Fracture clinic redesign: improving standards in patient care and interprofessional education.
Current fracture clinic models, especially with the advent of reductions in junior doctors' hours, may limit outpatient trainee education and patient care. We have designed a new fracture clinic model, involving an initial consultant-led case review focused on patient management and trainee education. Prospective outcomes for all new patients attending the redesigned fracture clinic over a 3-week period in 2010 (n = 240) were compared with a historical cohort from the same period in 2009 (n = 296). The primary outcome measure was the proportion of patients with direct consultant input. Secondary outcome measures included patient discharge rates, return rates, use of the nurse-led fracture clinic and the incidence of adverse event reporting. Trainees attending each clinic completed a five-point Likert questionnaire assessing the adequacy of education, support, staff morale and standards of patient care, before and after introduction of the clinic redesign. Using a separate Likert questionnaire, emergency room (ER) staff were evaluated to determine the impact of the new style clinic on their education, daily practice and interprofessional relations. Adverse events were gathered from the 'incident record 1' (IR1) reporting system. The percentage of cases given consultant input increased significantly from 33% in 2009 to 84% in 2010 (p <0.0001), while the proportion of patients requiring physical review by a consultant fell by 21% (p <0.0001). Return rates were reduced by 14% (p = 0.013) and use of the nurse-led fracture clinic improved by 10% (p = 0.0028). There was a median improvement in trainee perception of education from 2 (interquartile range 1.25-2.75) to 5 (4.25-5, p = 0.011), senior support from 2 (2-3) to 5 (4-5, p = 0.017) and patient care from 3 (3-4) to 5 (4-5, p = 0.015). ER staff found the new style clinic was educational, practice changing and improved interprofessional relations, but that it did not interfere with ER duties. The incidence of adverse incidents reported fell from 8 per year to 0 per year after the introduction of the new style clinic. Our model of fracture-clinic redesign has significantly enhanced consultant input into patient care without additional funding. In addition, we have demonstrated increased service efficiency and significant improvements in staff support, morale and education. In the face of current economic and training challenges, we recommend this new model as a tool that will enhance patient and trainee experience.


Nucleotide sequence and complementation analysis of a polycistronic sporulation operon, spoVA, in Bacillus subtilis.
We have determined the nucleotide sequence of a 3706 bp stretch of Bacillus subtilis chromosomal DNA that complements all known spoVA mutations. The sequence contains five consecutive large open reading frames capable of encoding proteins of molecular weights ranging from approximately 15000 to 36000. Analysis using integrational plasmids suggests that the region is likely to be transcribed as a single mRNA. A novel form of complementation analysis, based on derivatives of bacteriophage phi 105 carrying the cloned spoVA locus, has been used to define four distinct complementation groups among the eight previously characterized spoVA mutations. The spoVA locus is the largest polycistronic sporulation operon yet characterized.


[Effects of Chinese fir litter on soil organic carbon decomposition and microbial biomass carbon].
By using 13C stable isotope tracer technique, this paper studied the effects of Chinese fir litter addition on the soil organic carbon (SOC) decomposition, microbial biomass carbon, and dissolved organic carbon in 0-5 cm and 40-45 cm layers. The decomposition rate of SOC in 40-45 cm layer was significantly lower than that in 0-5 cm layer, but the priming effect induced by the Chinese fir litter addition showed an opposite trend. The Chinese fir litter addition increased the soil total microbial biomass carbon and the microbial biomass carbon derived from native soil significantly, but had less effects on the soil dissolved organic carbon. Turning over the subsoil to the surface of the woodland could accelerate the soil carbon loss in Chinese fir plantation due to the priming effect induced by the litters.


Clinical outcomes with high-dose-rate surface mould brachytherapy for intra-oral and skin malignancies involving head and neck region.
The literature and experience of high-dose-rate (HDR) surface mould brachytherapy (SMB) in head and neck cancer is sparse. We report our institutional experience of SMB for such tumours. Thirty-five patients with malignant localized early T1/T2, N0 (21 intra-oral and 14 skin) tumours treated with SMB during 2008-2014 were analyzed. Treatment was delivered using HDR 192Ir source to a median dose of 49 Gy (range, 38.5-52.5 Gy) as radical brachytherapy and 18 Gy (range, 15.5-30 Gy) as boost with 3-4 Gy/fraction twice daily using customized surface mould. Median follow-up was 52 months (range, 6 to 98 months). Local control (LC) for skin tumours and intra-oral malignancies at 5 years were 92% and 76%, respectively. Five-year cause specific survival was 92%. For T1 and T2 tumours, 5 year LC was 94.2% and 68.2%, respectively. T stage (p < 0.04) and dose/fractions (p < 0.003) were the only significant prognostic factors for LC on univariate analysis. Surface mould brachytherapy results in excellent LC rates for skin tumours and T1 intraoral tumours when considered as radical treatment, and preferable to consider it as a boost for T2 intraoral tumours. Surface mould brachytherapy results in excellent organ and function preservation.


[Anterior lead ST-segment depression in inferior wall infarction. Early angiographic study. Effect on the results of intracoronary thrombolysis].
Of 32 patients with inferior myocardial infarction undergoing coronary angiography in the first 6 hours for intracoronary streptokinase thrombolysis, 19 (Group I) had ST depression of more than 1 mm in the anterior chest wall leads (VI-V4) whilst 13 (Group II) had no ST changes in these leads. Quantitative analysis of left ventricular angiograph showed a significantly lower ejection fraction in Group I (52 +/- 8.5%) compared to Group II (59 +/- 8%, p less than 0.05) and that this difference was due to a greater zone of inferior wall hypokinesia, irrespective of whether this was assessed by measuring its surface area (HKS cm2: Gr I: 11 +/- 6, Gr II: 4 +/- 3, p less than 0.01) or percentage ventricular perimeter (HK%: Group I 45 +/- 15, Group II 26 +/- 12, p less than 0.001). On the other hand, anterior wall motion was normal in both groups. Coronary angiography showed proximal obstruction of the right coronary artery in 84% of patients in Group I. In Group II, the coronary obstruction tended to be distal or incomplete. The prevalence and average severity of associated stenosis of the left anterior descending artery were the same in both populations. The success rate of thrombolysis was not significantly different between the two groups. In successful procedures with a patent artery on the 14th day, improved regional contractility was only observed in Group I (HKS cm2: 11.5 +/- 6 vs 8 less than 4.4, p less than 0.05; HK%: 47 +/- 14 vs 38 +/- 9, p less than 0.05): the hypokinetic zone was unchanged in Group II.(ABSTRACT TRUNCATED AT 250 WORDS)


Recruiting American Indian women for a genetic epidemiology study.
Due to previous negative experiences, some American Indian communities are distrustful of research in general and genetic research in particular. The Turtle Mountain Community College was awarded a National Institutes of Health (NIH) grant with 3 aims: (1) to study possible genetic influences on pre-eclampsia, (2) to encourage tribal college students to consider biomedical careers and (3) to develop the local research infrastructure. Retrospectively identified case (91) and control (188) participants were recruited into Phase I over a 3-year period and additional participants (71) were concurrently recruited from a prenatal clinic into a prospective case/control study, Phase II. This paper describes some of the challenges and solutions we encountered in the process of recruiting American Indian participants into a genetic epidemiologic study.


Warfarin use and outcomes in patients with atrial fibrillation complicating acute coronary syndromes.
We examined warfarin use at discharge (according to Congestive heart failure, Hypertension, Age>75 years, Diabetes, Prior Stroke/transient ischemic attack score and bleeding risk) and its association with 6-month death or myocardial infarction in patients with post-acute coronary syndrome atrial fibrillation. Of the 23,208 patients enrolled in the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network A, and Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors trials, 4.0% (917 patients) had atrial fibrillation as an in-hospital complication and were discharged alive. Cox proportional hazards models were performed to assess 6-month outcomes after discharge. Overall, 13.5% of patients with an acute coronary syndrome complicated by atrial fibrillation received warfarin at discharge. Warfarin use among patients with atrial fibrillation had no relation with estimated stroke risk; similar rates were observed across Congestive heart failure, Hypertension, Age>75 years, Diabetes, Prior Stroke/transient ischemic attack (CHADS(2)) scores (0, 13%; 1, 14%; > or = 2, 13%) and across different bleeding risk categories (low risk, 11.9%; intermediate risk, 13.3%; high risk, 11.1%). Among patients with in-hospital atrial fibrillation, warfarin use at discharge was independently associated with a lower risk of death or myocardial infarction within 6 months of discharge (hazard ratio 0.39; 95% confidence interval, 0.15-0.98). Warfarin is associated with better 6-month outcomes among patients with atrial fibrillation complicating an acute coronary syndrome, but its use is not related to CHADS(2) score or bleeding risk.


Molecular studies of liver disease in erythropoietic protoporphyria.
The goal of this study was to define molecular determinants of liver disease in erythropoietic protoporphyria (EPP). EPP is a genetic disorder in which deficient ferrochelatase activity causes excessive production of protoporphyrin, which is excreted in bile. Some patients develop liver disease that necessitates transplantation. Ferrochelatase gene analysis was done in 25 families with EPP to identify mutations and a polymorphism (IVS3-48c) that causes low gene expression. Expression of multiple hepatic genes was also examined by DNA microarray analysis in patients who had liver transplantation to identify genes with altered regulation. Heterozygous ferrochelatase mutations were found in 43 individuals. In 94% of 31 symptomatic patients, 15 of whom had liver disease, the polymorphism was also present in the nonmutant allele. Explanted liver of patients who had transplantation showed significant change in expression of several genes involved in wound healing, organic anion transport, and oxidative stress. Patients with EPP who develop liver disease usually have a mutation in one ferrochelatase allele that alters enzyme function, together with a polymorphism in the nonmutant allele that causes low gene expression. This results in significant increase in the hepatobiliary excretion of protoporphyrin, which can damage the liver through both cholestatic injury and oxidative stress.


Atraumatic osteochondral fracture and osteoarthritis in a collegiate volleyball player: a case report.
To present the case of a collegiate athlete with an atraumatic osteochondral fracture influenced by the presence of osteoarthritis. Osteochondral fractures are fairly common occurrences in athletes, although it can be difficult to recognize such an injury in the absence of a traumatic event. Osteoarthritis is 1 condition that can increase an athlete's susceptibility to an atraumatic osteochondral fracture. However, because of the atraumatic nature of the injury, the possibility of an osteochondral fracture may be overlooked. Meniscal damage, osteochondritis dissecans, patellofemoral disorders. The osteochondral fragment was surgically removed, and fibrous growth was encouraged by drilling and laser smoothing. Osteochondral fractures are usually associated with some type of traumatic mechanism, such as a rotational and compressive force. Also, osteoarthritis is not common in young collegiate athletes. However, this 20-year-old volleyball player had no apparent injury and lacked the usual signs and symptoms (eg, locking, giving way, crepitus, loss of range of motion) associated with an osteochondral fracture. The athlete's susceptibility to an osteochondral fracture was increased by the presence of osteoarthritis. The athletic trainer should consider the possibility of an osteochondral fracture in an athlete with persistent effusion and pain in the absence of a traumatic mechanism of injury.


Antibacterial and antitoxin responses in the serum and milk of cholera patients.
Antibacterial and antitoxin responses in the acute and convalescent (7 to 10 days) sera of 14 cholera patients were determined by various serological techniques. Similar studies were also carried out with corresponding milk samples of six of these patients who were lactating women. A significant rise in antibacterial titers was observed in all convalescent serum and milk samples. A similar rise in antitoxin titers was observable in all serum and four milk samples. Specificity of the antibacterial titers was further evaluated by the indirect hemagglutination test using lipopolysaccharide antigen, and close correlations were noted between these titers and vibrio agglutination (P<0.001) and vibriocidal (P<0.001) titers of sera. Serum and milk convalescent cholera patients could effectively neutralize cholera toxin action in vivo, although the neutralizing activity of serum was higher than that of milk. Determination of antibody titers by the enzyme-linked immunosorbent assay demonstrated that anti-lipopolysaccharide activity in sera belonged predominantly to immunoglobulin M (IgM) and, to a lesser extent, to IgG and IgA, whereas such activity in milk was mostly contributed by secretory IgA, although some IgM antibodies also could be detected. On the other hand, antitoxic activity in convalescent sera primarily belonged to IgG, whereas such activity in milk was almost exclusively contributed by secretory IgA. These results demonstrate that an antibody response in the mammary gland was stimulated due to the antigen exposure in the gut and are consistent with the idea of a common homing pattern of immunocytes within the secretory immune system. Moreover, some differences in the antibody production mechanism between the systemic and secretory immune systems are indicated.


Transcription enhancers as major determinants of SV40 polyomavirus growth efficiency and host cell tropism.
The non-coding control region (NCCR) of polyomaviruses includes the promoters for early and late genes, a transcription enhancer and the origin of DNA replication. Particularly virulent variants of the human pathogens BKPyV and JCPyV, as well as of simian virus 40 (SV40), occur in vitro and in vivo. These strains often harbour rearrangements in their NCCR, typically deletions of some DNA segment(s) and/or duplications of others. Using an SV40-based model system we provide evidence that duplications of enhancer elements, whether from SV40 itself or from the related BKPyV and JCPyV, increase early gene transcription and replicative capacity. SV40 harbouring subsegments of the strong cytomegalovirus (HCMV) enhancer replicated better than the common 'wild-type' SV40 in the human cell lines HEK293 and U2OS. In conclusion, replacing the SV40 enhancer with heterologous enhancers can profoundly influence SV40's infective capacity, underscoring the potential of small DNA viruses to overcome cell type and species barriers.


24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival.
The major cholesterol metabolite in brain, 24(S)-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here, we review that nascent work. Our own studies have demonstrated that 24S-HC has potent positive modulatory effects on N-methyl-d-aspartate (NMDA) receptor (NMDAR) function. This could have implications not only for brain plasticity but also for pathological NMDAR overuse. Other work has demonstrated effects of 24S-HC on neuronal survival and as a possible biomarker of neurodegenerative disease. Depending on circumstances, both upregulation/mimicry of 24S-HC signaling and down-regulation/antagonism may have therapeutic potential. We are interested in the possibility that synthetic analogues of 24S-HC with positive effects at NMDARs may hold neurotherapeutic promise, given the role of NMDA receptor hypofunction in certain neuropsychiatric disorders.


The effect of a protein-bound polysaccharide from Coriolus versicolor on immunological parameters and experimental infections in mice.
The influence of PSK, a protein bound polysaccharide from Coriolus versicolor on various immunological parameters was studied, PSK was found to enhance B cell activity as measured by the spleen plaque-forming cell assay in mice, and to stimulate mouse macrophages as determined by an enhancement of carbon clearance and an increase in the phagocytosis of opsonized sheep red blood cells by peritoneal mouse macrophages in vitro. The activation of mouse macrophages by PSK appeared to correlate with the therapeutic effects of the compound. In mice made granulocytopenic with cyclophosphamide and subsequently infected with a variety of garm-negative pathogens or with Candida albicans, PSK prolonged the average survival time of the animals. The compound also led to a drastic increase in the number of animals surviving such experimental infections as compared to untreated controls. Possible mechanisms responsible for these protective effects by PSK are discussed.


Characterizing the Structural and Functional Properties of Soybean Protein Extracted from Full-Fat Soybean Flakes after Low-Temperature Dry Extrusion.
The soy protein isolates (SPI) extracted from different extruded full-fat soybean flakes (FFSF), and their conformational and functional properties were characterized. Overall, the free thiol (SH) content of SPI increased when the extrusion temperature was below 80 °C and decreased at higher temperatures. Soy glycinin (11S) showed higher stability than β-conglycinin (7S) during extrusion. Results also indicated that the increase in some hydrophobic groups was due to the movement of hydrophobic groups from the interior to the surface of the SPI molecules at extrusion temperatures from 60 to 80 °C. However, the aggregation of SPI molecules occurred at extrusion temperatures of 90 and 100 °C, with decreasing levels of hydrophobic groups. The extrusion temperature negatively affected the emulsifying activity index (EAI); on the other side, it positively affected the emulsifying stability index (ESI), compared to unextruded SPI.


[Potent natural inhibitors of tobacco mosaic virus multiplication].
The hypersensitivity reaction in Nicotiana tabacum var. Xanthi n.c. infected with Tobacco mosaic virus (T.M.V.) leads to the production of aromatic amides (ferulylputrescine, diferulylputrescine, p-coumarylputrescine and di-p-coumarylputrescine) inthe cells around the necroses. Similar compounds are formed in Xanthi plants after floral induction. p-coumarylputrescine, di-p-coumarylputrescine and caffeylputrescine strongly inhibit T.M.V. multiplication.


Medication and toxin-induced peripheral neuropathy.
Medication and toxin-induced neuropathies, although uncommon, are important to identify because of potential reversibility. Numerous medications and toxins are implicated with neuropathy, but objective proof is lacking for many. Chemotherapeutic agents, nucleoside analogs, and other medications and toxins have clear causative links with neuropathy, but many agents have only rare temporal associations. Neuropathies are being recognized from new medications approved for use and other medications, which have expanded indications. Some established associations with neuropathy are less widely known while others are overestimated. Peripheral neuropathy from chronic drug exposure is more problematic to determine. Axonal pathology is most common, but some agents cause demyelination and even conduction block, mimicking immune-mediated neuropathies. Multiple and varied toxic mechanisms are implicated. Neuropathy is a dose-limiting complication of some critical treatments and preventative agents are being actively pursued.


The pathogenesis of spinal cord involvement in the encephalomyelitis of mice caused by neuroadapted Sindbis virus infection.
Weanling mice develop an acute encephalomyelitis with high mortality after intracerebral inoculation of neuroadapted Sindbis virus. The mice develop kyphoscoliosis and hindlimb paralysis. Immunohistochemical and in situ hybridization studies have demonstrated virus in the gray matter of the brain and spinal cord. Ventral horn cells are prominently infected, providing an anatomical basis for the clinical poliomyelitis. A novel route of spread of inoculated virus within the central nervous system has been found. The virus enters the ventricular system, and then travels caudally in the central canal of the spinal cord where ependymal cells are infected. The virus subsequently spreads into the gray matter. The distribution of virus in the spinal cord is likely dependent both on variations in the susceptibility of neural cells and on this route of entry and subsequent spread.


Transcriptional Dynamics of Hepatic Sinusoid-Associated Cells After Liver Injury.
Hepatic sinusoidal cells are known actors in the fibrogenic response to injury. Activated hepatic stellate cells (HSCs), liver sinusoidal endothelial cells, and Kupffer cells are responsible for sinusoidal capillarization and perisinusoidal matrix deposition, impairing vascular exchange and heightening the risk of advanced fibrosis. While the overall pathogenesis is well understood, functional relations between cellular transitions during fibrogenesis are only beginning to be resolved. At single-cell resolution, we here explored the heterogeneity of individual cell types and dissected their transitions and crosstalk during fibrogenesis. We applied single-cell transcriptomics to map the heterogeneity of sinusoid-associated cells in healthy and injured livers and reconstructed the single-lineage HSC trajectory from pericyte to myofibroblast. Stratifying each sinusoidal cell population by activation state, we projected shifts in sinusoidal communication upon injury. Weighted gene correlation network analysis of the HSC trajectory led to the identification of core genes whose expression proved highly predictive of advanced fibrosis in patients with nonalcoholic steatohepatitis (NASH). Among the core members of the injury-repressed gene module, we identified plasmalemma vesicle-associated protein (PLVAP) as a protein amply expressed by mouse and human HSCs. PLVAP expression was suppressed in activated HSCs upon injury and may hence define hitherto unknown roles for HSCs in the regulation of microcirculatory exchange and its breakdown in chronic liver disease. Our study offers a single-cell resolved account of drug-induced injury of the mammalian liver and identifies key genes that may serve important roles in sinusoidal integrity and as markers of advanced fibrosis in human NASH.


A five-year study of cosmetic reactions.
During 64 months (1977 to 1983), twelve dermatologists from various sections of the United States studied a total of 713 patients with cosmetic dermatitis out of an estimated total of 13,216 patients with contact dermatitis. The number of patients seen for all causes during this period was 281,100. An important finding was that half of the patients or physicians were unaware that a cosmetic was responsible for their dermatitis. Skin care products, hair preparations (including colors), and facial makeup were responsible for the majority of the reactions. The most important objective was identification of causative ingredients. Eighty-seven percent of the subjects had patch tests. Fragrance, preservatives (Quaternium-15, formaldehyde, imidazolidinyl urea, and parabens), p-phenylenediamine, and glyceryl monothioglycolate were the most frequently identified allergic sensitizers, in that order. In addition to the clinical data, the study permitted assessment of the frequency of cosmetic reactions, although the data may not be entirely representative of the country at large because of the special interests of the dermatologists involved.


Single-molecule analysis of ultradilute solutions with guided streams of 1--microm water droplets.
We describe instrumentation for real-time detection of single-molecule fluorescence in guided streams of 1-microm (nominal) water droplets. In this technique, target molecules were confined to droplets whose volumes were comparable with illumination volumes in diffraction-limited fluorescence microscopy and guided to the waist of a cw probe laser with an electrostatic potential. Concentration detection limits for Rhodamine 6G in water were determined to be approximately 1 fM, roughly 3 orders of magnitude lower than corresponding limits determined recently with diffraction-limited microscopy techniques for a chemical separation of similar dyes. In addition to its utility as a vehicle for probing single molecules, instrumentation for producing and focusing stable streams of 1-2-microm-diameter droplets may have other important analytical applications as well.


Tooth preparation for full-coverage restorations using the enamel milling technique.
There are many acceptable methods of tooth preparation for full-coverage restorations. The technique used should be systematic, with step-by-step procedures to produce an easily followed routine. This will minimize undesirable, haphazard tooth reduction. The technique presented in this paper is a simple, exacting, and conservative method of tooth reduction, requiring a minimum of instrumentation.


Strategies and Perspectives to Catch the Missing Pieces in Energy-Efficient Hydrogen Evolution Reaction in Alkaline Media.
Transition metal hydroxides (M-OH) and their heterostructures (X|M-OH, where X can be a metal, metal oxide, metal chalcogenide, metal phosphide, etc.) have recently emerged as highly active electrocatalysts for hydrogen evolution reaction (HER) of alkaline water electrolysis. Lattice hydroxide anions in metal hydroxides are primarily responsible for observing such an enhanced HER activity in alkali that facilitate water dissociation and assist the first step, the hydrogen adsorption. Unfortunately, their poor electronic conductivity had been an issue of concern that significantly lowered its activity. Interesting advancements were made when heterostructured hydroxide materials with a metallic and or a semiconducting phase were found to overcome this pitfall. However, in the midst of recently evolving metal chalcogenide and phosphide based HER catalysts, significant developments made in the field of metal hydroxides and their heterostructures catalysed alkaline HER and their superiority have unfortunately been given negligible attention. This review, unlike others, begins with the question of why alkaline HER is difficult and will take the reader through evaluation perspectives, trends in metals hydroxides and their heterostructures catalysed HER, an understanding of how alkaline HER works on different interfaces, what must be the research directions of this field in near future, and eventually summarizes why metal hydroxides and their heterostructures are inevitable for energy-efficient alkaline HER.


Prognostic value of blood lactate, blood glucose, and hematocrit in canine babesiosis.
Canine babesiosis typically causes hemolytic anemia but also can result in multiple organ dysfunction. Human patients with severe disease often have persistent hyperlactatemia, and blood lactate concentration is correlated with survival rate. In dogs, blood lactate concentration has been shown to be of prognostic value in patients with gastric dilatation-volvulus and in dogs admitted to intensive care units. Serial blood lactate and glucose concentrations and hematocrit on admission were determined in 90 dogs with naturally occurring, severe or complicated canine babesiosis. Forty-five dogs (50%) had hyperlactatemia (blood lactate concentration >22.5 mg/dL) and 20 (22.2%) had hypoglycemia (blood glucose concentration <59.4 mg/dL) at presentation. Measurements significantly associated with mortality were hypoglycemia on admission, blood lactate concentration >45 mg/dL on admission, blood lactate concentration >22.5 mg/dL at 8, 16, and 24 hours after admission, and increase or <50% decrease in blood lactate concentration within 8 and 16 hours after admission. Blood lactate concentration persistently >40 mg/dL indicated a very poor prognosis. We conclude that serial blood lactate measurements are useful in predicting survival in dogs with severe and complicated canine babesiosis.


Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment In COVID-19.
At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.


p300/CBP-associated factor histone acetyltransferase processing of a peptide substrate. Kinetic analysis of the catalytic mechanism.
p300/CBP-associated factor (PCAF) is a histone acetyltransferase that plays an important role in the remodeling of chromatin and the regulation of gene expression. It has been shown to catalyze preferentially acetylation of the epsilon-amino group of lysine 14 in histone H3. In this study, the kinetic mechanism of PCAF was evaluated with a 20-amino acid peptide substrate derived from the amino terminus of histone H3 (H3-20) and recombinant bacterially expressed PCAF catalytic domain (PCAF(cat)). The enzymologic behavior of full-length PCAF and PCAF(cat) were shown to be similar. PCAF-catalyzed acetylation of the substrate H3-20 was shown to be specific for Lys-14, analogous to its behavior with the full-length histone H3 protein. Two-substrate kinetic analysis displayed an intersecting line pattern, consistent with a ternary complex mechanism for PCAF. The dead-end inhibitor analog desulfo-CoA was competitive versus acetyl-CoA and noncompetitive versus H3-20. The dead-end analog inhibitor H3-20 K14A was competitive versus H3-20 and uncompetitive versus acetyl-CoA. The potent bisubstrate analog inhibitor H3-CoA-20 was competitive versus acetyl-CoA and noncompetitive versus H3-20. Taken together, these inhibition patterns support an ordered BiBi kinetic mechanism for PCAF in which acetyl-CoA binding precedes H3-20 binding. Viscosity experiments suggest that diffusional release of product is not rate-determining for PCAF catalysis. These results provide a mechanistic framework for understanding the detailed catalytic behavior of an important subset of the histone acetyltransferases and have significant implications for molecular regulation of and inhibitor design for these enzymes.


[Relationship between anti-NMDAR encephalitis and acute juvenile female non-herpetic encephalitis (AJFNHE)].
The relationships between AJFNHE (Kamei S: 2004) and anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis (Dalmau J et al: 2007) is discussed. The comparative clinical features in both reports revealed that most were young adult women, a prodrome was presented in 80%, the first neurological symptom was psychosis, the main symptoms included convulsions, consciousness disturbance, and involuntary movements, and mechanical ventilation was required in 80%. Dalmau reported that ovarian teratoma was demonstrated in 11 out of 12 patients, and mediastinal teratoma in 1 patient. We had yet to examine these conditions at the time of publication. AJFNHE and anti-NMDAR encephalitis are thus considered to be the same condition. AJFNHE represents a clinical concept based on the specific clinical features, and anti-NMDAR encephalitis represents a clinical entity based on the neuro-oncological findings. A nationwide survey of AJFNHE was undertaken in Japan. Collected patients predominantly were young adult women. Their clinical features were uniform and also in concordance with those previously reported as AJFNHE. This survey revealed that the annual incidence was 0.33/10(6) population, respiratory failure was observed in 70% and required care with mechanical ventilation, associated tumors were demonstrated in 40% and ovarian teratoma was the most frequent.


Age-related change in muscle strength, muscle mass, and fat mass between the dominant and non-dominant upper limbs.
Any form of physical activity is recommended for the older adults to maintain their physical function; however, the effect of daily activities on muscle function still needs to be investigated. Humans always use one dominant hand to perform tasks, providing a natural situation for research on the effect of daily activities on muscle function. Five hundred and twenty-six healthy adults were recruited from the community in Beijing. Muscle strength was assessed using a handgrip dynamometer, lean mass, fat mass, bone area and bone mineral content of upper limbs were assessed using dual-energy X ray-absorptiometry. The results were compared between the dominant and non-dominant upper limbs. The dominant upper limb had better muscle strength, lean mass, bone area and bone mineral content than the non-dominant side. The difference in muscle strength and lean mass between the two upper limbs decreased with the advanced age. In older age, fat mass of upper limbs increased in men, but not in women. Daily activities can maintain better muscle function in the dominant upper limb than in the non-dominant side; however, the delaying effect on age-related decline in muscle function was limited.


Hydrogen-driven denitrification of wastewater in an anaerobic submerged membrane bioreactor: potential for water reuse.
An anaerobic submerged membrane bioreactor was coupled with a novel hydrogen delivery system for hydrogenotrophic denitrification of municipal final effluent containing nitrate. The biological treatment unit and hydrogen delivery unit were proven successful in removing nitrate and delivering hydrogen, respectively. Complete hydrogen transfer resulted in reducing nitrate below detectable levels at a loading of 0.14 kg Nm(-3) d(-1). The produced water met all drinking water guidelines except for color and organic carbon. However, the organic carbon was removed by 72% mostly by membrane rejection. To reduce the organic carbon and color of the effluent, post treatment of the produced water is required.


Identification of human lymphoma cells by antisera to malignancy-associated nucleolar antigens.
The non-Hodgkin's lymphomas (NHL) are a diverse group of human lymphoid neoplasms that have long presented pathologists with formidable diagnostic challenges. These tumors of the immune system are thought to represent neoplastic transformations of most of the recognized stages in T and B lymphocyte ontogeny. Lymphoma cells, however, often simulate their normal lymphocytic counterparts both morphologically and cell surface phenotypically, creating difficulties in discriminating normal from neoplastic lymphocytes. We have used heteroantisera to the human malignancy-associated nucleolar antigen (HMNA) to prospectively evaluate its efficacy in identifying the morphologically neoplastic cells in NHL lesions. In 65 cases of T and B cell histopathologic types of NHL, the antisera reacted with nucleoli in the morphologically and cytogenetically neoplastic lymphoma cells, but not with normal-appearing lymphoid and other cell types present in the lesions. Control specimens from normal and hyperplastic lymphoid tissue also failed to react with anti-HMNA antibodies. Normal activated lymphoid cells in vitro and growth-factor-dependent normal lymphoid cell lines also failed to express the nucleolar antigen(s). These data suggest that the HMNA is a valuable tumor cell marker for neoplastic human lymphoid cell populations and can be used with other types of cell markers for a better definition of the neoplastic cells in NHL.


Theoretical analysis of crystallization by homogeneous nucleation of water droplets.
We propose a novel method for analyzing the crystallization process from supercooled water droplets. The method, which is based on nucleation theory, simultaneously evolves homogeneous ice nucleation and crystal growth in the cooling process and obtains the crystallization temperature and the number of crystal nuclei in the droplets. The model can reproduce not only the crystallization of water but also the vitrification process. The model well replicated the results of previous laboratory experiments, especially, the different responses of the crystallization temperatures of the micrometer- and nanometer-sized particles as a function of cooling rates. For particle sizes ranging from 1 to 1000 μm and cooling rates below 104 K s-1, the crystallization temperature was 230-240 K. At cooling rates above 104 K s-1, the crystallization temperature decreased rapidly. On the other hand, the crystallization temperature of 10 nm particles was 200-230 K at cooling rates below 104 K s-1. When describing the interfacial tension by σ = 29.1 + 0.1(T - 273.15) erg cm-2 (where T is the water droplet temperature in K), the analyses explained well the previously reported crystallization temperatures of droplets sized from a few nm to 100 μm under various cooling conditions. Our model also predicts the critical cooling rate for vitrification of the liquid water droplets. The critical cooling rate of vitrification is predicted to be 107-108 K s-1, consistent with the experimental rates. These analyses are useful not only for comprehensively understanding the ice nucleation process but also for predicting the crystallization processes in various environments such as cirrus clouds, which are difficult to reproduce in experiments.


Push-fast recommendation on performing CPR causes excessive chest compression rates, a manikin model.
Increasing chest compression rate during cardiopulmonary resuscitation can affect the workload and, ultimately, the quality of chest compression. This study examines the effects of compression at the rate of as-fast-as-you-can on cardiopulmonary resuscitation (CPR) performance. A crossover, randomized-to-order design was used. Each participant performed chest compressions without ventilation on a manikin with 2 compression rates: 100 per minute (100-cpm) and "push as-fast-as you-can" (PF). The participants performed chest compressions at a rate of either 100-cpm or PF and subsequently switched to the other after a 50-minute rest. Forty-two CPR-qualified nonprofessionals voluntarily participated in the study. During the PF session, the rescuers performed CPR with higher compression rates (156.8 vs 101.6 cpm), more compressions (787.2 vs 510.8 per 5 minutes), and more duty cycles (51.0% vs 41.7%), but a lower percentage of effective compressions (47.7% vs 57.9%) and a lower compression depth (35.6 vs 38.0 mm) than they did during the 100-cpm session. The CPR quality deteriorated in numbers and percentile of effective compression since the third minute in the PF session and the fourth minute in the 100-cpm session. The percentile of compressions with adequate depth in the 100-cpm sessions was higher than that in the PF sessions during the second, third, and fourth minutes of CPR. Push-fast technique showed a significant decrease in the percentile of effective chest compression compared with the 100-cpm technique during the 5-minute hand-only CPR. The PF technique exhibited a trend toward increased fatigue in the rescuers, which can result in early decay of CPR quality.


The effect of clozapine therapy on frontal lobe dysfunction in schizophrenia: neuropsychology and event-related potential measures.
There are several reports that performance-based measures as well as symptom ratings improve with clozapine in patients with schizophrenia who previously responded poorly to typical neuroleptic treatment. It is not clear whether improved cognitive function following initiation of clozapine is simply related to relief of psychotic symptoms and extrapyramidal side-effects associated with prior use of typical neuroleptics, or reflects another dimension of the greater efficacy of clozapine compared with typical neuroleptics. To elucidate this issue and better specify the cognitive changes associated with use of clozapine, the authors have assessed cognitive function psychometrically and using event-related potentials (ERPs), pre- and 8-12 wk post-initiation of clozapine treatment. Patients were rated on the BPRS, the SAPS and the SANS and completed a number of tests tapping aspects of frontal lobe function. ERP recordings were conducted using an auditory task twice, which was repeated under passive and active attention conditions. It was found that clozapine differentially affects tests reflecting executive and planning function, and not stimulus-driven cognitive functions. The results were not consistent with the hypothesis that these effects were simply due to relief of medication side-effects but could be related to the D(1) receptor antagonist actions of clozapine.


Comparison of modified one- and two-layer microsurgical vasovasostomy.
To compare the outcome of a modified one-layer and two-layer vasovasotomy (VV) in two groups of similar men undergoing vasectomy reversal. The charts and surgical records of all surgical procedures performed on men undergoing a modified one- or two-layer VV between June 1992 and July 1994 were retrospectively reviewed. A successful outcome (patency) was defined as sperm present at follow-up (mean follow-up 8 weeks). A modified one-layer VV was used in 17 men (group 1) and a two-layer VV in 23 (group 2). Sperm were present in both groups if surgery was undertaken after vasal obstruction lasting < 36 months. The modified one- and two-layer VV had equal patency (88% and 90%, respectively) when undertaken after an obstructed interval of 36-96 months; outcomes were poorer if surgery was performed after > 96 months. The mean operative duration was 96 min for a modified one-layer VV and 167 min for the two-layer VV. The simpler and faster modified one-layer VV provides sufficient accuracy for successful vasectomy reversal in most cases. For most patients, both procedures have equivalent patency.


Laparoscopic Roux-en-Y gastric bypass in the "megaobese".
Laparoscopic Roux-en-Y gastric bypass is a safe and effective procedure in patients with a body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) of 70 or greater. A retrospective analysis of patients with a BMI of 70 or greater who underwent laparoscopic Roux-en-Y gastric bypass by a single surgeon. A university-affiliated community hospital in Allentown, Pa. A nonconsecutive series of 9 patients with a BMI of 70 or greater who met traditional criteria for a bariatric procedure. Laparoscopic approach to Roux-en-Y gastric bypass with stapled anastomoses. Patient medical records were reviewed for length of stay, complications, operative time, comorbidities, and weight loss. Seven patients were women and 2 were men. Comorbidities included dyspnea on exertion, peripheral edema, arthritis, sleep apnea, hypertension, diabetes mellitus, asthma, hypothyroidism, gastroesophageal reflux disease, peptic ulcer disease, and heart disease. Eight of 9 procedures were successfully completed laparoscopically. One patient was converted to an open procedure. One patient developed a marginal ulcer postoperatively. No other complications occurred. Operative time ranged from 122 to 330 minutes (mean, 203 minutes). Length of stay averaged 1.2 days. Overall weight loss was 49% of excess body weight at 1 year after surgery. Laparoscopic Roux-en-Y gastric bypass is safe and effective in patients with a BMI of 70 or greater.


An endogenous MDCK lysosomal membrane glycoprotein is targeted basolaterally before delivery to lysosomes.
Using surface immunoprecipitation at 37 degrees C to "catch" the transient apical or basolateral appearance of an endogenous MDCK lysosomal membrane glycoprotein, the AC17 antigen, we demonstrate that the bulk of newly synthesized AC17 antigen is polarly targeted from the Golgi apparatus to the basolateral plasma membrane or early endosomes and is then transported to lysosomes via the endocytic pathway. The AC17 antigen exhibits very similar properties to members of the family of lysosomal-associated membrane glycoproteins (LAMPs). Parallel studies of an avian LAMP, LEP100, transfected into MDCK cells revealed colocalization of the two proteins to lysosomes, identical biosynthetic and degradation rates, and similar low levels of steady-state expression on both the apical (0.8%) and basolateral (2.1%) membranes. After treatment of the cells with chloroquine, newly synthesized AC17 antigen, while still initially targeted basolaterally, appears stably in both the apical and basolateral domains, consistent with the depletion of the AC17 antigen from lysosomes and its recycling in a nonpolar fashion to the cell surface.


Consulting with anxious medical patients. Part II: Diagnostic and therapeutic considerations.
In consulting with anxious medical patients, the psychiatrist needs to consider the possibility of organic disease, differentiate anxiety and depression, and ascertain whether comorbid conditions are present. Guidelines for differential diagnosis are presented. With the anxious patient, treatment goals are to establish rapport, help the patient mobilize intellectual defenses, and enhance self-esteem. Many anxious medical patients will benefit from benzodiazepines, selective serotonin reuptake inhibitors, or doxepin. The therapeutic potential of the consultation is increased by the psychiatrist's meeting with the nursing staff and by a humanistic approach to the patient.


Prevalence of caffeine use in elite athletes following its removal from the World Anti-Doping Agency list of banned substances.
The aim of this investigation was to determine the use of caffeine by athletes after its removal from the World Anti-Doping Agency list. For this purpose, we measured the caffeine concentration in 20 686 urine samples obtained for doping control from 2004 to 2008. We utilized only urine samples obtained after official national and international competitions. Urine caffeine concentration was determined using alkaline extraction followed by gas chromatography-mass spectrometry. The limit of detection (LOD) was set at 0.1 µg·mL(-1). The percentage of urine samples below the LOD was 26.2%; the remaining 73.8% of the urine samples contained caffeine. Most urine samples (67.3%) had urinary caffeine concentrations below 5 µg·mL(-1). Only 0.6% of urine samples exceeded the former threshold for caffeine doping (12 µg·mL(-1)). Triathlon (3.3 ± 2.2 µg·mL(-1)), cycling (2.6 ± 2.0 µg·mL(-1)), and rowing (1.9 ± 1.4 µg·mL(-1)) were the sports with the highest levels of urine caffeine concentration; gymnastics was the sport with the lowest urine caffeine concentration (0.5 ± 0.4 µg·mL(-1)). Older competitors (>30 y) had higher levels of caffeine in their urine than younger competitors (<20 y; p < 0.05); there were no differences between males and females. In conclusion, 3 out of 4 athletes had consumed caffeine before or during sports competition. Nevertheless, only a small proportion of these competitors (0.6%) had a urine caffeine concentration higher than 12 µg·mL(-1). Endurance sports were the disciplines showing the highest urine caffeine excretion after competition.


The impact of circadian phenotype and time since awakening on diurnal performance in athletes.
Circadian rhythms, among other factors, have been shown to regulate key physiological processes involved in athletic performance. Personal best performance of athletes in the evening was confirmed across different sports. Contrary to this view, we identified peak performance times in athletes to be different between human "larks" and "owls" (also called "morningness/eveningness types" or "chronotypes" and referred to as circadian phenotypes in this paper), i.e., individuals with well-documented genetic and physiological differences that result in disparities between their biological clocks and how they entrain to exogenous cues, such as the environmental light/dark cycle and social factors. We found time since entrained awakening to be the major predictor of peak performance times, rather than time of day, as well as significant individual performance variations as large as 26% in the course of a day. Our novel approach combining the use of an athlete-specific chronometric test, longitudinal circadian analysis, and physical performance tests to characterize relevant sleep/wake and performance parameters in athletes allows a comprehensive analysis of the link between the circadian system and diurnal performance variation. We establish that the evaluation of an athlete's personal best performance requires consideration of circadian phenotype, performance evaluation at different times of day, and analysis of performance as a function of time since entrained awakening.


Association of lipoprotein-associated phospholipase A2 mass and activity with coronary and aortic atherosclerosis: findings from the Dallas Heart Study.
Our aim was to characterize the association of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) with coronary and aortic atherosclerosis in a large population-based study. Lp-PLA(2) mass and activity were measured in 2171 subjects 30-65 years old participating in the Dallas Heart Study. We examined the association of Lp-PLA(2) levels with 3 atherosclerosis phenotypes: coronary artery calcium (CAC) measured by electron-beam computed tomography and abdominal aortic plaque (AAP) and aortic wall thickness (AWT) measured by magnetic resonance imaging. CAC and AAP were detected in 21% and 40% of subjects, respectively, and mean AWT (SD) was 1.70 (0.32) mm. In univariable analyses, Lp-PLA(2) mass (but not activity) was higher in both men (P = 0.04) and women (P = 0.02) with detectable CAC. Lp-PLA(2) mass and activity were higher (P = 0.004 and P = 0.01, respectively) and AWT was greater (P < 0.001 and P = 0.02, respectively) in women with aortic atheroma, but not in men. After adjustment for traditional atherosclerosis risk factors and C-reactive protein concentrations, Lp-PLA(2) mass and activity were not associated with AAP or AWT in either sex, but Lp-PLA(2) mass remained modestly associated with detectable CAC only in men (odds ratio 1.20 per 1 standard deviation increase, 95% CI 1.01-1.42, P = 0.04). Although Lp-PLA(2) mass was independently associated with CAC in men, it was not associated with AAP or AWT in men or with any of the atherosclerosis phenotypes in women. These findings suggest that if Lp-PLA(2) independently influences clinical events, it does so by promoting atherosclerotic plaque instability rather than by stimulating atherogenesis.


Extent and severity of myocardial hypoperfusion as predictors of prognosis in patients with suspected coronary artery disease.
The ability of exercise-induced myocardial hypoperfusion on thallium scintigraphy to predict coronary events was assessed in 1,689 patients with symptoms suggestive of coronary artery disease but without prior myocardial infarction or coronary artery bypass surgery. A total of 74 patients had a coronary event in the year after testing (12 cardiac deaths, 20 nonfatal infarctions and 42 referrals for bypass surgery more than 60 days after testing). Stepwise logistic regression identified only three independent predictors: the number of myocardial regions with reversible hypoperfusion (an index of the extent of hypoperfusion), the maximal magnitude of hypoperfusion (an index of the severity of hypoperfusion) and the achieved heart rate (an index of exercise performance). Both extent and severity were exponentially correlated with event rate (r greater than 0.97 and p less than 0.01 for each), whereas achieved heart rate was linearly correlated with event rate (r = 0.79 and p less than 0.05). On the basis of these data, a prognostic model was defined that employs extent and severity as stress-dependent orthogonal variables. Using this model, the predicted coronary event rate ranged over two orders of magnitude--from a low of 0.4% in patients able to exercise adequately without developing severe and extensive hypoperfusion at a low heart rate (less than 85% of their maximal predicted heart rate). Extent and severity of myocardial hypoperfusion, therefore, are important independent variables of prognosis in patients with suspected coronary artery disease.


Optogenetic localization and genetic perturbation of saccade-generating neurons in zebrafish.
The optokinetic response (OKR) to a visual stimulus moving at constant velocity consists of a series of two alternating components, a slow phase, during which the eyes follow the stimulus, and a quick phase, which resets the eyes to begin a new response cycle. The quick phases of the OKR resemble the saccades observed during free viewing. It is unclear to what extent the premotor circuitry underlying these two types of jerky, conjugate eye movements is conserved among vertebrates. Zebrafish (Danio rerio) larvae, broadly expressing halorhodopsin (NpHR) or channelrhodopsin-2 (ChR2) in most neurons, were used to map the location of neurons involved in this behavior. By blocking activity in localized groups of NpHR-expressing neurons with an optic fiber positioned above the head of the fish and by systematically varying the site of photostimulation, we discovered that activity in a small hindbrain area in rhombomere 5 was necessary for saccades to occur. Unilateral block of activity at this site affected behavior in a direction-specific manner. Inhibition of the right side suppressed rightward saccades of both eyes, while leaving leftward saccades unaffected, and vice versa. Photostimulation of this area in ChR2-transgenic fish was sufficient to trigger saccades that were precisely locked to the light pulses. These extra saccades could be induced both during free viewing and during the OKR, and were distinct in their kinetics from eye movements elicited by stimulating the abducens motor neurons. Zebrafish double indemnity (didy) mutants were identified in a chemical mutagenesis screen based on a defect in sustaining saccades during OKR. Positional cloning, molecular analysis, and electrophysiology revealed that the didy mutation disrupts the voltage-gated sodium channel Scn1lab (Nav1.lb). ChR2 photostimulation of the putative hindbrain saccade generator was able to fully reconstitute saccades in the didy mutant. Our studies demonstrate that an optogenetic approach is useful for targeted loss-of-function and gain-of-function manipulations of neural circuitry underlying eye movements in zebrafish and that the saccade-generating circuit in this species shares many of its properties with that in mammals.


Introduction of Positive Charges into Zwitterionic Phospholipid Monolayers Disrupts Water Structure Whereas Negative Charges Enhances It.
The interfacial water structure and phosphate group hydration of 1,2-dioleoyl- sn-glycero-3-phosphatidylcholine monolayers were investigated at air/water interfaces. Both vibrational sum frequency spectroscopy (VSFS) and Langmuir monolayer compression measurements were made. The PC lipids oriented water molecules predominantly through their phosphate-choline (P-N) dipoles and carbonyl moieties. Upon the introduction of low concentrations of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), a positively charged double chain surfactant, the TAP headgroups were attracted to the phosphate moieties on adjacent PC lipids. This attraction caused the monolayers to contract, expelling water molecules that were hydrogen bonded to the phosphate groups. Moreover, amplitude of the OH stretch signal decreased. At higher DOTAP concentrations, the positive charge on the monolayer caused an increase in the area per headgroup and water molecules in the near-surface bulk region became increasingly aligned. Under these latter conditions, the OH stretch amplitude was linearly proportional to the surface potential. By contrast, introducing 1,2-dioleoyl- sn-glycero-3-phosphatidylglycerol, a negatively charged lipid, did not change the area per lipid or the phosphate-water hydrogen bonding network. As the interfacial potential grew more negative, the OH stretch amplitude increased continuously. Significantly, changes in the interfacial water spectrum were independent of the chemistry employed to create the positive or negative interfacial potential. For example, Ca2+ and tetracaine (both positively charged) disrupted the water structure similarly to low DOTAP concentrations, whereas SCN- and ibuprofen (both negatively charged) enhanced the water structure. These results suggest a direct correlation amongst the interfacial water structure, area per lipid, and surface charge density.


A bivalent form of a RBD-specific synthetic antibody effectively neutralizes SARS-CoV-2 variants.
Coronavirus Disease 2019 (COVID-19) pandemic is severely impacting the world, and tremendous efforts have been made to deal with it. Despite many advances in vaccines and therapeutics, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains an intractable challenge. We present a bivalent Receptor Binding Domain (RBD)-specific synthetic antibody, specific for the RBD of wild-type (lineage A), developed from a non-antibody protein scaffold composed of LRR (Leucine-rich repeat) modules through phage display. We further reinforced the unique feature of the synthetic antibody by constructing a tandem dimeric form. The resulting bivalent form showed a broader neutralizing activity against the variants. The in vivo neutralizing efficacy of the bivalent synthetic antibody was confirmed using a human ACE2-expressing mouse model that significantly alleviated viral titer and lung infection. The present approach can be used to develop a synthetic antibody showing a broader neutralizing activity against a multitude of SARS-CoV-2 variants.


Encapsulation of Ibuprofen in CD-MOF and Related Bioavailability Studies.
Although ibuprofen is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs), it exhibits poor solubility in aqueous and physiological environments as a free acid. In order to improve its oral bioavailability and rate of uptake, extensive research into the development of new formulations of ibuprofen has been undertaken, including the use of excipients as well as ibuprofen salts, such as ibuprofen lysinate and ibuprofen, sodium salt. The ultimate goals of these studies are to reduce the time required for maximum uptake of ibuprofen, as this period of time is directly proportional to the rate of onset of analgesic/anti-inflammatory effects, and to increase the half-life of the drug within the body; that is, the duration of action of the effects of the drug. Herein, we present a pharmaceutical cocrystal of ibuprofen and the biocompatible metal-organic framework called CD-MOF. This metal-organic framework (MOF) is based upon γ-cyclodextrin (γ-CD) tori that are coordinated to alkali metal cations (e.g., K+ ions) on both their primary and secondary faces in an alternating manner to form a porous framework built up from (γ-CD)6 cubes. We show that ibuprofen can be incorporated within CD-MOF-1 either by (i) a crystallization process using the potassium salt of ibuprofen as the alkali cation source for production of the MOF or by (ii) absorption and deprotonation of the free-acid, leading to an uptake of 23-26 wt % of ibuprofen within the CD-MOF. In vitro viability studies revealed that the CD-MOF is inherently not affecting the viability of the cells with no IC50 value determined up to a concentration of 100 μM. Bioavailability investigations were conducted on mice, and the ibuprofen/CD-MOF pharmaceutical cocrystal was compared to control samples of the potassium salt of ibuprofen in the presence and absence of γ-CD. From these animal studies, we observed that the ibuprofen/CD-MOF-1 cocrystal exhibits the same rapid uptake of ibuprofen as the ibuprofen potassium salt control sample with a peak plasma concentration observed within 20 min, and the cocrystal has the added benefit of a 100% longer half-life in blood plasma samples and is intrinsically less hygroscopic than the pure salt form.


A rare embryological malformation of brain - Dandy-Walker syndrome - and its association with Kallmann's syndrome.
Dandy-Walker malformation, a rare congenital brain malformation, is described as a triad of cystic dilatation of the fourth ventricle, complete or partial agenesis of the cerebellar vermis, and an enlarged posterior fossa with elevated tentorium. We aimed to report an association of Kallmann's syndrome and Dandy-Walker malformation. A fifteen years old boy was referred to endocrinology department due to delayed puberty. Stages of male genital development according to Marshall and Tanner, was stage G1 and P1 respectively. In the LHRH test, peak LH level was 40th min.:15.3 IU/ml. Peak growth hormone with insulin tolerance test was 14.5 microg/L. Olfactory test revealed light anosmia. With these findings the patient was accepted as isolated gonadotropin deficiency (Kalmann's syndrome). In computed tomography of the brain, cerebellar vermis was found to be hypoplastic and 4th ventricle was large and in posterior fossa broad hypodens area with cerebrospinal fluid density were seen (Dandy-Walker malformation). We reported an association of Kallmann's syndrome and Dandy-Walker malformation. This is second reported case probably.


Validity and reliability of the EQ-5D-5 L in family caregivers of leukemia patients.
This study aimed to test the validity and reliability of the five-level EuroQol five-dimensional (EQ-5D-5 L) instrument in family caregivers (FCs) of leukemia patients in Heilongjiang of China. A cross-sectional survey was conducted on 298 family caregivers (FCs) of leukemia patients from three major cancer centers in the capital city of Heilongjiang province of China. Their dimensional scores of the EQ-5D-5 L were compared with those of the WHOQOL-BREF to test the convergent validity (constructs measuring the same concept) and divergent validity (constructs measuring different concepts) of the EQ-5D-5 L. Repeated surveys were conducted on 271 participants to determine the test-retest reliability of the EQ-5D-5 L. The four physical dimensions (mobility, self-care, usual activities, and pain/discomfort) of the EQ-5D-5 L had moderate or high correlations with the physical health domain of the WHOQOL-BREF, with a correlation coefficient (r) ranging from 0.459 to 0.559. The anxiety/depression dimension of the EQ-5D-5 L had a high correlation (r = 0.667) with the psychological domain of the WHOQOL-BREF. By contrast, lower but still significant physical-to-psychological correlations were found between the two instruments (r ranging from 0.219 to 0.396). In addition, the EQ-5D-5 L dimensional scores showed no or weak correlations with the environment and social domains of the WHOQOL-BREF (r ranging from 0.016 to 0.207). High test-retest reliability (> 0.7) was evident. The Chinese version of the EQ-5D-5 L has satisfactory reliability and validity in FCs of leukemia patients. It can be used to elicit utility of health-related quality of life in FCs of leukemia.


A Comprehensive Oral Preventive Care Protocol for Caring for the Renal Transplant Population.
Candidates and recipients of kidney transplants are at high risk for oral infections due to systemic co-morbidities, and disease and drug-induced immunosuppression. Developing oral infections while on the waiting list can jeopardize candidacy for receiving a kidney, and post-operatively increases the chance for organ rejection. Therefore, it is imperative to minimize oral disease risks in this population. A comprehensive, oral preventive care protocol is presented to guide dental professionals with patient management throughout the process of care. Proper dental and dental hygiene care can help to prevent oral infections, optimize oral health, and enhance overall health and quality of life for the renal transplant population.


Emergent patterns of population genetic structure for a coral reef community.
What shapes variation in genetic structure within a community of codistributed species is a central but difficult question for the field of population genetics. With a focus on the isolated coral reef ecosystem of the Hawaiian Archipelago, we assessed how life history traits influence population genetic structure for 35 reef animals. Despite the archipelago's stepping stone configuration, isolation by distance was the least common type of genetic structure, detected in four species. Regional structuring (i.e. division of sites into genetically and spatially distinct regions) was most common, detected in 20 species and nearly in all endemics and habitat specialists. Seven species displayed chaotic (spatially unordered) structuring, and all were nonendemic generalist species. Chaotic structure also associated with relatively high global FST. Pelagic larval duration (PLD) was not a strong predictor of variation in population structure (R2=0.22), but accounting for higher FST values of chaotic and invertebrate species, compared to regionally structured and fish species, doubled the power of PLD to explain variation in global FST (adjusted R2=0.50). Multivariate correlation of eight species traits to six genetic traits highlighted dispersal ability, taxonomy (i.e. fish vs. invertebrate) and habitat specialization as strongest influences on genetics, but otherwise left much variation in genetic traits unexplained. Considering that the study design controlled for many sampling and geographical factors, the extreme interspecific variation in spatial genetic patterns observed for Hawaìi marine species may be generated by demographic variability due to species-specific abundance and migration patterns and/or seascape and historical factors.


Workplace tobacco policies and smoking cessation practices of physicians.
To further our understanding of the workplace smoking policies and smoking cessation practices of physicians in Nigeria. Cross-sectional survey distributed to 619 physicians practicing in two teaching hospitals in southwestern Nigeria. Three-hundred-seventy-three physicians who returned completed surveys. Physician's self-reported workplace smoking policies, attitudes toward smoking cessation, and use of recommended smoking cessation guidelines/policies. Physicians rated quitting as "extremely important." The majority assessed their patients smoking status over the past three months (81%) and thought counseling smokers would help them quit (95%). However, < 1% prescribed pharmacotherapy for smoking cessation in the last three months. Significant differences were found in the workplace smoking policies of the two teaching hospitals (p < 0.001). Differences were also found in the attitudes and smoking cessation practices of physicians in Hospital A and Hospital B. Physicians are aware of smoking and the importance of quitting but few have guidelines/policies to assist their patients with quitting. Workplace smoking policies appear to impact the smoking cessation attitudes and practices of physicians in Nigeria. Encouraging the adoption of workplace smoking restrictions, as well as training physicians to use recommended smoking cessation interventions, is critical to addressing the tobacco epidemic in Nigeria.


Transcatheter aortic valve implantation versus redo surgery for failing surgical aortic bioprostheses: a multicentre propensity score analysis.
Transcatheter aortic valve implantation for a failing surgical bioprosthesis (TAV-in-SAV) has become an alternative for patients at high risk for redo surgical aortic valve replacement (redo-SAVR). Comparisons between these approaches are non-existent. This study aimed to compare clinical and echocardiographic outcomes of patients undergoing TAV-in-SAV versus redo-SAVR after accounting for baseline differences by propensity score matching. Patients from seven centres in Europe and Canada who had undergone either TAV-in-SAV (n=79) or redo-SAVR (n=126) were identified. Significant independent predictors used for propensity scoring were age, NYHA functional class, number of prior cardiac surgeries, urgent procedure, pulmonary hypertension, and COPD grade. Using a calliper range of ±0.05, a total of 78 well-matched patient pairs were found. All-cause mortality was similar between groups at 30 days (6.4% redo-SAVR vs. 3.9% TAV-in-SAV; p=0.49) and one year (13.1% redo-SAVR vs. 12.3% TAV-in-SAV; p=0.80). Both groups also showed similar incidences of stroke (0% redo-SAVR vs. 1.3% TAV-in-SAV; p=1.0) and new pacemaker implantation (10.3% redo-SAVR vs. 10.3% TAV-in-SAV; p=1.0). The incidence of acute kidney injury requiring dialysis was numerically lower in the TAV-in-SAV group (11.5% redo-SAVR vs. 3.8% TAV-in-SAV; p=0.13). The TAV-in-SAV group had a significantly shorter median total hospital stay (12 days redo-SAVR vs. 9 days TAV-in-SAV; p=0.001). Patients with aortic bioprosthesis failure treated with either redo-SAVR or TAV-in-SAV have similar 30-day and one-year clinical outcomes.


Using area health education centers to promote interest in rural practice.
In the USA, area health education centers (AHECs) work to recruit and educate students to serve in medically underserved communities, primary care, and rural settings. One important aspect of their work is connecting students with rural clinical experiences. Within these experiences, AHECs incorporate a community health/socioeconomic experience within the family medicine clerkship that may not be as prevalent in the standard family medicine clerkship experiences. The purpose of the study was to assess the relationship between AHEC-sponsored family medicine clerkships with a self-reported intent to practice in a rural setting upon graduation. The study compared third-year medical students with the Indiana University School of Medicine, which participated in AHEC-sponsored family medicine clerkships to the standard family medicine clerkship. Following the 4-week clerkship, students were asked to report their intent to work in a rural setting using a five-point Likert scale. A χ2 test was used to determine the association of AHEC sponsorship, clerkship site location (rural/urban) and intent to practice in a rural setting. The study consisted of 587 students. There was a statistically significant association between self-reported intent and rural clerkship site, χ2 (1, N=587)=6.542, p=0.01. Furthermore, 21.6% (n=25) of students with a rural clerkship experience reported a greater intent compared to 12.3% (n=58) of students with non-rural clerkship experience. The study confirmed a significantly positive association between participation in medical clerkship experiences in a rural primary care setting and the intent to practice in a rural setting upon graduation. The results also support the potential value-added benefits through academic-community partnerships with AHECs, family medical and other primary care specialty clerkship programs may perhaps succeed in increasing student interest in pursuing a practice serving in rural communities upon graduation.


Association of acculturation levels and prevalence of diabetes in the multi-ethnic study of atherosclerosis (MESA).
The prevalence of type 2 diabetes among Hispanic and Asian Americans is increasing. These groups are largely comprised of immigrants who may be undergoing behavioral and lifestyle changes associated with development of diabetes. We studied the association between acculturation and diabetes in a population sample of 708 Mexican-origin Hispanics, 547 non-Mexican-origin Hispanics, and 737 Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes was defined as fasting glucose >/=126 mg/dl and/or use of antidiabetic medications. An acculturation score was calculated for all participants using nativity, years living in the U.S., and language spoken at home. The score ranged from 0 to 5 (0 = least acculturated and 5 = most acculturated). Relative risk regression was used to estimate the association between acculturation and diabetes. For non-Mexican-origin Hispanics, the prevalence of diabetes was positively associated with acculturation score, after adjustment for sociodemographics. The prevalence of diabetes was significantly higher among the most acculturated versus the least acculturated non-Mexican-origin Hispanics (prevalence ratio 2.49 [95% CI 1.14-5.44]); the higher the acculturation score is, the higher the prevalence of diabetes (P for trend 0.059). This relationship between acculturation and diabetes was partly attenuated after adjustment for BMI or diet. Diabetes prevalence was not related to acculturation among Chinese or Mexican-origin Hispanics. Among non-Mexican-origin Hispanics in MESA, greater acculturation is associated with higher diabetes prevalence. The relation is at least partly mediated by BMI and diet. Acculturation is a factor that should be considered when predictors of diabetes in racial/ethnic groups are examined.


Convenience of work and the job constraint of children.
This paper investigates whether convenient working conditions reduce the constraint of children on married women working. It is assumed that convenient working conditions are most important for women with heavy child-care responsibilities. Therefore, differentials in participation rates, by presence and age of children, are expected to be less pronounced in those occupations where a high proportion of jobs have convenient working conditions. Data are selected from the 1960 1/1000 Public Use Sample of the United States population. Those studied comprise white married women living with their husbands. The paper involves a comparison of differential participation rates of women by presence of children, between occupations grouped according to measures of convenience, using a multivariate analysis. The results indicate that differentials are least pronounced in those occupational groupings which have the highest percentage of convenience factors.


Continuous absorbable vs interrupted nonabsorbable fascial closure. A prospective, randomized comparison.
A prospective, randomized comparison of continuous, absorbable, No. 2, coated, polyglycolic acid suture (Dexon-Plus) vs interrupted, nonabsorbable, No. 28 monofilament stainless steel wire suture was performed in 105 patients for midline fascial closure following gastric surgery for morbid obesity. The preoperative weight, sex distribution, and type of operation were not significantly different between the two groups. No significant difference was found in the wound complication rate between the two closure methods (7/54 for wire and 8/51 for polyglycolic acid). There were one dehiscence and five incisional hernias in the wire group and five hernias in the polyglycolic acid group. Continuous closure was accomplished in significantly less time (21 +/- 8 minutes) than interrupted closure (43 +/- 19 minutes). An additional 121 patients underwent continuous No. 2 polyglycolic acid fascial closure after the end of the randomized trial, with 13 wound complications, including ten incisional hernias. In conclusion, continuous, absorbable suture closure for laparotomy wounds is recommended for its economy of time and the lack of significant difference from an interrupted, nonabsorbable wound closure.


Child Sexual Abuse and Adult Mental Health, Sexual Risk Behaviors, and Drinking Patterns Among Latino Men Who Have Sex With Men.
One in five Latino men who have sex with men has experienced child sexual abuse. Although concerning in itself, child sexual abuse may increase an individuals' likelihood of depression and risk-taking in adult life, including engagement in HIV risk behaviors and alcohol and substance use. It is therefore urgent that researchers and practitioners better understand the long-term effects of child sexual abuse. We utilized logistic and linear regression to assess associations between child sexual abuse (operationalized as forced or coerced sexual activity before age 17) and depression, sexual behaviors, and drinking patterns in a sample of 176 adult Latino men who have sex with men from New York City. Over one-fifth (22%) of participants reported child sexual abuse. In multivariable models, participants with histories of child sexual abuse were significantly more likely than participants without such histories to screen for clinically significant depressive symptoms and heavy drinking and reported more anal sex acts, male sexual partners, and incidents of condomless anal intercourse in the previous three months. These findings confirm a high prevalence of child sexual abuse among Latino men who have sex with men and associations between child sexual abuse and adulthood depressive symptoms, high-risk alcohol consumption, and sexual risk behaviors. We recommend that providers who serve Latino men who have sex with men incorporate child sexual abuse screenings into mental health, HIV prevention, and substance use treatment programs, utilizing approaches that are inclusive of resilience.


Effect of menopause on hormonal receptors in ampullae of the fallopian tube with a special reference to the p53 signature.
Age-related changes in the expression of hormonal receptors have not been well examined in the fallopian tube (FT). We herein report the effect of menopause on the hormone receptors in ampullae of the FTs (AFTs), in comparison with cortical inclusion cysts (CICs) of the ovary. A total of 84 AFTs and 16 fimbriae of FTs, which were obtained from 26 premenopausal and 58 postmenopausal women; and 27 postmenopausal CICs were immunohistochemically studied for the expression of p53, Ki-67, estrogen receptor-alpha (ER-α), and progesterone receptor A (PRA). Apoptotic cells were identified using a TUNEL assay. Postmenopausal AFTs showed a significantly lower labeling index (LI) for Ki-67 (P<0.001), apoptosis (P=0.03), and PRA (P<0.001) than premenopausal AFTs. No significant correlation with immunohistochemical markers was found in premenopausal AFTs, but the LI for PRA was positively correlated with that for Ki-67 (P=0.004) and inversely with that for p53 (P=0.023) in postmenopausal AFTs. The expression of immunohistochemical markers was closely correlated between ampullae and fimbriae of the FT. The p53 signature (p53S) was detected in five postmenopausal AFTs (mean age: 70.2 years) and was not detected in any CICs. The immunohistochemical profile of p53S was low expression of Ki-67, apoptosis, and PRA, and high expression of ER-α. The expression of PRA in CICs was significantly higher than that in AFTs (P=0.001). The expression of PRA was significantly lower in postmenopausal AFTs than in premenopausal AFTs, whereas the expression of PRA was well preserved in postmenopausal CICs.


Structure and dynamics of gold nanoparticles decorated with chitosan-gentamicin conjugates: ReaxFF molecular dynamics simulations to disclose drug delivery.
With the aim of designing an efficient procedure for producing biocompatible drug delivery systems based on nanoparticle carriers for in situ controlled antibiotic release, we have defined a novel computational approach resorting to a reactive force field capable of realistically describing hybrid systems. The modeling procedure was focused on well-known components, namely gold nanoparticles, citrate, chitosan and gentamicin, and the experiments tuned on purpose. On the one hand, gold nanoparticles were synthesized, fuctionalized with chitosan, loaded with gentamicin and characterized by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), UV-visible (UV-vis) spectroscopy, and Fourier transform infrared spectroscopy (FTIR). On the other hand, an effective model of a functionalized gold nanoparticle was created and its structure and dynamics were explored by classical reactive molecular dynamics simulations in solution based on the ReaxFF atomistic description. The structure, dynamics and drug release were reproduced realistically disclosing the motion of all the molecular components, their adsorption on the metal support, desorption, intermolecular interactions and self-assembly. The system size was very close to the experimental conditions and all the calculations could efficiently identify the most probable binding modes, the locations of the adsorbed molecules, the characteristic arrangements of the chains and the effects due to the surrounding environment. The role played by the substrate and water molecules in the releasing process was described in detail. In line with the literature it was found that the antibiotic activity was preserved and the drug release from the carrier could be tuned by changing the chitosan/getamicin weight ratio and the deposition pattern of the adsorbed layers.


Ceramide-containing liposomes with doxorubicin: time and cell-dependent effect of C6 and C12 ceramide.
Doxorubicin, a widely used chemotherapeutic drug, has several potential high-risk side effects including cardiomyopathy. Furthermore, cellular resistance to this drug develops with time. By using liposomes as carrier vesicles both the side effects and drug resistance might be avoided. In this study we have investigated the cytotoxic effect of doxorubicin encapsulated in liposomes with and without ceramides containing 6 or 12 carbon atoms in the N-amidated fatty acyl chains. The short-chain ceramide species were included in the liposomal compositions due to their pro-apoptotic properties, which might cause a synergistic anticancer effect. We demonstrate that the ceramide species enhance the liposomal doxorubicin toxicity in a cell-specific manner. The C6-ceramide effect is most pronounced in cervical cancer cells (HeLa) and colon cancer cells (HCT116), whereas the C12-ceramide effect is strongest in breast cancer cells (MDA-MB-231). Moreover, the study reveals the importance of investigating cell toxicity at several time points and in different cell-lines, to assess drug-and formulation-induced cytotoxic effects in vitro. Furthermore, our data show that the cytotoxicity obtained with the nanocarriers in vitro, does not necessarily reflect their ability to inhibit tumor growth in vivo. We speculate that the larger effect of Caelyx® than our liposomes in vivo is due to a greater in vivo stability of Caelyx®.


Induction of extracellular proteinase in Candida albicans.
Pulse-chase experiments indicated that the extracellular proteinase (EPR) of Candida albicans originates as a 45 kDa precursor protein which is processed to a 43 kDa protein prior to secretion. Secretion was routinely stimulated in EPR induction medium which contains bovine serum albumin (BSA) and glucose. Although EPR was not induced without glucose as a carbon source, EPR secretion was induced without the addition of BSA or other nitrogen sources. Furthermore, it was shown that EPR production was not induced at pH > 6.0, irrespective of the presence of a nitrogen source. This suggests that medium pH may act directly upon EPR induction, and not as a secondary effect of the nitrogen supply from EPR-mediated protein digestion, which exhibited a pH optimum of around pH 3.5. When germ tube induced cells were transferred to EPR induction medium, EPR was not induced. Thus, EPR production and germ tube formation may not be induced by the same conditions. We speculate that EPR production and germ tube formation do not co-operate in the invasive process but play different and separate roles.


Spine configuration associated with various sleep surfaces.
The effects of various types of sleepware on the changes in spinal shape were investigated. Since any departure in the shape of the spine from its natural erect position causes tension in the lower back muscles, the study concentrated on changes in the spinal shape associated with subjects in a supine position on the sleepware. Since the subjects' spines were not visually exposed, indirect measurements were made by means of a sonic echoing device. The shape of the spine was determined for each subject by combining the data taken from the erect position and the data from the supine position. Results for a selected group of subjects are presented and discussed.


Efficacy of four commercially available multivalent modified-live virus vaccines against clinical disease, viremia, and viral shedding in early-weaned beef calves exposed simultaneously to cattle persistently infected with bovine viral diarrhea virus and cattle acutely infected with bovine herpesvirus 1.
To evaluate the efficacy of 4 commercially available multivalent modified-live virus vaccines against clinical disease, viremia, and viral shedding caused by bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BHV1) in early-weaned beef calves. 54 early-weaned beef steers (median age, 95 days). Calves were randomly assigned to 1 of 5 groups and administered PBSS (group A [control]; n = 11) or 1 of 4 commercially available modified-live virus vaccines that contained antigens against BHV1, BVDV types 1 (BVDV1) and 2 (BVDV2), parainfluenza type 3 virus, and bovine respiratory syncytial virus (groups B [11], C [10], D [11], and E [11]). Forty-five days after vaccination, calves were exposed simultaneously to 6 cattle persistently infected with BVDV and 8 calves acutely infected with BHV1 for 28 days (challenge exposure). For each calf, serum antibody titers against BVDV and BHV1 were determined before vaccination and before and after challenge exposure. Virus isolation was performed on nasal secretions, serum, and WBCs at predetermined times during the 28-day challenge exposure. None of the calves developed severe clinical disease or died. Mean serum anti-BHV1 antibody titers did not differ significantly among the treatment groups at any time and gradually declined during the study. Mean serum anti-BVDV antibody titers appeared to be negatively associated with the incidence of viremia and BVDV shedding. The unvaccinated group (A) had the lowest mean serum anti-BVDV antibody titers. The mean serum anti-BVDV antibody titers for group D were generally lower than those for groups B, C, and E. Results indicated differences in vaccine efficacy for the prevention of BVDV viremia and shedding in early-weaned beef calves.


Dialogues on mixed-methods and mental health services research: anticipating challenges, building solutions.
Increasingly, contemporary mental health services research projects aim to combine qualitative and quantitative components. Yet researchers often lack theoretical and practical guidance for undertaking such studies. In September 2006 the authors convened under the auspices of the National Institute of Mental Health at a working conference, "Mixed Methods in Community-Based Mental Health Services Research." This meeting provided the opportunity for participants to share their experiences in conducting mixed-methods research, to critically consider problems they had encountered and their solutions, and to develop guiding principles for others conducting similar research. The authors' discussions, which are described in this article, emphasize that the problems encountered by mixed-methods research teams are rarely simple misunderstandings but often reflect epistemological differences that are overlooked in the study planning phases. Failure to acknowledge these different worldviews may result in significant tensions between members of the study team, use of qualitative methods that are insufficient or inappropriate for a particular research question, or serious conflicts when team members belatedly discover they are interpreting key concepts -- or each other's research techniques -- differently. The authors conclude that ongoing communication is the organizing principle for robust and effective mixed-methods research. Among the recommendations for preventing problems are collaboration between quantitative and qualitative researchers during the study design phase; open acknowledgement of the philosophical approaches brought to the study by various team members; and because not all challenges can be anticipated, a shared willingness to negotiate emerging problems.


Difference Matters: Teaching Students a Contextual Theory of Difference Can Help Them Succeed.
Today's increasingly diverse and divided world requires the ability to understand and navigate across social-group differences. We propose that interventions that teach students about these differences can not only improve all students' intergroup skills but also help disadvantaged students succeed in school. Drawing on interdisciplinary research, this article theorizes that teaching students a contextual understanding of difference can accomplish both of these important goals. Understanding difference as contextual means recognizing that social-group differences come from participating in and adapting to diverse sociocultural contexts. This article begins by reviewing research that highlights two distinct understandings of social-group differences-as contextual or essential-and demonstrates their consequences for intergroup outcomes. We then review research on multicultural and social justice education that highlights the potential benefits of educating students about social-group differences. We propose that these educational approaches are associated with intergroup and academic benefits for one key reason: They teach students a contextual theory of difference. Finally, to illustrate and provide causal evidence for our theory of how a contextual understanding of difference affords these benefits, this article provides an overview of the first social psychological intervention to teach students a contextual understanding of difference: difference-education.


[Morphologic manifestations of the preclinical stage of diabetic nephropathy].
Kidney biopsies from 10 patients with diagnosed insulin-dependent diabetes mellitus of various duration with clinical manifestations of hyperglycemia, increased rate of glomerular filtration, presence or absence of microalbuminuria, were studied morphologically. Gradual increase of kidney alterations was observed: changes of thickness and loosening of basal membrane of glomerular capillaries, its focal homogenization, partial mesangium increase due to the increase of membranous substance and decrease of cellular component. These alterations positively correlate with immunohistochemistry of renal glomeruli. Dynamics of morphological changes does not show a direct connection with the patient age and the duration of diagnosed disease but is stipulated by the presence of one or another antigen of the class II major histocompatibility complex.


Does employee resistance during a robbery increase the risk of customer injury?
Retail business robberies can lead to employee and customer injury. Previous work demonstrates that employee resistance increases employee injury risk; limited research has investigated customer injuries. This study examines associations between employee resistance against perpetrators and the risk of customer injury. Retail and service robbery reports were obtained from a metropolitan police department. Generalized estimating equations estimated risk ratios and 95% confidence intervals (CIs). Customers were injured in 75 out of 697 robberies. Employees resisted the perpetrator in 32 out of 697 robberies. Customers had higher injury risk when employees resisted the perpetrator, compared with robberies where employees did not resist (adjusted risk ratio [95% CI], 2.6 [1.5 to 4.5]). Employee resistance against a perpetrator during a robbery increased customer injury risk. Businesses can train employees to not resist during a robbery, providing benefits for both customers and the business itself.


Downstream events in mammary gland morphogenesis mediated by reexpression of the alpha2beta1 integrin: the role of the alpha6 and beta4 integrin subunits.
Our previous studies demonstrated that reexpression of the alpha2beta1 integrin by a poorly differentiated breast carcinoma cell line, Mm5MT, resulted in dramatic reversion of a malignant phenotype to a differentiated epithelial phenotype. We hypothesized that reexpression of the alpha2beta1 integrin may regulate expression of other genes, the expression of which contributed to the dramatic phenotypic change. We now show that reexpression of the alpha2beta1 integrin results in up-regulation of both the alpha6 and beta4 integrin subunits but no change in the alpha1, alpha3, alpha5, or beta1 integrin subunits or E-cadherin. To further investigate the role of the alpha6 and beta4 integrin subunits in mediating the phenotypic changes elicited by reexpression of the alpha2beta1 integrin, the alpha6 or beta4 integrin subunit was expressed in our Mm5MT model. Expression of either subunit increased adhesion to laminin-1. Although adhesion to collagen was unaltered, contraction of three-dimensional collagen gels was reduced. Expression of either the alpha6 or beta4 integrin subunit also restored some aspects of a less malignant phenotype, including the acquisition of contact inhibition and diminution of anchorage-dependent and anchorage-independent growth rates. The alpha6 and beta4 transfectants formed three-dimensional organized structures when grown in gels of reconstituted basement membrane but did not form the highly branched, duct-like structures formed by the alpha2 transfectants. In contrast to the reduced invasiveness of the alpha2 transfectants, the alpha6 and beta4 transfectants retained an invasive phenotype. These results suggest that expression of the alpha6beta4 integrin contributes to some but not all of the phenotypic changes elicited by reexpression of the alpha2 integrin subunit and modulates the function of other integrins on these cells. Using our Mm5MT model, we are defining the cascade of integrin expression required for maintenance of the differentiated mammary epithelial cell phenotype.


Genetics of cardiac arrhythmias.
Continued research into the identification of mutated genes that cause inherited arrhythmogenic diseases has helped forward understanding into their pathophysiology. Over the last two decades the progress that has been made in the realm of genetic arrhythmias has made it possible not only for symptomatic patients to improve their outcomes, but also family members to better understand their risks and allow them in conjunction with their care providers to make the best decisions for their care. With this continued progress, significant changes will continue to occur in clinical practice. The advances in technology coupled with the improving understanding of genetically determined arrhythmias assists in earlier recognition of potentially fatal diseases, which leads to earlier implementation of treatment. It is the aim of this article to abridge the current knowledge of the genetic background of inherited arrhythmogenic diseases, namely long QT syndrome, short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia. Pathogenesis and genotype-phenotype correlations are also discussed.