA for colorectal neoplasm complicating IBD were included. Patients with preoperatively known rectal cancer were excluded. Pathological results were compared with preoperative endoscopic results. A totalof 36 patients [mean age 49 ± 14 years], comprising 10 women [31%] and 26 men [69%], underwent IPAA for colorectal neoplasm complicating IBD, with [n = 8; 22%] or without [n = 28; 78%] TME. Rectal cancer rate in pathological specimens was 0% [0/20] in patients with preoperatively known neoplasm only limited to the colon, 0% [0/8] among patients with preoperative rectal low-grade dysplasia, and 62% [5/8] among patients with preoperatively rectal high-grade dysplasia. These results do not support systematic TME during IPAA for colonic neoplasm complicating IBD. Considering its association with postoperative sexual disorder, TME should be discussed only on a case-by-case basis.


Performance Evaluation of Membrane-Based Septic Tank and Its Reuse Potential for Irrigating Crops.
Membrane technology, being the most emerging wastewater treatment option, has gained substantial importance with the massive objective of the reuse potential of wastewater. Keeping this in view, the present study was conducted with the rationale to evaluate the performance efficiency of membrane-based septic tank (MBST), and its reuse perspective for irrigating crops. The septic tank was designed by submerging a woven fiber microfiltration membrane module to treat domestic wastewater. Three crops Triticum aestivum (wheat), Coriandrum sativum (coriander), and Mentha arvensis (mint) were selected to be irrigated with treated MBST effluent, untreated wastewater, and tap water (as a control) for comparative growth analysis. Two pathogenic strains, Escherichia coli and Salmonella sp. were selected as reference microbes and their translocation rate was observed in root, shoot, and leaves. Upon maturity, the roots, shoots, and leaves of the above-mentioned plants were aseptically removed for microbiological analysis. Strains were analyzed, using analytical profile index and PCR analysis. Maximum removal efficiencies for MBST in terms of chemical oxygen demand (COD), turbidity, nutrients deduction (phosphorus), and indicator bacteria (Escherichia coli) were found to be 73, 96, 48, and 88%, respectively. Significant bacterial load reduction (p < 0.001) in terms of E. coli (3.8 log CFU/100 mL) and helminths (2 eggs/L) was observed in treated water. High plant yield was observed when irrigated with treated water as compared to tap water, as minimal nutrient removal (48%) was recorded in treated water, with the germination percentage of 88.8%.