Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells.
Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media. The effects of prolonged hypoxic culture on growth and pro-angiogenic properties were investigated using human ASC cultured at 1%, 5% and 21% oxygen. The effect of trypsinization on the expression of pro-angiogenic genes was also determined. Trypsinization induced up-regulation of the vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) genes independent of oxygen concentration. The expression of VEGF and IGF-1 was up-regulated in ASC cultured at 1% oxygen for 13 days compared with 4 days. The VEGF concentration in ASC-conditioned media was higher after prolonged hypoxic culture compared with short-term culture, while the IGF-1 and chemokine (CXC motif) ligand 12 (CXCL12) concentrations were unchanged. The VEGF receptor blocker SU5416 abolished angiogenesis in a cultured rat aortic ring model. Media from cells exposed to hypoxia increased angiogenesis, an effect that was dependent on factors other than just the VEGF concentration in the added media. Optimization of the angiogenic potential of stem cell-based therapy in the treatment of vascular disease is important. We have demonstrated that prolonged hypoxic culture and trypsinization augment the therapeutic angiogenic potential of ASC.


(3 + 2)-Cycloaddition of Donor-Acceptor Cyclopropanes with Selenocyanate: Synthesis of Dihydroselenophenes and Selenophenes.
We present a Lewis-acid-catalyzed (3 + 2)-cycloaddition of donor-acceptor cyclopropanes and selenocyanate (as its tetramethylammonium salt) for the synthesis of dihydroselenophenes. The transformation proceeded with moderate to excellent yields and showed a high functional group tolerance. Further oxidation using DDQ delivered selenophenes.


Involvement of creatine kinase B in cigarette smoke-induced bronchial epithelial cell senescence.
Cigarette smoke induces damage to proteins and organelles by oxidative stress, resulting in accelerated epithelial cell senescence in the lung, which is implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Although the detailed molecular mechanisms are not fully understood, cellular energy status is one of the most crucial determinants for cell senescence. Creatine kinase (CK) is a constitutive enzyme, playing regulatory roles in energy homeostasis of cells. Among two isozymes, brain-type CK (CKB) is the predominant CK in lung tissue. In this study, we investigated the role of CKB in cigarette smoke extract (CSE)-induced cellular senescence in human bronchial epithelial cells (HBECs). Primary HBECs and Beas2B cells were used. Protein carbonylation was evaluated as a marker of oxidative protein damage. Cellular senescence was evaluated by senescence-associated β-galactosidase staining. CKB inhibition was examined by small interfering RNA and cyclocreatine. Secretion of IL-8, a hallmark of senescence-associated secretary phenotype, was measured by ELISA. CKB expression levels were reduced in HBECs from patients with COPD compared with that of HBECs from nonsmokers. CSE induced carbonylation of CKB and subsequently decreased CKB protein levels, which was reversed by a proteasome inhibitor. CKB inhibition alone induced cell senescence, and further enhanced CSE-induced cell senescence and IL-8 secretion. CSE-induced oxidation of CKB is a trigger for proteasomal degradation. Concomitant loss of enzymatic activity regulating energy homeostasis may lead to the acceleration of bronchial epithelial cell senescence, which is implicated in the pathogenesis of COPD.


Biomimetic mineralization induced by fibrils of polymers derived from a bile acid.
A polymer containing bile acid pendant groups was prepared by free-radical polymerization of the 3alpha-methacrylate derivative of cholic acid. The polymer formed fibrils of about 1 nm in diameter in aqueous media and further assembled into bundles or lamella plates, as observed by transmission electron microscopy. After immersing the fibrils in simulated body fluid with ion concentrations equivalent to those in human plasma, plate-like crystals formed on the surface of the fibril assembly. The diffraction pattern corresponding to the (001) plane of hydroxyapatite was identified by transmission electron microscopy and selected area electron diffraction. The plate-like, single crystal hydroxyapatite formed on such a polymeric assembly may be useful in the matrix design for biomimetic mineralization and in the development of scaffold materials for hard tissue engineering.


Synergy between two transcription factors directs gene expression in Dictyostelium tip-organiser cells.
cotC requires the transcription factor CudA for its expression in the posterior, prespore cells of the slug, while the expL7 gene requires CudA for its expression in the anterior, tip-organiser region. In order to identify additional transcription factors that might mediate tip-organiser specific expression, we performed affinity chromatography on slug nuclear extracts. The affinity matrix bore cap-site distal sequences from region A of the expL7 promoter; an essential region located upstream of the CudA binding domain. One of the proteins purified was G-box binding factor (GBF), a zinc finger transcription factor which binds to G-rich elements, known as G boxes, that are present in the promoters of many developmental genes, including cotC. Previous work identified an essential sequence motif within region A and we show that this element is a G box, that binds recombinant GBF. Moreover, a G box from within the cotC promoter can substitute for region A of expL7 in directing tip-organiser specific expression of expL7. Thus the same two transcription factors, CudA and GBF, seem to co-operate to direct both tip-organiser and prespore gene expression. How then is specificity achieved? Replacing a CudA binding region in the cotC promoter with the CudA binding domain from expL7 strongly represses cotC promoter activity. Hence we suggest that differences in the topology of the multiple CudA half- sites contained within the two different CudA binding regions, coupled with differences in the signalling environment between tip-organiser cells and prespore cells, ensure correct expL7 expression.


Porous microwells for geometry-selective, large-scale microparticle arrays.
Large-scale microparticle arrays (LSMAs) are key for material science and bioengineering applications. However, previous approaches suffer from trade-offs between scalability, precision, specificity and versatility. Here, we present a porous microwell-based approach to create large-scale microparticle arrays with complex motifs. Microparticles are guided to and pushed into microwells by fluid flow through small open pores at the bottom of the porous well arrays. A scaling theory allows for the rational design of LSMAs to sort and array particles on the basis of their size, shape, or modulus. Sequential particle assembly allows for proximal and nested particle arrangements, as well as particle recollection and pattern transfer. We demonstrate the capabilities of the approach by means of three applications: high-throughput single-cell arrays; microenvironment fabrication for neutrophil chemotaxis; and complex, covert tags by the transfer of an upconversion nanocrystal-laden LSMA.


Effects of recombinant GM-CSF on the blast cells of acute myeloblastic leukemia.
The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) were compared to those of media conditioned by the continuous bladder carcinoma line, HTB9 (HTB9-CM), using three criteria. First, both GM-CSF and HTB9-CM stimulated blast colony formation in methylcellulose cultures, patient-to-patient variations were seen in the dose-response curves, and GM-CSF was effective, but less so that HTB9-CM. Second, GM-CSF also enhanced growth of blast progenitors in suspension culture, indicating its capacity to support self-renewal. GM-CSF was as effective as HTB9-CM in the production of adherent cells during the growth of blast cells in suspension, a finding that is interpreted to mean that GM-CSF also supports postdeterministic events in blast differentiation. Finally, colonies growing in the presence of GM-CSF were not phenotypically different than those stimulated by HTB9-CM.


Improvement of postherpetic neuralgia after treatment with intravenous acyclovir followed by oral valacyclovir.
Postherpetic neuralgia (PHN) is a complication of shingles (herpes zoster), a painful rash due to varicella-zoster virus reactivation. Studies of patients with PHN and zoster sine herpete (radicular pain without rash) support the notion that low-grade viral ganglionitis contributes to pain. If chronic pain reflects active infection, then antiviral therapy may help patients with PHN. To determine whether antiviral treatment helps reduce PHN-associated pain. Prospective, open-label phase I/II clinical trial. Tertiary care university hospital. Fifteen patients with moderate to severe PHN. Intravenous acyclovir at a dosage of 10 mg/kg every 8 hours for 14 days followed by oral valacyclovir at a dosage of 1000 mg 3 times per day for 1 month. Numeric Rating Scale for Pain score. As defined by a decrease of 2 or more points on the Numeric Rating Scale for Pain, 8 (53%) of 15 patients reported improvement. Clinical improvement reported by most of our patients warrants further investigation in a larger, randomized, double-blind, placebo-controlled trial.


Control of autoimmune diabetes in NOD mice by GAD expression or suppression in beta cells.
Glutamic acid decarboxylase (GAD) is a pancreatic beta cell autoantigen in humans and nonobese diabetic (NOD) mice. beta Cell-specific suppression of GAD expression in two lines of antisense GAD transgenic NOD mice prevented autoimmune diabetes, whereas persistent GAD expression in the beta cells in the other four lines of antisense GAD transgenic NOD mice resulted in diabetes, similar to that seen in transgene-negative NOD mice. Complete suppression of beta cell GAD expression blocked the generation of diabetogenic T cells and protected islet grafts from autoimmune injury. Thus, beta cell-specific GAD expression is required for the development of autoimmune diabetes in NOD mice, and modulation of GAD might, therefore, have therapeutic value in type 1 diabetes.


Optimizing yeast for high-level production of kaempferol and quercetin.
Two important flavonoids, kaempferol and quercetin possess remarkably potent biological impacts on human health. However, their structural complexity and low abundance in nature make both bulk chemical synthesis and extraction from native plants difficult. Therefore microbial production via heterologous expression of plant enzymes can be a safe and sustainable route for their production. Despite several attempts reported in microbial hosts, the production levels of kaempferol and quercetin still stay far behind compared to many other microbial-produced flavonoids. In this study, Saccharomyces cerevisiae was engineered for high production of kaempferol and quercetin in minimal media from glucose. First, the kaempferol biosynthetic pathway was reconstructed via screening various F3H and FLS enzymes. In addition, we demonstrated that amplification of the rate-limiting enzyme AtFLS could reduce the dihydrokaempferol accumulation and improve kaempferol production. Increasing the availability of precursor malonyl-CoA further improved the production of kaempferol and quercetin. Furthermore, the highest amount of 956 mg L- 1 of kaempferol and 930 mg L- 1 of quercetin in yeast was reached in fed-batch fermentations. De novo biosynthesis of kaempferol and quercetin in yeast was improved through increasing the upstream naringenin biosynthesis and debugging the flux-limiting enzymes together with fed-batch fermentations, up to gram per liter level. Our work provides a promising platform for sustainable and scalable production of kaempferol, quercetin and compounds derived thereof.


General practitioners' views on genetic screening for common diseases.
In a questionnaire survey of 359 general practitioners (response rate 94%), 60% accepted the need to provide genetic services, but far fewer felt competent to do so. Nevertheless, as many as 76% had referred patients to a genetics unit in the past year, and 50% had counselled about genetics.


Light at the end of the tunnel for denials management.
Denials management is too important to a provider's financial health to be addressed haphazardly. The Six Sigma performance-improvement methodology can ensure your organization receives the full payment to which it is entitled.


Occupational relevance of positive standard patch-test results in employed persons with an initial report of an occupational skin disease.
It is commonly accepted that the standard screening tray is an essential diagnostic test in patch testing supporting the diagnosis of contact dermatitis, the most common type of occupational skin disease (OSD). In this study standard patch-test results of employed persons with an initial report of an OSD were analyzed within 24 occupational groups. An evaluation was made of employed persons recorded in the Register of Occupational Skin Diseases in Northern Bavaria (Berufskrankheitenregister Haut-Nordbayern; BKH-N) between 1990 and 1999, catering for those standard screening tray allergens tested over the 10-year period. Nickel sulfate was the most common sensitizer (29.5%), showing occupational relevance in only 11% of the cases sensitized. Other common sensitizers were cobalt chloride (13.5%), p-phenylenediamine free base (10.7%), potassium dichromate (9.8%), fragrance mix (5.4%), thiuram mix (4.2%), balsam of Peru (4.0%), chloromethylisothiazolinone/methylisothiazolinone (4.0%), and formaldehyde (4.0%). The most occupationally relevant sensitizers were thiuram mix (71%), epoxy resin (67%), p-phenylenediamine free base (59%), p-phenylenediamine-black-rubber mix/ N-isopropyl- N'-phenyl- p-phenylenediamine (53%), potassium dichromate (48%), formaldehyde (38%), chloromethylisothiazolinone/methylisothiazolinone (37%), and mercapto-mix/mercaptobenzothiazole (35%). Occupational groups at risk of acquiring delayed-type sensitization were, in particular, electroplaters, tile setters and terrazzo workers, construction and cement workers, solderers, wood processors, and leather and fur processors. The standard series contributes valuable information and asserts its position in clarifying the causes of OSDs. Based on the study results, the rate of occupationally relevant sensitization to each single allergen is demonstrated, and the difficulties in verifying the occupational relevance are discussed.


Effect of carvacrol on pulmonary function tests, and total and differential white blood cell counts in healthy volunteers: A randomized clinical trial.
This is the first study to evaluate the effect of carvacrol on pulmonary function tests (PFT), and total and differential white blood cell (WBC) counts in healthy volunteers. Thirty healthy volunteers were recruited based on the inclusion and exclusion criteria. The subjects were treated with two doses of carvacrol (1 and 2 mg/kg/day) for 1 month. Total and differential WBC counts and PFT were examined before and after the treatment period. There were no statistically significant differences in terms of total and differential WBC counts between pre and post-treatment with the two doses of carvacrol. Also, results of PFT tests indicated that administration of 1 mg/kg/day carvacrol had no effect on PFT parameters when comparing post-treatment values with pre-treatment values. Treatment with 2 mg/kg/day carvacrol for 1 month increased forced expiratory volume in first second (FEV1) (p<0.05). However, the changes in total and differential WBC counts as well as PFT values after 1-month treatment were not significantly different between two groups. The results of this study indicated that treatment of healthy individuals with 1 and 2 mg/kg carvacrol for 1 month has no negative effects on total and differential WBC counts nor PFT values.


Genetic dissection of the AZF regions of the human Y chromosome: thriller or filler for male (in)fertility?
The azoospermia factor (AZF) regions consist of three genetic domains in the long arm of the human Y chromosome referred to as AZFa, AZFb and AZFc. These are of importance for male fertility since they are home to genes required for spermatogenesis. In this paper a comprehensive analysis of AZF structure and gene content will be undertaken. Particular care will be given to the molecular mechanisms underlying the spermatogenic impairment phenotypes associated to AZF deletions. Analysis of the 14 different AZF genes or gene families argues for the existence of functional asymmetries between the determinants; while some are prominent players in spermatogenesis, others seem to modulate more subtly the program. In this regard, evidence supporting the notion that DDX3Y, KDM5D, RBMY1A1, DAZ, and CDY represent key AZF spermatogenic determinants will be discussed.


The approach of medical students towards studies of the humanities and social sciences.
To analyze the attitudes of the medical students from Kaunas University of Medicine, Krakow Jagiellonian University, and St. Petersburg State University towards the studies of the humanities and social sciences. The survey was carried out in three universities (Kaunas University of Medicine, Krakow Jagiellonian University, and St. Petersburg State University) during 2004-2005. The questionnaire for the investigation was developed based on R. D. Stenberg's works on the ways of knowledge-, practice-, and personality-oriented thinking. After the analysis of students' attitudes towards the importance of the disciplines of ethics, philosophy, sociology, and psychology at the universities of Kaunas, Krakow, and St. Petersburg, important differences have been found among them. Students gave the highest priority to ethics in their profession. Answering the question, "Are philosophical studies important in medical studies," statistically significant differences appeared among Krakow, Kaunas, and St. Petersburg universities. Students of all the universities agreed that sociology and psychology studies were important for their future profession. Having estimated the opinions of medical students' attitudes towards the importance of the humanities and social sciences, we may state that the students of Krakow and St. Petersburg universities more often agreed that ethics and philosophy were important for their studies. The importance of psychology science was emphasized by the students of all universities, and the students of Kaunas University of Medicine and St. Petersburg State University agreed more often that the discipline of sociology was important for the future studies.


Increased cortical expression of an RNA editing enzyme occurs in major depressive suicide victims.
RNA editing is a posttranscriptional process which critically modulates the function of several neurotransmitter receptors regulating mood, anxiety, learning, and memory. Data from several postmortem studies have shown increased 5-hydroxytryptamine-2C receptor RNA editing in mood disorders and suicide, and therefore the 5-hydroxytryptamine-2C receptor might be expected to have reduced signal transduction in these patients. In this study, we have tested the hypothesis that the expression levels of the enzymes which catalyze RNA editing, adenosine deaminase acting on RNA 1 (ADAR1) and ADAR2, are also abnormal in suicide. Gene expression was measured in the dorsolateral prefrontal cortex of individuals from the Stanley Consortium Brain series, which includes patients with schizophrenia (n=15), major depression (n=15), bipolar disorder (n=15), and a comparison group (n=14). Of the psychiatric patients, 20 were suicide victims. ADAR1 expression was found to be significantly increased in major depressive suicide victims compared with patients who did not commit suicide. Neither ADAR1 nor ADAR2 expression was altered in any of the other diagnostic groups. These data indicate that ADAR1 could play a role in the pathophysiology of suicide in patients with major depression.


Novel abietane diterpenoids from Salvia prionitis.
Two hitherto unknown highly modified abietane diterpenoids, namely salviapritin A (1) and salviapritin B (2), were isolated from the ethanol extract of Salvia prionitis, together with 17 known compounds. Their chemical structures were established by extensive spectroscopic methods (ESIMS, HRESIMS, 1D and 2D NMR) and by comparison of their NMR data with those of related analogues. Salviapritin A is the first example of a trinorabietane diterpenoid possessing an acenaphthylene skeleton from the Salvia genus. Additionally, a plausible biogenetic pathway for salviapritin B is proposed. [Formula: see text].


Shock trauma.
Trauma - accidental or intentional injury - is a major health and social problem. It is still the chief cause of death in people between the ages of 1 and 38 years. In the United States, the mortality due to trauma between the ages of 15 and 24 years increased by 13% from 1960 to 1978. During the same period, the mortality for people aged 25 to 64 years declined by 16%. Murders have increased from 8464 in 1960, to 26 000 in 1982. The overall death rate of American teenagers and young adults is 50% higher than that of their counterparts in Britain, Sweden and Japan. Trauma affects young, productive citizens, and the estimated costs for death, disability and loss of productivity exceed $230 million a day. The most tragic statistic is that at least 40% of the deaths are needless and preventable if better treatment and prevention programs were available. Trauma deaths that might be prevented are those due to motor vehicle accidents, homicide, burns, and alcohol and drug abuse. In this paper suggestions for prevention are made. They include improved crash worthiness of motor vehicles, revocation of drunk drivers' licences, use of devices that limit drunk drivers, increased tax on alcohol and random breathalyser tests, and the use of seat belts and motorcycle helmets. Control of hand-guns and burn characteristics of cigarettes could also reduce deaths. The problems and issues in trauma care can be divided into two broad categories: system and professional. System problems include prehospital care, in-hospital care, rehabilitation and prevention. Professional problems include education, research, economics, and quality.(ABSTRACT TRUNCATED AT 250 WORDS)


Structural characteristics of oriented mesostructured silica thin films.
Mesoporous thin films synthesized via an electrochemical strategy (ref 1) generally show granular domains, each of which is composed of hexagonally packed one-dimensional channels oriented uniquely perpendicular to the film surface. Grain boundaries either parallel or normal to the channel direction might affect the properties and subsequent application of the film. In this study, the structural details of oriented mesostructured silica thin films have been examined by transmission electron microscope. The pore structures are characterized using the traditional crystallographic concepts but show different structural properties from that of polycrystalline materials. The boundary structures vary much depending on the residual internal stress and the orientation relationship between the bounded grains. A variety of structural features, typically near the large-angle tilt boundaries, have been observed including coincidence site lattices, lattice distortion, lattice displacement, and dislocations. According to the present structural analysis, microstructure evolution and potential applications have been discussed with respect to the oriented mesoporous films.


Relationship between the amount of propranolol permeating through the stratum corneum of guinea pig skin after application of propranolol adhesive patches and skin irritation.
In the present study we evaluated the relationship between the cumulative amount of propranolol permeating through the stratum corneum and the formation of erythema, a skin irritation reaction, after transdermal application of adhesive patches containing propranolol to the skin of guinea pigs. The intensity of erythema was expressed in terms of a* values measured with a chromameter. The a* values increased in guinea pigs after application of the adhesive patches containing 0.4 mg/cm2 of propranolol to the skin. Since the adhesive patches showed good adhesion to the skin (propranolol content is less than the saturated concentration in the adhesive base) and the cumulative amount of propranolol permeating through the stratum corneum is small, the development of erythema was considered to be mainly due to physical factors such as peeling. Even in adhesive patches containing 0.8 mg/cm2 or 1.2 mg/cm2 of propranolol, a* values increased, although adhesion to the skin is low because of crystallization of propranolol in the adhesive base. On the other hand, in these two adhesive patches, the cumulative amount of propranolol permeating through the stratum corneum increased up to 24 h after application. These findings suggest that the skin irritation reaction is due to propranolol mainly absorbed transdermally, because there is a high correlation between the cumulative amount of propranolol permeating through the stratum corneum and the a* values (r = 0.928).


Synaptic and extrasynaptic GABA transporters as targets for anti-epileptic drugs.
Inhibition of the GABA transporter subtype GAT1 by the clinically available anti-epileptic drug tiagabine has proven to be an effective strategy for the treatment of some patients with partial seizures. In 2005, the investigational drug EF1502 was described as possessing activity at both GAT1 and BGT-1. When combined with the GAT1 selective inhibitor tiagabine, EF1502 was found to possess a synergistic anti-convulsant action in the Frings audiogenic seizure-susceptible mouse model of reflex epilepsy. This effect was subsequently attributed to inhibition of BGT-1. In this study, the anti-convulsant effect of the GAT2/3 inhibitor SNAP-5114 was assessed in the Frings audiogenic seizure-susceptible mouse alone, and in combination with tiagabine and EF1502. The results showed that SNAP-5114 produced a synergistic anti-convulsant effect in combination with EF1502 but not when used in combination with tiagabine. These findings support anatomical evidence that GAT2/3 are most likely located at the synapse in close proximity to GAT1; whereas BGT-1 is located some distance away from the synapse and GAT1 and GAT2/3. Lastly, EF1502 and tiagabine were evaluated alone, and in combination, in the corneal kindled mouse model of partial epilepsy. The results of this evaluation provide further evidence in support of a role for BGT-1 in the control of seizure activity. In addition, they suggest that the combined inhibition of GAT1 and BGT-1 may afford some advantage over inhibiting either transporter alone.


Idiopathic macular telangiectasia type 2 (idiopathic juxtafoveolar retinal telangiectasis type 2A, Mac Tel 2).
Macular telangiectasia type 2-also known as idiopathic perifoveal telangiectasia and juxtafoveolar retinal telangiectasis type 2A or Mac Tel 2-is an acquired bilateral neurodegenerative macular disease that usually manifests itself during the fourth to sixth decades of life and is characterized by minimal dilatation of the parafoveal capillaries with graying of the retinal area involved, a lack of lipid exudation, right-angled retinal venules, refractile deposits in the superficial retina, hyperplasia of the retinal pigment epithelium, foveal atrophy, and subretinal neovascularization (SRNV). Optical coherence tomography images typically demonstrate intraretinal hyporeflective spaces that are usually not related to retinal thickening or fluorescein leakage. The typical fluorescein angiographic finding is a deep intraretinal hyperfluorescent leakage in the temporal parafoveal area. With time the leakage may involve the whole parafovea, but does not extend to the center of the fovea. Long-term prognosis for central vision is variable and depends on the development of SRNV or macular atrophy. Pathogenesis remains unclear, but Müller cells and macular pigment appear to play a central role. Currently there is no known treatment for the underlying cause of this condition, but treatment of the SRNV may be beneficial.


Assessment of Soil Features on the Growth of Environmental Nontuberculous Mycobacterial Isolates from Hawai'i.
Environmental nontuberculous mycobacteria (NTM), with the potential to cause opportunistic lung infections, can reside in soil. This might be particularly relevant in Hawai'i, a geographic hot spot for NTM infections and whose soil composition differs from many other areas of the world. Soil components are likely to contribute to NTM prevalence in certain niches as food sources or attachment scaffolds, but the particular types of soils, clays, and minerals that impact NTM growth are not well-defined. Hawai'i soil and chemically weathered rock (saprolite) samples were examined to characterize the microbiome and quantify 11 mineralogical features as well as soil pH. Machine learning methods were applied to identify important soil features influencing the presence of NTM. Next, these features were directly tested in vitro by incubating synthetic clays and minerals in the presence of Mycobacteroides abscessus and Mycobacterium chimaera isolates recovered from the Hawai'i environment, and changes in bacterial growth were determined. Of the components examined, synthetic gibbsite, a mineral form of aluminum hydroxide, inhibited the growth of both M. abscessus and M. chimaera, while other minerals tested showed differential effects on each species. For example, M. abscessus (but not M. chimaera) growth was significantly higher in the presence of hematite, an iron oxide mineral. In contrast, M. chimaera (but not M. abscessus) counts were significantly reduced in the presence of birnessite, a manganese-containing mineral. These studies shed new light on the mineralogic features that promote or inhibit the presence of Hawai'i NTM in Hawai'i soil.IMPORTANCE Globally and in the United States, the prevalence of NTM pulmonary disease-a potentially life-threatening but underdiagnosed chronic illness-is prominently rising. While NTM are ubiquitous in the environment, including in soil, the specific soil components that promote or inhibit NTM growth have not been elucidated. We hypothesized that NTM culture-positive soil contains minerals that promote NTM growth in vitro Because Hawai'i is a hot spot for NTM and a unique geographic archipelago, we examined the composition of Hawai'i soil and identified individual clay, iron, and manganese minerals associated with NTM. Next, individual components were evaluated for their ability to directly modulate NTM growth in culture. In general, gibbsite and some manganese oxides were shown to decrease NTM, whereas iron-containing minerals were associated with higher NTM counts. These data provide new information to guide future analyses of soil-associated factors impacting persistence of these soil bacteria.


Adverse drug reactions to osteoporosis treatments.
Treatments for postmenopausal osteoporosis are generally safe, but are linked to some rare serious adverse drug reactions, for which causality is not always certain. The bisphosphonates are associated with gastrointestinal effects, acute phase reactions, and musculoskeletal pain, and, more rarely, cases of atrial fibrillation, subtrochanteric fracture, osteonecrosis of the jaw, cutaneous hypersensitivity reactions and renal impairment. It is too soon for pharmacovigilance data on denosumab, but it has been associated with cutaneous effects and possibly osteonecrosis of the jaw (to date, only in metastatic cancer). The selective estrogen receptor modulators may induce hot flushes and leg cramps, and--more rarely--venous thromboembolism and stroke. Strontium ranelate is associated with headache, nausea and diarrhea, and, more rarely, cutaneous hypersensitivity reactions and venous thromboembolism, while teriparatide and parathyroid hormone(1-84) are associated with headache, nausea, dizziness and limb pain. The management of osteoporosis should entail weighing the probability of adverse reactions against the benefits of therapy--that is, reduction of fracture risk.


Topological solitons in nondegenerate one-component chains.
The possibility of the existence of topological solitons in one-component chains with a nondegenerate potential of gradient type is proven. The existence and stability of the solitons are ensured by the competing nonlinear nearest-neighbor potential V1 and parabolic second-nearest-neighbor potential V2. Solitonic solutions have been found analytically for piecewise-parabolic V1 and numerically for smoothened nearest-neighbor (NN) potential V(1,delta). Numerical results for the soliton velocity and front width are in good agreement with analytical estimates. The solitons are shown to move at a unique velocity and actually maintain the constant profile as long as the NN potential is smooth enough. The impact of two solitons of different sign is inelastic and leads to their recombination. It is argued that the soliton propagation may constitute an elementary event of structural transformations in the chain.


C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation.
Hedgehog (Hh) morphogens are involved in embryonic development and stem cell biology and, if misregulated, can contribute to cancer. One important post-translational modification with profound impact on Hh biofunction is its C-terminal cholesteroylation during biosynthesis. The current hypothesis is that the cholesterol moiety is a decisive factor in Hh association with the outer plasma membrane leaflet of producing cells, cell-surface Hh multimerization, and its transport and signaling. Yet, it is not decided whether the cholesterol moiety is directly involved in all of these processes, because their functional interdependency raises the alternative possibility that the cholesterol initiates early processes directly and that these processes can then steer later stages of Hh signaling independent of the lipid. We generated variants of the C-terminal Hh peptide and observed that these cholesteroylated peptides variably impaired several post-translational processes in producing cells and Hh biofunction in Drosophila melanogaster eye and wing development. We also found that substantial Hh amounts separated from cholesteroylated peptide tags in vitro and in vivo and that tagged and untagged Hh variants lacking their C-cholesterol moieties remained bioactive. Our approach thus confirms that Hh cholesteroylation is essential during the early steps of Hh production and maturation but also suggests that it is dispensable for Hh signal reception at receiving cells.


Serum micronutrients and the subsequent risk of oral and pharyngeal cancer.
To investigate the relationship between serum micronutrients and the subsequent risk of oral and pharyngeal cancer, a nested case-control study was conducted within a cohort of 25,802 adults in Washington County, MD, whose blood samples were collected in 1974 and stored at -70 degrees C for subsequent assays. The serum levels of nutrients in 28 individuals who developed oral and pharyngeal cancer during 1975 to 1990 were compared with levels in 112 matched controls. Serum levels of all individual carotenoids, particularly beta-carotene, were lower among subjects who developed oral and pharyngeal cancer. The risks of this malignancy decreased substantially with increasing serum level of each individual carotenoid. Persons in the highest tertile of total carotenoids had about one-third the cancer risk as those in the lowest tertile. High serum levels of alpha-tocopherol also were related to a low oral cancer risk in later years, but the risks were elevated significantly with increasing serum levels of gamma-tocopherol and selenium. The findings from this study are consistent with many previous epidemiological investigations of dietary factors for oral and pharyngeal cancer and provide further evidence for the potential role of carotenoids and alpha-tocopherol in the chemoprevention of these malignancies.


Evolution of the Nematic Susceptibility in LaFe_{1-x}Co_{x}AsO.
We report a systematic elastoresistivity study on LaFe_{1-x}Co_{x}AsO single crystals, which have well separated structural and magnetic transition lines. All crystals show a Curie-Weiss-like nematic susceptibility in the tetragonal phase. The extracted nematic temperature is monotonically suppressed upon cobalt doping, and changes sign around the optimal doping level, indicating a possible nematic quantum critical point beneath the superconducting dome. The amplitude of the nematic susceptibility shows a peculiar double-peak feature. This could be explained by a combined effect of different contributions to the nematic susceptibility, which are amplified at separated doping levels of LaFe_{1-x}Co_{x}AsO.


Zinc stabilizes adenomatous polyposis coli (APC) protein levels and induces cell cycle arrest in colon cancer cells.
In the present study, we investigated the mechanisms by which zinc causes growth arrest in colon cancer cells. The results suggest that zinc treatment stabilizes the levels of the wild-type adenomatous polyposis coli (APC) protein at the post-translational level since the APC mRNA levels and the promoter activity of the APC gene were decreased in HCT-116 cells (which express the wild-type APC gene) after treatment with ZnCl2. Increased levels of wild-type but not truncated APC proteins were required for the ZnCl2-mediated G2/M phase arrest in different colon cancer cell lines. We further tested whether serum-stimulation, which induces cell cycle arrest in the S phase, can relieve ZnCl2-induced G2/M phase arrest of HCT-116 cells. Results showed that in the HCT-116 cells pretreated with ZnCl2, the serum-stimulation neither changed the distribution of G2/M phase arrested cells nor the increased levels of APC protein. The G2/M phase arrest correlated with retarded growth of HCT-116 cells. To further establish that wild-type APC protein plays a role in ZnCl2-induced G2/M arrest, we treated SW480 colon cancer cells that express truncated APC protein. We found that ZnCl2 treatment did not induce G2/M phase arrest in SW480 cells; however, the cell growth was retarded due to the loss of E-cadherin and alpha-tubulin levels. These results suggest that ZnCl2 inhibits the proliferation of colon cancer cells (which carry the wild-type APC gene) through stabilization of the APC protein and cell cycle arrest in the G2/M phase. On the other hand, ZnCl2 inhibits the proliferation of colon cancer cells (which carry the mutant APC gene) by disrupting cellular attachment and microtubule stability.


Development and initial validation of the Structured Interview for Self-Destructive Behaviors.
This article describes the initial validation of the Structured Interview for Self-Destructive Behaviors (SI-SDB), a brief interview assessing suicidality, self-injury, substance abuse, disordered eating, and risky sexual behaviors. Self-destructive behaviors present clinical and practical challenges for mental health treatment providers. Participants were 217 psychiatric inpatients with a wide variety of diagnoses who completed the SI-SDB and other measures of psychiatric symptoms, trauma exposure, and other childhood experiences. Internal validity analyses revealed an internally consistent measure with 2 major factors. External validity analyses indicated that the Substance Abuse and Disordered Eating scales were predictive of related psychiatric diagnoses. All scales except Substance Abuse were significantly correlated with psychiatric symptoms and childhood abuse. These findings indicate that the SI-SDB is a valid means of assessing 5 significant domains of dangerous behaviors in clinical and research settings. Further research on the reliability of reports over time, interrater consistency, and convergent validity with longer measures of the SI-SDB domains is needed.


Effect of calcitonin on vertebral and other fractures.
We examined the incidence of vertebral and non-vertebral fractures in published randomised clinical trials using calcitonin by parenteral injection or intranasal spray. Trials were reviewed that compared calcitonin with placebo, no therapy, or calcium with or without vitamin D, and that mentioned fracture as an outcome. Studies that compared the effect of calcitonin with other active treatments were excluded. Fourteen trials with 1309 men and women were identified. In the calcitonin and the control groups, vertebral and non-vertebral fractures were summed and divided by the number of individuals originally allocated to the treatment groups. The relative risk of any fracture for individuals taking calcitonin versus those not taking calcitonin was 0.43 (95% CI 0.38-0.50). The effect was apparent for both vertebral fracture (RR 0.45; 95% CI 0.39-0.53) and non-vertebral fractures (RR 0.34; 95% CI 0.17-0.68). When studies identifying patients with fracture, rather than numbers of fractures were pooled, the magnitude of effect was less (RR 0.74; 95% CI 0.60-0.93), and the separate effects on vertebral and non-vertebral fractures was of borderline significance. We conclude that, within the limitations of this study, treatment with calcitonin is associated with a significant decrease in the number of vertebral and non-vertebral fractures.


Factor inhibiting hypoxia-inducible factor (FIH) and other asparaginyl hydroxylases.
FIH (Factor inhibiting hypoxia-inducible factor), an asparaginyl beta-hydroxylase belonging to the super-family of 2-oxoglutarate and Fe(II)-dependent dioxygenases, catalyses hydroxylation of Asn-803 of hypoxia-inducible factor, a transcription factor that regulates the mammalian hypoxic response. Only one other asparaginyl beta-hydroxylase, which catalyses hydroxylation of both aspartyl and asparaginyl residues in EGF (epidermal growth factor)-like domains, has been characterized. In the light of recent crystal structures of FIH, we compare FIH with the EGFH (EGF beta-hydroxylase) and putative asparagine/asparaginyl hydroxylases. Sequence analyses imply that EGFH does not contain the HXD/E iron-binding motif characteristic of most of the 2-oxoglutarate oxygenases.


A prospective, randomised study to compare goserelin acetate (Zoladex) versus cyproterone acetate (Cyprostat) versus a combination of the two in the treatment of metastatic prostatic carcinoma.
A prospective randomised study was performed to test the hypothesis that total androgen ablation, achieved by combining an LHRH analogue, goserelin acetate (Zoladex), with an antiandrogen, cyproterone acetate (Cyprostat), is more effective than conventional monotherapy in delaying the time to progression of metastatic prostatic cancer. 525 patients were recruited at 18 UK centres between May 1986 and January 1989, 175 patients being allocated to each arm. Patients were clinically and biochemically assessed at 1, 2, 3, 6, 9 and 12 months after initiation of therapy and then every 6 months until a maximum duration of 48 months. There was no statistically significant difference in terms of median time to progression between the combination treatment arm and either monotherapy arm, although there was a statistically significant difference between goserelin acetate alone and cyproterone acetate alone, in favour of goserelin acetate (p = 0.016). All treatment regimens were well tolerated and cyproterone acetate reduced both tumour flare reactions and hot flushes in patients receiving goserelin acetate. It is concluded that total androgen ablation using cyproterone acetate (300 mg/day) and goserelin acetate (3.6 mg every 28 days) confers no advantage in terms of time to progression, to conventional monotherapy, but can reduce certain side effects caused by LHRH analogue treatment alone.


Safety assessment of alkyl glyceryl ethers as used in cosmetics.
Alkyl glyceryl ethers function mostly as skin-conditioning agents in cosmetic products applied to the skin and hair. The Cosmetic Ingredient Review expert panel reviewed the available animal toxicity and clinical data, including the low dermal absorption, and concluded that the alkyl glyceryl ethers are safe in the present practices of use and concentration described in this safety assessment.


Recovery profile after desflurane with or without ondansetron compared with propofol in patients undergoing outpatient gynecological laparoscopy.
We studied the effect of combining prophylactic ondansetron (4 mg intravenously [IV]) to desflurane-based anesthesia in 90 ASA grade I or 11 women undergoing outpatient gynecological laparoscopy. Recovery after anesthesia, with special focus on postoperative nausea and vomiting (PONV), was assessed. Control groups received a similar desflurane anesthetic (placebo) or a propofol-infusion-based (active control) anesthetic. The study design was randomized, controlled, and double-blind (regarding ondansetron) and single-blind (regarding the anesthetic technique). Early recovery (eye opening, orientation, following commands, sitting) was similar in the three groups. However, overall home readiness (toleration of oral fluids, walking, pain tolerable by oral analgesics, no or only mild nausea) was achieved faster in the desflurane group receiving ondansetron (109 [21-937] min, P < 0.01) and in the propofol group (110 [33-642] min, P < 0.001) when compared to the desflurane only group (372 [45-723] min) (median [range]). The total incidence of PONV in the desflurane-only group was 80% (P < 0.01), compared to 40% and 20% in the desflurane group receiving ondansetron and the propofol group, respectively. The postoperative antiemetic requirements were consistently and significantly (P < 0.01) higher in the desflurane-only group compared to the other two groups. Postoperative sedation, analgesic requirements, and psychomotor recovery (assessed by the Maddox Wing and the Digit Symbol Substitution Tests) were similar in the three groups. Our results suggest that in order to achieve a propofol-like recovery profile in patients with a high likelihood of PONV, desflurane should be combined with a potent antiemetic (e.g., ondansetron).


Using site-saturation mutagenesis to explore mechanism and substrate specificity in thiamin diphosphate-dependent enzymes.
For almost 20 years, site-saturation mutagenesis (SSM) has been used to evolve stereoselective enzymes as catalysts for synthetic organic chemistry. Much of this work has focused on enzymes such as lipases and esterases, although the range is rapidly expanding. By contrast, using SSM to study enzyme mechanisms is much less common. Instead, site-directed mutagenesis is more generally employed, with a particular emphasis on alanine variants. In the present review, we provide examples of the growing use of SSM to study not only substrate and reaction selectivity, but also the reaction mechanism of thiamin diphosphate (ThDP)-dependent enzymes. We report that the use of SSM to examine the roles of the catalytic residues of benzoylformate decarboxylase gave rise to results that were at odds with earlier kinetic and structural studies using alanine substitutions and also questioned their conclusions. SSM was also employed to examine the long held tenet that a bulky hydrophobic residue provides a fulcrum by which the V-conformation of the ThDP cofactor is maintained. X-ray structures showed that ThDP stayed in the V-conformation even when the replacement residues were charged or did not contact the cofactor. We also summarize the results obtained when SSM was used to evolve new substrate specificity and/or enantioselectivity in ThDP-dependent enzymes such as benzoylformate decarboxylase, transketolase, 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase and the E1 component of the 2-oxoglutarate dehydrogenase complex.


The role of cancer stem cells in relapse of solid tumors.
Recurrence at secondary locations, often years after removal of the primary tumor, accounts for most of the mortality associated with solid tumors. Metastasis, resistance to chemo- and radiotherapy, and eventual relapse have been attributed to a distinct tumor subpopulation known as cancer stem cells (CSCs). In this review, we consider the properties of CSCs that lead to these outcomes, in particular the relation between epithelial-to-mesenchymal transition, stemness, and tumor initiation. We compare recent clinical and laboratory studies of breast cancer, glioblastoma, and melanoma that illustrate how most current anticancer regimens select for cells with mesenchymal and CSC properties and therefore sow the seeds of relapse. Finally, we discuss the emerging paradigm of combined therapy that targets both CSC and non-CSC tumor components.


alpha-dl-Difluoromethylornithine, a Specific, Irreversible Inhibitor of Putrescine Biosynthesis, Induces a Phenotype in Tobacco Similar to That Ascribed to the Root-Inducing, Left-Hand Transferred DNA of Agrobacterium rhizogenes.
alpha-dl-Difluoromethylarginine (DFMA) and alpha-dl-difluoromethylornithine (DFMO), specific irreversible inhibitors of putrescine biosynthesis were applied to Nicotiana tabacum var. Xanthi nc during floral induction. DFMO, but not DFMA, induced a phenotype in tobacco that resembles the transformed phenotype attributed to the root-inducing, left-hand, transferred DNA of Agrobacterium rhizogenes, including wrinkled leaves, shortened internodes, reduced apical dominance, and retarded flowering. Similar treatment of transformed plants (T phenotype) accentuated their phenotypic abnormalities. Cyclohexylammonium and methylglyoxal bis (guanylhydrazone), inhibitors of spermidine and spermine biosynthesis, produced reproductive abnormalities, but did not clearly mimic the transformed phenotype. This work strengthens the previously reported correlation between the degree of expression of the transformed phenotype due to the root-inducing, left-hand, transferred DNA and inhibition of polyamine accumulation, strongly suggesting that genes carried by the root-inducing, transferred DNA may act through interference with polyamine production via the ornithine pathway.


Developmental outcome of children born from extrauterine pregnancies.
From 1947 to 1984, 45 advanced ectopic pregnancies were delivered at Freedmen's Hospital and its successor, Howard University Hospital. Four patients of extrauterine pregnancies were contacted to determine their developmental outcome. At the time of the study, their ages ranged from infancy to adulthood. Results are presented of two children who received in-depth interdisciplinary evaluations at the Howard University Child Development Center. The authors reviewed the literature and questioned other authors, who, based on single examinations, reported normal function in children born after extrauterine pregnancies.


Time course and spatial distribution of phenylalanine ammonia-lyase and peroxidase activity in wounded potato tuber tissue.
The time course and spatial distribution of wound-induced activities of phenylalanine ammonia-lyase and peroxidase were determined to establish correlations between molecular and cellular aspects of the wound-induced pattern of cell differentiation in potato (Solanum tuberosum L.) tissue. A high correlation between peroxidase activity and suberization was observed. Peroxidase activity increased for several days after wounding. Peroxidase content of suberizing cells was more than 10 times higher than that of the immediately adjacent dividing cells. Suberizing and dividing cells contained different isoperoxidases. Neither time course nor spatial distribution of the wound-induced activity of phenylalanine ammonia-lyase was directly correlated with the wound-induced pattern of cell differentiation.


[A survey of diabetes mellitus among inpatients in Guangdong province].
To investigate the prevalence of diabetes and impaired glucose regulation (IGR) among the inpatients and their clinical features. A cross-sectional survey was conducted among the inpatients registered in ten university hospitals of Guangdong, China during the week before the Diabetes Day of 2004. The fasting plasma glucose (FPG) levels of first screen when the patients were hospitalized were recorded. Those with the FPG levels from 5.6 to 6.9 mmol/l. who had not been previously diagnosed as with diabetes (P-DM) underwent oral glucose tolerance test (OGTT). The patients were classified into 5 groups according to the OGTT results: normal glucose tolerance (NGT), DM, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and IGT accompanied with IFG, the last 3 groups being called by a joint name of impaired glucose regulation (IGR). Those with FPG >or= 7.0 mmol/L who had not been diagnosed as with DM previously were diagnosed as newly-diagnosed DM (New-DM). Of the 8753 inpatients investigated 8.3% were with P-DM, 6.8% were diagnosed as with New-DM, and 4.9% were with IGR. OGTT was carried out in 433 inpatients. 27.9% of which were classified as with New-DM, and 49.9% with IGR. In the New-DM patients, 41.8% were accompanied with hypertension, 43.2% with proteinuria, and 67.6% with dyslipidemia. The prevalence rates of diabetes and IGR were 15.1% and 4.9% respectively among the inpatients investigated. The rate of diabetes was 27.9% among the patients underwent OGTT. Proteinuria, dyslipidemia, and hypertension were the concomitant disorders frequently found in New-DM.


Old and sticky-adhesive mechanisms in the living fossil Nautilus pompilius (Mollusca, Cephalopoda).
Nautiloidea is the oldest group within the cephalopoda, and modern Nautilus differs much in its outer morphology from all other recent species; its external shell and pinhole camera eye are the most prominent distinguishing characters. A further unique feature of Nautilus within the cephalopods is the lack of suckers or hooks on the tentacles. Instead, the animals use adhesive structures present on the digital tentacles. Earlier studies focused on the general tentacle morphology and put little attention on the adhesive gland system. Our results show that the epithelial parts on the oral adhesive ridge contain three secretory cell types (columnar, goblet, and cell type 1) that differ in shape and granule size. In the non-adhesive aboral epithelium, two glandular cell types (cell types 2 and 3) are present; these were not mentioned in any earlier study and differ from the cells in the adhesive area. The secretory material of all glandular cell types consists mainly of neutral mucopolysaccharide units, whereas one cell type in the non-adhesive epithelium also reacts positive for acidic mucopolysaccharides. The present data indicate that the glue in Nautilus consists mainly of neutral mucopolysaccharides. The glue seems to be a viscous carbohydrate gel, as known from another cephalopod species. De-attachment is apparently effectuated mechanically, i.e., by muscle contraction of the adhesive ridges and tentacle retraction.


Vaccination and inflammatory arthritis: overview of current vaccines and recommended uses in rheumatology.
Patients with autoimmune inflammatory rheumatic diseases are prone to infectious complications during the course of their disease. The underlying disease with an impaired immune system and additional different immunosuppressive medication render patients more susceptible to infections, some of which are potentially preventable with vaccination. Since it is not clear how strongly the underlying and medication-induced immunosuppression interferes with vaccination, a lot of questions remain about its indications, efficacy and safety . Due to these unresolved questions, in 2011, EULAR published general guidelines about vaccination in patients with autoimmune rheumatic diseases. These guidelines provide a basis for patient care and are also the basis of the following review article. With more available and earlier used immunosuppressive medications, a lot of questions still remain about optimal use of vaccines, the role of different medication combinations on efficacy and safety of vaccinations especially of the actual prevention of disease, the role of age, gender, disease activity and duration, and optimal revaccination schedules in this patient group. Actual studies elute the role of different medication combinations on efficacy and safety mainly addressing influenza and pneumococcal vaccination. In addition, interesting new data on basic immunological processes during TNF-α-blockade open up questions for further research.


Bacteriological contamination of well water in Makurdi town, Benue State, Nigeria.
Bacteriological contamination of well water in Makurdi town, of Benue State, Nigeria was investigated. A total of 15 water samples were collected from hand dug wells and analyzed for total bacteria count as it affect the quality of drinking water for both wet and dry season. The analysis was done according to standard methods of water examination and as reported in WHO guide limit for drinking water. The investigation revealed that the wells examined were highly contaminated with bacteria. Wells 6 and 7 showed highest total bacteria counts of 7.0 x 10(5)/100 mL and 8.2 x 10(5)/100 mL in the wet season, while wells 7 and 2 showed highest total bacteria counts of 8.0 x 10(5)/100 mL and 5.5 x 10(5)/100 mL in the dry season. The contamination of all wells could be due to improper construction of wells, refuse dumping sites and various human activities around the wells. Water generally from these wells is not safe for drinking except some form of treatment is carried out.


Determination of the optical constants (n, k) of thin dielectric films.
A method for the determination of the optical constants and the thickness of thin dielectric films on transparent substrates is proposed. It requires measurements at normal incidence of the transmission from two films of different thicknesses. The derivation is complicated by the existence of multiple solutions of the relevant equations. A procedure is given for determining the correct solutions for the indices of refraction and absorption and also for accurately fixing the thickness of the films. Advantages of the present method over existing methods are better accuracy and readily available measurement facilities. The method has been applied successfully to films of titanium oxide.


The effect of in vivo ethanol consumption on cyclic AMP and delta-opioid receptors in mouse striatum.
In this study the effect of in vivo ethanol consumption on cyclic AMP (cAMP) and [D-Ala2,D-Leu5]enkephalin (DADLE) inhibition of forskolin-stimulated cAMP production was examined in mouse striatum. Effects of ethanol on striatal delta-opioid receptor (DOR) density and mRNA were also examined. Mice had unlimited access to 7% (v/v) ethanol alone or water for 1 or 7 days and were then sacrificed and striatum removed for analysis. There was no difference in basal cAMP formation between water and ethanol-treated mouse striatum following 7 day treatment, and a small, but statistically significant increase in basal cAMP in the ethanol group following 1 day treatment. Both 1 day and 7 day ethanol treatment did not significantly alter the percentage increase in cAMP following treatment with 10 microM forskolin. There was a significant effect of ethanol treatment on the maximum inhibitory effect of DADLE on forskolin-stimulated cAMP formation following both 1 and 7 day ethanol treatment. The DADLE IC50 was unaffected by ethanol treatment. Saturation binding studies ([3H]Deltorphin II) indicated no effect of ethanol on Bmax or Kd in striatum. Similarly, no difference between water and ethanol-treated was observed for DOR mRNA in striatum. These data indicate that ethanol consumption can alter opioid regulation of cAMP formation. However, this effect is not related to changes in any delta-opioid receptor parameters that were examined.


Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis.
We previously reported encouraging results of down-staging of hepatocellular carcinoma (HCC) to meet conventional T2 criteria (one lesion 2-5 cm or two to three lesions <3 cm) for orthotopic liver transplantation (OLT) in 30 patients as a test of concept. In this ongoing prospective study, we analyzed longer-term outcome data on HCC down-staging in a larger cohort of 61 patients with tumor stage exceeding T2 criteria who were enrolled between June 2002 and January 2007. Eligibility criteria for down-staging included: (1) one lesion >5 cm and up to 8 cm; (2) two to three lesions with at least one lesion >3 cm and not exceeding 5 cm, with total tumor diameter up to 8 cm; or (3) four to five lesions with none >3 cm, with total tumor diameter up to 8 cm. A minimum observation period of 3 months after down-staging was required before OLT. Tumor down-staging was successful in 43 patients (70.5%). Thirty-five patients (57.4%) had received OLT, including two who had undergone live-donor liver transplantation. Treatment failure was observed in 18 patients (29.5%), primarily due to tumor progression. In the explant of 35 patients who underwent OLT, 13 had complete tumor necrosis, 17 met T2 criteria, and five exceeded T2 criteria. The Kaplan-Meier intention-to-treat survival at 1 and 4 years after down-staging were 87.5% and 69.3%, respectively. The 1-year and 4-year posttransplantation survival rates were 96.2% and 92.1%, respectively. No patient had HCC recurrence after a median posttransplantation follow-up of 25 months. The only factor predicting treatment failure was pretreatment alpha-fetoprotein >1,000 ng/mL. Successful down-staging of HCC can be achieved in the majority of carefully selected patients and is associated with excellent posttransplantation outcome.


p-Cymene Complexes of Ruthenium(II) as Antitumor Agents.
In this work, the cytotoxic behavior of six ruthenium(II) complexes of stoichiometry [(η6-p-cymene)RuCl2L] (I-VI), L = 4-cyanopyridine (I), 2-aminophenol (II), 4-aminophenol (III), pyridazine (IV), and [(η6-p-cymene)RuClL2]PF6; L = cyanopyridine (V), L = 2-aminophenol(VI) towards three cell lines was studied. Two of them, HeLa and MCF-7, are human carcinogenic cells from cervical carcinoma and human breast cancer, respectively. A comparison with healthy cells was carried out with BGM cells which are monkey epithelial cells of renal origin. The behavior of complex II exhibits selectivity towards healthy cells, which is a promising feature for use in cancer treatment since it might reduce the side effects of most current therapies.


Determining customer satisfaction in anatomic pathology.
Measurement of physicians' and patients' satisfaction with laboratory services has become a standard practice in the United States, prompted by national accreditation requirements. Unlike other surveys of hospital-, outpatient care-, or physician-related activities, no ongoing, comprehensive customer satisfaction survey of anatomic pathology services is available for subscription that would allow continual benchmarking against peer laboratories. Pathologists, therefore, must often design their own local assessment tools to determine physician satisfaction in anatomic pathology. To describe satisfaction survey design that would elicit specific information from physician customers about key elements of anatomic pathology services. The author shares his experience in biannually assessing customer satisfaction in anatomic pathology with survey tools designed at the Henry Ford Hospital, Detroit, Mich. Benchmarks for physician satisfaction, opportunities for improvement, and characteristics that correlated with a high level of physician satisfaction were identified nationally from a standardized survey tool used by 94 laboratories in the 2001 College of American Pathologists Q-Probes quality improvement program. In general, physicians are most satisfied with professional diagnostic services and least satisfied with pathology services related to poor communication. A well-designed and conducted customer satisfaction survey is an opportunity for pathologists to periodically educate physician customers about services offered, manage unrealistic expectations, and understand the evolving needs of the physician customer. Armed with current information from physician customers, the pathologist is better able to strategically plan for resources that facilitate performance improvements in anatomic pathology laboratory services that align with evolving clinical needs in health care delivery.


Breaking the silence on AIDS.
South Africa's Deputy President, Thabo Mbeki, has addressed the country with the aim of raising awareness regarding HIV/AIDS. He pledged support in the areas of prevention, care, and nondiscrimination. This marks the beginning of a new campaign to form partnerships to fight the epidemic. At midday on October 16, 1998, all South Africans were urged to stop work for 10 minutes to listen to Mr. Mbeki and to contemplate the implications of the epidemic. Flags flew at half mast on government buildings and community leaders pledged themselves to the President's Partnership Against AIDS. Mbeki says the Partnership will "break the silence against the disease. We have closed our eyes as a nation and allowed the virus to spread." More than 3 million of the country's 37.9 million population are estimated to be HIV-positive and every day another 1500 South Africans are infected.


Driven colloidal fluids: construction of dynamical density functional theories from exactly solvable limits.
The classical dynamical density functional theory (DDFT) provides an approximate extension of equilibrium DFT to treat nonequilibrium systems subject to Brownian dynamics. However, the method fails when applied to driven systems, such as sheared colloidal dispersions. The breakdown of DDFT can be traced back to an inadequate treatment of the flow-induced distortion of the pair correlation functions. By considering the distortion of the pair correlations to second order in the flow-rate we show how to systematically correct the DDFT for driven systems. As an application of our approach we consider Poiseuille flow. The theory predicts that the particles will accumulate in spatial regions where the local shear rate is small, an effect known as shear-induced migration. We compare these predictions to Brownian dynamics simulations with generally good agreement.


COVID-19 in-vitro Diagnostics: State-of-the-Art and Challenges for Rapid, Scalable, and High-Accuracy Screening.
The world continues to grapple with the devastating effects of the current COVID-19 pandemic. The highly contagious nature of this respiratory disease challenges advanced viral diagnostic technologies for rapid, scalable, affordable, and high accuracy testing. Molecular assays have been the gold standard for direct detection of the presence of the viral RNA in suspected individuals, while immunoassays have been used in the surveillance of individuals by detecting antibodies against SARS-CoV-2. Unlike molecular testing, immunoassays are indirect testing of the viral infection. More than 140 diagnostic assays have been developed as of this date and have received the Food and Drug Administration (FDA) emergency use authorization (EUA). Given the differences in assasy format and/or design as well as the lack of rigorous verification studies, the performance and accuracy of these testing modalities remain unclear. In this review, we aim to carefully examine commercialized and FDA approved molecular-based and serology-based diagnostic assays, analyze their performance characteristics and shed the light on their utility and limitations in dealing with the COVID-19 global public health crisis.


A Fast-growing Benign Metastasizing Leiomyoma Mimicking Malignancy.
We herein report a rare case of fast-growing benign metastasizing leiomyoma. A 52-year-old woman was admitted to our hospital with abnormal chest shadows. Chest computed tomography showed well-circumscribed cystic tumors. Because malignancy could not be completely distinguished in fast-growing tumors, video-assisted thoracic surgery was performed. The pathological findings revealed many cysts and the proliferation of smooth muscle cells. According to the Stanford criteria, the tumor was diagnosed as benign metastasizing leiomyoma. One possible reason for the fast growth of the tumor was enlargement of the cysts. Malignant diseases characterized by cystic tumors are rare but occasionally reported. Therefore, differentiation by a pathological examination is essential.


Mechanistic insight into the recognition of single-stranded and double-stranded DNA substrates by ABH2 and ABH3.
The human ABH2 and ABH3 proteins are functionally complementary in the oxidative demethylation of N(1)-methyl adenine (1-meA) and N(3)-methyl cytosine (3-meC) nucleotide bases. ABH3 displays higher activities with single-stranded DNA (ssDNA) in vitro, whereas ABH2 acts as the primary housekeeping enzyme in mammals for effectively repairing endogenously formed alkylated lesions in double-stranded DNA (dsDNA). Structurally, their overall protein folding is quite similar, but the most significant differences occur in the nucleotide recognition lid and the β-hairpin motif. We present here a site-directed mutational analysis and motif-swapping study to gain mechanistic insight into DNA substrate selection by ABH2 and ABH3. A V101A-F102A double mutant notably reduced ABH2 activity in dsDNA, indicating that this hydrophobic region appears to be important for damage searching and repair. The phenylalanine finger F102 is found to be crucial for ssDNA selection and repair as well; however, V101 shows reduced demethylating activity for only ssDNA and not dsDNA. The ABH2 R110A mutant completely loses the methyl base repair activity, suggesting that R110 is likely to be involved in the base flipping process. E175 and F124 contribute to nucleotide base specific selection and stabilization in the active site for repair. Additionally, swapping the RED residues in ABH3 to equivalent VFG residues in ABH2 endows ABH3 with activity in dsDNA repair as efficient as wild-type ABH2. Surprisingly, by changing just a few residues, the ABH3 protein can have very different selectivity towards ssDNA or dsDNA. This result indicates that the RED motif most likely prevents ABH3 binding and repair of dsDNA. Consistently, swapped ABH3 cross-links with dsDNA very well, confirming the determining roles of these residues in the initial DNA strand recognition. Overall, this work has provided a detailed understanding of the structural features of the ssDNA and dsDNA preferences of ABH2 and ABH3.


Analysis of genetic variation in ribosomal DNA internal transcribed spacer and the NADH dehydrogenase subunit 4 mitochondrial genes of the onchocerciasis vector Simulium ochraceum.
Onchocerciasis is a serious disease vectored by black flies in the genus Simulium that are infected with the filarial parasite Onchocerca volvulus. In the Americas, black flies of the Simulium ochraceum s.l. species complex are important vectors of this parasite. Cytological studies have suggested that this species complex consists of at least three cytotypes that inhabit distinct habitats. In this study, the NADH dehydrogenase subunit four (ND4) and internal transcribed spacer (ITS) of the ribosomal RNA gene cluster were used to explore the degree of genetic diversity among S. ochraceum s.l. populations found in the three O. volvulus foci in Mexico. Both sequence regions were found to exhibit intra- and interpopulation variation. Four different ND4 alleles were found among the populations examined. Similarly, variation was noted in the ITS domain sequences within and among populations. Variation within the ITS sequence was primarily confined to a complex microsatellite locus. Four ITS length variants were observed, two of which were only seen in flies collected from the onchocerciasis focus in northern Chiapas. These data suggest that the ND4 and ITS sequences may prove to be useful markers for exploring interactions within and among the S. ochraceum s.l. populations in Mexico.


Relationship between non-antigen-specific immunodepression and persisting immune complexes induced by pertussis in mice.
A temporal relationship has been demonstrated between persisting immune complexes and non-antigen-specific immunodepression. Mice were given intraperitoneal injections of Bordetella pertussis at weekly intervals. After 7 weeks they developed circulating immune complexes, the levels of which increased with continued administration of pertussis. The increase in immune complex levels was accompanied by a diminished primary immune response to intraperitoneally injected sheep erythrocytes (SRBC) as judged by a reduction in their direct and indirect plaque-forming cell response and serum agglutination titres. Spleen cells from immunodepressed pertussis-treated mice were transferred to irradiated normal recipients and displayed a normal response to SRBC. By contrast, spleen cells transferred from normal donors to irradiated pertussis-treated recipients had an impaired response to SRBC. Thus, the immunodepression caused by pertussis treatment is a property of the environment and not the lymphocytes themselves. It is considered that chronic circulating immune complexes induced by pertussis administration may cause non-antigen-specific immunodepression.


Resistive Memory Devices Based on Reticular Materials for Electrical Information Storage.
Recently, reticular materials, such as metal-organic frameworks and covalent organic frameworks, have been proposed as an active insulating layer in resistive switching memory systems through their chemically tunable porous structure. A resistive random access memory (RRAM) cell, a digital memristor, is one of the most outstanding emergent memory devices that achieves high-density electrical information storage with variable electrical resistance states between two terminals. The overall design of the RRAM devices comprises an insulating layer sandwiched between two metal electrodes (metal/insulator/metal). RRAM devices with fast switching speeds and enhanced storage density have the potential to be manufactured with excellent scalability owing to their relatively simple device architecture. In this review, recent progress on the development of reticular material-based RRAM devices and the study of their operational mechanisms are reviewed, and new challenges and future perspectives related to reticular material-based RRAM are discussed.


Predictive factors of successful redo varicocelectomy in infertile patients with recurrent varicocele.
To examine the predictive factors of successful redo varicocelectomy in infertile patients with recurrent varicocele, we made a retrospective study. Twenty-one patients who had improved quality of spermatozoon 6 months after RV were designated as group 1, those with no improvement as group 2 (17 subjects) and those who received close surveillance as group 3 (10 patients) were recruited. The predictive factors included were time to recurrent varicocele; semen quality; testicular volume; number of ligated veins; body mass index; serum levels of follicle-stimulating hormone (FSH), luteinising hormone and testosterone; scrotal temperature; and peak retrograde flow (PRF) and maximal vein diameter (MVD) by colour Doppler ultrasound. The quality of spermatozoon improved significantly 6 months after RV in group 1 patients (21, 55.3%), and no improvement in group 2 and 3 patients. Patients in group 1 also had significantly lower FSH and PRF, longer time to recurrent varicocele, higher number of ligated veins and larger testicular volume than the group 2 (17, 44.7%) and group 3 patients. The significant predictive factors of successful RV were lower FSH and PRF; longer time to recurrent varicocele; and larger testicular volume preoperatively and a higher number of ligated veins during redo varicocelectomy.


Ventilatory Support via Mouthpiece to Facilitate Ambulation.
The aim of the study was to evaluate the efficacy of noninvasive ventilatory assistance/support via mouthpiece to improve performance in 6-min walk tests for individuals with severe restrictive ventilatory disorders. Each subject performed the 6-min walk test breathing spontaneously and again while using mouthpiece noninvasive ventilatory assistance/support at full ventilatory support. Oxyhemoglobin saturation (O2 sat), heart rate, Borg scale, distance walked, and ambulation duration were recorded. Eighteen patients using nocturnal nasal noninvasive ventilatory assistance/support, median (interquartile range) age of 58.5 (20) yrs, were studied. Their median baseline forced vital capacity and PaCO2 were 940 (385) ml and 54.1 (6) mm Hg, respectively. All used noninvasive ventilatory assistance/support for at least overnight hours for 36 (111) mos. Because of the progression of ventilatory impairment and hypercapnia, daytime mouthpiece noninvasive ventilatory assistance/support was initiated. All the 6-min walk test parameters improved significantly by using noninvasive ventilatory assistance/support. Both initial and final values of O2 saturation significantly increased (92% [6] vs 96% [2], P < 0.001) and (80% [19] vs 85.50% [13], P = 0.001), respectively. The median distance walked increased by 43% with noninvasive ventilatory assistance/support (175 [218] m vs 250 [113] m, P = 0.017), and the total ambulation time also increased with noninvasive ventilatory assistance/support (5.45 [3] mins vs. 6 [0] mins, P = 0.008). The exercise tolerance of patients with severe ventilatory impairment can improve by using noninvasive ventilatory support.


The N6-Methyladenosine Modification and Its Role in mRNA Metabolism and Gastrointestinal Tract Disease.
The N6-methyladenosine (m6A) modification is the most abundant internal modification of messenger RNA (mRNA) in higher eukaryotes. Under the actions of methyltransferase, demethylase and methyl-binding protein, m6A resulting from RNA methylation becomes dynamic and reversible, similar to that from DNA methylation, and this effect allows the generated mRNA to participate in metabolism processes, such as splicing, transport, translation, and degradation. The most common tumors are those found in the gastrointestinal tract, and research on these tumors has flourished since the discovery of m6A. Overall, further analysis of the mechanism of m6A and its role in tumors may contribute to new ideas for the treatment of tumors. m6A also plays an important role in non-tumor diseases of the gastrointestinal tract. This manuscript reviews the current knowledge of m6A-related proteins, mRNA metabolism and their application in gastrointestinal tract disease.


Molecular dynamics simulations highlight the altered binding landscape at the spike-ACE2 interface between the Delta and Omicron variants compared to the SARS-CoV-2 original strain.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 variant (Omicron), represents a significant deviation in genetic makeup and function compared to previous variants. Following the BA.1 sublineage, the BA.2 and BA.3 Omicron subvariants became dominant, and currently the BA.4 and BA.5, which are quite distinct variants, have emerged. Using molecular dynamics simulations, we investigated the binding characteristics of the Delta and Omicron (BA.1) variants in comparison to wild-type (WT) at the interface of the spike protein receptor binding domain (RBD) and human angiotensin converting enzyme-2 (ACE2) ectodomain. The primary aim was to compare our molecular modelling systems with previously published observations, to determine the robustness of our approach for rapid prediction of emerging future variants. Delta and Omicron were found to bind to ACE2 with similar affinities (-39.4 and -43.3 kcal/mol, respectively) and stronger than WT (-33.5 kcal/mol). In line with previously published observations, the energy contributions of the non-mutated residues at the interface were largely retained between WT and the variants, with F456, F486, and Y489 having the strongest energy contributions to ACE2 binding. Further, residues N440K, Q498R, and N501Y were predicted to be energetically favourable in Omicron. In contrast to Omicron, which had the E484A and K417N mutations, intermolecular bonds were detected for the residue pairs E484:K31 and K417:D30 in WT and Delta, in accordance with previously published findings. Overall, our simplified molecular modelling approach represents a step towards predictive model systems for rapidly analysing arising variants of concern.


[Modified variant of macroscopic study of the myocardium in cases of sudden death from cardiovascular diseases].
A method for examination of the myocardium modified for forensic medical expert evaluations is described. The number of incisions made to open the heart cavities is decreased. The incisions for examining the myocardium are made at an angle of 45 degrees to the axis of the heart, which is simpler, allows the restoration of the organ shape, and permits the examination of a larger area of sections for detecting the slightest changes in the myocardium.


Synthesis and photocytotoxicity of S-glucosylated 5,10,15,20-Tetrakis(tetrafluorophenyl)porphyrin metal complexes as efficient (1)O(2)-generating glycoconjugates.
5,10,15,20-Tetrakis(4-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosylthio)-2,3,5,6-tetrafluorophenyl)porphyrin 2a and its Zn(II), Pd(II), and Pt(II) complexes 2b, 2c, and 2d were prepared in excellent yields by nucleophilic substitution of the corresponding free-base porphyrin and metalloporphyrins with acetyl 2,3,4,6-tetra-O-acetyl-1-thio-beta-d-glucopyranoside. Deprotection of 2a, 2b, 2c, and 2d by alkaline hydrolysis afforded the corresponding S-glucosylated porphyrin 3a and its metal complexes 3b, 3c, and 3d. The structures and purity of all new photosensitizers were confirmed by elemental analysis and (1)H, (13)C, and (19)F NMR, UV-vis, and steady-state luminescence spectroscopy. The relative efficiency of singlet oxygen ((1)O(2)) production increased in the order of free-base fluoroporphyrins (2a and 3a) < Zn(II) complexes (2b and 3b) < Pd(II) complexes (2c and 3c), which can be explained in terms of the heavy-atom effect, while the (1)O(2)-producing efficiency of Pt(II) complexes (2d and 3d) were exceptionally low. In vitro photocytotoxicity of these eight S-glucosylated photosensitizers was examined in HeLa cells. Although all protected photosensitizers 2a, 2b, 2c, and 2d showed no photocytotoxicity, the photosensitizers 3a, 3b, and 3c exerted potent photocytotoxicity. These results clearly indicated that the sugar moieties of 3a, 3b, and 3c act as not only water-solubility-enhancing functionalities but also cellular-uptake-enhancing elements. Photocytotoxicity testing of 3a, 3b, and 3c in the presence of reactive oxygen species inhibitors suggested that (1)O(2) is the major mediator of cell death. Hence, the Zn(II) and Pd(II) complexes 3b and 3c are promising photosensitizers having cellular uptake-facilitating units (sugar moieties) and enhanced (1)O(2) generation due to the heavy-atom effect.


Human 3-D aVOR with and without otolith stimulation.
We describe in detail the frequency response of the human three-dimensional angular vestibulo-ocular response (3-D aVOR) over a frequency range of 0.05-1 Hz. Gain and phase of the human aVOR were determined for passive head rotations in the dark, with the rotation axis either aligned with or perpendicular to the direction of gravity (earth-vertical or earth-horizontal). In the latter case, the oscillations dynamically stimulated both the otolith organs and the semi-circular canals. We conducted experiments in pitch and yaw, and compared the results with previously-published roll data. Regardless of the axis of rotation and the orientation of the subject, the gain in aVOR increased with frequency to about 0.3 Hz, and was approximately constant from 0.3 to 1 Hz. The aVOR gain during pitch and yaw rotations was larger than during roll rotations. Otolith and canal cues combined differently depending upon the axis of rotation: for torsional and pitch rotations, aVOR gain was higher with otolith input; for yaw rotations the aVOR was not affected by otolith stimulation. There was a phase lead in all three dimensions for frequencies below 0.3 Hz when only the canals were stimulated. For roll and pitch rotations this phase lead vanished with dynamic otolith stimulation. In contrast, the horizontal phase showed no improvement with additional otolith input during yaw rotations. The lack of a significant otolith contribution to the yaw aVOR was observed when subjects were supine, prone or lying on their sides. Our results confirm studies with less-natural stimuli (off-vertical axis rotation) that the otoliths contribute a head-rotation signal to the aVOR. However, the magnitude of the contribution depends on the axis of rotation, with the gain in otolith-canal cross-coupling being smallest for yaw axis rotations. This could be because, in humans, typical yaw head movements will stimulate the otoliths to a much lesser extent then typical pitch and roll head movements.


Comparative Analysis of the Magnetic Resonance Imaging Features Between Anaplastic Meningioma and Atypical Meningioma.
The aim of the study was to investigate the differences in the imaging feature between anaplastic meningioma (World Health Organization grade III) and atypical meningioma (World Health Organization grade II), summarize its specificity of image features, and provide the basis for accurate preoperative diagnosis. The magnetic resonance imaging features of 20 patients of anaplastic meningioma were compared with those of 30 patients of atypical meningioma retrospectively, all of which were confirmed by surgery and pathology. The imaging features of the 2 groups of tumors were statistically analyzed using χ tests. The 2 tumor types differed in several features, including lobulated or irregular shape (P < 0.05), cystic and necrotic changes (P < 0.05), peritumoral edema (P < 0.05), and brain-tumor interface (P < 0.01). There were no significant differences in hemorrhage, homogeneous enhancement of the tumor, dural tail sign, or adjacent bone change (P > 0.05). Differences in the imaging feature between anaplastic meningioma and atypical meningioma can improve the differential diagnosis and allow a more appropriate approach to therapy. The article focuses on examining the differences of the magnetic resonance imaging features between anaplastic meningiomas and atypical meningiomas have been examined in only a few studies.


Surgically treated aneurysm of the trunk of the persistent primitive trigeminal artery--case report.
A 62-year-old man presented with a very rare cerebral aneurysm arising from the trunk of the persistent primitive trigeminal artery (PPTA) manifesting as subarachnoid hemorrhage. Angiography showed a saccular aneurysm at the curved mid-section of the trunk of the left PPTA of the adult type. The patient underwent surgery via the left subtemporal approach, and the aneurysm was successfully eliminated by clipping without sequelae. Aneurysm formation at this point was probably due to hemodynamic stress. The perforating arteries from the PPTA may be important in supply of the hindbrain, so PPTA patency should be preserved if possible.


Nurses' elicitation of patient error as a practice in training end-stage renal patients in automated home peritoneal dialysis.
As part of a reorganisation of the delivery of health care in Denmark therapies for chronic medical conditions are moved out of hospitals and disease-specific patient education programmes instituted to train patients to assume responsibility for treating their disease at home, that is, perform tasks and functions traditionally done by healthcare professionals. Drawing on video-recordings (90:25h) from a programme for self-management of end-stage renal disease through automated home peritoneal dialysis, the study employs conversation analysis to examine nurses' instructional practices for providing patients with the necessary knowledge, skill and competences. Showing training to rely on an error-based monitoring strategy, the study demonstrates that rather than solely waiting for random errors to emerge, nurses on occasion steer patients towards specific errors to bring about particular instructional opportunities. Surprising given the seriousness of the therapy, this elicitation of error is shown to reflect a deliberate instructional choice; nurses promote select errors to impart patients with an understanding of the procedural logic behind the therapy and medical technology. The study argues that training patients for chronic disease self-management and providing them with a proficiency level, normally associated with certified professionals, necessitates pushing patients beyond what is strictly accurate and exposing them to medically delicate events.


Harmonization of Osteoporosis Guidelines: Paving the Way for Disrupting the Status Quo in Osteoporosis Management in the Asia Pacific.
In the Asia Pacific (AP) region, osteoporosis and its consequence of fragility fractures are not widely recognized as a major public health problem. Several challenges including underdiagnosis and undertreatment exist. The Asia Pacific Consortium on Osteoporosis (APCO) is a nonpartisan and apolitical organization comprising musculoskeletal experts and stakeholders from both private and public sectors who have united to develop tangible solutions for these substantive challenges. APCO's vision is to reduce the burden of osteoporosis and fragility fractures in the AP region. Heterogeneity in both scope and recommendations among the available clinical practice guidelines (CPGs) contribute to the large osteoporosis treatment gap in the Asia Pacific. APCO has therefore developed a pan Asia-Oceania harmonized set of standards of care (The Framework), for the screening, diagnosis, and management of osteoporosis. First, a structured analysis of the 18 extant AP CPGs was completed. Subsequently, a prioritization of themes and agreement on fundamental principles in osteoporosis management were made through a Delphi process of consensus building. This approach, ensuring the opinions of all participating members were equally considered, was especially useful for a geographically diverse group such as APCO. It is hoped that the Framework will serve as a platform upon which new AP national CPGs can be developed and existing ones be revised. APCO is currently embarking on country-specific engagement plans to embed the Framework in clinical practice in the AP region. This is through partnering with regulatory bodies and national guidelines development authorities, through peer-to-peer health care professional education and by conducting path finder audits to benchmark current osteoporosis services against the Framework standards. The principles underpinning the harmonization of guidelines in the AP region can also be utilized in other parts of the world that have similar socioeconomic diversity and heterogeneity of healthcare resources. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


[Fixation of acetabulum posterior column fracture, arthroscopy assisted].
Arthroscopic surgery of the hip has evolved significantly over the last years, offering an opportunity of treatment in several intra-articular pathologies. Recent methods and instrumental advances have allowed more frequent use of this procedure, with various indications such as: hip pain, acetabular labrum lesions, extraction of foreign bodies, debridement in septic arthritis, pincer impingement, and some extra-articular injuries. Another intra-articular hip pathology that benefits from arthroscopic assistance could be found in the management of simple acetabular fractures. Therefore, this report presents the case of a patient with a posterior column fracture treated with an arthroscopic approach. Arthroscopic techniques for the fixation of intra-articular fractures offer the advantage of a direct visualization of the articular surface, which results in an anatomical reduction. In addition, arthroscopic techniques also present a benefit for intra-articular injuries such as the posterior labral lesion in this case. In simple fractures of the posterior acetabular column with minimum displacement, where percutaneous screw fixation is useful as a definitive fixation method, hip arthroscopy is useful for the reduction process and verifies the extra-articular screw trajectory.


FIT FOR PURPOSE IN ACTION: DESIGN, IMPLEMENTATION, AND EVALUATION OF THE NATIONAL INTERNET FLU SURVEY.
Researchers strive to design and implement high-quality surveys to maximize the utility of the data collected. The definitions of quality and usefulness, however, vary from survey to survey and depend on the analytic needs. Survey teams must evaluate the trade-offs of various decisions, such as when results are needed and their required level of precision, in addition to practical constraints like budget, before finalizing the design. Characteristics within the concept of fit for purpose (FfP) can provide the framework for considering the trade-offs. Furthermore, this tool can enable an evaluation of quality for the resulting estimates. Implementation of a FfP framework in this context, however, is not straightforward. In this article, we provide the reader with a glimpse of a FfP framework in action for obtaining estimates on early season influenza vaccination coverage estimates and on knowledge, attitudes, behaviors, and barriers related to influenza and influenza prevention among civilian noninstitutionalized adults aged 18 years and older in the United States. The result is the National Internet Flu Survey (NIFS), an annual, two-week internet survey sponsored by the US Centers for Disease Control and Prevention. In addition to critical design decisions, we use the established NIFS FfP framework to discuss the quality of the NIFS in meeting the intended objectives. We highlight aspects that work well and other survey traits requiring further evaluation. Differences found in comparing the NIFS to the National Flu Survey, the National Health Interview Survey, and Behavioral Risk Factor Surveillance System are discussed via their respective FfP characteristics. The findings presented here highlight the importance of the FfP framework for designing surveys, defining data quality, and providing a set a metrics used to advertise the intended use of the survey data and results.


[Risk patients in dentistry].
Authors study the risk diseases in dental practice. They analyze the possible complications and the methods of their prevention in each risk group. They take deal with the importance of antibiotic prophylaxis, the problems of local anaesthesia and the management of patients who suffer from coagulation disturbances. They present the management of risk patients in two cases. They emphasize the importance of anamnestic history in every case before dental treatment.


Medial knee cartilage is unlikely to withstand a lifetime of running without positive adaptation: a theoretical biomechanical model of failure phenomena.
Runners on average do not have a high risk of developing knee osteoarthritis, even though running places very high loads on the knee joint. Here we used gait analysis, musculoskeletal modeling, and a discrete-element model of knee contact mechanics to estimate strains of the medial knee cartilage in walking and running in 22 young adults (age 23 ± 3 years). A phenomenological model of cartilage damage, repair, and adaptation in response to these strains then estimated the failure probability of the medial knee cartilage over an adult lifespan (age 23-83 years) for 6 km/day of walking vs. walking and running 3 km/day each. With no running, by age 55 the cumulative probability of medial knee cartilage failure averaged 36% without repair and 13% with repair, similar to reports on incidence of knee osteoarthritis in non-obese adults with no knee injuries, but the probability for running was very high without repair or adaptation (98%) and remained high after including repair (95%). Adaptation of the cartilage compressive modulus, cartilage thickness, and the tibiofemoral bone congruence in response to running (+1.15 standard deviations of their baseline values) was necessary for the failure probability of walking and running 3 km/day each to equal the failure probability of walking 6 km/day. The model results suggest two conclusions for further testing: (i) unlike previous findings on the load per unit distance, damage per unit distance on the medial knee cartilage is greater in running vs. walking, refuting the "cumulative load" hypothesis for long-term joint health; (ii) medial knee cartilage is unlikely to withstand a lifetime of mechanical loading from running without a natural adaptation process, supporting the "cartilage conditioning" hypothesis for long-term joint health.