Catalytic C-H bond functionalisation chemistry: the case for quasi-heterogeneous catalysis.
This feature article examines the potential of heterogeneous Pd species to mediate catalytic C-H bond functionalisation processes employing suitable substrates (e.g. aromatic/heteroaromatic compounds). A focus is placed on the reactivity of supported and non-supported Pd nanoparticle (PdNPs) catalysts, in addition to the re-appropriation of well-established heterogeneous Pd catalysts such as Pd/C. Where possible, reasonable comparisons are made between PdNPs and traditional 'homogeneous' Pd precatalyst sources (which form PdNPs). The involvement of higher order Pd species in traditional cross-coupling processes, such as Mizoroki-Heck, Sonogashira and Suzuki-Miyaura reactions, allows the exemplification of potential future topics for study in the area of catalytic C-H bond functionalisation processes.


Meckel's diverticulum and laparoscopy of children. What's new?
Laparoscopy has not changed the diagnostic approach in Meckel's diverticulum (MD). Preoperative echography and scintigraphy are still indicated in case of symptomatic diverticulum. During each submesocolic laparoscopy we must meticulously look for Meckel's diverticulum. There are two surgical procedures for MD resection: 1. Short intestinal resection after exteriorization (celio-assisted surgery) is advocated in young patients or in complicated MD. 2. Laparoscopic resection by the Endo GIA stapler is advocated in older patients and latent MD with a narrow base.


Risk factors for nephrotoxicity in patients treated with aminoglycosides.
Risk factors for nephrotoxicity in patients treated with aminoglycosides were determined from the case records of 214 patients in two prospective, randomized clinical trials of gentamicin and tobramycin. Nephrotoxicity, defined as a 50% or greater fall in calculated creatinine clearance, developed in 30 patients (14.1%). Patients with nephrotoxicity had higher initial calculated creatinine clearances, were more often women, and were more likely to have liver disease. Using stepwise discriminant analysis, these factors were selected with the initial 1-hour post-dose aminoglycoside level, patient age, and shock. An equation was generated that was accurate in discriminating between patients with and without nephrotoxicity when validated in an independent population. Factors that did not add significantly to the equation were diabetes, dehydration, serum bicarbonate, bacteremia, urinary tract infection, gentamicin or tobramycin use, duration of therapy, total aminoglycoside dose, or the use of clindamycin, furosemide, or cephalothin.


Mycobacterium gordonae-induced humidifier lung.
Nontuberculous mycobacteria are well known to be a cause of hot tub lung, however, to our knowledge, there exists no case report of humidifier lung induced by mycobacteria. A case of a nonimmunocompromised female patient with Mycobacterium gordonae-induced humidifier lung is described. She spontaneously recovered after discontinuing ultrasonic humidifier use. When subjected to a provocation test, she demonstrated acute respiratory distress with signs and symptoms, consistent with hypersensitivity pneumonitis. Before and after the provocation test, water in the humidifier reservoir revealed only Mycobacterium gordonae by the microbiologic analyses. To our knowledge, this is the first report of humidifier lung induced by nontuberculous mycobacteria. Although nontuberculous mycobacteria are well-known to be agents of hot tub lung or metal working fluid lung, physicians should also consider the pathogen as a cause of hypersensitivity lung reaction associated with humidifier use.


Endocrine profile of follicles containing oocytes with subsequent polyploid fertilization.
In an attempt to identify oocytes at risk for polypronuclear fertilization, follicular fluids were obtained retrospectively that contained oocytes that fertilized normally and abnormally. Whenever possible, each patient served as her own control during the same stimulation cycle. Twenty-six of 169 patients had oocytes that became polypronuclear, and of those 26, 21 had oocytes that fertilized and cleaved normally. Follicular fluids were analyzed for estradiol, progesterone, androstenedione, transferrin, and insulin. Insulin levels were noted to be significantly elevated (P less than 0.05) in the polypronuclear group when compropose that insulin, a known growth factor for granulosa cells cultured in vitro, when present in excessive concentrations may predispose to polypronuclear fertilization.


Dual mode operation, highly selective nanohole array-based plasmonic colour filters.
Taking advantage of nanostructured metal films as plasmonic colour filters (PCFs) has been evolved remarkably as an alternative to the conventional technologies of chemical colour filtering. However, most of the proposed PCFs depict a poor colour purity focusing on generating either the additive or subtractive colours. In this paper, we present dual mode operation PCFs employing an opaque aluminium film patterned with sub-wavelength holes. Subtractive colours like cyan, magenta, and yellow are the results of reflection mode of these filters yielding optical efficiencies as high as 70%-80% and full width at half maximum of the stop-bands up to 40-50 nm. The colour selectivity of the transmission mode for the additive colours is also significant due to their enhanced performance through the utilization of a relatively thick aluminium film in contact with a modified dielectric environment. These filters provide a simple design with one-step lithography in addition to compatibility with the conventional CMOS processes. Moreover, they are polarization insensitive due to their symmetric geometry. A complete palette of pure subtractive and additive colours has been realized with potential applications, such as multispectral imaging, CMOS image sensors, displays, and colour printing.


Absorption of missile energy in soft tissue.
Soft tissue wounds caused by spherical steel projectiles at various impact velocities have been studied. Energy absorption by the penetrated tissues and the size, form and location of the maximum of the temporary cavity are discussed on the basis of theoretical calculations. Morphological and angiographic findings support the assumption that steel spheres hitting at high velocity cause most damage near the beginning of the wound channel. The possible occurrence of transonic strong shock waves above certain velocity limits and their role in increasing the destructive effects of the temporary cavity, are discussed.


Energy, climate, food and health.
On June 3-5, 2008, international organizations and heads of state met in Rome to discuss the critical situation in global food supplies and prices during the World Food Crisis Summit. The intent of this column is to provide approaches to identifying the complex issues that impact public health, public safety, and nutrition on a global basis. The Web sites selected provide a background for the complex issues involved (energy, climate and environment, agriculture, and politics) and reveal controversial and competing agendas with many far-reaching implications.


[Nasal polyposis: postoperative long term results (5 years) after endoscopic sinus surgery].
The purpose of this study is to evaluate the results after endoscopic sinus surgery in cases of nasal polyposis. We include 54 patients with diffuse nasal polyposis suffering from nasal obstruction. An endoscopic sinus surgery under general anesthesia with excision of the polyposis was performed. There were no complications. The patients were followed closely and treated with local and systemic steroids. After 5 years, the 75% of these patients were free of nasal symptoms and in the 67% the mucosa appeared normal. We also review the influence of some factors (ASA triad, anosmia, allergy...) in the recurrence of the disease.


Analysis of multiple casualty incidents - a prospective cohort study.
Our aim was to report the rate and causes for multiple casualty incidents (MCI) to analyse the prehospital part of responding to MCIs, report mortality and find areas for improvement. A prospective cohort study conducted in an urban emergency medical service (EMS) between 1.3.1998 and 28.2.2004. Fifty-nine MCIs involving 263 patients (167 walking, 96 non-walking) occurred. The incidence of MCIs was 1.8/100,000 inhabitants year(-1). Traffic accidents were the most common cause followed by residential fires, intoxications and stabbings or shootings. Early MCI alarm by the dispatching centre was performed in 18 MCIs. Deviations from standard emergency medical care occurred in 12% of patients. Lack of immobilization of the neck or back in trauma patients and lack of administration of 100% oxygen in suspected carbon monoxide intoxication were the most common deviations. Deviations were related to the lack of presence of on-scene medical command (P = 0.0013) and inadequate resources (P = 0.0342). One hundred and ninety-two patients were transported to emergency departments. Mortality during the prehospital phase was 4.9% (13/263) and during the next 28 days 2.3% (6/263). Adequate resources for safe and effective management of a MCI were related to an early MCI alarm by the dispatching centre (P = 0,022) and to the presence of on-scene medical command (P < 0,001). Traffic accidents, residential fires and intoxications were the leading causes for MCIs. Emergency medical service could respond to most MCIs efficiently and safely. Majority of deviations from standard medical care seemed potentially preventable. Several areas for improvement were identified. From prehospital links, the dispatching centre and on-scene medical command had a vital role in the successful management of MCIs.


Antimicrobial activity of linezolid combined with minocycline against vancomycin-resistant Enterococci.
Vancomycin-resistant Enterococci (VRE) cause serious infections that are difficult to treat. We carried out this study to determine the mutant prevention concentration (MPC) of linezolid when combined with minocycline against VRE strains, to determine the mechanism of drug resistance in vitro, and to provide a theoretical basis for the rational use of drugs against VRE. The minimum inhibitory concentrations (MICs) of linezolid and minocycline against 30 Enterococci (E.) isolates (including 20 VRE strains) were determined by the broth microdilution method. Drug interactions were assessed by the checkerboard microdilution tests and confirmed by time-kill studies. Two vancomycin-susceptible strains N27 and N40 (linezolid MIC, 2 g/ml; minocycline MIC, 4 µg/ml) and control strains E. faecalis ATCC 29212 and ATCC 51299 were also tested. The MPCs of linezolid and minocycline (alone and combined) were determined using the agar dilution method. Strains showing stable resistance were analyzed by polymerase chain reaction (PCR) amplification of domain V of the 23S rRNA gene. Checkerboard titration studies revealed synergistic effects of combination therapy in 26.7% of 30 E. isolates. Antagonism was not observed. The G2576U mutation was detected in stable linezolid-resistant strains of ATCC 29212, N40, and N27 before and after resistance screening, and MIC values increased with the number of G2576U mutations. The MPC of linezolid against E. decreased dramatically when combined with minocycline, and vice versa. Linezolid or minocycline alone produce resistant strains; however, their joint use may reduce the MPC of each agent against VRE, thereby decreasing resistant mutants and bacterial infections.


[Expression and clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in non-small cell lung carcinoma].
Vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR-3) play important roles in lymphangiogenesis of malignant tumors; their expression are closely related to lymphatic metastasis of malignant tumors. This study was designed to investigate the expression and clinical significance of VEGF-C and VEGFR-3 in non-small cell lung cancer (NSCLC). The expression of VEGF-C and VEGFR-3 in 77 specimens of NSCLC were detected by immunohistochemistry; their correlations to lymphatic vessel density (LVD), tumor size, histological type, differentiation, lymphatic metastasis, clinical recurrence, and survival time of the patients were analyzed. Positive rate of VEGF-C was 58% in NSCLC, and that of VEGFR-3 was 42%. The expression of VEGF-C protein was negatively correlated with the differentiation of NSCLC (r=-0.32, P=0.018). The expression of VEGF-C and VEGFR-3 were related to lymphatic metastasis, LVD, tumor size, and survival time of the patients. The expression of VEGF-C was positively related with that of VEGFR-3 (r=0.23, P=0.045). The expression of VEGF-C and VEGFR-3 are closely related with lymphatic metastasis and prognosis of NSCLC; their high expression indicate high risk of lymphatic metastasis and poor prognosis.


Theoretical considerations for understanding a Purkinje cell timing mechanism.
In classical conditioning, cerebellar Purkinje cells learn an adaptively timed pause in spontaneous firing. This pause reaches its maximum near the end of the interstimulus interval. While it was thought that this timing was due to temporal patterns in the input signal and selective engagement of changes in synapse strength, we have shown Purkinje cells learn timed responses even when the conditional stimulus is delivered to its immediate afferents.(1) This shows that Purkinje cells have a cellular timing mechanism. The cellular models of intrinsic timing we are aware of are based on adapting the rise time of the concentration of a given ion. As an alternative, we here propose a selection mechanism in abstract terms for how a Purkinje cell could learn to respond at a particular time after an external trigger.


Subwavelength displacement of the far-field image of a radiating dipole.
The field lines of the Poynting vector for light emitted by a dipole with a rotating dipole moment show a vortex pattern near the location of the dipole. In the far field, each field line approaches a straight line, but this line does not appear to come exactly from the location of the dipole. As a result, the image of the dipole in its plane of rotation seems displaced. Secondly, the image in the far field is displaced as compared with the image of a source for which the field lines run radially outward. It turns out that both image displacements are the same. The displacements are of subwavelength scale, and they depend on the angles of observation. The maximum displacement occurs for observation in the plane of rotation and equals lambda/pi, where lambda is the wavelength of the light.


Neurocysticercosis: fireflies in the central nervous system.
Neurocysticercosis (NCC) is caused by cysticerci spreading to spinal or brain tissue. NCC causes headaches, seizures, and focal neurological deficits. NCC is one of the main causes of epilepsy worldwide. NCC can cause death if it is not adequately treated. NCC is preventable through education of proper handwashing techniques proper food handling, and separation of human and pig living quarters (CDC 1998). The International League Against Epilepsy (ILAE), the World Health Organization (WHO), and other international health organizations are attempting to rid the world of NCC through education. Cysticerci create cavities in the brain and other body tissue where their tiny bodies grow sometimes into tapeworms two to seven meters in length and can live up to 25 years in the human body. On magnetic resonance imaging (MRI) wormholes appear Often times, if best practice is followed, the patient's entire body is scanned and more craters appear. Some authors have stated that cysticerci on a computed topography (CT) scan are similar to a starry sky or fireflies (Kapur et al. 2007).


The global regulator genes from biocontrol strain Serratia plymuthica IC1270: cloning, sequencing, and functional studies.
The biocontrol activity of various fluorescent pseudomonads towards plant-pathogenic fungi is dependent upon the GacA/GacS-type two-component system of global regulators and the RpoS transcription sigma factor. In particular, these components are required for the production of antifungal antibiotics and exoenzymes. To investigate the effects of these global regulators on the expression of biocontrol factors by plant-associated bacteria other than Pseudomonas spp., gacA/gacS and rpoS homologues were cloned from biocontrol strain IC1270 of Serratia plymuthica, which produces a set of antifungal compounds, including chitinolytic enzymes and the antibiotic pyrrolnitrin. The nucleotide and deduced protein sequence alignments of the cloned gacA/gacS-like genes-tentatively designated grrA (global response regulation activator) and grrS (global response regulation sensor) and of the cloned rpoS gene revealed 64 to 93% identity with matching genes and proteins of the enteric bacteria Escherichia coli, Pectobacterium carotovora subsp. carotovora, and Serratia marcescens. grrA, grrS, and rpoS gene replacement mutants of strain IC1270 were deficient in the production of pyrrolnitrin, an exoprotease, and N-acylhomoserine lactone quorum-sensing signal molecules. However, neither mutant appeared to differ from the parental strain in the production of siderophores, and only grrA and grrS mutants were deficient in the production of a 58-kDa endochitinase, representing the involvement of other sigma factors in the regulation of strain IC1270's chitinolytic activity. Compared to the parental strain, the grrA, grrS, and rpoS mutants were markedly less capable of suppressing Rhizoctonia solani and Pythium aphanidermatum under greenhouse conditions, indicating the dependence of strain IC1270's biocontrol property on the GrrA/GrrS and RpoS global regulators.


The genetics of smoking related behavior: a brief review.
Smoking behavior is influenced by both genetic and environmental factors. Many years of twin and adoption studies have demonstrated that heritability is at least 50% for both smoking initiation and smoking persistence. Furthermore, the extent to which genetic and environmental factors contribute to smoking behavior in men is significantly different from that in women. It has been reported that polymorphisms of candidate genes, such as cytochrome P450, dopamine receptor and transporter, and serotonin transporter genes, are associated with smoking behavior. However, many of these reports have not yet received independent confirmation. Based on the results from genome-wide linkage and association analyses on different subject populations, 15 loci located on 8 chromosomes were reported to harbor susceptibility genes for nicotine and other substances of abuse. It is expected that a newly completed human genome sequence, as well as advances in genomic technologies such as genotyping and array analysis, will greatly enhance progress toward the identification of genes associated with smoking behavior.


Reproductive health in indigenous Chihuahua: giving birth 'alone like the goat'.
Indigenous peoples in the state of Chihuahua, Mexico, are known to outsiders as the Tarahumaras. The Tarahumaras are one of the few cultural groups known to have no traditional birth attendants, and Tarahumara women often give birth alone and outdoors. Currently, little is known about this group, their health status or their culture. The objective of this study was to assess the state of reproductive health outcomes, risks, protective factors, beliefs and behaviors in the Tarahumara population. This paper reports on the qualitative results of a mixed methods study, comprised of focus groups, interviews, participatory exploratory methods, ethnographic observation and household surveys investigating the reproductive health status of the Tarahumara peoples and contextual factors influencing it. Qualitative data is presented, supported by preliminary quantitative findings. This study supports speculation that the Tarahumara population is burdened by severe maternal health problems. The sample size was too small to definitively assess risk factors for the outcome of maternal mortality, but qualitative findings point to some important contextual issues that contribute to participants' perceptions of susceptibility to and severity of the problem, their reproductive health beliefs and behaviors, and barriers to behavior change. Major issues included disparities in biomedical knowledge, trust between non-indigenous providers and indigenous patients, and structural issues including access to medical facilities and infrastructure. Qualitative data is drawn upon to make recommendations and identify lessons applicable to similar situations where cultural minorities suffer serious health inequities. This study underscores the importance of needs and assets assessment, as it reveals unique contextual factors that must be taken into account in intervention design. Also, collaborative partnership with community members and leaders proved to be invaluable in the research, warranting further collaboration by both governmental and non-governmental groups attempting to improve the health of this population. This becomes especially important when making and enforcing health policy.


Elucidating the role played by bone marrow in visceral leishmaniasis.
Leishmaniasis is a widespread group of infectious diseases that significantly impact global health. Despite high prevalence, leishmaniasis often receives inadequate attention in the prioritization of measures targeting tropical diseases. The causative agents of leishmaniasis are protozoan parasites of the Leishmania genus, which give rise to a diverse range of clinical manifestations, including cutaneous and visceral forms. Visceral leishmaniasis (VL), the most severe form, can be life-threatening if left untreated. Parasites can spread systemically within the body, infecting a range of organs, such as the liver, spleen, bone marrow and lymph nodes. Natural reservoirs for these protozoa include rodents, dogs, foxes, jackals, and wolves, with dogs serving as the primary urban reservoir for Leishmania infantum. Dogs exhibit clinical and pathological similarities to human VL and are valuable models for studying disease progression. Both human and canine VL provoke clinical symptoms, such as organ enlargement, fever, weight loss and abnormal gamma globulin levels. Hematologic abnormalities have also been observed, including anemia, leukopenia with lymphocytosis, neutropenia, and thrombocytopenia. Studies in dogs have linked these hematologic changes in peripheral blood to alterations in the bone marrow. Mouse models of VL have also contributed significantly to our understanding of the mechanisms underlying these hematologic and bone marrow abnormalities. This review consolidates information on hematological and immunological changes in the bone marrow of humans, dogs, and mice infected with Leishmania species causing VL. It includes findings on the role of bone marrow as a source of parasite persistence in internal organs and VL development. Highlighting gaps in current knowledge, the review emphasizes the need for future research to enhance our understanding of VL and identify potential targets for novel diagnostic and therapeutic approaches.


An evaluation of the opinions of hospital employees regarding the contribution of internal marketing to the application of total quality management in Turkey.
This research was conducted in a training-research hospital in Ankara, the capital of Turkey, in order to assess the contributions of internal marketing to the success of TQM applications by means of employee communication and participation. The key findings of this research indicate that the cultural changes needed to maintain the success of TQM applications in the organization were not achieved, there were problems in the internal communication system, effective participation of employees was not achieved, and public relations and internal marketing activities were not employed in a sufficient manner. Specific managerial recommendations are offered in regard to ensuring effective employee support and participation in TQM applications, improving internal communication, and effective application of modern internal marketing tools and methods.


Conducting Nursing Research to Advance and Inform Health Policy.
The primary roles of nurse scientists in conducting health policy research are to increase knowledge in the discipline and provide evidence for informing and advancing health policies with the goal of improving the health outcomes of society. Health policy research informs, characterizes, explains, or tests hypotheses by employing a variety of research designs. Health policy research focuses on improving the access to care, the quality and cost of care, and the efficiency with which care is delivered. In this article, we explain how nurses might envision their research in a policy process framework, describe research designs that nurse researchers might use to inform and advance health policies, and provide examples of research conducted by nurse researchers to explicate key concepts in the policy process framework. Health policies are well informed and advanced when nurse researchers have a good understanding of the political process. The policy process framework provides a context for improving the focus and design of research and better explicating the connection between research evidence and policy. Nurses should focus their research on addressing problems of importance that are on the healthcare agenda, work with interdisciplinary teams of researchers, synthesize, and widely disseminate results.


The Production of Sex Pheromone in Lady Beetles Is Conditioned by Presence of Aphids and Not by Mating Status.
Female Harmonia axyridis (Coleoptera: Coccinellidae) produce a sex pheromone to attract males. In the present study, we tested two hypotheses: (i) production of sex pheromone in H. axyridis is conditioned by perception of prey in their vicinity, and (ii) virgin females invest in the production of the sex pheromone, while mated females reduce their pheromone emissions. To test the first hypothesis, newly hatched larvae were divided into three groups: those fed with Ephestia kuehniella eggs, those fed with pea aphids, and those exposed to aphid volatile cues but fed with Ephestia eggs. All females produced a pheromone blend of five-components in similar relative proportions, but with contrasting absolute quantities: Females fed with Ephestia eggs produced lower amounts of pheromone (0.5 ± 0.4 ng.female-1), compared to females fed with aphids (44.2 ± 24.4 ng.female-1). The females of the third group produced intermediate concentrations of pheromone (6.0 ± 3.2 ng.female-1). To test the second hypothesis, two groups of lady beetles were made: one group of females was placed in the presence of males, while females of the other group were not. Mated and virgin females produced statistically similar amounts of pheromone (144.1 ± 49.7 ng and 43.7 ± 24.1 ng.female-1, respectively). These results suggest that H. axyridis females initiate pheromone production upon exposure to volatile cues released by their aphids prey. Females continue to release sex pheromone after mating, probably to increase the chance of multiple mating which is known to improve egg fertility.


Interaction between T cell receptor beta chain and immunoglobulin heavy chain region genes in susceptibility to insulin-dependent diabetes mellitus.
Despite some reports of an association between insulin-dependent diabetes mellitus (IDDM) and a BglII RFLP in the T cell receptor beta chain (TCRB) constant region, results of several recent studies, including our own, have failed to support such an association. However, we here report evidence for an IDDM-TCRB relationship which is dependent on immunoglobulin heavy-chain-region genes. We analyzed 198 unrelated diabetics and 84 normal siblings (maximum one sibling per diabetic) typed for the BglII TCRB RFLP and Gm immunoglobulin allotypes Glm(1), Glm(2), G2m(23), and G3m(5), which identify the four common Gm haplotypes. The BglIII TCRB genotype frequencies were significantly different between diabetics positive and negative for G2m(23) (P = .017) and G3m(5) (P = .021) but were not different between normal siblings positive and negative for those allotypes (P = .94 and P = .77, respectively). Thus, there were significant interactions between TCRB, Gm, and IDDM for two of the four immunoglobulin allotypes examined. We have previously reported interactions between HLA, Gm (particularly G2m(23)), and IDDM and postulate that the TCRB-Gm-IDDM and HLA-Gm-IDDM interaction effects may be functionally related.


Synthesis, density functional theory and kinetic studies of aminopyridine based α-glucosidase inhibitors.
Aims: The current study aimed to develop new thiourea derivatives as potential α-glucosidase inhibitors for the management of hyperglycemia in patients of Type 2 diabetes, with a focus on identifying safer and more effective antidiabetic agents. Materials & methods: New thiourea derivatives (1-16) were synthesized through single-step chemical transformation and evaluated for in vitro α-glucosidase inhibition. Kinetic studies identified the mode of inhibition, free energy and type of interactions were analyzed through density functional theory and molecular docking. Results & conclusion: Compound 5 was identified as the most potent, noncompetitive and noncytotoxic inhibitor of α-glucosidase enzyme with a half-maximal inhibitory concentration of 24.62 ± 0.94 μM. Computational studies reinforce experimental results, demonstrating significant enzyme interactions via hydrophobic and π-π stacking forces.


Pacing site in pacemaker dependency: is right ventricular septal lead position the answer?
The right ventricular apex has been the traditional site for lead placement in patients with atrioventricular block. Pacing at the right ventricular apex may have long-term deleterious effects on left ventricular (LV) function, promoting heart failure and increasing mortality. Pacing at the right ventricular septum has been proposed to minimize deterioration in LV function. Although experimental data suggest that septal pacing protects LV function, clinical studies have provided conflicting results. A recent large study in patients with heart block did not show a protective effect with septal pacing. Other pacing approaches are becoming increasingly relevant; however, prediction of what method should be employed in which patient is not currently possible. Other factors such as baseline LV function and associated co-morbidities impact LV function, irrespective of pacing site. Continued monitoring of cardiac function post-implant is therefore critical to ongoing care. An algorithm for managing patients with atrioventricular block is proposed.


A visible light photocatalyst: effects of vanadium substitution on ETS-10.
Hybrid density functional theory/molecular mechanics (DFT/MM) methods have been used to investigate the effects of vanadium substitution in ETS-10. Models have been developed to contain varying concentrations of V(IV) and V(V) within the O-M-O (M = Ti, V) chain. Most of the V-substituted models have a localized mid-gap state. The occupation of this localized state depends upon the dopant oxidation state, leading to the addition of multiple low energy transitions. A linear correlation has been identified between band gap energies estimated using ground state orbital energies and those calculated using the more accurate and computationally demanding time-dependent DFT (TDDFT) method for a variety of transition metal substituted models of ETS-10. Consistent with experimental data for V substitution, our models predict a decrease in the optical band gap with increasing [V], due to a lowering of the delocalized d-orbital states at the bottom of the conduction band with increasing V d-orbital character. This effect is more pronounced in the case of V(V) substitution than V(IV). Excitation energies for the V-doped models, calculated with TDDFT methods correlate well with experimental data, allowing for the assignment of specific optical transitions to experimental UV-Vis spectra. The electronic structure of V-substituted ETS-10 at high V concentration demonstrates band gap energies within the visible range of the spectrum. Additionally, at high [V] the band gap energy and presence of low energy electron traps can be controlled by the relative concentration of V(IV) and V(V) along the O-M-O chain, establishing V-substituted ETS-10 as a promising visible light photocatalyst.


Regenerating the periodontium: is there a magic formula?
Left untreated, periodontal disease results in destruction of periodontal tissues including cementum, bone and the periodontal ligament, and subsequently, tooth loss. Increased research efforts focused on understanding periodontal disease at the cellular, molecular and clinical level have resulted in improved modalities for arresting disease progression; however, outcomes of existing procedures are not predictable and often disappointing. Critical to improving the predictability of regenerative therapies is targeting studies toward enhancing our understanding of the cellular and molecular events required to restore periodontal tissues. Toward this goal our laboratory has focused on defining cells, mechanisms and factors regulating development of periodontal tissues, using in vitro and in vivo rodent models. Results from these studies have enabled us to identify attractive candidate factors/cells including: 1) products secreted by epithelial cells that act on mesenchymal cells (amelogenins): we observed that both follicle cells and cementoblasts are responsive to amelogenin-like molecules resulting in changes in the expression of genes associated with cell maturation; 2) morphogens (bone morphogenetic proteins, BMP): we report that follicle cells respond differently to BMPs vs. cementoblasts, depending on dose of and specific BMP used; 3) phosphates: existing data suggest that phosphates act as signaling molecules regulating the expression of genes associated with cementoblast maturation. Knowledge gained from these studies has provided insight as to the cells/factors required for designing improved regenerative therapies.


Toxicity study of oxalicumone A, derived from a marine-derived fungus Penicillium oxalicum, in cultured renal epithelial cells.
Oxalicumone A (POA), a novel dihydrothiophene-condensed chromone, was isolated from the marine‑derived fungus Penicillium oxalicum. Previous reports demonstrated that POA exhibits strong activity against human carcinoma cells, thus it has been suggested as a bioactive anticancer agent. To research the toxic effect of POA on cultured normal epithelial human kidney‑2 (HK‑2) cells and evaluate its clinical safety, cell survival was evaluated by the Cell Counting Kit-8 assay and apoptosis was evaluated by Hoechst 33258 staining, flow cytometry, caspase‑3 activity assay and western blotting. 2',7'-Dichlorofluorescin diacetate and JC‑1 dye staining was used to evaluate reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP), respectively. The results indicated that POA inhibited HK-2 cell growth and promoted apoptosis, by increasing levels of Fas cell surface cell receptor and the B‑cell lymphoma 2 associated protein X apoptosis regulator (Bax)/B‑cell lymphoma 2 apoptosis regulator (Bcl-2) ratio. POA treatment also induced release of ROS and loss of MMP in HK‑2 cells. Compared with untreated control, a significant decrease was also demonstrated in superoxide dismutase activity and glutathione content with POA treatment, accompanied by enhanced release of N‑acetyl‑β‑D‑glucosaminidase, increased leakage of lactate dehydrogenase, increased malondialdehyde formation and increased release of nitric oxide. In conclusion, the present in vitro study revealed that POA exhibits antiproliferation activity on HK‑2 cells, through stimulation of apoptosis and oxidative stress injury, which may be relevant to its clinical application. The present study may, therefore, offer valuable new information regarding the use of POA as a candidate novel antitumor drug for clinical use.


Fracture resistance of post and core in immediate and delayed post space in trauma simulated teeth.
This research aims to assess and analyze the fracture resistance of GC Everstick post with separate composite core buildup and Edelweiss prefabricated resin composite post and core single unit into immediate and delayed post space prepared teeth. A total of 120 extracted human mandibular premolars have been subjected to a standardized protocol of mechanical trauma to simulate tooth fracture. Teeth samples were randomly divided into four groups (n = 30) on the basis of time taken for the preparation of post space (approximately following root canal obturation and 24 h after root canal obturation) for the single unit Edelweiss post and core system and GC post with separate core buildup. Compressive load has been utilized to do the analysis necessary to establish the fracture resistance using a universal testing machine. The fracture force calculated was in Newtons (N), and a stereomicroscope was utilized for investigating the common causes of failure. In an immediate post space prepared tooth, the GC post exhibited a mean failure load of 970.584 N. In contrast, the Edelweiss post, and core system showed a significantly higher mean failure load of 1250.349 N. In delayed post space prepared tooth, the GC Everstick post exhibited a mean failure load of 950.287 N. In contrast, the Edelweiss post, and core system showed a significantly higher mean failure load of 1229.348 N. This study aims to assess and analyze the fracture resistance of the GC Everstick post with separate composite core buildup and the Edelweiss prefabricated resin composite post and core single unit in immediate and delayed post space prepared teeth. The study results showed that the failure modes in both groups were non-catastrophic in nature. These findings suggest that the Edelweiss post and core system may be a more suitable option for restoring teeth that have been subjected to traumatic conditions. The study provides valuable information for dental professionals in their decision-making process for post and core restoration techniques in teeth that have been subjected to trauma.


[Successful RF ablation in a patient with paroxysmal atrial fibrillation induces by atrioventricular nodal reentrant tachycardia].
We describe a case of 47-year old patient with frequent episodes of paroxysmal atrial fibrillation (PAF) with fast ventricular rate. During electrophysiological study an atrioventricular nodal reentrant tachycardia (AVNRT) was diagnosed with rapid degeneration into atrial fibrillation. Successful RF ablation of slow pathway was performed. There were no PAF recurrences during six months follow-up.


May-Thurner syndrome and other obstructive iliac vein lesions: meaning, myth, and mystery.
Acute and chronic venous disorders of the lower extremities affect millions of people and cause substantial disability. Long ago, surgeons and pathologists identified the presence of 'spur-like' abnormalities of the left common iliac vein; these abnormalities were hypothesized to result from compression and/or irritation from the adjacent crossing right common iliac artery. In the 1990s, physicians, starting to perform catheter-directed thrombolysis to treat extensive deep vein thrombosis (DVT), observed that about 50% of patients had an iliac vein stenosis. Vascular physicians have become aware of the occasional patient with otherwise-unexplained extremity swelling and/or pain but without a DVT history who is subsequently found to have an iliac vein abnormality. These 'lesions' have been hypothesized to elevate ambulatory venous pressures and thereby produce lower-extremity symptoms, increase the risk of initial and recurrent DVT episodes, and increase the risk of treatment failure with medical and endovascular therapies for thrombotic and non-thrombotic venous conditions. As a result, many practitioners now actively seek iliac venous obstructive 'lesions' when evaluating patients with known or suspected venous disease. However, for many patients, it continues to be unclear what degree of obstruction to venous blood flow is being caused by such lesions, how clinically significant they are, how much emphasis should be placed on identifying them, and when they should be treated. This article seeks to improve the knowledge base of vascular practitioners who make clinical decisions about the diagnosis and treatment of obstructive iliac vein lesions.


Remarkable effects of chirality on deslipping reactions of diastereomeric rotaxanes and relevant mechanism involving pre-equilibrium.
The first clear differentiation on deslipping rates affected by the difference in the diastereomeric stereocenters of rotaxanes up to 8.4 times and unexpectedly large steric kinetic isotope effect on the deslipping reaction (ca. 20%) were observed. On the basis of the kinetic parameters, steric kinetic isotope effect, and (1)H NMR spectra of the nondeuteriated and deuteriated rotaxanes, we propose a deslipping mechanism involving pre-equilibrium.


Natural products triptolide, celastrol, and withaferin A inhibit the chaperone activity of peroxiredoxin I.
Peroxiredoxin I (Prx I) plays an important role in cancer development and inflammation. It is a dual-functional protein which acts as both an antioxidant enzyme and a molecular chaperone. While there have been intensive studies on its peroxidase activity, Prx I's chaperone activity remains elusive, likely due to the lack of chaperone inhibitors. Here we report that natural product triptolide selectively inhibits the chaperone activity of Prx I, but not its peroxidase activity. Through direct interaction with corresponding cysteines, triptolide triggers dissociation of high-molecular-weight oligomers of Prx I, and thereby inhibits its chaperone activity in a dose-dependent manner. We have also identified celastrol and withaferin A as novel Prx I chaperone inhibitors that are even more potent than triptolide in the chaperone activity assay. By revealing the exact molecular mechanisms of interaction and inhibition, the current study provides the first Prx I chaperone inhibitors as promising pharmacological tools for modulating and dissecting the chaperone function of Prx I.


Microcarrier cell culture of neonatal human corneal endothelium.
Fresh isolates of neonatal human corneal endothelial cells were maintained in tissue culture using a technique employing collagen-coated, dextran-based microcarrier beads. This method provides large yields of endothelial cells suitable for biochemical and/or transplant studies without exposing the cells to enzymatic passage. Our results suggest that microcarrier culture of human corneal endothelial cells can provide a useful in vitro system for the growth and maintenance of actively mitotic cells.


Pulmonary immunity during respiratory infections in early life and the development of severe asthma.
Asthma affects 10% of the population in Westernized countries, being most common in children. It is a heterogeneous condition characterized by chronic allergic airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR) to normally innocuous antigens. Combination therapies with inhaled corticosteroids and bronchodilators effectively manage mild to moderate asthma, but there are no cures, and patients with severe asthma do not respond to these treatments. The inception of asthma is linked to respiratory viral (respiratory syncytial virus, rhinovirus) and bacterial (Chlamydia, Mycoplasma) infections. The examination of mouse models of early-life infections and allergic airway disease (AAD) provides valuable insights into the mechanisms of disease inception that may lead to the development of more effective therapeutics. For example, early-life, but not adult, Chlamydia respiratory infections in mice permanently modify immunity and lung physiology. This increases the severity of AAD by promoting IL-13 expression, mucus hypersecretion, and AHR. We have identified novel roles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and IL-13 in promoting infection-induced pathology in early life and subsequent chronic lung disease. Genetic deletion of TRAIL or IL-13 variously protected against neonatal infection-induced inflammation, mucus hypersecretion, altered lung structure, AHR, and impaired lung function. Therapeutic neutralization of these factors prevented infection-induced severe AAD. Other novel mechanisms and avenues for intervention are also being explored. Such studies indicate the immunological mechanisms that may underpin the association between early-life respiratory infections and the development of more severe asthma and may facilitate the development of tailored preventions and treatments.


Fabrication of Conductive Copper Films on Flexible Polymer Substrates by Low-Temperature Sintering of Composite Cu Ink in Air.
The development of a thermal sintering method for Cu-based inks under an air atmosphere could greatly expand their application for printed electronics. However, it is well-known that Cu-based inks cannot produce conductive Cu films when sintered at low temperatures in air because Cu readily oxidizes under such conditions. In this study, we have successfully demonstrated air atmosphere sintering at low temperatures (less than 150 °C) via a simple hot plate heat treatment for producing conductive Cu films on flexible polymer substrates, using a novel Cu-based composite ink with sub-10 nm Cu nanoparticles protected with 1-amino-2-propanol with micrometer-sized Cu particles and submicrometer-sized Cu particles; oxalic acid was also added to prevent the oxidation of the Cu during sintering. The Cu films showed a minimum resistivity of 5.5 × 10-5 Ω·cm when sintered in air at 150 °C for a very short period of 10 s. To the best of our knowledge, this is the first report of sintering of Cu-based inks in air at less than 150 °C. Another novel property of the present Cu-based composite ink is the lowest reported resistivity at 80 °C under N2 flow (5.3 × 10-5 Ω·cm at 80 °C and 8.4 × 10-6 Ω·cm at 120 °C). This fast, efficient, and inexpensive technology for thermal sintering in ambient air using composite inks could be a commercially viable method for fabricating printed electronics on flexible substrates.


(Anti)estrogenic activity impacted by complex environmental matrices: A DOM and multiphase distribution approach.
The presence of estrogenic endocrine disruptors in aquatic environments has been a concern and bioassays are recommended tools for their monitoring. However, the physicochemical properties of contaminants and the environmental matrix features may influence the resultant response. This study aimed to assess this influence on the Yeast Estrogen Screen (YES) assay. Mixtures of 17β-estradiol (E2) and humic acid (HA) were evaluated through the Schild approach aiming to investigate the interactions between estrogens and dissolved organic matter (DOM). Moreover, environmental samples from municipal landfill leachate and wastewater treatment plant (WWTP) influents and effluents were screened for (anti)estrogenic activity at both dissolved and particulate phases. Finally, results were statistically confronted with physicochemical parameters through principal component analysis (PCA). The HA test concentrations strongly reduced the E2 response, even at low levels. Humic substances may not only reduce estrogen bioavailability, but also interfere with the assay mechanism through enzymatic inhibition thus masking the sample estrogenic potential. Landfill leachate had total E2-Eq in the range 1282-2591 ng L-1, while WWTP influent and effluent were in the range 12.1-41.4 and <DL-2.3 ng L-1, so estrogenicity was reduced 92% in average. Particulate phase was responsible for 33-100% of measured E2-Eq between matrices, though cytotoxicity occurred in some extracts. Antiestrogenic activity was observed in both phases and might also have masked the estrogenicity of samples. PCA did not resulted in positive correlations supporting a multiphase distribution pattern of estrogenic compounds. Nevertheless, the solids and organic matter characteristics supported the data interpretation. In conclusion, the in vitro YES assay is subjected to factors intrinsic to the environmental sample that can influence on the measured estrogenic response. Therefore, results interpretation should be performed together with organic matter characterization parameters, cytotoxicity and antiestrogenic activity evaluation.


Association of mTORC1‑dependent circulating protein levels with cataract formation: a mendelian randomization study.
The mechanistic target of rapamycin (mTOR) signal pathway plays a critical regulating role in the occurrence and development of cataract. However, the role of mTORC1 downstream proteins, including ribosomal protein S6K (RP-S6K), eukaryotic initiation factor 4E-binding protein (EIF4EBP), eukaryotic initiation factor 4G (EIF-4G), eukaryotic initiation factor 4E (EIF-4E), and eukaryotic initiation factor 4A (EIF-4A), in regulating cataract development is still unknown. Herein, we conducted a mendelian randomization (MR) study to understand the function of mTORC1 signaling in the process of cataract development. The causal estimate was evaluated with inverse-variance weighted (IVW) estimate, weighted median estimator, MR-Egger and MR robust adjusted profile score (MR. RAPS). The single-nucleotide polymorphisms (SNPs), P<5 × 10- 6 and r2<0.05, were selected to genetically predict the RP-S6K, EIF4EBP, EIF-4E, EIF-4A, and EIF-4G. We included a total of 26,758 cases and 189,604 controls in this MR study. The study revealed causal association between circulating EIF4EBP (OR 1.09, 95% confidence interval 1.03,1.16, P = 0.004), RP-S6K (OR 1.04, 95% confidence interval 1.01, 1.08, P = 0.02) and cataract formation with IVW estimate. Whereas after correcting outliers, MR robust adjusted profile score (MR. RAPS) shows consistent result with IVW for EIF4EBP (OR = 1.08, 95%CI:1.05-1.11, P = 0.007). The observation strengthened the confidence in the true causal associations. However, no association was found for circulating EIF-4E (OR 1.03, 95% confidence interval 0.97, 1.09, P = 0.31), EIF-4A (OR 1.02, 95% confidence interval 0.98, 1.07, P = 0.34), and EIF-4G (OR 1.02, 95% confidence interval 0.94, 1.01, P = 0.64) levels with cataract formation. No evidence of heterogeneity and unbalanced horizontal pleiotropy was detected. The MR study suggests that EIF4EBP is a high-risk factor for cataract development. There may be a potential causal association between the mTORC1/EIF4EBP axis and cataract. This research highlights the potential mechanism for cataract development and a genetic target to prevent as well as treat cataracts.


Bioreclamation of coalmine overburden dumps--with special empasis on micronutrients and heavy metals accumulation in tree species.
Major environmental impacts of opencast mining are degradation of landscape and aesthetics of the area by creating huge overburden dumps and deep voids at the mining sites. These overburden dumps are characterised by high rock fragment contents, low moisture retention capacity, higher bulk density, low nutrients, lower pH and elevated metal concentrations. Overburden dumps are reclaimed by tree species for stabilising as well as pollution control and overall improvement of the visual aesthetics. A field study was carried out in the old reclaimed coal mine overburden dumps at KD Heslong project, Central Coalfields, India to study the physico-chemical changes in the reclaimed overburden dumps and determines the magnitude of trace elements accumulation in the planted tree species. Total, bioavailable and acid extractable trace metals concentration in minesoils of overburden dump and topsoil in the mining areas was compared with undisturbed soil. The study showed that tree plantation improves the moisture contents, bulk density, pH and overall nutrient contents of minesoils. The study revealed that lower pH in the minesoils increases the bioavailabity of metals but concentration were found within toxic limits. However, ratio between total and bioavailable metals was found lower in overburden dumps than topsoil due to low pH and lack of organic matter. Out of six tree species studied, Bambusa shows highest accumulation of Fe and Cr. Bioaccumulation coefficient for Cr and Zn was found 74 times in Bambusa and 83 times in Dalbergia sissoo. The results of the study underscore the need for close monitoring of trace elements in reclaimed overburden dumps. Tree species like Dalbergia sissoo, Eucalyptus, Cassia seamea, Acaccia mangium and Peltaphorum were found to be the best species for bioreclamation of overburden dumps.


Anterior elongation as a minimally invasive alternative for sagittal imbalance-a case series.
Degenerative and iatrogenic conditions may lead to flat back or even to kyphotic deformity, and sagittal imbalance can cause significant clinical impairment. Minor imbalance cases are usually treated with conservative care. Among currently popular surgical techniques for the correction of sagittal imbalance are posterior-based procedures, which are associated with access-related risks (mostly neurological) and postoperative morbidity risks. This study aims to report a minimally invasive lateral approach using hyperlordotic cages in the treatment of mild sagittal imbalance. Radiological correction, clinical improvement, and safety will be analyzed. Eight patients (mean age 71.8 years, SD 7.8; mean BMI 27.5, SD 2.3) with symptomatic sagittal imbalance were retrospectively reviewed. Eight cases were treated by anterior interbody fusion with lordotic cages. A minimally invasive lateral retroperitoneal approach was used in the surgical procedures, with or without percutaneous pedicle screw supplementation. No major complications occurred and just one case needed revision for direct decompression. Clinical outcomes Visual Analog Scale score changed from 88 at preoperative visit to 51 at 1-week visit, and Oswestry Disability Index score decreased from 82 at preoperative visit to 44 at 6-week visit. The 6-month radiological assessment revealed improvement in spinopelvic parameters: Focal lordosis improved from 2.3° ± 7.7 to 27.1° ± 6.7. Sagittal vertical alignment improved from 11.7 ± 5.3 to 6.2 ± 4.0 cm. Preoperative sacral slope improved from 20.1° ± 5.8 to 29.4° ± 10.3 and preoperative pelvic tilt improved from 35.2° ± 5.2 to 23.8° ± 4.3. Short-term results indicate that the minimally invasive lateral approach can be applied to the treatment of mild sagittal imbalance, with special advantage in elderly patients or those in which posterior approaches are relatively contraindicated.


Determination of whole blood and plasma viscosity in term neonates by flow curve analysis with the LS300 viscometer1.
Determination of shear stresses at given shear rates allow approximation of flow curves by mathematical models and to calculate viscosities of non-Newtonian fluids. In term neonates, the mean arterial blood pressure (MAP) is markedly below that of adults, therefore rheological properties of blood play an important role in maintaining perfusion. Whole blood viscosity was measured in umbilical cord blood taken from 62 term neonates using the LS 300 viscometer. Individual parameters that influence the viscosity of whole blood were measured: red blood cell (RBC) aggregation, plasma viscosity, hematocrit, and RBC deformability. The flow curve of whole blood of neonates was approximated by the method of Ostwald with the highest quality whereas in adults the best approximation was found by the method of Casson. With hematocrits of 0.40, the viscosity of whole blood in newborns approximated by Ostwald (9.84 ± 5.12 mPa·s) was significantly lower than that of adults (15.34 ± 3.01 mPa·s). The aggregation index of the blood of newborns was markedly lower (2.98 ± 2.12) than in adults (14.63 ± 3.50) whereas RBC deformability was higher in neonates. The viscosity of plasma determined by Ostwald revealed a lower exponent (n) in neonates (0.94 ± 022) compared to adults (1.01 ± 0.12) and the viscosity determined by Newton was lower in neonates (1.04 ± 0.16 mPa·s) than in adults (1.19 ± 0.07 mPa·s). The flow curve of neonatal blood which is best approximated by the model of Ostwald emphasizes its important viscous properties necessary for conditions with physiologically low blood pressure.


Promotion of ventricular tachycardia induction by procainamide in dogs with inducible ventricular fibrillation late after myocardial infarction.
The influence of procainamide on inducible ventricular tachyarrhythmias was evaluated in 35 dogs with experimental myocardial infarction, and 9 normal dogs. Programmed stimulation was performed from the right ventricular apex via a percutaneously positioned electrode catheter, using up to five extrastimuli before and after intravenous administration of procainamide (15 mg/kg). Procainamide levels in postinfarct dogs were 8.5 +/- 0.7 micrograms/mL (range 5.3-13.6 micrograms/mL). Procainamide exerted its greatest effect in postinfarct dogs with reproducible baseline ventricular fibrillation. Six of nine dogs (P less than 0.05) with ventricular fibrillation had sustained monomorphic ventricular tachycardia (cycle length: 147 +/- 4 msec) induced after procainamide administration. This ventricular tachycardia required significantly more extrastimuli than baseline ventricular fibrillation (3 +/- 0.3 extrastimuli before vs 4 +/- 0.3 extrastimuli after procainamide). Procainamide never converted ventricular fibrillation to ventricular tachycardia in normal dogs. Procainamide had minimal effect on inducible ventricular tachycardia after myocardial infarction. Ventricular tachycardia induction was abolished in only 2 of 17 dogs despite significant prolongation of electrophysiological parameters. Ventricular tachycardia cycle length, and the number of extrastimuli required were unchanged by procainamide in this subgroup. Ventricular tachycardia is insensitive to the antiarrhythmic properties of procainamide in this model. In contrast, procainamide is able to convert postinfarction ventricular fibrillation to ventricular tachycardia, presumably by promoting sustained, organized reentry. This previously undescribed action is an unusual form of proarrhythmic effect, and suggests that this drug should be used cautiously in patients after myocardial infarction.


Hyperacute rejection of xenografts. I. Differences in affinity to ConA--Sepharose of IgG--fraction of the affluent and effluent blood.
The immunoglobulin fraction from affluent and effluent sera from the rabbit liver transplanted to a dog partially purified on ion exchange DEAE--Sephadox A-50 was chromatographed on ConA-Sepharose. The picture of SDS polyacrylamide slab gel electrophoresis (PAGE) showed in the xenograft serum a considerably higher intensity of bands corresponding to the mobility of heavy and light IgG chains. This suggested the presence of glycoproteins coupled to IgG. Immunoelectrophoresis proved occurrence in the transplant serum of at least six additional components precipitating with whole anti-dog serum. These components could be either glycoprotein antigens or complement components, free or bound to IgG subclasses.


Vasopressin for Septic Shock in a Medical-Surgical Intensive Care Unit.
Critically ill patients often need vasopressors to treat hypotension related to septic shock and to maintain adequate systemic perfusion. Although the 2017 guidelines of the Surviving Sepsis Campaign recommend norepinephrine as first-line therapy, they also state that vasopressin may be considered as an adjunctive agent for patients with refractory shock. Limited evidence is available for directing optimal administration of vasopressin. As such, prescribing practices are not standardized and may vary according to the particular clinician, the clinical scenario, and various patient-specific factors. To review the current practice of administering concomitant norepinephrine and vasopressin therapy to patients with septic shock, to describe variability in vasopressin administration, and to evaluate effects on patient safety in a medical-surgical intensive care unit (ICU). This single-centre retrospective chart review involved 100 adult patients admitted to the ICU who received vasopressin and norepinephrine for septic shock between April and December 2017. The data were analyzed with descriptive statistics. The mean time to initiation of vasopressin was 12.0 (standard deviation [SD] 21.6) h after initiation of norepinephrine. The mean dose of norepinephrine at the time of vasopressin initiation was 29.5 (SD 19.7) μg/min. The mean vasopressin dose prescribed was 0.04 (SD 0.03) units/min, with a range of tapering and discontinuation regimens. The mean duration of vasopressin therapy was 49.1 (SD 65.2) h, and vasopressin was discontinued before norepinephrine in 49 of the patients. A total of 60 hypotensive events occurred after vasopressor discontinuation and were more common when vasopressin was discontinued before norepinephrine. Vasopressin dosing was comparable to that reported elsewhere; however, discontinuation practices were inconsistent. These results show that variability in the literature supporting vasopressin use has led to variability in vasopressin administration and discontinuation practices; however, correlation with improvement in clinical outcomes, such as mortality or ICU length of stay, is unclear, and further research is required to determine the ideal approach to vasopressin use.


Comorbidities and treatment outcomes in multidrug resistant tuberculosis: a systematic review and meta-analysis.
Little is known about the impact of comorbidities on multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) treatment outcomes. We aimed to examine the effect of human immunodeficiency virus (HIV), diabetes, chronic kidney disease (CKD), alcohol misuse, and smoking on MDR/XDRTB treatment outcomes. We searched MEDLINE, EMBASE, Cochrane Central Registrar and Cochrane Database of Systematic Reviews as per PRISMA guidelines. Eligible studies were identified and treatment outcome data were extracted. We performed a meta-analysis to generate a pooled relative risk (RR) for unsuccessful outcome in MDR/XDRTB treatment by co-morbidity. From 2457 studies identified, 48 reported on 18,257 participants, which were included in the final analysis. Median study population was 235 (range 60-1768). Pooled RR of unsuccessful outcome was higher in people living with HIV (RR = 1.41 [95%CI: 1.15-1.73]) and in people with alcohol misuse (RR = 1.45 [95%CI: 1.21-1.74]). Outcomes were similar in people with diabetes or in people that smoked. Data was insufficient to examine outcomes in exclusive XDRTB or CKD cohorts. In this systematic review and meta-analysis, alcohol misuse and HIV were associated with higher pooled OR of an unsuccessful outcome in MDR/XDRTB treatment. Further research is required to understand the role of comorbidities in driving unsuccessful treatment outcomes.


Dithiolato-bridged nickel-iron complexes as models for the active site of [NiFe]-hydrogenases.
The structural and functional modeling of the active site of [NiFe]-hydrogenases has been proved to be challenging to a great extent. Herein, we report the synthesis, structures, and some properties of the NiFe-based dicarbonyl, terminal hydride, and μ-hydroxo models for the active site of [NiFe]-hydrogenases.


[Structural analysis of the information value of lung ventilation parameters for assessment of bronchodilation response in patients with bronchial asthma].
The goal of this work was to perform structural analysis of the information value of lung ventilation parameters for assessment of bronchodilation response in patients with bronchial asthma. The information value of lung ventilation parameters is considered as a function of the initial level of ventilation disorders and the method of calculation of bronchodilation response. Structural analysis revealed that different lung ventilation parameters have different information value for assessment of bronchodilation response in patients with bronchial asthma. The effect of the method of calculation and the initial severity of ventilation disorders on the information value of lung ventilation parameters is also rather complex. Parameters with maximal information value for analysis of the results of broncholytic tests in patients with bronchial asthma are determined. These parameters have high information value independently of the method of calculation.


Emergence of ST1193 Clone in Maternal and Neonatal ESBL-Producing E. coli Isolates.
The emerging epidemic of extended-spectrum β-lactamase-producing E. coli (ESBL-EC) is a global public health crisis. ESBL-EC infections are increasing worldwide and contribute to morbidity and mortality among newborn infants. However, the antimicrobial resistance characteristics and clonal transmission of maternal and neonatal ESBL-EC isolates need to be further deciphered. We performed phenotypic and genotypic characterization of 33 ESBL-EC isolates from pregnant women and newborn during 2019-2020. Minimum inhibitory concentrations of 17 antimicrobial agents showed that all isolates were multidrug-resistant (MDR) and had a resistance rate of 100% to ampicillin, and mild resistance to florfenicol, gentamicin, ceftazidime, and amoxicillin-clavulanate. Additionally, imipenem, meropenem, polymyxin, and tigecycline exhibited good activity against the tested ESBL-EC isolates with low MIC50 (0.06-1 μg/mL) and MIC90 (0.06-1 μg/mL). Whole genome sequencing indicated that ESBL-EC isolates contained diverse antimicrobial resistant genes (blaCTX-M, blaTEM, blaSHV, tetA, etc.) and toxin genes (ompA, csg, fimH, hybtA, etc.). blaCTX-M genes were the main ESBL genotype. ST1193 (18.2%) was the second most abundant ST among the ESBL-EC isolates (ST131 was the most common, with 30.3%), and this is the first report of its mother-to-infant colonization transmission in China. These findings revealed the occurrence of high-risk ST1193 clone among ESBL-EC isolates from pregnant women and newborn colonization in China. Further national or regional multicenter studies are needed to assess the dissemination and evolution of ESBL-EC ST1193 clone as a nosocomial pathogen in China.


[Structure of Aerobic Denitrification Bacterial Community in Response to Dissolved Organic Matter in Baiyangdian Lake During the Water Delivery Period].
Dissolved organic matter (DOM) plays an important role in the evolution of microbial communities. Meanwhile, ecological water delivery is an important feature of Baiyangdian Lake. To explore how the structure of the aerobic denitrification bacteria community responds to DOM during the water delivery period, the DOM components of water were examined and high-throughput sequencing of aerobic denitrification bacteria was performed. The results showed significant differences in DOM concentration in Baiyangdian Lake, with the estuary area exhibiting lower DOM concentrations. The water exhibited strong autogenous source, while DOM in the estuary area had a higher molecular weight and degree of humification. Three protein-like substances (C1, C2, and C4) and one humic-like substance (C3) were identified through PARAFAC. The protein-like substances accounted for the major proportion of DOM, which was consistent with the results of fluorescence regional integration (FRI). The genera of the water body were mainly in the Protebacterice phylum, including Cupriavidus, Aeromonas, Thauera, Shewanella, and Pseudomonas. Meanwhile, Cupriavidus, Thauera, Shewanella, Agrobacterium, and Pseudomonas were the main indicator species, according to random forest (RF) analysis. Through network analysis, 35 key nodes of the network were obtained, belonging to Thauera, Cupriavidus, and Unclassified_bacteria, respectively. Redundancy analysis (RDA) showed that a humic-like substance was the main environmental factor regulating the whole structure of the aerobic denitrification bacterial community, while protein-like substances played important roles in changes to the indicator species and key nodes of the community. Overall, protein-like substances could provide an important reference for selecting carbon sources during the screening of efficient and cold resistance aerobic denitrification bacteria that are adapted to actual water bodies.


Psychophysics of reading. VI--The role of contrast in low vision.
The effect of contrast on reading performance was measured in 19 low-vision observers with a wide range of visual disorders and degrees of vision loss. The observers read text composed of 6 deg letters, ranging in contrast from 0.96 down to contrast threshold for reading. Reading performance was characterized by two parameters: peak reading rate is the reading rate at maximum contrast, and critical contrast is the contrast at which reading rate drops to half its maximum value. Peak reading rates were lower in observers with central field loss than in observers with intact central vision. In 16 of 19 cases, critical contrasts were higher for low-vision observers than for normal observers (averaging 3.9 times higher), indicating a decreased tolerance to contrast reduction. Values of critical contrast were closely linked to contrast sensitivity for letters (r = 0.87), but did not vary systematically with type of vision loss. Five observers read white-on-black text faster than black-on-white at both high and low contrasts. Four of the five had cloudy ocular media. We attribute this contrast polarity effect to abnormal light scatter in eyes with cloudy media. We examined the hypothesis that our low-vision observers' deviation from normal performance could be characterized (1) by a contrast scaling factor representing an attenuation of effective contrast and (2) that this scale factor could be identified with reduced contrast sensitivity. Such a description provided a good account for subjects with cloudy ocular media, where contrast attenuation results from intraocular light scatter. It provided a first order, but incomplete account for subjects with field loss where contrast attenuation is related to contrast sensitivity losses due to neural factors.


Modified glasgow prognostic score in patients with small-cell lung cancer.
Systemic inflammatory response, which represents the presence of cachexia, is observed often in patients with lung cancer. To evaluate the prognostic significance of the presence of a systemic inflammatory response in small cell lung cancer (SCLC) patients, a retrospective study using modified Glasgow prognostic Score (mGPS) was performed. This score is composed of serum albumin and C-reactive protein levels. All the patients with SCLC who were diagnosed in Tsukuba University Hospital, Tsukuba Medical Center Hospital and Mito Medical Center between April 1999 and July 2016 were included in this study. During the study period, 332 patients with SCLC were consecutively admitted to these hospitals. Among them, 54 (16.9%) had mGPS=1, and 73 (22.9%) had mGPS=2. Male sex, advanced stage, poor performance status and no chemotherapy were unfavorable prognostic factors in uni- and multivariate-analysis. In addition, the presence of a systemic inflammatory response was confirmed as an unfavorable prognostic factor. In patients with SCLC, an existing systemic inflammatory response adversely affected the outcome. The patient's extent of disease as well as medical conditions including systemic inflammatory response must be taken into consideration when deciding whether to offer a standard therapy that may increase treatment-associated mortality.


Vaccines, Pesticides, and Narratives of Exposure and Evidence.
This essay considers the cultural work performed by two public health narratives - the DDT narrative and the vaccine narrative - as they appeared in popular and professional discourse concerning two recent media events: controversy over an antivaccination film, and the emergence of a Zika global public health emergency. Like all narratives in the history of medicine, the stories historians and others tell about DDT and about vaccines organize a shared past to explain the present. They also point to a hoped-for future. The DDT and vaccine narratives share several themes: public health, expertise, evidence, exposure, and power. Their inclusions and exclusions, however, convey distinct messages about these themes, particularly regarding the right conduct of health citizens in the pursuit of public health. These narratives are analyzed to compare their agendas, and to propose a case study of how historical work can shed light on contemporary public health norms, practice, and challenges.


Relationship between muscle swelling and stiffness after eccentric exercise.
The time courses of muscle compartmental swelling and passive stiffness change were measured to determine whether muscle compartmental swelling accounted for increased stiffness. Eleven untrained female college students exercised eccentrically by lowering a weight with their elbow flexors. Measurements of muscle compartment volume, stiffness, relaxed elbow angle, circumference, and pain were recorded before exercise, immediately after exercise, and 1-5, 7, 9, and 11 d after exercise. Muscle compartment volume was calculated from cross-sectional ultrasound images taken along the upper arm. Stiffness was measured using a device that extended the elbow and recorded the torque required to hold the forearm at successive angles. Elbow flexor volume increased gradually to peak on the fourth day (26.1 +/- 4.3%, P < 0.05) and then decreased to baseline values over days 7-11. Stiffness increased immediately after exercise (59.9 +/- 14.1%, P < 0.05) and remained at or above this level until decreasing to pre-exercise levels over days 7-11. This suggests that muscle swelling does not account for the sudden increase in stiffness of the elbow flexor muscles within the first 48 h after exercise but may play a role in the subsequent time course of stiffness.


Migratory bats respond to artificial green light with positive phototaxis.
Artificial light at night is spreading worldwide at unprecedented rates, exposing strictly nocturnal animals such as bats to a novel anthropogenic stressor. Previous studies about the effect of artificial light on bats focused almost exclusively on non-migratory species, yet migratory animals such as birds are known to be largely affected by light pollution. Thus, we conducted a field experiment to evaluate if bat migration is affected by artificial light at night. In late summer, we presented artificial green light of 520 nm wavelength to bats that were migrating south along the shoreline of the Baltic Sea. Using a light on-off treatment, we observed that the activity of Pipistrellus nathusii and P. pygmaeus, the two most abundant migratory species at our site, increased by more than 50% in the light-on compared to the light-off treatment. We observed an increased number of feeding buzzes during the light-on compared to the light-off treatment for P. nathusii. However, feeding activity was low in general and did not increase disproportionately during the light-on treatment in relation to the overall echolocation call activity of bats. Further, P. nathusii were attracted towards the green light at a distance of about 23 m, which is way beyond the echolocation detection range for insects of Nathusius' bats. We therefore infer that migratory bats were not attracted to artificial green light because of high insect densities, but instead by positive phototaxis. We conclude that artificial light at night may potentially impact bat migration in a yet unrecognized way.


Antibacterial activity of polihexanide formulations in a co-culture of HaCaT keratinocytes and Staphylococcus aureus and at different pH levels.
Complex stalled wounds feature an alkaline milieu that favors tissue destruction and microbial growth. The presence of bacteria in turn perpetuates the inflammatory response. However, only limited knowledge exists of pH dependency on the antibacterial efficacy of polyhexamethylene biguanide (PHMB) or the influence of surfactants or delivery vehicle used in antiseptic formulations. So far, PHMB alone has been shown to protect the keratinocytes from bacterial damage in such a co-culture system as well as exhibiting increased antimicrobial activity at higher pH values. Here, the interaction of PHMB with the surfactants macrogolum and undecylenamidopropyl betaine that are most commonly used as additives in antiseptics and rinsing solutions such as Lavasept and Prontosan has been explored in addition to the PHMB-containing biocellulose dressing Suprasorb X + PHMB. Undecylenamidopropyl betaine was found to lower the antimicrobial activity of polihexanide in the co-culture system, while macrogolum and the biocellulose increased polihexanide efficiency to reduce Staphylococcus aureus especially in the presence of serum. The increasing antibacterial efficacy of PHMB with rising pH was not altered by undecylenamidopropyl betaine, macrogolum, or the biocellulose. The results suggest that application of PHMB with macrogolum or by delivery through a biocellulose dressing might be advantageous for management of wound infections.


Innovative testing method for an integrated radiology-histology curriculum.
A module of radiology instruction was incorporated into an existing histology course for first-year medical students (n = 177). An innovative testing methodology for assessing the instructional effectiveness of the integrated radiology-histology module was developed and tested. Test items were designed to measure the students' ability to integrate the two disciplines successfully. Radiologic and histologic images were displayed at each of seven stations, to which the content of the images either were or were not related. The seven stations were incorporated into three traditional histology laboratory examinations. For purposes of data analysis, each test was divided into three components, including histology alone, histology in combination, and radiology in combination. Testing lengths were equated using the Spearman-Brown statistical adjustment. Analysis of the test results showed the reliability coefficients to be comparable to the traditional testing methods used previously in the course. Correct responses were similar in all three sections, ranging between 85 to 97%. This methodology thus appears to be an effective means of testing an integrated curriculum.


Primary insular carcinoid of the ovary.
Primary ovarian carcinoids are very rare tumors that account for less than 5% of all carcinoids and 0.1% of all ovarian malignancies. We present a rare case of a primary, non-functioning, insular carcinoid of the left ovary in a 44-year-old woman originating from the outer surface of a mature cystic teratoma. After an uneventful unilateral salpingo-oophorectomy, the patient had no sign of recurrence with computed tomography and 5-HIAA evaluation at 3-year follow-up. Although rare, primary ovarian insular carcinoid tumors that are confined to the ovary and treated with surgery are expected to have an excellent overall outcome.


The DRPLA CAG repeats in an Italian population sample: evaluation of the polymorphism for forensic applications.
The DRPLA CAG repeats polymorphism has been studied in an Italian population sample. PCR amplification, manual PAGE and silver staining were employed. A total of 16 different alleles, spanning the range from 5 to 21 CAG triplettes, was observed. The heterozygosity was 0.81 and no significant deviation from Hardy-Weinberg equilibrium was found 81 meioses from parentage testing were also analyzed and a Mendelian pattern of inheritance was observed in all cases. In addition, we could successfully type DRPLA locus in some forensic specimens, 1 ng of DNA allowing clear definition of alleles. The authors conclude that the DRPLA CAG repeats analysis may be useful for forensic applications.


Construction of cDNA bank from biopsy specimens for multiple gene analysis of cancer.
We constructed a "cDNA bank" of human colorectal cancer and surrounding normal tissues with our unique mRNA assay system. Total nucleic acids extracted from patients' tissues were applied to 96-well plates, where poly(dT) sequences of oligonucleotides were immobilized. After hybridization, the cDNA was reverse-transcribed on the plate with the captured mRNA as a template, followed by synthesis of double-stranded (ds) cDNA. The resulting sense cDNA was removed from the plate, then used in PCR for analysis of various genes. The sense strand of the cDNA was repeatedly synthesized by using the immobilized antisense cDNA as a template even from plates used once and stored at 4 degrees C for as long as 6 months. Furthermore, the results of PCR could be easily compared among different specimens if the same amount of total mRNA were applied to the plate for the ds cDNA synthesis. This demonstrated that the cDNA bank constructed from clinical materials provides almost unlimited supplies of cDNA for multiple gene analysis of cancer.


New Approaches to Treat Osteoarthritis with Mesenchymal Stem Cells.
Osteoarthritis is one of the most common chronic health problems in the world that causes disability and chronic pain with reduced mobility and is a progressive degenerative disease in weight-bearing joints such as the knee. The pathology of the joint resulting from OA includes loss of cartilage volume and cartilage lesions leading to inflammation of the articular joint structures; its incidence and progression are associated with a variety of risk factors. Most of the current treatments focus on symptom management such as physical and occupational therapies, pharmacological intervention for pain management, and surgical intervention with limited success and do not address nor halt the progression of the disease. In this review, we will describe the current treatment options for OA and the exciting new translational medical research currently underway utilising mesenchymal stem cells for OA therapy.


Clinical crown lengthening in the esthetic zone.
Periodontal surgical procedures consisting of gingival flaps and osseous recontouring are indicated for crown lengthening of several contiguous teeth in the esthetic zone; both in cases where restorations are required and in cases where no restorations are planned, such as in patients with excessive gingival display due to altered passive eruption. Forced tooth eruption via orthodontic extrusion is the technique of choice when clinical crown lengthening is necessary on isolated teeth in the esthetic zone.


[Thanatophoric dysplasia: case-based bioethical analysis].
This paper presents a case report of thanatophoric dysplasia diagnosed in the prenatal period using ultrasound standards. The course of the case pregnancy, birth process, and postnatal period is described. This report invites bioethical analysis using its principles, appealing to human dignity, diversity and otherness, particularly in the mother-child dyad and their family. An early diagnosis allows parental support as they face the course of this condition and its potentially fatal outcome.


The total resection rate of glioma can be improved by the application of US-MRI fusion combined with contrast-enhanced ultrasound.
This study was performed to evaluate the diagnostic performance of ultrasound-magnetic resonance imaging (MRI) fusion combined with contrast-enhanced ultrasound and to explore its role in improving the total tumor resection rate. Between January 2018 and December 2018, 16 patients in the observation group and 23 patients in the control group were enrolled in this study. The tumor depth and brain shift distance were analyzed, as well as the peak intensity and microvessel density of different grades of gliomas in the observation group. Finally, we compared the difference in total resection rate between the observation and control groups. Using ultrasound during operations, we found a significant negative correlation between brain shift distance and tumor depth, with correlation coefficient r=-0.868(P<0.05). In glioma, the peak intensity and microvessel density increased synchronously with glioma grade(r=0.806, P<0.05). The total resection rate of lesions was significantly higher in the observation group than in the control group (P<0.05). The application of ultrasound-MRI fusion combined with contrast-enhanced ultrasound can improve the total resection rate of lesions, thus playing an important role in clinical practice.


The regulation of vestibular afferent information during monocular vision while standing.
The purpose of this study was to investigate the contribution of the vestibular system to postural control during monocular vision using binaural-bipolar galvanic vestibular stimulation (GVS). Four visual (both eyes, dominant eye, non-dominant eye, and no vision) conditions were tested during GVS in five healthy subjects while focusing on a target placed in front of them. GVS evoked similar upper body postural sway during both monocular and no vision conditions that were significantly greater to those during binocular vision. Changes in ground reaction forces to the anode side followed that same trend, although data for vision with the dominant eye were not significantly different from that for binocular vision. These data suggest an increase in the weighting of vestibular afferent information during monocular vision for standing postural control.


Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design.
As small molecule drugs become harder to develop and less cost effective for patient use, efficient strategies for their property improvement become increasingly important to global health initiatives. Improvements in the physical properties of Active Pharmaceutical Ingredients (APIs), without changes in the covalent chemistry, have long been possible through the application of binary component solids. This was first achieved through the use of pharmaceutical salts, within the last 10-15years with cocrystals and more recently coamorphous systems have also been consciously applied to this problem. In order to rationally discover the best multicomponent phase for drug development, intermolecular interactions need to be considered at all stages of the process. This review highlights the current thinking in this area and the state of the art in: pharmaceutical multicomponent phase design, the intermolecular interactions in these phases, the implications of these interactions on the material properties and the pharmacokinetics in a patient.


Decreased long non-coding RNA SPRY4-IT1 contributes to ovarian cancer cell metastasis partly via affecting epithelial-mesenchymal transition.
Long non-coding RNAs play important roles in the regulation of cellular processes including cell proliferation, differentiation, and metastasis. The dysregulation of long non-coding RNAs, such as the SPRY4-IT1 (SPRY4 intronic transcript 1), has been associated with various types of malignancies. However, the functional roles and regulatory mechanism of SPRY4-IT1 in ovarian cancer remain to be elucidated. Here, we quantified the expression level of SPRY4-IT1 in ovarian cancer patients and found its downregulation in ovarian cancer tissues compared to the adjacent normal tissues. Patients with lower SPRY4-IT1 expression were associated with a relatively poor prognosis. In consistency, the expression of SPRY4-IT1 was found to be reduced in four human ovarian cancer cell lines compared to normal ovarian epithelial cells. Next, two ovarian cancer cell lines SKOV3 and HO8910 were employed in vitro assays to investigate biological functions of SPRY4-IT1 in ovarian cancer. The cell proliferation was reduced following SPRY4-IT1 overexpression in SKOV3/HO8910 cells based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. The SPRY4-IT1 overexpression also dramatically arrested cell cycle and promoted cell apoptosis. Both wound-healing and transwell-based assays demonstrated that cell migration and invasion were inhibited following SPRY4-IT1 overexpression. Meanwhile, overexpression of SPRY4-IT1 increased E-cadherin and decreased N-cadherin and vimentin protein levels, indicating that SPRY4-IT1 may regulate ovarian cancer cell metastasis through the inhibition of epithelial-mesenchymal transition. Taken together, our findings suggest that SPRY4-IT1 regulates various cellular processes of ovarian cancer cells and its downregulation may contribute to ovarian cancer progression and metastasis partly via affecting the epithelial-mesenchymal transition.


Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1.
Somatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported in patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations and unique bone marrow (BM) features in 16 patients with VEXAS. All patients were male and had a history of severe autoinflammatory and rheumatologic manifestations and a somatic UBA1 mutation (p.Met41). Ten patients had hematologic disorders: myelodysplastic syndrome (MDS; 6 of 16), multiple myeloma (2 of 16), monoclonal gammopathy of undetermined significance (2 of 16), and monoclonal B-cell lymphocytosis (2 of 16), and a few of those patients had 2 co-existing clonal processes. Although macrocytic anemia (100%) and lymphopenia (80%) were prevalent in all patients with VEXAS, thrombocytopenia and neutropenia were more common in patients with progression to MDS. All BMs in VEXAS patients had prominent cytoplasmic vacuoles in myeloid and erythroid precursors. In addition, most BMs were hypercellular with myeloid hyperplasia, erythroid hypoplasia, and varying degrees of dysplasia. All patients diagnosed with MDS were lower risk (low blast count, very good to intermediate cytogenetics) according to standard prognostic scoring with no known progression to leukemia. In addition, 10 of 16 patients had thrombotic events, including venous thromboembolism and arterial stroke. Although VEXAS presents symptomatically as a rheumatologic disease, morbidity and mortality are associated with progression to hematologic disease. Given the increased risk of developing MDS and multiple myeloma, surveillance for disease progression is important.


Nonenzymatic reaction of dihydroxyacetone with hydrogen peroxide enhanced via a Fenton reaction.
An analysis of the reaction of dihydroxyacetone with hydrogen peroxide was performed using HPLC with electrochemical and spectrophotometric detection and EPR spectroscopy of the reactants and products. Glycolate production in such a reaction has been documented, and the glycolate yield analyzed at different pH values. The participation of hydroxyl free radical is shown with DEPMPO spin trap. Two types of mechanisms are proposed, one at higher pH values and pronounced participation of free radicals (enhanced by the presence of metal ions and Fenton reaction) and the other at lower pH values, with decreased free radical production and lower glycolate yield.


Use of nonlinear methods to assess effects of clonidine on blood pressure in spontaneously hypertensive rats.
In spontaneously hypertensive rats (SHR), chronic infusion of clonidine failed to decrease blood pressure and blood pressure variability. We used nonlinear methods to get a deeper insight on the effects of clonidine on blood pressure dynamics. For 24 h and 4 wk, clonidine (0.1 mg . kg-1 . day-1 sc) was infused by minipumps in the conscious SHRs, and, for comparison, a vehicle was infused in SHRs and in Wistar-Kyoto rats. Blood pressure was recorded for 30 min before and after treatments. We used the Lyapunov exponent, approximated by the inverse of the lmax index derived from the recurrence plot method, to characterize nonlinear dynamics. Before treatment, lmax index of blood pressure was lower (P < 0.01) in the SHRs than in the Wistar-Kyoto rats. Clonidine significantly increased lmax (P < 0.01) to the level observed in normotensive rats, at 24 h and up to 4 wk after infusion. We conclude that clonidine has a significant chronic effect on blood pressure dynamics, as evidenced by nonlinear methods. Our study also suggests that the mechanisms governing blood pressure variations are nonlinear.


Biofilm Formation by Streptococcus mutans is Enhanced by Indole via the Quorum Sensing Pathway.
Interspecies interactions among oral microorganisms in the pathogenic biofilms causing dental caries have not yet been elucidated in detail. We herein demonstrated that indole and its derivatives induced biofilm formation by Streptococcus mutans. Indole is an intercellular signaling molecule that is produced by oral bacteria other than S. mutans. The amounts of biofilm and extracellular DNA were significantly increased by the addition of indole and 4-hydroxyindole (4-HI). An examination with quorum sensing mutants showed that the induction of biofilm formation by indole and 4-HI required a quorum sensing system. These results suggest that this intercellular signaling molecule plays a role in pathogenic biofilm formation.


Endoscopic recurrent laryngeal neuropathy grade prevalence in a sample of thoroughbred yearlings at public auction in South Africa (2013-2019).
Endoscopy of thoroughbred (TB) yearlings at public auctions is common in South Africa. Laryngeal function (LF) is a common concern of buyers of young TBs. Cancellation of sale because of LF abnormalities is a concern for both the vendor and the buyer, with recurrent laryngeal neuropathy (RLN) being a common cause of sale cancellation. The aim of this descriptive study was to determine the prevalence of RLN at South African premier TB yearling sales. This study was designed as a retrospective descriptive analysis of upper respiratory tract (URT) endoscopic examinations to determine RLN grade, performed at two premier TB yearling sales in South Africa. Results of buyer-requested endoscopic examination from 2013 to 2019 were included. Results from the yearling sales were analysed for prevalence of RLN grade (using Rakestraw's 4-point system) and compared to similar previously published studies. For analysis of effects of gender on RLN grading, horses were grouped and Fisher's exact test was used to determine if there was a relationship between gender and grade. For comparison of the effects of age on grade, and sales year on grade, a Kruskal-Wallis test was conducted. A value of p 0.05 was considered significant. A total of 858 horses were examined out of 4149 offered for sale; there were 57.58% colts and 42.42% fillies (mean age of 18.1 months). The annual percentage for grade 1 was 84.04% ± 9.98%, for grade 2: 14.49% ± 10.69%, for grade 3: 0.71% ± 0.57% and for grade 4: 0.76% ± 0.94%. There were no other significant findings. The exclusive nature of the sale and the increasing proclivity for pre-sale scoping may have skewed the results. This study shows that RLN grade incidences in TB yearlings at public auctions in South Africa are as follows: grade 1: 84.04%, grade 2: 14.49%, grade 3: 0.71% and grade 4: 0.76%. The results were similar to that of an adult population of horses examined in South Africa in a previous study.


Computers in medicine. Virtual rehabilitation: dream or reality?
Coronary heart disease is the number one cause of death for men and women in the United States and internationally. Identification of persons at risk for cardiovascular disease and reduction of cardiovascular risk factors are key factors in managing this tremendous societal burden. The internet holds great promise in helping to identify and manage persons at high risk of a cardiac or vascular event. The Internet has the capability to assess risk and provide support for cardiovascular risk reduction for large numbers of persons in a cost effective and time efficient manner. The purpose of this report is to describe important advances in the use of the Internet in identifying persons at risk for a cardiovascular event and in the Internet's ability to provide interventions designed to reduce this risk.


Improving Major Depressive Episode Assessment: A New Tool Developed by Formal Psychological Assessment.
Aim: Major depressive episode (MDE) can manifest with different features. Discriminating between different types of MDEs is crucial for proper treatment. The aim of this study is to propose a new tool for MDE assessment in bipolar disorder (BD) or major depressive disorder (MDD) to overcome some limitations of current rating scales. The proposed tool investigates all of the clinical features of different MDEs and gives qualitative information, differentiating patients with the same score but different symptoms and psychopathology severity. To achieve this purpose authors used a new methodology called Formal Psychological Assessment (FPA). FPA allows creating relations between the items of an assessment tool, and the set of diagnostic criteria of a given clinical disorder. In the application at hand, given the capability to analyze all clinical features, FPA appears a useful way to highlight and differentiate between inhibited and agitated depressive symptoms. Method: The new tool contains 41 items constructed through 23 clinical criteria from the DSM-5 and literature symptoms. In line with FPA, starting from a set of items and a set of clinical criteria, a Boolean matrix was built assigning to each item its own set of clinical criteria. The participants include 265 in the control group and 38 patients with MDE (diagnosed with MDD or BD) who answered the QuEDS. After 1 month, 63 participants performed the test again and 113 took the Depression-Anxiety-Stress Scale to analyze convergent-divergent validity. Results: The scale showed adequate reliability and validity. A hierarchical confirmatory factor analysis highlighted the presence of three sub factors (affective, somatic, and cognitive) and one high-order factor (depression). Conclusions: The new tool is potentially able to inform clinicians about the patients' most likely diagnostic configuration. Indeed, the clinical state of a patient consists of the subset of items he/she answered affirmatively, along with his/her subset of specific symptoms. Qualitative information is fundamental from a clinical perspective, allowing for the analysis and treatment of each patient according to his/her symptoms in an effective way.