Functional roles for the glutamines within the glutamine-rich region of the transcription factor sigma 54.
Single and multiple point mutations were introduced to change the 12 glutamine residues within a 37-amino acid region of sigma 54. Multiple changes are shown to be required in order to interfere significantly with the function of this protein which is associated with enhancer-dependent bacterial transcription. Mutation of the central 4 glutamines leads to the production of less m-RNA, caused by an inability to fully open the promoter start site. DNA binding, however, is normal. Mutation of 4 other adjacent glutamines causes the promoter start site to open more readily than wild type, although this enhanced opening is not accompanied by more mRNA. The enhanced DNA melting is not caused by enhanced promoter binding, as indicated by normal protection of the polymerase-bound promoter against dimethyl sulfate attack. The results suggest that multiple glutamines play a role in transducing the melting signal from the enhancer protein to the polymerase.


Modeling initial attack success of wildfire suppression in Catalonia, Spain.
In southern European regions, the few fires that escape initial attack (IA) account for most of the burned area. Nonetheless, limited effort has been conducted to develop spatiotemporal models aiming at improving pre-positioning and deployment of fire-fighting brigades on the first dispatch. To this end, we calibrated a model to assess the probability of containment of fire by IA in Catalonia (northeastern Spain). The model was trained using machine learning algorithms from georeferenced historical fire ignition locations, fire response and weather conditions. Our results indicated that early detection, ground accessibility, and aerial support governed the broad spatial pattern of fire containment probability, with strong gradients that ranged from lowest chances of containment in northwestern mountains to highest in the coastal belt. In turn, weather conditions and fire simultaneity were crucial to explain the differences during wildfire season. We found that fires igniting above the 85th percentile of temperature and wind speed, during simultaneous fire episodes (n > 10), and 12.5 km away from the nearest fire station will probably escape IA, and grow into large events. These hazardous fire danger conditions were met 13 days per year on average during the period 1998-2015, with 5 fire simultaneous episodes escaping IA that burned 1546 ha in total. Results were provided as a set of high-resolution raster grids (100 m), which replicated the most typical weather and fire occurrence scenarios that first responders are likely to face during the wildfire season. This study reveals existing limitations in the dominant fire exclusion policy of Mediterranean areas and advocates for a comprehensive long-term wildfire management solution. Our model may help inform science-based decision-making on IA and general fire response planning in the study area.


Growth inhibition of human in vitro and mouse in vitro and in vivo mammary tumor models by retinoids in comparison with tamoxifen and the RU-486 anti-progestagen.
Retinoids constitute a very promising class of agents for the chemoprevention or treatment of breast cancer. These retinoids exert their biological activity through two distinct classes of retinoic acid (RA) receptors (R), the RAR isotypes (alpha, beta, and gamma) and the three RXR isotypes (alpha, beta, and gamma) and their numerous isoforms which bind as RXR/RAR heterodimers to the polymorphic cis-acting response elements of RA target genes. With respect to these numerous receptor sub-types, the retinoid-induced effects at the biological level include marked modifications with respect to both cell proliferation and cell death (apoptosis), and also in the induction of differentiation processes. The present study aims to characterize the effect which four retinoids (TTNPB, 9-cis-RA, LGD 1069, 4-HPR) with distinct RAR/RXR binding properties induced on various in vitro and in vivo mouse and human breast cancer models. The experiments with the retinoids were carried out in comparison with the anti-estrogen tamoxifen and the anti-progestagen RU-486 compounds. The results show that the 6 compounds under study were markedly more efficient in terms of growth inhibition in the human T-47D cell line when maintained under anchorage-independent culture conditions than when maintained under anchorage-dependent ones. While RU-486 exhibited a weak statistically significant (p < 0.05) influence on the growth of the T-47D stem cells, tamoxifen had a marked inhibitory influence on the growth of these cells. Of the four retinoids, 4-HPR was the least effective since the lowest doses tested (1 and 0.1 nM) exhibited no statistically (p > 0.05) significant influence on the growth of the stem cells. The most efficient retinoid was TTNPB. It was only at the highest dose (10 microM) that tamoxifen and RU-486 showed a weak inhibitory influence on the growth of the T-47D non-stem cells while all 4 retinoids exerted a significant inhibitory influence on the growth of these non-stem cells, with 4-HPR being the most efficient (P < 0.001) at the highest dose, but ineffective (P > 0.05) at the lowest. Tamoxifen and TTNPB were tested in vivo on hormone-sensitive (HS) and hormone-insensitive (HI) strains of the MXT murine mammary carcinoma. While TTNPB appeared to be equally efficient in terms of growth inhibition in both MXT-HS and MXT-HI models, tamoxifen had only a marginal inhibitory influence on the growth of the MXT-HI strain but did inhibit growth in the case of the MXT-HS one. TTNPB was markedly more efficient than tamoxifen in terms of both inhibiting the cell proliferation level (measured by means of computer-assisted microscopy applied to Feulgen-stained nuclei, a method which enables the percentage of cells in the S phase of the cell cycle to be determined) and triggering cell death (measured by means of the determination of the transglutaminase activity) in both the MXT-HI and MXT-HS models. The very significant TTNPB-induced inhibition of the macroscopic MXT-HS growth rate relates to the triggering of cell death (apoptosis) rather than to an inhibition of cell proliferation. All these results clearly indicate that retinoids are very efficient agents against breast cancer, at least as efficient as tamoxifen.


The use of new procoagulants in blunt and penetrating trauma.
Uncontrolled bleeding in trauma secondary to a combination of surgical bleeding and trauma-induced complex coagulopathy is a leading cause of death. Prothrombin complex concentrates (PCCs), recombinant activated factor seven (rFVIIa) and recombinant human prothrombin act as procoagulants by increasing thrombin generation and fibrinogen concentrate aids stable clot formation. This review summarizes the current evidence for procoagulant use in the management of bleeding in trauma, and data and evidence gaps for routine clinical use. Retrospective and prospective studies of PCCs (±fibrinogen concentrate) have demonstrated a decreased time to correction of trauma coagulopathy and decreased red cell transfusion with no obvious effect on mortality or thromboembolic outcomes. PCCs in a porcine model of dilutional coagulopathy demonstrated a sustained increase in thrombin generation, unlike recombinant human prothrombin which showed a transient increase and has been studied only in animals. In other retrospective studies, there is a suggestion that lower doses of PCCs may be effective in the setting of acquired coagulopathy. There is increasing evidence that early correction of coagulopathy has survival benefits, and the use of procoagulants as first-line therapy has the potential benefit of rapid access and timely treatment. This requires confirmation in prospective studies.


Projective invariance and picture perception.
Four experiments test the assumption that, in the visual perception of pictures, observers have reliable and direct access to the equivalence of shapes in projective geometry. The assumption is that perception of projective equivalence is the basis of shape constancy ('the projective thesis'). Observers matched or reproduced abstract planar shapes under conditions of rotation in the picture plane, and pictured rotation in depth. Departure from projective equivalence was assessed in each study by measuring the planar analogue of cross ratio. Projective equivalence was not found to be perceived uniformly where Euclidean equivalence was not judged uniformly, either in recognition tasks or in production tasks. When the projective thesis is put to a suitably general test, confidence in the thesis is undermined.


Different sensitivity to the dexamethasone treatment of the lymphoid organs of Rana perezi in two different seasons.
Adult female frogs (Rana perezi) have been used to analyze structural and morphometrical changes which affect lymphoid organs after treatment with a single dose of dexamethasone (DX). Special attention was given to the distinct sensitivity observed during two different periods of the year. Morphological differences were found between adult control frogs sacrificed in November and February. In February, frogs showed degenerated thymic reticular epithelial cells but lesser numbers of cortical pycnotic and mitotic thymocytes than in November. Splenic lymphoid tissue was clearly less well developed in February. No significant variations were found in the morphometrical parameters of jugular bodies whereas the number of lymphocytes of both peripheral blood and bone marrow was significantly higher in February than in November. In contrast, frogs sacrificed in February exhibited less drastic variations as well as a more delayed response to DX-treatment than those of November. The reported differential changes could be attributed to possible distinct levels of circulating sexual and nonsexual steroids during both seasonal periods.


Clinical picture of intracranial non-traumatic dissecting aneurysm.
Non-traumatic intracranial arterial dissection has been accepted as a unique entity of 'cerebral infarction in otherwise healthy young adults', and is particularly prevalent in Western countries. A recent data collection and analysis have revealed additional clinical features. The nationwide study in Japan conducted in 1996 has provided new information on the natural history and current treatment of intracranial dissecting aneurysms in Japan. The incidence of symptomatic dissection was found to be much higher in the vertebrobasilar system than in the carotid system. The mean age of the patients was 51.3 years. Patients with carotid lesions were younger (mean 43.8 years). The male/female ratio was 2: 1. Fifty-eight percent of patients presented with subarachnoid hemorrhage. Recurrence was more frequent in patients with subarachnoid hemorrhage (14%) than in patients with no hemorrhage (4.2%). Common radiological findings were dilatation, 'pearl and string' sign and narrowing of the affected artery. Surgical treatment involved a variety of procedures including proximal occlusion, entrapment, wrapping and endovascular embolization. Patients with subarachnoid hemorrhage (61%) underwent surgical treatment more frequently than patients with no hemorrhage (17%). Good recovery was achieved in 64% of all patients. Outcome was better in patients with no subarachnoid hemorrhage compared with those with hemorrhage.


Differential Toxicities of Nickel Salts to the Nematode Caenorhabditis elegans.
This study focused on assessing whether nickel (Ni) toxicity to the nematode Caenorhabditis elegans was affected by the molecular structure of the Ni salt used. Nematodes were exposed to seven Ni salts [Ni sulfate hexahydrate (NiSO4·6H2O), Ni chloride hexahydrate (NiCl2·6H2O), Ni acetate tetrahydrate (Ni(OCOCH3)2·4H2O), Ni nitrate hexahydrate (N2NiO6·6H2O), anhydrous Ni iodide (NiI2), Ni sulfamate hydrate (Ni(SO3NH2)2·H2O), and Ni fluoride tetrahydrate (NiF2·4H2O)] in an aquatic medium for 24 h, and lethality curves were generated and analyzed. Ni fluoride, Ni iodide, and Ni chloride were most toxic to C. elegans, followed by Ni nitrate, Ni sulfamate, Ni acetate, and Ni sulfate. The LC50 values of the halogen-containing salts were statistically different from the corresponding value of the least toxic salt, Ni sulfate. This finding is consistent with the expected high bioavailability of free Ni ions in halide solutions. We recommend that the halide salts be used in future Ni testing involving aquatic invertebrates.


The strength recovery effect of scarf bonding on the CFRP laminates with impact damage.
Impact damage can affect the carrying capacity and service life of aerospace composite structures seriously. In this study, the carbon fiber/epoxy composite (ZT7H/EC3448) was used for scarf bonding repair for CFRP (Z7TH/QY9611) laminates to restore strength. In view of the impact sensitivity of bonding repair of CFRP laminates, a three-dimensional (3D) finite element model (FEM) of the whole damaged response from impact to compression-after-impact (CAI) was established by the subroutine of ABAQUS finite element simulation software. Combined with the experiments of low-velocity impact and compression, the impact damage mode and CAI response of the intact laminates and the wet bonding repaired laminates were evaluated by analyzing the impact response, the failure situation and the residual strength. The results show that the damage of both started in the impacted area and expanded to complete failure in the direction of the vertical fiber. Unlike the intact laminates, the patch of the repaired laminates absorbed a lot of impact energy, which greatly reduced the damage to the original laminates, and the CAI performance for the wet bonding repaired laminates by ZT7H/EC3448 recovered to 97.7% of the intact one.


New approaches for cancer immunotherapy.
Immunotherapy is a promising field that offers alternative methods for treatment of cancer. The current strategy consists of cancer vaccines, monoclonal antibodies, and cellular therapies. Cancer vaccines aim to eradicate cancer cells via immune system. Thus, they may attack these cells derived from any type of cancer, besides their role in preventing cancer. Lymphocytes and dendritic cells are often used in cellular therapy. In addition, monoclonal antibodies are designed to target specific antigens found in cancer cells. Currently, at least 12 clinically approved monoclonal antibodies are being used and many cancer vaccines are being developed with ongoing phase studies for cancer therapy. Relevant studies are focused on glioma and several other cancer types. Correspondingly, the combination of effective methods may enhance the efficacy of immunotherapy. It is thought that particularly immune checkpoint inhibitors will play a crucial role in immunotherapeutic approaches.


[Causes of belief in conspiracy narratives and recommendations for successful risk communication in healthcare].
Throughout the COVID-19 pandemic, the belief in conspiracy narratives within the population strongly influenced the implementation of containment measures and medical recommendations. Conspiracy narratives involve the belief that a group perceived as powerful would pursue secret plans to harm society, which distinguishes them from misinformation or disinformation. This paper presents findings from the research literature on the causes of conspiracy beliefs, their effects on individual health behaviors, and ways to counteract their spread.In situations where people have less capacity and motivation for deeper information processing, they form their opinions more heuristically, which increases vulnerability to cognitive biases. People become particularly susceptible to receiving misinformation or disinformation, which are frequently linked to the emotionalization of facts and simplistic responses. Belief in conspiracy narratives may become more easily established, with additional issues of personal identity and various psychological motives playing a role, among others. A general distrust of people who are perceived as "powerful," such as representatives from science, medicine, and politics, can arise. Digital networks additionally contribute to the spread of conspiracy narratives.There are several ways that healthcare institutions can reduce the emergence and spread of misinformation, disinformation, and conspiracy narratives through their risk and crisis communications. The Crisis and Emergency Risk Communication Model (CERC) provides important approaches in this regard.


Studies of methylmalonyl coenzyme A carbonylmutase activity in methylmalonic acidemia. I. Correlation of clinical, hepatic, and fibroblast data.
Methylmalonyl-CoA carbonylmutase (mutase) activity was measured in fibroblast extracts from 15 patients with methylmalonic acidemia and in extracts of postmortem tissues from 6 of these children. Propionate oxidation and synthesis of 5-deoxyadenosylcobalamin (AdoCbl, the vitamin B12 coenzyme that is part of the mutase holoenzyme) were measured in intact fibroblasts. Mutase activity was low in the absence of added AdoCbl in fibroblast extracts from both control subjects and patients. When the assay included supplemental AdoCbl, mutase activity increased in the control subjects (to 24.0 pmol succinate/mg protein/min) and in extracts from eight of the patients (20.8 pmol/mg protein/min), but showed almost no change in extracts from the other seven patients (0.16 pmol/mg protein/min). We have defined the eight fibroblast lines that showed normal mutase activity in the presence of AdoCbl as "responsive lines" and the other seven lines as "nonresponsive." In the liver or kidney extracts of postmortem tissues, mutase activity responded to AdoCbl supplementation if fibroblast mutase activity from that patient had responded, and failed to respond if fibroblast activity failed to respond. Mean propionate oxidation in intact fibroblasts was much higher in control lines than in either responsive or nonresponsive lines (0.728 vs 0.097 vs 0.080 nmol CO2/10(6) cells/hr, respectively). AdoCbl synthesis was normal (0.27 pg AdoCbl/mg cells wet weight) in nonresponsive fibroblasts but was undetectable (less than 0.005 pg/mg cells) in the responsive lines. Thus, the deficiency of mutase activity in responsive fibroblast lines is due to the failure to synthesize significant amounts of AdoCbl, whereas the deficiency in nonresponsive lines is due to some other abnormality, presumably a defect in the mutase apoenzyme.


The burden of paediatric intensive care: an Australian and New Zealand perspective.
Most seriously ill children in Australia and New Zealand are cared for in specialised intensive care units associated with tertiary children's hospitals. Highly regionalised models of care are in operation. Children from remote areas are transported to intensive care by paediatric emergency transport services. Indigenous children have disease and injury patterns similar to parts of the developing world and are over-represented in the intensive care population. The outcome for children admitted to intensive care compares favourably with international benchmarks. There is also evidence of uniformity of outcomes across paediatric intensive care units in the region and that outcomes have been improving. Although there are some downward pressures on intensive care workloads (preventative strategies such as immunisation, safety campaigns), these are counterbalanced by new surgical initiatives and increasing expectations of extended high tech support for children with life shortening diseases and disabilities. This expanding group of technology-dependent children will be one of the major challenges facing health authorities and intensive care physicians in this region in the coming decade.


[Visualization of the superior vena cava in the supraclavicular acoustic window].
The ultrasound-guided venipuncture of the internal jugular vein for placement of a central venous catheter is well established. For verification of the catheter tip position mostly intracardiac ECG or chest radiography are used. Previously, we established the right supraclavicular fossa view for ultrasound based verification of the catheter placement in the superior vena cava utilizing a microconvex probe. The microconvex probe has a small footprint. However, not all ultrasound systems used in the operating theater are equipped with a microconvex transducer. Thus, we systematically compared the visibility of intrathoracic vessels obtained by a linear and a microconvex prone via the right supraclavicular view. We assessed the visibility of the junction of the brachiocephalic veins, the superior vena cava, the right pulmonary artery, the ascending aorta and the internal jugular vein, comparing a linear with a microconvex probe when using the right supraclavicular view in healthy volunteers. The superior vena cava also was identified using Doppler ultrasound. With the microconvex probe the superior vena cava was visible in all 30 healthy volunteers, but with a linear transducer it was visible in only 53 %. The combined view of the superior vena cava and the right pulmonary artery was possible in all cases when using the microconvex probe, but in only 38 % when using the linear probe. The junction of the brachiocephalic veins was seen in 75 % of the volunteers with the microconvex probe and in 38 % with the linear one. The aorta was visible in 87 % of cases with the microconvex transducer, but only in 30 % with the linear probe. The internal jugular vein was always visible with either probe. The microconvex transducer as compared to the linear probe is superior in visualizing the superior vena cava. Possible reasons are a smaller footprint, a better degree of freedom for angulation and a greater penetration depth of the microconvex probe.


[New kinds of relationships on the internet. Virtual object relations in psychotherapy].
Communication in the internet by e-mail is gaining in significance in counseling and psychotherapy of suicidal patients as well as an additional communication in face-to-face psychotherapy. E-Mail contacts during psychodynamic psychotherapy are defined as a transference offer of a virtual object relation. In two case descriptions of suicidal patients, examples of making contact with psychotherapy on the internet are presented. The concept of the virtual object is explained and its application for understanding these initial scenes and phenomena is discussed.


Nitroreductase activity of ferredoxin reductase BphA4 from Dyella ginsengisoli LA-4 by catalytic and structural properties analysis.
Ferredoxin reductase BphA4 was well known as a component of biphenyl dioxygenase. However, there was little information about whether it could utilize nonphysiological oxidants as electron acceptors. In the present study, we reported the novel nitroreductase activity of BphA4(LA)₋₄. The homology model of ferredoxin reductase BphA4 from Dyella ginsengisoli LA-4 was constructed. According to the alignment of three-dimensional structures, it was supposed that BphA4(LA)₋₄ could function as nitroreductase. Recombinant His-tagged BphA4(LA)₋₄ was purified with a molecular mass of 49.6 ± 1 kDa. Biochemical characterization of purified BphA4(LA)₋₄ possessed the nitroreductase activity with the optimal temperature 50°C and pH 8.0. The substrate spectrum and kinetics indicated BphA4(LA)₋₄ could reduce several nitroaromatics with different apparent K(m) values: m-dinitrobenzene (560 μM), o-dinitrobenzene (1,060 μM), o-nitroaniline (1,570 μM), m-nitrobenzoic acid (1,300 μM) and m-nitrophenol (67 μM). The nitroreductase activity was further explained by docking studies, which was indicated that Arg 288 should play an important role in binding nitroaromatics. Moreover, there existed a good linear correlation between lnK(m) and calculated binding energy.


Initial results with an activated pyrolytic carbon tip electrode.
The initial results acquired from testing of a new activated pyrocarbon electrode for cardiac pacing are presented. In vitro testing has shown energy efficiency to be higher than for platinum electrodes. Histologic examination of implanted leads in animals has demonstrated a less significant tissue reaction at the tip. Finally, in a clinical trial of 121 patients with these leads, strength-duration curves have low rheobase values. Chronic thresholds are often consistently low. These reports suggest very satisfactory results with this pyrolytic carbon electrode.


Rapid determination of pseudoephedrine in human plasma by high-performance liquid chromatography.
A rapid high-performance liquid chromatographic method for the quantitation of pseudoephedrine in human plasma is presented. The sample preparation involved liquid-liquid extraction of pseudoephedrine from alkalised plasma with hexane-isoamylalcohol (9:1, v/v) and back-extraction of the drug to 0.02 M hydrochloric acid. Liquid chromatography was performed on an octadecylsilica column (50 x 4 mm, 5 microm particles); the mobile phase consisted of acetonitrile-phosphate buffer containing 0.1% of triethylamine, pH 2.4 (5:95, v/v). The run time was 4 min. The spectrophotometric detector was operated at 195 nm. Codeine was used as the internal standard. The limit of quantitation was 5.8 ng/ml using 0.5 ml of plasma. Within-day and between-day precision expressed by relative standard deviation was less than 7% and inaccuracy did not exceed 8%. The assay was applied to the analysis of samples from a pharmacokinetic study.


Dienophile-Modified Mannosamine Derivatives for Metabolic Labeling of Sialic Acids: A Comparative Study.
Sialic acids play an important role in numerous cell adhesion processes, and sialylation levels are known to be altered under certain pathogenic conditions, such as cancer. Metabolic glycoengineering with mannosamine derivatives is a convenient way to introduce non-natural chemical reporter groups into sialylated glycoconjugates, offering the opportunity to label sialic acids by using bioorthogonal ligation chemistry. The labeling intensity depends not only on the rate of the ligation reaction but also on the extent to which the natural sialic acids are replaced by the modified ones; that is, the incorporation efficiency. Here, we present a comparative study of eight mannosamine derivatives featuring terminal alkenes as chemical reporter groups that can be labeled by an inverse-electron-demand Diels-Alder (DAinv) reaction. The derivatives differed in chain length as well as the type of linkage (carbamates, amides, and a urea) that connects the terminal alkene to the sugar. As a general trend, increasing chain lengths resulted in higher DAinv reactivity and, at the same time, reduced incorporation efficiency. Carbamates were better accepted than amides with the same chain length; nevertheless, the latter resulted in more intense cell-surface staining, visible by live-cell fluorescence microscopy. A urea derivative was also shown to be accepted.


Links between chemsex and reduced mental health among Norwegian MSM and other men: results from a cross-sectional clinic survey.
The use of specific drugs to facilitate, enhance or prolong sexual sessions is referred to as 'chemsex'. The popularity of the behavior seems to be growing, but there is a paucity of information on the mental health aspects associated with chemsex and no data on chemsex from Nordic countries. We investigated the link between chemsex and mental health among men who have sex with men (MSM) and other men in Norway. We recruited participants from a walk-in sexually transmitted infections (STI) clinic. Participants completed a piloted, anonymous self-administered survey. It consisted of questions about men's sociodemographic characteristics, mental health, sexual behaviors, substance use, and chemsex. The outcome we investigated was reduced mental health, measured with the validated Hopkins Symptom Check List. We obtained descriptive statistics and performed univariate and multivariate logistic regression analyses. 1013 (96%) of the surveys were complete and could be analysed. The mean age of the sample was 33, 51% were MSM, and 21.7% had reduced mental health. More MSM than other men engaged in chemsex in the past year (17% vs 12%). The most frequently reported chemsex drugs were cocaine and gamma hydroxybutyrate/gamma butyrolactone (GHB/GBL). Men engaged in chemsex primarily to enhance sexual pleasure and excitement, and about half reported almost never or never using condoms for chemsex. In univariate analyses, significant predictors of reduced mental health was chemsex (Odds Ratio [OR] = 1.82), being unemployed (OR = 3.54), and having sex with only women (OR = 0.58). In multivariate analyses, two variables remained significantly associated with reduced mental health: chemsex (adjusted OR = 2.18, 95%CI = 1.25-3.78) and being unemployed (adjusted OR = 4.10, 95%CI = 2.13-7.87). In our sample of men from an STI clinic in Norway, about 14% self-reported engaging in chemsex in the past year and about a fifth of the men had reduced mental health. Men who engaged in chemsex, which more MSM engaged in than other men, had two times greater odds of reduced mental health. These findings suggest that mental health assistance should be among the interventions offered to men engaging in chemsex.


How prokaryotes 'encode' their environment: Systemic tools for organizing the information flow.
An important issue related to code biology concerns the cell's informational relationships with the environment. As an open self-producing system, a great variety of inputs and outputs are necessary for the living cell, not only consisting of matter and energy but also involving information flows. The analysis here of the simplest cells will involve two basic aspects. On the one side, the molecular apparatuses of the prokaryotic signaling system, with all its variety of environmental signals and component pathways (which have been called 1-2-3 Component Systems), including the role of a few second messengers which have been pointed out in bacteria too. And in the other side, the gene transcription system as depending not only on signaling inputs but also on a diversity of factors. Amidst the continuum of energy, matter, and information flows, there seems to be evidence for signaling codes, mostly established around the arrangement of life-cycle stages, in large metabolic changes, or in the relationships with conspecifics (quorum sensing) and within microbial ecosystems. Additionally, and considering the complexity growth of signaling systems from prokaryotes to eukaryotes, four avenues or "roots" for the advancement of such complexity would come out. A comparative will be established in between the signaling strategies and organization of both kinds of cellular systems. Finally, a new characterization of "informational architectures" will be proposed in order to explain the coding spectrum of both prokaryotic and eukaryotic signaling systems. Among other evolutionary aspects, cellular strategies for the construction of novel functional codes via the intermixing of informational architectures could be related to the persistence of retro-elements with obvious viral ancestry.


Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity.
Reduced serotonin neurotransmission is implicated in disorders of impulse control, but the involvement of serotonin in inhibitory processes in healthy human subjects remains unclear. To investigate the effects of an acute manipulation of serotonin and genotype at a functional polymorphism in a gene coding for the serotonin transporter (5-HTT) on an established measure of response inhibition. Serotonin function was reduced by the acute tryptophan depletion (ATD) procedure in a double-blind, crossover design in 42 healthy subjects. The Stop Signal Task (SST) was administered 5-7 h after drink administration. The influences of 5-HTT polymorphism, gender and trait impulsivity were investigated. ATD was associated with significant depletion of plasma tryptophan levels but did not increase the stop signal reaction time in comparison to the balanced (placebo) amino acid mixture. Subjects possessing the short allele of the 5-HTT polymorphism were not more impulsive on the SST than subjects homozygous for the long allele under placebo conditions and were not disproportionately sensitive to the effects of ATD. There was no effect of gender or trait impulsivity on ATD-induced change. We find no support for the involvement of brain serotonin neurotransmission in this form of inhibitory control in healthy human subjects.


Usefulness of electrophysiologic studies for new-onset sustained ventricular tachyarrhythmias shortly after coronary artery bypass grafting.
We retrospectively studied a group of 17 patients who developed life-threatening ventricular tachyarrhythmias shortly after coronary artery bypass grafting. The initial clinical event was sustained monomorphic ventricular tachycardia (VT) in 15 and ventricular fibrillation (VF) in 2, occurring at an average of 3.6 days postoperatively. All patients underwent electrophysiologic testing, with sustained monomorphic tachyarrhythmias inducible in 7. Three early deaths occurred after this initial evaluation. Among the 9 survivors with nonsustained, nonclinical or noninducible VT, 4 received no antiarrhythmic therapy and remained free of recurrence, whereas of the 5 that received drugs, implantable defibrillators, or both, 2 had spontaneous recurrence. For the surviving subgroup with inducible monomorphic VT, serial drug testing culminated in maintenance therapy with class IA agents or amiodarone, whereas defibrillators were also implanted in 3 patients. Overall, recurrence of life-threatening tachyarrhythmias beyond the immediate postoperative period was seen in 40% of patients with monomorphic clinical tachycardias and inducible sustained monomorphic VT. Ventricular tachyarrhythmias appearing shortly after cardiac surgery demonstrate significant chronicity and resistance to antiarrhythmic drug therapy, while statistically significant predictors of inducibility or their recurrence remain undefined.


[Childhood kidney tumors -- the relevance of imaging].
Kidney tumors represent 6.2% of malignant tumors in children. History, clinical course and radiological findings are necessary elements in the differential diagnosis of the different renal tumors. In the case of nephroblastoma, chemotherapy is based solely on the radiological diagnosis without prior histology. In therapy-optimizing studies of the Society of Pediatric Oncology and Hematology, preoperative chemotherapy is performed. Therapy monitoring is performed in the course of and after preoperative chemotherapy to verify tumor response. Radiological staging plays a significant role in deciding on further treatment and in operative planning. Three-dimensional visualization of the abdominal situs can assist preoperative planning. In summary, diagnostic imaging in renal tumors in children plays a role in differential diagnosis, staging, monitoring of therapy, and surgical planning.


Metal protein interactions.
Proteins associated with metals serve many important biological functions. The amino acid residues provide the functional groups in a protein which are the potential ligands for a metallic cation. Metals impart various effects on protein structure and bring about overall structural stability. These effects are seen in quarternary, secondary and tertiary structures of the protein. There are varieties of approaches to study metal protein interactions. The earliest technique being the equilibrium dialysis which is still used extensibly to determine the binding strength and the number of metals bound per protein molecule. There are a number of other techniques available which provide precise information about the nature of metal binding sites. They include electron spin resonance, UV and visible spectoscopy, nuclear magnetic resonance, resonance Raman, X-ray crystallography, X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (XAFS), etc. Selected metal protein interactions are discussed in this review. Albumin is the major plasma protein in blood which transports a number of metals. Detailed studies of Cu(II) and Ni(II) binding to albumin suggests that both metals have the same specific binding site at the NH2-terminal tripeptide sequence (Asp1-Ala2-His3...) involving the Asp alpha-NH2, His3 N (1) imidazole, two deprotonated peptide nitrogens (Ala2NH and His3NH), and Asp1 COO- group. Transferrin transports Fe(III) in blood. The protein possesses two metal-binding sites, each within a domain of bilobal proteins. Presence of carbonate is an important feature of Fe(III)-binding to transferrin. The binding site has been postulated as one involving Tyr 185 and Tyr 188 and suggests that two of the three histidines His 119, His 207 and His 249 also serve as ligands. Arginine 145 is a likely anchor for the carbonate anion. Superoxide dismutase is an enzyme found in erythrocytes which catalyzes the dismutation of superoxide radical. The protein is a dimer made up of two equivalent subunits. The subunits are held together by noncovalent interactions. For optimal enzymatic activity, at least two of the protein's four metal ions must be cupric. The results of the X-ray crystal structural analysis for Cu(II) and Zn(II) containing protein have been reported. In the metal-binding region of one subunit, Cu(II) and Zn(II) are separated by approximately 6A. The Cu(II) is bound to imidazole side chains of histidines 44, 46, 61 and 118 in a distorted square planar arrangement. The imidazole ring of histidine 61 is believed to be deprotonated and to serve as a bridge between Cu(II) and Zn(II).(ABSTRACT TRUNCATED AT 400 WORDS)


Optimizing the oxygen balance during initial reperfusion with 2,3-butanedione monoxime attenuates cardiac reperfusion injury.
The effect of 20 mmol/L butanedione monoxime on myocardial ischemia/reperfusion damage was studied in isolated guinea pig hearts. Three groups of hearts (n = 8) were perfused in the Langendorff mode and cardioplegic arrest was induced with St. Thomas Hospital II solution (STS) at 37 degrees C for 50 min. Myocardial oxygen demand, recovery of myocardial function, and creatine kinase release during 30 min of reperfusion were monitored. Preservation of myocardial ultrastructure was determined by electron microscopy. Control (C) hearts underwent cardioplegic arrest and reperfusion without treatment. BDM was added during cardioplegic arrest in BDMSTS hearts, or to the initial (20 min) reperfusate in BDMREP hearts. BDM during initial reperfusion markedly reduced O2 demand and prevented creatine kinase release from cardiac myocytes, resulting in improved recovery of myocardial function and attenuation of myocardial ultrastructural damage after washout of the drug. In contrast, addition of BDM to the cardioplegic solution provided no protection from ischemic or reperfusion injury.


Novel potentiometric and optical silver ion-selective sensors with subnanomolar detection limits.
Ten Ag+-selective ionophores have been characterized in terms of their potentiometric selectivities and complex formation constants in solvent polymeric membranes. The compounds with pi-coordination show much weaker interactions than those with thioether or thiocarbamate groups as the coordinating sites. Long-term studies with the best ionophores show that the lower detection limit of the best Ag+ sensors can be maintained in the subnanomolar range for at least 1 month. The best ionophores have also been characterized in fluorescent microspheres. The so far best lower detection limits of 3 x 10(-11) M (potentiometrically) and 2 x 10(-11) M Ag+ (optically) are found with bridged thiacalixarenes.


Dendritic branching in cortical pyramidal cells in response to ovariectomy in adult female rats: suppression by neonatal exposure to testosterone.
Female Long-Evans rats were treated with oil or testosterone propionate (TP) at birth (postnatal day zero, PN0) and PN1. As adults, animals from each group were ovariectomized or sham operated. Four months later the brains were prepared using a modified Golgi-Cox staining procedure. In neonatally oil-treated females, ovariectomy in adulthood increased the dendritic arbor of layer II/III pyramidal neurons of the parietal cortex; in addition, there were modest increases in apical dendritic spine density. The dendritic arbor of the pyramidal neurons of intact neonatally TP-treated females was greater than that of intact oil-treated females, but in these animals there was no increase in dendritic arbor in response to ovariectomy.


Thermal sensitization through ROS modulation: a strategy to improve the efficacy of hyperthermic intraperitoneal chemotherapy.
The purpose of this study was to investigate whether modulation of cellular reactive oxygen species (ROS) provides a synergistic effect with hyperthermia to induce tumor cell death in a colon cancer cell line. HT-29 colon cancer cells were exposed to heat (43 degrees C) in the presence of the ROS-generating drug, 2-2'-azobis-(2-amidinopropane) dihydrochloride (AAPH) for 1 h. Viable cell mass and apoptosis was measured by MTT and annexin V staining, respectively. Oxidative stress was evaluated by DCFH fluorescence. Protein levels were determined by Western blot analysis. A synergistic effect on cell viability with AAPH was noted under hyperthermic conditions as compared with hyperthermia alone (P < .05). The number of nonviable cells after hyperthermia and AAPH exposure was also significantly increased compared with AAPH at 37 degrees C (42% vs 20%, P < .05). ROS levels were increased modestly with AAPH at 37 degrees C, whereas they increased significantly in a dose-dependent manner with AAPH at 43 degrees C. Transient increases of phosphorylated-p38 and ERK and decreases in phosphorylated-AKT were observed in the cells exposed to AAPH at 43 degrees C. Pretreatment of inhibitors of p38 yielded additional decreases in cell mass when used in combination with AAPH and hyperthermia (P < .05). Increased expression of HSP 27 observed at 43 degrees C was abrogated with AAPH exposure. Oxidative stress increased the cytotoxic effects of hyperthermia in colon cancer cells. Thermal sensitization through modulation of cellular ROS may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.


Reliability and Validity Evidence for Brief Sexual Attitudes Scale (BSAS) Among Filipino Men: A Confirmatory Factor Analysis.
Background and Purpose: It is essential to address sexual health to ensure quality of life and sexual well-being; however, studies to measure sexual attitudes remain scarce. This aimed to find reliability and validity evidence of the Brief Sexual Attitudes Scale (BSAS) using confirmatory factor analysis (CFA) among Filipino men. Methods: A cross-sectional study was conducted. Results: BSAS shows Cronbach's alpha of 0.90. CFA demonstrates goodness of fit (adjusted goodness-of-fit index = .82; goodness-of-fit index = .86; comparative fit index = .91; incremental fit index = .91; expected cross-validation index = 2.27; root mean square error of approximation = .08; [χ2 (213) = 927.45, p ≤ .001], χ2/df ratio 4.35). Conclusions: BSAS is a valid and reliable questionnaire to assess sexual attitudes among Filipino men. Further research is needed to evaluate sexual attitudes in the promotion of sexual health across cultures.


Light microscopic observations on cat Renshaw cells after intracellular staining with horseradish peroxidase. I. The axonal systems.
Five intracellularly HRP-stained Renshaw cells were subjected to light microscopic analysis of the trajectories, branching patterns, and projections of the axonal systems. The cell bodies were located ventrally in lamina VII. In three neurons the axon originated from the cell body and in the remaining two cells from a dendrite. After a 600-870-microns distance the axons entered the ventral funiculus, where all of them continued rostrally. Two axons also gave off a caudal branch in the funiculus. The diameters of the main axons varied between 2.1 and 10.0 microns. The main axons gave off one to four first-order collaterals before entering the ventral funiculus and up to three collaterals could be seen to originate from the same node of Ranvier. In the ventral funiculus up to five first-order collaterals could be traced from the same main axon. The axon collateral trees were often very extensive and daughter branches up to the 22nd order were observed. The distance between two successive branching points varied between 4 and 410 microns. A large number of boutonlike swellings were found along (59%) or at the ends of the collateral branches. At the most, 1,278 swellings originated from a single axon collateral tree. Most of the swellings were located in lamina IX, but they also appeared ventrally and dorsolaterally in lamina VII.


Perfusion brain SPECT in assessing motor improvement after deep brain stimulation in Parkinson's disease.
High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an established therapeutic approach for the management of patients with late-stage idiopathic Parkinson's disease (PD). The aim of the present study was to assess regional cerebral blood flow (rCBF) changes related to motor improvement. Twenty-one PD patients underwent two rCBF SPECT studies at rest, once preoperatively in the off-meds state and the other postoperatively (at 6 ± 2 months) in the off medication/on stimulation state. Patients were classified according to the UPDRS and H&Y scale. NeuroGam software was used to register, quantify, and compare two sequential brain SPECT studies of the same patient in order to investigate rCBF changes during STN stimulation in comparison with preoperative rCBF. The relationship between rCBF and UPDRS scores was used as a covariate of interest. Twenty patients showed clinical improvement during the first months after surgery, resulting in a 44 % reduction of the UPDRS motor score. The administered mean daily levodopa dose significantly decreased from 850 ± 108 mg before surgery to 446 ± 188 mg during the off-meds state (p < 0.001, paired t test). At the 6-month postoperative assessment, we noticed rCBF increases in the pre-supplementary motor area (pre-SMA) and the premotor cortex (PMC) (mean rCBF increase = 10.2 %, p < 0.05), the dorsolateral prefrontal cortex and in associative and limbic territories of the frontal cortex (mean rCBF increase = 8.2 %, p > 0.05). A correlation was detected between the improvement in motor scores and the rCBF increase in the pre-SMA and PMC (r = 0.89, p < 0.001). Our study suggests that STN stimulation leads to improvement in neural activity and rCBF increase in higher-order motor cortical areas.


Characterization of the fluorescence of the antitumor agent, mitoxantrone.
Studies have been conducted on the absorption, fluorescence excitation and fluorescence emission of mitoxantrone, an important antineoplastic agent. Mitoxantrone has been found to fluoresce with excitation maxima at 610 and 660 nm and emission maximum at 685 nm. Further characterizations of the fluorescence were undertaken to study its usefulness in biological studies. Mitoxantrone fluorescence intensity is altered by pH and the emission spectrum is red-shifted by DNA. Furthermore, the fluorescence polarization is enhanced by DNA, confirming the binding of the antitumor agent to DNA. The fluorescence spectra are slightly modified by changes in ionic strength and the addition of albumin. Data establishing the usefulness of fluorescence to measure serum concentrations in the range of 0.0 to 100 nM are presented. Such determinations can distinguish serum mitoxantrone from its non-fluorescent primary metabolite.


A nuclear role for Kaposi's sarcoma-associated herpesvirus-encoded K13 protein in gene regulation.
Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded viral FLICE inhibitory protein K13 interacts with a cytosolic IkappaB kinase (IKK) complex to activate nuclear factor-kappaB (NF-kappaB). We recently reported that K13 antagonizes KSHV lytic regulator RTA (replication and transcription activator) and blocks lytic replication, but spares RTA-induced viral interleukin-6 (vIL6). Here we report that K13 is also present in the nuclear compartment, a property not shared by its structural homologs. K13 interacts with and activates the nuclear IKK complex, and binds to the IkappaBalpha promoter. K13 mutants that are retained in the cytosol lack NF-kappaB activity. However, neither the IKKs nor NF-kappaB activation is required for nuclear localization of K13. Instead, this ability is dependent on a nuclear localization signal located in its N-terminal 40 amino acids. Finally, K13, along with p65/RelA, binds to the promoters of a number of KSHV lytic genes, including RTA, ORF57 and vGPCR, but not to the promoter of the vIL6 gene. Thus, K13 has an unexpected nuclear role in viral and cellular gene regulation and its differential binding to the promoters of lytic genes may not only contribute to the inhibition of KSHV lytic replication, but may also account for the escape of vIL6 from K13-induced transcriptional suppression.


Modeling COVID-19 pandemic using Bayesian analysis with application to Slovene data.
In the paper, we propose a semiparametric framework for modeling the COVID-19 pandemic. The stochastic part of the framework is based on Bayesian inference. The model is informed by the actual COVID-19 data and the current epidemiological findings about the disease. The framework combines many available data sources (number of positive cases, number of patients in hospitals and in intensive care, etc.) to make outputs as accurate as possible and incorporates the times of non-pharmaceutical governmental interventions which were adopted worldwide to slow-down the pandemic. The model estimates the reproduction number of SARS-CoV-2, the number of infected individuals and the number of patients in different disease progression states in time. It can be used for estimating current infection fatality rate, proportion of individuals not detected and short term forecasting of important indicators for monitoring the state of the healthcare system. With the prediction of the number of patients in hospitals and intensive care units, policy makers could make data driven decisions to potentially avoid overloading the capacities of the healthcare system. The model is applied to Slovene COVID-19 data showing the effectiveness of the adopted interventions for controlling the epidemic by reducing the reproduction number of SARS-CoV-2. It is estimated that the proportion of infected people in Slovenia was among the lowest in Europe (0.350%, 90% CI [0.245-0.573]%), that infection fatality rate in Slovenia until the end of first wave was 1.56% (90% CI [0.94-2.21]%) and the proportion of unidentified cases was 88% (90% CI [83-93]%). The proposed framework can be extended to more countries/regions, thus allowing for comparison between them. One such modification is exhibited on data for Slovene hospitals.


Poverty and blindness in Africa.
Africa carries a disproportionate responsibility in terms of blindness and visual impairment. With approximately 10 per cent of the world's population, Africa has 19 per cent of the world's blindness. It is no surprise that this reality also mirrors the situation in terms of the burden of world poverty. There is an increasing recognition of the need to highlight the link between poverty, development and health care. Blindness, disabling visual impairment and the overall lack of eye-care services are too often the result of social, economic and developmental challenges of the developing world. The state of eye care in Africa stands in alarming contrast to that in the rest of the world. Poor practitioner-to-patient ratios, absence of eye-care personnel, inadequate facilities, poor state funding and a lack of educational programs are the hallmarks of eye care in Africa, with preventable and treatable conditions being the leading cause of blindness. Eye diseases causing preventable blindness are often the result of a combination of factors such as poverty, lack of education and inadequate health-care services. The challenge that Vision 2020 has set itself in Africa is enormous. Africa is not a homogenous entity, the inter- and intra-country differences in economic development, prevalence of disease, delivery infrastructure and human resources amplify the challenges of meeting eye-care needs. The successful implementation of Vision 2020 programs will be hindered without the development of a comprehensive, co-ordinated strategy that is cognisant of the differences that exist and the need for comprehensive solutions that are rooted in the economic and political realities of the continent as well as the individual countries and regions within countries. This strategy should recognise the need for economic growth that results in greater state funded eye-care services that focus on health promotion to ensure the prevention of eye disease, the development of eye clinics in hospitals and health clinics, and the training of the appropriate human resources.


Pediatric Oral Health Policy: Its Genesis, Domains, and Impacts.
Over recent years, pediatric oral health has become well established in the United States as an essential component of pediatric health policy as evidenced by the programs authorized and funded by Congress. These actions have improved access and utilization of dental care, engaged primary care pediatrics in oral health, and improved children's oral health outcomes. Nonetheless, there remains a host of authorized but unfunded approaches to addressing children's oral health through coverage, workforce, safety net, prevention, and surveillance. Child health advocates and practitioners need to actively engage as advocates if further improvements are to be attained through policymaking.


Thrombin Hemostatic Matrix Reduces Heterotopic Ossification in Acetabular Fractures Fixed Through the Kocher-Langenbeck Approach.
To determine whether an injectable thrombin product [thrombin hemostatic matrix (THM)] at closure of a Kocher-Langenbeck approach reduces the risk of heterotopic ossification (HO) formation after an acetabular fracture. Case control. Two Level 1 trauma centers. Patients with operatively treated acetabulum fractures fixed through Kocher-Langenbeck from 2013 to 2018. Records were reviewed for demographics, history of traumatic brain injury, HO medication or radiation prophylaxis, THM (Surgiflo, Ethicon, Bridgewater New Jersey) administration, and length of follow-up. Radiographs were reviewed for dislocation, fracture, Letournel and Orthopaedic Trauma Association classifications, HO, and Brooker grade if applicable. Patients receiving HO prophylaxis (eg, nonsteroidal anti-inflammatory drugs and radiation) were excluded. Remaining patients were divided into 2 groups: THM administration (intervention) and no THM. Continuous variables were compared using t-tests and categorical variables with chi-square or Fisher's exact tests. Risk ratios for the association between HO occurrence and THM administration. Three-hundred and twenty-eight acetabular fractures met inclusion criteria (126 intervention, 202 control) in patients with a mean age of 38.7 ± 15.9 years; 62.2% were male, and 42.1% were African American. Traumatic brain injury and posterior dislocation rates were equivalent between groups (P = 0.505, 0.754, respectively). HO rate in the control group was 42.6% compared with 21.4% in the THM group (P < 0.001). Booker grade 3/4 in control group was 17.3% versus 3.2% in the THM group (P < 0.001). Patients receiving THM had a 50% reduced risk of HO (95% confidence interval 0.35-0.73) compared to those who did not; adjustment for age, gender, ethnicity, and traumatic brain injury did not meaningfully change the association (risk ratio 0.46; 95% confidence interval 0.29-0.73; P < 0.001). The use of a surgiflo product at closure of a KO approach may reduce the risk of HO formation by 50% after an acetabular fracture. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Acute myeloblastic leukemia (M2) with translocation (7;11) followed by marked eosinophilia and additional abnormalities of chromosome 5.
We present an 18-year-old woman who was diagnosed with acute myeloblastic leukemia (AML M2), and in whom chromosome analysis of bone marrow cells revealed t(7;11), an abnormality rarely found in leukemias with a differentiation potency. She relapsed 1 year after complete remission was achieved by chemotherapy. Bone marrow examination then revealed a t(7;11) abnormality in 48 of 50 metaphases examined, even when there were less than 7.5% leukemic blasts in the marrow, indicating that the morphologically normal cells were derived from leukemic blasts. The number of leukemia clones with the additional abnormalities in chromosome 5 increased, with concurrent development of eosinophilia, fever, asthma-like symptoms, erythema, itching, and hepatosplenomegaly. Elevation of interleukin 5 (IL-5) in serum and an enhanced expression of IL-5 mRNA were also detected. The increase in IL-5 may have been produced by an abnormality on chromosome 5.


'Continuity of Care Experiences' within pre-registration midwifery education programs: A scoping review.
Midwifery is based on the philosophy of woman-centred care. The continuity of care experience in pre-registration education programs exemplifies this philosophy. Wide variation in how education providers implement 'Continuity of Care Experiences' into their programs of study can challenge this valuable learning opportunity. To provide a comprehensive analysis of the governance and empirical evidence of knowledge, practice and enablers to support continuity of care experiences within pre-registration midwifery education. A scoping review of research, policy and professional documents pertaining to the continuity of care experience in pre-registration education programs was conducted with 46 articles meeting the inclusion criteria. Several factors were identified that support the implementation, facilitation and evaluation of the continuity of care experience within pre-registration midwifery education. These include: a woman-centred model of maternity care; enabling midwifery students and women to develop 'relational continuity'; tripartite support models; optimising the sequencing of these experiences within the program and, woman-led evaluations of student performance. There was little consensus regarding the pedagogical intent and, therefore, an inability to clearly define and measure the learning outcomes of the continuity of care experience. In countries where the predominant model of maternity care is fragmented and not woman-centred, further research is required to understand the pedagogical intent of the continuity of care experience.


Pathogenesis of colonic diverticula.
Diverticula are herniations through the colonic wall and are therefore likely to be due to a weakness within the wall, an alteration in intracolonic pressures or a combination of these factors. This article reviews these aspects in relation to the pathogenesis of colonic diverticula. Medline and Science Citation Index searches were performed to locate English language articles relating to the pathogenesis of colonic diverticulosis published since 1960. Manual cross-referencing was also performed and some historical articles were included. Several theories now exist about the development of colonic diverticula. The majority of the evidence suggests that the morphological changes are the response to a lifelong consumption of a low-residue diet. However, there are complex relations between colonic structure, motility and dietary factors, and it is likely that all of these (and possibly genetic influences) play a role in the pathogenesis to a greater or lesser degree.


Biotechnological approaches for conservation and improvement of rare and endangered plants of Saudi Arabia.
Genetic variation is believed to be a prerequisite for the short-and long-term survival of the plant species in their natural habitat. It depends on many environmental factors which determine the number of alleles on various loci in the genome. Therefore, it is important to understand the genetic composition and structure of the rare and endangered plant species from their natural habitat to develop successful management strategies for their conservation. However, rare and endangered plant species have low genetic diversity due to which their survival rate is decreasing in the wilds. The evaluation of genetic diversity of such species is very important for their conservation and gene manipulation. However, plant species can be conserved by in situ and in vitro methods and each has advantages and disadvantages. DNA banking can be considered as a means of complimentary method for the conservation of plant species by preserving their genomic DNA at low temperatures. Such approach of preservation of biological information provides opportunity for researchers to search novel genes and its products. Therefore, in this review we are describing some potential biotechnological approaches for the conservation and further manipulation of these rare and endangered plant species to enhance their yield and quality traits.


Controlled oxygen administration in acute respiratory failure in chronic obstructive pulmonary disease: a reappraisal.
Controlled oxygen therapy may aggravate carbon dioxide retention during acute exacerbations of chronic obstructive pulmonary disease (COPD). Of 50 consecutive patients with COPD and acute respiratory failure, 13 required intubation because of carbon dioxide narcosis. With discriminant analysis of their arterial oxygen tension (PaO2) and pH on admission, a diagram separated patients into those at high risk and those at low risk for carbon dioxide narcosis. This diagram was then used to predict carbon dioxide narcosis in 73 patients with COPD and acute respiratory failure who were treated with controlled oxygen. In 16 of these patients carbon dioxide narcosis developed. Thirteen (81 per cent) were predicted by the diagram to be at high risk for this complication. Only two (4 per cent) patients judged by the diagram to be at low risk for carbon dioxide narcosis required mechanical ventilation. Utilizing an oxygen tension (PO2), carbon dioxide tension (PCO2) diagram a patient's ventilatory response was compared to that of ambulatory patients with COPD. These data suggest that hypoxemia and acidosis are more discriminatory for "carbon dioxide narcosis" than hypercapnia.


High dose ketoconazole in the treatment of cerebral aspergilloma.
A 32-year-old Chinese woman with bilateral occipital aspergilloma was treated successfully with high dose ketoconazole (1200 mg/day) for six months in conjunction with amphotericin B and 5-fluorocytosine. No unacceptable side effects occurred. The use of high dose ketoconazole could be considered in CNS aspergillosis unresponsive to conventional anti-fungal therapy.


Differential gene regulation in Yersinia pestis versus Yersinia pseudotuberculosis: effects of hypoxia and potential role of a plasmid regulator.
The molecular basis of the biological differences between Yersinia pestis and Yersinia pseudotuberculosis remains largely unknown, and relatively little is known about environmental regulation of gene expression in these bacteria. We used a proteomic approach to explore the regulatory response of each bacterium to carbon dioxide-supplemented hypoxic conditions. Both organisms responded similarly and the magnitude of their responses was similar to what was observed in low iron conditions. We also identified proteins that were expressed at different levels in Y. pestis and Y. pseudotuberculosis, and found that SodB is expressed more strongly at both the protein and RNA levels in Y. pseudotuberculosis than in Y. pestis. Enzyme activity did not directly correlate with levels of protein expression, and we propose that an amino acid change difference between these orthologous proteins has the potential to affect catalytic activity. In addition, the upstream regulatory regions of several chromosomal genes were found to exhibit specific binding with a putative transcription factor, CDS4, from the Y. pestis-specific pPCPI plasmid. The potential role of this protein in modulating Y. pestis- specific gene regulation warrants further investigation.


Orphan G protein-coupled receptors (GPCRs): biological functions and potential drug targets.
The superfamily of G protein-coupled receptors (GPCRs) includes at least 800 seven-transmembrane receptors that participate in diverse physiological and pathological functions. GPCRs are the most successful targets of modern medicine, and approximately 36% of marketed pharmaceuticals target human GPCRs. However, the endogenous ligands of more than 140 GPCRs remain unidentified, leaving the natural functions of those GPCRs in doubt. These are the so-called orphan GPCRs, a great source of drug targets. This review focuses on the signaling transduction pathways of the adhesion GPCR family, the LGR subfamily, and the PSGR subfamily, and their potential functions in immunology, development, and cancers. In this review, we present the current approaches and difficulties of orphan GPCR deorphanization and characterization.


Validity and reliability of an electromyography-based similarity index to quantify lower extremity selective voluntary motor control in children with cerebral palsy.
To quantify selective voluntary motor control (SVMC) objectively and more precisely, we combined the "Selective Control Assessment of the Lower Extremity" (SCALE) with surface electromyography. The resulting Similarity Index (SI) measures the similarity of muscle activation patterns. This study evaluated the preliminary validity and reliability of this novel SISCALE measure in children with cerebral palsy (CP). We investigated concurrent validity by correlating the SISCALE of 24 children with CP (median age 10.6 years) with comparator assessments. For discriminative validity, the patients' SISCALE scores were compared to 31 neurologically intact age-matched peers. Test-retest reliability was quantified using intraclass correlation coefficients (ICC) and minimal detectable change (MDC) values. The SISCALE correlated strongly with the SCALE (ρ = 0.90, p < .001) and the Gross Motor Function Classification System (ρ = -0.74, p < .001). SISCALE scores were significantly lower in children with CP compared to healthy peers. Test-retest reliability appeared good (for the more and less affected leg, ICC ≥ 0.84, and MDC ≤ 0.17). Validity and reliability of the SISCALE leg and total scores lay within clinically acceptable ranges. Further clinimetric analyses should include responsiveness. A neurophysiology-based assessment could contribute to a more refined assessment of SVMC impairments.


Characterization of Na+/H+ exchange in FRTL-5 thyroid cells. Evidence for dependence on activation of protein kinase C.
Na+/H+ exchange activity was investigated in cultured rat thyroid follicular FRTL-5 cells using the pH sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Basal intracellular pH (pHi) was 7.13 +/- 0.10 in cells incubated in Hepes-buffered saline solution. The intracellular buffering capacity beta i was determined using the NH4Cl-pulse method, yielding a beta i value of 85 +/- 12 mM/pH unit. The relationship between extracellular Na+ and the initial rate of alkalinization of acid-loaded cells showed simple saturation kinetics, with an apparent Km value of 44 +/- 26 mM, and an Vmax value of 0.3 +/- 0.01 pH unit/min. The agonist-induced activation of Na+/H+ exchange was investigated in cells acidified with nigericin. Addition of 12-O-tetradecanoylphorbol 13-acetate (TPA) or ATP induced rapid cytosolic alkalinization in acid-loaded cells. The action of both TPA and ATP was abolished by preincubating the cells with 100 microM amiloride, by substituting extracellular Na+ with equimolar concentrations of choline+, and by pretreating the cells with TPA for 24 h. Chelating extracellular Ca2+, or depleating intracellular Ca2+ pools did not affect the ATP-induced alkalinization. The results indicate, that FRTL-5 cells have a functional Na+/H+ exchange mechanism. Furthermore, stimulation of protein kinase C activity is of importance in activating the antiport.


Fabrication and nano-engineering of non-/noble metal-coupled plasmonic heterostructures for ultrasensitive photoelectrochemical immunoassays.
To achieve reliable and ultrasensitive detection for disease markers in PEC bioanalysis, constructing and nano-engineering of ideal photoelectrodes and signal transduction strategies are of vital importance. Herein, a non-/noble metal coupled plasmonic nanostructure (TiO2/r-STO/Au) was tactically designed with high-efficient PEC performance. Evidenced by the DFT and FDTD calculations, the reduced SrTiO3 (r-STO) was found to support the localized surface plasmon resonance due to the sufficiently increased and delocalized local charge in r-STO. Under the synergistic coupling of plasmonic r-STO and AuNPs, the PEC performance of TiO2/r-STO/Au was found remarkably promoted with reduced onset potential. This merit supported TiO2/r-STO/Au as a self-powered immunoassay via a proposed oxygen-evolution-reaction mediated signal transduction strategy. With the increase of the target biomolecules (PSA), the catalytic active sites of TiO2/r-STO/Au would be blocked and result in the decrease of the oxygen evaluation reaction. Under optimal conditions, the immunoassays exhibited an excellent detection performance with a LOD as low as 1.1 fg/mL. This work proposed a new type of plasmonic nanomaterial for ultrasensitive PEC bioanalysis.


Bone marrow-derived cells from the footprint infiltrate into the repaired rotator cuff.
Cells from the bone marrow are considered important during the rotator cuff repair process, but the kinetics of bone marrow-derived cells in this process is unknown. To analyze the kinetics of bone marrow cells during the rotator cuff repair process, to review whether or not they are histologically involved in rotator cuff healing, and to analyze the biomechanics of the repaired tissues. Bone marrow chimeric rats that express green fluorescent protein (GFP) only in bone marrow- and circulation-derived cells were created. Bilateral supraspinatus tendons were separated from the greater tuberosity of the humeral head to produce a rotator cuff transection model. Drilling into the bone marrow was performed in the greater tuberosity of the right humerus and the supraspinatus tendon was repaired (drilling group), while the supraspinatus tendon was repaired on the left shoulder without drilling (control group). We examined the histology of the rotator cuff, the ultimate force-to-failure, and the proportion of GFP-positive cells in the repaired rotator cuff at 2, 4 and 8 weeks after surgery. Mesenchymal cells were observed in the repaired rotator cuff at 2 weeks in both groups. There were more GFP-positive cells in the drilling group than the control group at 2, 4 and 8 weeks. The ultimate force-to-failure was significantly higher in the drilling group than the control group at 4 and 8 weeks. Bone marrow-derived cells passed through holes drilled in the humerus footprint, infiltrated the repaired rotator cuff and contributed to postsurgical rotator cuff healing.


Glycan Engineering for Cell and Developmental Biology.
Cell-surface glycans are a diverse class of macromolecules that participate in many key biological processes, including cell-cell communication, development, and disease progression. Thus, the ability to modulate the structures of glycans on cell surfaces provides a powerful means not only to understand fundamental processes but also to direct activity and elicit desired cellular responses. Here, we describe methods to sculpt glycans on cell surfaces and highlight recent successes in which artificially engineered glycans have been employed to control biological outcomes such as the immune response and stem cell fate.


The effect of nonmalignant systemic disease on tolerance to radiation therapy.
Some patients with nonmalignant systemic diseases, like collagen vascular disease (CVD), hypertension, diabetes mellitus, and inflammatory bowel disease (IBD), tolerate radiation therapy poorly. Although the mechanisms of each of these disease processes are different, they share a common microvessel pathology that is potentially exacerbated by radiotherapy. This article reviews and evaluates available data examining the effects of these benign disease processes on radiation tolerance. We conducted a thorough review of the Anglo-American medical literature from 1960 to 2001 on the effects of radiotherapy on CVD, hypertension, diabetes mellitus, and IBD. Fifteen studies were identified that examined the effects of radiation therapy for cancer in patients with CVDs. Thirteen of 15 studies documented greater occurrences of acute and late toxicities (range 7%-100%). Higher rates of complications were noted especially for nonrheumatoid arthritis CVDs. Nine studies evaluated the effects of hypertension and diabetes on radiation tolerance. All nine studies documented higher rates of late toxicities than in a "control" group (range 34%-100%). When patients had both diabetes and hypertension, the risk of late toxicities was even higher. Six studies examined radiation tolerance of patients with IBD irradiated to the abdomen and pelvis. Five of these six studies showed greater occurrences of acute and late toxicities for patients with IBD, even with precautionary measures like reduced fraction size and volume and patient immobilization (13%-29%). The majority of published studies documented lower radiation tolerance for patients who have CVD, diabetes mellitus, hypertension, and IBD. This may reflect a publication bias, as the majority of these studies are retrospective with small numbers of patients and use different scoring scales for complications. These factors may contribute to an overestimation of true radiation-induced morbidity. Although the paucity of data makes precise estimates difficult, a subset of patients, in particular, those with active CVD, IBD, or a combination of uncontrolled hypertension with type I diabetes, is likely to be at higher risk. Future prospective trials need to document these disease entities when reporting treatment-related complications and also must monitor toxicities associated with quiescent versus active IBD and CVD, type I versus type II diabetes, and levels of hypertension (controlled versus uncontrolled) matched for radiation-specific treatment sites, field size, fractionation, and total dose.


Optimized spirooxindole-pyrazole hybrids targeting the p53-MDM2 interplay induce apoptosis and synergize with doxorubicin in A549 cells.
Recently, cancer research protocols have introduced clinical-stage spirooxindole-based MDM2 inhibitors. However, several studies reported tumor resistance to the treatment. This directed efforts to invest in designing various combinatorial libraries of spirooxindoles. Herein, we introduce new series of spirooxindoles via hybridization of the chemically stable core spiro[3H-indole-3,2'-pyrrolidin]-2(1H)-one and the pyrazole motif inspired by lead pyrazole-based p53 activators, the MDM2 inhibitor BI-0252 and promising molecules previously reported by our group. Single crystal X-ray diffraction analysis confirmed the chemical identity of a representative derivative. Fifteen derivatives were screened for cytotoxic activities via MTT assay against a panel of four cancer cell lines expressing wild-type p53 (A2780, A549, HepG2) and mutant p53 (MDA-MB-453). The hits were 8h against A2780 (IC50 = 10.3 µM) and HepG2 (IC50 = 18.6 µM), 8m against A549 (IC50 = 17.7 µM), and 8k against MDA-MB-453 (IC50 = 21.4 µM). Further MTT experiments showed that 8h and 8j potentiated doxorubicin activity and reduced its IC50 by at least 25% in combinations. Western blot analysis demonstrated that 8k and 8m downmodulated MDM2 in A549 cells. Their possible binding mode with MDM2 were simulated by docking analysis.


Mitochondrial dysfunction caused by outer membrane vesicles from Gram-negative bacteria activates intrinsic apoptosis and inflammation.
Sensing of microbes activates the innate immune system, depending on functional mitochondria. However, pathogenic bacteria inhibit mitochondrial activity by delivering toxins via outer membrane vesicles (OMVs). How macrophages respond to pathogenic microbes that target mitochondria remains unclear. Here, we show that macrophages exposed to OMVs from Neisseria gonorrhoeae, uropathogenic Escherichia coli and Pseudomonas aeruginosa induce mitochondrial apoptosis and NLRP3 inflammasome activation. OMVs and toxins that cause mitochondrial dysfunction trigger inhibition of host protein synthesis, which depletes the unstable BCL-2 family member MCL-1 and induces BAK-dependent mitochondrial apoptosis. In parallel with caspase-11-mediated pyroptosis, mitochondrial apoptosis and potassium ion efflux activate the NLRP3 inflammasome after OMV exposure in vitro. Importantly, in the in vivo setting, the activation and release of interleukin-1β in response to N. gonorrhoeae OMVs is regulated by mitochondrial apoptosis. Our data highlight how innate immune cells sense infections by monitoring mitochondrial health.


New evidence for secondary axonal degeneration in demyelinating neuropathies.
Development of peripheral nervous system (PNS) myelin involves a coordinated series of events between growing axons and the Schwann cell (SC) progenitors that will eventually ensheath them. Myelin sheaths have evolved out of necessity to maintain rapid impulse propagation while accounting for body space constraints. However, myelinating SCs perform additional critical functions that are required to preserve axonal integrity including mitigating energy consumption by establishing the nodal architecture, regulating axon caliber by organizing axonal cytoskeleton networks, providing trophic and potentially metabolic support, possibly supplying genetic translation materials and protecting axons from toxic insults. The intermediate steps between the loss of these functions and the initiation of axon degeneration are unknown but the importance of these processes provides insightful clues. Prevalent demyelinating diseases of the PNS include the inherited neuropathies Charcot-Marie-Tooth Disease, Type 1 (CMT1) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) and the inflammatory diseases Acute Inflammatory Demyelinating Polyneuropathy (AIDP) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Secondary axon degeneration is a common feature of demyelinating neuropathies and this process is often correlated with clinical deficits and long-lasting disability in patients. There is abundant electrophysiological and histological evidence for secondary axon degeneration in patients and rodent models of PNS demyelinating diseases. Fully understanding the involvement of secondary axon degeneration in these diseases is essential for expanding our knowledge of disease pathogenesis and prognosis, which will be essential for developing novel therapeutic strategies.


Vibrational analysis on the revised potential energy curve of the low-barrier hydrogen bond in photoactive yellow protein.
Photoactive yellow protein (PYP) has a characteristic hydrogen bond (H bond) between p-coumaric acid chromophore and Glu46, whose OH bond length has been observed to be 1.21 Å by the neutron diffraction technique [Proc. Natl. Acad. Sci. 106, 440-4]. Although it has been expected that such a drastic elongation of the OH bond could be caused by the quantum effect of the hydrogen nucleus, previous theoretical computations including the nuclear quantum effect have so far underestimated the bond length by more than 0.07 Å. To elucidate the origin of the difference, we performed a vibrational analysis of the H bond on potential energy curve with O…O distance of 2.47 Å on the equilibrium structure, and that with O…O distance of 2.56 Å on the experimental crystal structure. While the vibrationally averaged OH bond length for equilibrium structure was underestimated, the corresponding value for crystal structure was in reasonable agreement with the corresponding experimental values. The elongation of the O…O distance by the quantum mechanical or thermal fluctuation would be indispensable for the formation of a low-barrier hydrogen bond in PYP.


A magnetic resonance imaging-safe method for the study of human eyeblink conditioning.
Eyeblink conditioning (EBC) is a widely used translational probe of cerebellar function in both humans and non-human animals. Decades of animal research have identified the cerebellum as critical for EBC. While there is evidence for the involvement of the cerebellum in human EBC, the neural circuitry of EBC in healthy humans has yet to be fully elucidated. The purpose of this study was to design and validate a highly customisable system for EBC stimulus presentation and response recording using infrared (IR) reflectance suitable for use in magnetic resonance imaging (MRI) environments; in this way, the neural activity of EBC could be investigated using fMRI in humans. Four participants underwent delay EBC and simultaneous fMRI. The results indicate (1) a high signal-to-noise ratio in the IR reflectance data that effectively quantifies the eyeblink morphology and timing and (2) evidence of conditioning in the fMRI environment. The quality of the data, the feasibility of conducting EBC experiments in the fMRI environment, and the customisability of the current system to fit a variety of EBC experimental design parameters are discussed.


Public Health Data in Action: An Analysis of Using Louisiana Vital Statistics for Quality Improvement and Payment Reform.
Introduction In 2012, the Louisiana (LA) Department of Health and Hospitals revised the LA birth certificate to include medical reasons for births before 39 completed weeks' gestation. We compared the completeness and validity of these data with hospital discharge records. Methods For births occurring 4/1/2012-9/30/2012 at Woman's Hospital of Baton Rouge, we linked maternal delivery and newborn birth data collected through the National Perinatal Information Center with LA birth certificates. Among early term births (37-38 completed weeks' gestation), we quantified the reasons for early delivery listed on the birth certificate and compared them with ICD-9-CM codes from Woman's discharge data. Results Among 4353 birth certificates indicating delivery at Woman's Hospital, we matched 99.8% to corresponding Woman's administrative data. Among 1293 early term singleton births, the most common reasons for early delivery listed on the birth certificate were spontaneous active labor (57.5%), gestational hypertensive disorders (15.3%), gestational diabetes (8.7%), and premature rupture of membranes (8.1%). Only 2.7% of births indicated "other reason" as the only reason for early delivery. Most reasons for early delivery had >80% correspondence with ICD-9-CM codes. Lower correspondence (35 and 72%, respectively) was observed for premature rupture of membranes and abnormal heart rate or fetal distress. Discussion There was near-perfect ability to match LA birth certificates with Woman's Hospital records, and the agreement between reasons for early delivery on the birth certificate and ICD-9-CM codes was high. A benchmark of 2.7% can be used as an attainable frequency of "other reason" for early delivery reported by hospitals. Louisiana implemented an effective mechanism to identify and explain early deliveries using vital records.


Effect of hexachlorophene intoxication on learning in rats.
Neurotoxicity in the form of hindlimb paralysis is known to be associated with brain lesions characterized by vacuolation of the white matter following hexachlorophene (HCP) intoxication; these paralytic and histopathological effects are reversible with time after discontinuance of HCP exposure. The rates of acquiring a bar-pressing escape and avoidance behavior were measured in female rats after recovery from paralysis following daily oral dosing with HCP (25 mg/kg). Learning deficits were seen as a delay in reaching a 90% escape performance level, as an increase in the number of sessions required to reach a 50% avoidance criterion, as an increase in training time needed to transfer from escape to avoidance responding, and by an increase in the number of sessions needed to reach a maximum level of avoidance behavior over a 35-session period. Peak responding eventually reached a level comparable to controls only after prolonged periods. Brain lesions seen 2-3 months after HCP intoxiciation correlated with the lag in learning ability but not with the maximum avoidance acquisition before sacrifice. These results indicate a long-lasting behavioral deficiency following neurotoxicity which is slowly reversible.


Three-Dimensional Evaluation of Implant Bed Preparation and the Influence on Primary Implant Stability After Using 2 Different Surgical Techniques.
Surgical techniques affect primary implant stability, which is required for osseointegration. The aim of this study was to investigate the influence of full-guided surgery on the dimension of implant site in relation to primary stability. After implant site preparation in artificial bone by full-guided (FG) or non-guided (NG) workflows to create final diameters of 3.3, 4.1, and 4.8mm and depths of 8 or 12 mm, computed tomograms were obtained and the volume of the osteotomies was analyzed 3 dimensionally. After comparing implant insertions, the implant stability quotient (ISQ) was measured by resonance frequency analysis (RFA). Volume analysis of the implant site showed significant differences (P < .0001) between surgical procedures (FG vs NG) at a depth of 12 mm for all diameters (3.3 mm, 61.98 ± 5.84 vs 80.96 ± 9.65 mm(3); 4.1 mm, 107.45 ± 6.91 vs 132.07 ± 5.16 mm(3); 4.8 mm, 158.62 ± 10.21 vs 182.00 ± 6.25 mm(3)) and at a depth of 8 mm for diameters of 4.1 mm (71.76 ± 8.38 vs 83.64 ± 7.54 mm(3)) and 4.8 mm (103.84 ± 6.73 vs 120.55 ± 14.63 mm(3)). RFA showed significant differences for implants with a diameter of 4.8 mm and lengths of 12 mm (ISQ, 69.3 ± 4.09 for FG vs 65.05 ± 5.61 for NG; P = .0007) and 8 mm (64.5 ± 4.16 for FG vs 58.85 ± 6.72 for NG; P = .0107). The use of FG implant surgery decreases the bone volume removed during osteotomy preparation, which can lead to greater primary stability.


Interventions to improve oral health of older people: A scoping review.
A range of interventions have been tested to improve oral health of older people. We performed a scoping review to map interventions' aims, outcome measures and findings, and to locate them on different levels of care. We systematically screened for (1) controlled studies on (2) people over 65 years of age, (3) comparing at least two interventions to improve oral health. Interventions were summarized according to their aims and the employed intervention type, mapped on their level of action, and classified as primary/secondary/tertiary prevention. Studies retrieved via MEDLINE, EMBASE, CINAHL. Eighty-one studies (published 1997-2019, conducted mainly in high-income countries) were included. Sample sizes varied (n = 24-1987). Follow-up was 0.25-60 months. Most studies (64/81) found a statistically significant benefit of the intervention. A total of 13 different aims were identified, and a range of intervention types employed (e.g. educational interventions, professional oral healthcare, restorative treatment, fluoride application and, generally, dentifrices, mouthwashes, chewing gums/food supplements). Most studies were located on the carer/patient level (56/81 studies) or the system/policy-maker level (44/81). The majority of studies aimed for primary prevention (64/81). Oral health improvement interventions are widely studied. However, study aims, methods and outcome measures are highly heterogeneous, which limits the ability for robust conclusions. Current research focusses on primary prevention on the level of patients/carers or system/policy-maker level. Future studies may want to consider interventions on dentists' level focussing on secondary prevention. These studies should rely on a core set of comprehensive, standardized set of outcome measures. While specific interventions seem efficacious to improve older people's oral health, the current body of evidence is neither comprehensive (significant gaps exists in relevant levels of the care process) nor comparable enough to draw robust conclusions.


Anti-inflammatory efficacy of petasin-incorporated zinc oxide eugenol sealer - An in vivo zebrafish study.
The eugenol from zinc oxide eugenol (ZnOE) sealer tends to diffuse to the periapical region resulting in inflammation. Several modifications of ZnOE sealer have been formulated to minimize the inflammatory potential of the ZnOE sealer. Petasites hybridus contains petasin which possesses anti-inflammatory property used in treatment of migraine and allergic rhinitis. The aim of the study was to evaluate the anti-inflammatory property of petasin-incorporated ZnOE sealer on zebrafish. The study has been reviewed and approved by the Institutional Review Board (SRMU/MandHS/SRMDC/2018/S/025) and by the in-house Institutional Animal Ethics Committee (IAEC) of Pentagrit Research Lab and conducted with compliance to ICH harmonization and principles for animal housing and handling (IAEC Study No: 215/Go06/IAEC). The samples were implanted in the caudal portion of the zebrafish. The samples (n = 50) were divided into five groups (n = 10) - Group 1: incision only (negative control), Group 2: zinc oxide (ZnO) (positive control), Group 3: ZnO + eugenol and petasin in ratio of 10:1, Group 4: ZnO + eugenol and petasin in ratio of 5:1, and Group 5: ZnO + eugenol and petasin in ratio of 1:1. The experimental groups were further subdivided into two subgroups based on time intervals at 24 h and 48 h. The tissue samples were assessed using smear pathology test, and the percentage of inflammation was evaluated. The data were statistically analyzed using SPSS software version 22.0 with a significance level fixed as 5% (α = 0.05). The presence of inflammatory cells and congestion of arterioles were taken as the criteria to assess inflammatory action. It was maximum in ZnOE sealer followed by ZnOE sealer modified with the addition of petasin to eugenol in the ratio of 10:1, 5:1, and 1:1, respectively. The addition of petasin extract to ZnOE reduces the inflammation potential of ZnOE sealers. ZnOE sealer containing eugenol and petasin in the ratio of 1:1 showed a maximal reduction in inflammation.


U-shaped association of body mass index in early adulthood with unintentional mortality from injuries: a cohort study of Swedish men with 35 years of follow-up.
To investigate the dose-response association between body mass index (BMI) in young adulthood and the risk of mortality caused by unintentional injuries. We performed a cohort study including 7 43 398 men identified by linkage of the Multigeneration Register and the Military Service Conscription Register. Cox regression models were used to examine crude and adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the relationships between BMI at age 18-20 years and the risk of death from all unintentional injuries as well as from specific unintentional injuries. We then estimated the population attributable fractions (PAFs)-the proportion of unintentional deaths that was attributable to underweight, overweight and obesity in this population-based cohort. During 35.9 years of follow-up, 6461 deaths occurred from unintentional injuries, including 3064 deaths from road injury, 978 from poisoning, 503 from falls, 243 from fire and 348 from drowning. Underweight subjects had a higher risk of mortality in all unintentional injuries (HR, 1.05; 95% CI, 1.03-1.10) and mortality in burns (HR, 1.65; 95% CI, 1.13-2.40) compared with BMI between 18.5 and 22.5 kg m(-2) (reference group). BMI >25 kg m(-2) was associated with increased risk of death from all unintentional injuries (HR, 1.36; 95% CI, 1.12-1.65) and road accidents (HR, 1.50; 95% CI, 1.14-1.97). Estimates of PAF suggested that 4.4% of the mortality in Swedish men caused by unintentional injuries could have been avoided if BMI values were kept between 18.5 and 22.5 kg m(-2). A U-shaped association was observed between BMI and risk of unintentional death. Both underweight and overweight were associated with increased mortality risk for all unintentional injuries and for subtype causes. Our study suggests that BMI might be a significant target for preventive interventions on deaths caused by unintentional injuries.


Injectable hydrogel for sustained delivery of progranulin derivative Atsttrin in treating diabetic fracture healing.
Hydrogels with long-term storage stability, controllable sustained-release properties, and biocompatibility have been garnering attention as carriers for drug/growth factor delivery in tissue engineering applications. Chitosan (CS)/Graphene Oxide (GO)/Hydroxyethyl cellulose (HEC)/β-glycerol phosphate (β-GP) hydrogel is capable of forming a 3D gel network at physiological temperature (37 °C), rendering it an excellent candidate for use as an injectable biomaterial. This work focused on an injectable thermo-responsive CS/GO/HEC/β-GP hydrogel, which was designed to deliver Atsttrin, an engineered derivative of a known chondrogenic and anti-inflammatory growth factor-like molecule progranulin. The combination of the CS/GO/HEC/β-GP hydrogel and Atsttrin provides a unique biochemical and biomechanical environment to enhance fracture healing. CS/GO/HEC/β-GP hydrogels with increased amounts of GO exhibited rapid sol-gel transition, higher viscosity, and sustained release of Atsttrin. In addition, these hydrogels exhibited a porous interconnected structure. The combination of Atsttrin and hydrogel successfully promoted chondrogenesis and osteogenesis of bone marrow mesenchymal stem cells (bmMSCs) in vitro. Furthermore, the work also presented in vivo evidence that injection of Atsttrin-loaded CS/GO/HEC/β-GP hydrogel stimulated diabetic fracture healing by simultaneously inhibiting inflammatory and stimulating cartilage regeneration and endochondral bone formation signaling pathways. Collectively, the developed injectable thermo-responsive CS/GO/HEC/βG-P hydrogel yielded to be minimally invasive, as well as capable of prolonged and sustained delivery of Atsttrin, for therapeutic application in impaired fracture healing, particularly diabetic fracture healing.


A convenient preparation of 3-substituted furans: synthesis of perillene and dendrolasin.
A variety of 3-substituted furans, including the natural products perillene and dendrolasin, are obtained in good yield via reductive annulation of 1,1,1-trichloroethyl propargyl ethers using catalytic Cr(II) regenerated by Mn/TMSCl. [reaction: see text]


Association of neurotoxin treatment likelihood with sex of television journalists.
Neurotoxin procedures have been increasing in popularity since they were approved for cosmetic use in 2002, with predominately women being treated. Our objectives were to determine likelihood of neurotoxin treatment in television journalists based on demographics and social media popularity. Likelihood of neurotoxin treatment was determined from by grading forehead and glabellar rhytides in videos using a standardized scale. A greater percentage of women vs. men were "likely/highly likely" to have had glabellar (23% vs. 17%, respectively) and forehead neurotoxins (42% vs. 13%, respectively) neurotoxins (both P < 0.05). A greater proportion of anchors vs. non-anchors were "likely/highly likely" to have had glabellar neurotoxins (37% vs. 11%; P < 0.05). In sum, we found that women broadcasters are more likely to pursue neurotoxin treatments compared to male broadcasters and uncovered potential gender-based aesthetic treatment biases in the media industry.


Ultrasound-guided interventional procedures of the liver during laparoscopy: technical considerations.
The increased application of laparoscopy to oncological cases has also expanded the applications of laparoscopic ultrasound (LUS). LUS-guided interventional procedures are often used for the staging of neoplastic disease. However, considerable expertise is required to perform the US-guided maneuvers. Based on our 7-year experience with laparoscopic ultrasound, we discuss a number of technical and practical aspects related to the performance of interventional procedures during LUS of the liver. We performed 146 laparoscopic ultrasound exams in patients with neoplastic diseases. In all, 244 liver lesions were biopsied and 151 needle placements were made to perform radiofrequency ablation or ethanol injection. We discuss our choice of laparoscopic equipment and type of needle required (whether for biopsies or for interventional procedures). We also describe the technical characteristics of ultrasound probes and equipment, the correct approach to the patient, and the method that we employ to identify and then puncture the target lesion. The proper technique for interventional procedures during laparoscopic ultrasound can be mastered relatively quickly by a surgeon who is already familiar with traditional ultrasound techniques.


Impact of seaweed intake on health.
Seaweeds contain minerals, vitamins, soluble dietary fibers, and flavonoids, which are regarded as preventive agents against lifestyle-related diseases. Seaweeds are consumed commonly in East Asian countries including Japan. Thus, intake of seaweeds might contribute to Japanese longevity via prevention of lifestyle-related diseases. Recently, two large Japanese cohort studies have reported the association of seaweed intake with reduced risk of cardiovascular diseases. On the other hand, seaweeds also contain iodine and heavy metals such as arsenic species, which are considered to have adverse effects on health. We here reviewed studies of the association between seaweed intake and mortality from or incidence of cancer and cardiovascular diseases, and their risk factors such as blood pressure or serum lipids. We also summarized the adverse effects of iodine and arsenic species in seaweeds. Although seaweeds have not been widely consumed in Western countries, dietary diversification and an increased proportion of immigrants from East Asia may increase seaweed consumption in those countries. Further epidemiological studies including observational and interventional studies are necessary to clarify the effects of seaweeds on disease and health.