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Food allergy is related to increasing risk of the development of allergic asthma, but the precise interplay between sensitization to different allergens in different compartments of the body is not fully understood. The aim of this study was to develop a novel humanized murine model of mixed food and respiratory allergy that recapitulates the human anaphylactic response and to more clearly understand the impact of food allergies on asthma. Immunodeficient mice transferred with peripheral blood mononuclear cells (PBMCs) from donors with peanut and house dust mite (HDM) allergy were exposed and challenged to peanut. Between peanut exposure and challenge, mice were intranasally treated to HDM. Allergic parameters were analyzed. Allergen-specific immunoglobulin (Ig)E in sera could only be measured in mice treated with peripheral blood mononuclear cells (PBMCs) plus allergen. A preceding peanut exposure increased IgE levels, histamine release, bronchial hyper-responsiveness and lung inflammation. Recruitment of inflammatory cells to the airways was aggravated associated with an enhanced T helper type 2 (Th2)/Th17 cytokine secretion when the two allergies were present. A preceding peanut exposure amplifies allergic asthma in this humanized model, which may contribute to the understanding of underlying immunological mechanism of polysensitization occurring in allergic individuals and evaluation of therapeutic interventions.

The association of brain malformations and symptomatic epilepsy in the setting of neurofibromatosis type 1 (NF1) is rarely reported. When it occurs, patients can present clinically with infantile spasms, focal seizures, generalized tonic clonic seizures or atypical absences. We report on a 10-year-old (molecularly proven) NF1 girl manifesting a complex epileptic syndrome resembling the Foix-Chavany-Marie spectrum (also known as opercular syndrome) associated with bilateral (opercular and paracentral lobular) polymicrogyria (PMG). Anecdotal cases of unilateral PMG in the setting of NF1 have been described in association with other-than-opercular epileptic syndromes. The typical clinical opercular syndrome consisting in mild mental retardation, epilepsy and pseudobulbar palsy is usually associated to bilateral perisylvian PMG (BPP) CONCLUSION: To the best of our knowledge, the complex epileptic syndrome hereby reported has not been previously recorded in the setting of NF1. In addition, the present girl manifested all the clinical features of an opercular syndrome but had an asymmetrical PMG (not a BPP).

Salivary glands are essential structures in the oral cavity. A variety of diseases, such as cancer, autoimmune diseases, infections and physical traumas, can alter the functionality of these glands, greatly impacting the quality of life of patients. To date, no definitive therapeutic approach can compensate the impairment of salivary glands, and treatment are purely symptomatic. Understanding the cellular and molecular control of salivary glands function is, therefore, highly relevant for therapeutic purposes. In this review, we provide a starting platform for future studies in basic biology and clinical research, reporting classical ideas on salivary gland physiology and recently developed technology to guide regeneration, reconstruction and substitution of the functional organs.

An atrial detector electrode was introduced by mediastinoscopy in 82 patients requiring permanent cardiac pacing. There were no complications. An adequate P wave was recorded in 80 patients. During the following week, the P wave became ineffective in 5 patients; angina occurred in 2 and atrial arrhythmias in 2. Atrially triggered ventricular pacing established in 73 patients and was followed in 71 patients for a period of 1 to 113 months. In 17 cases, it had to be terminated because of an ineffective or unstable P wave,in 6 cases because of atrial arrhythmias, and in 4 cases because of advanced age and recurrent infections. The method is technically simple and place little stress on the patient.

Total knee arthroplasty (TKA) is an effective procedure for relieving pain and restoring function in osteoarthritis, with a significant proportion of patients having severe disease bilaterally. However, although there are differences in patient selection criteria for bilateral procedures, there is no consensus regarding the optimal timing for bilateral TKA. The aim of this study was to compare rates and causes of revision and 30-day mortality between simultaneous and staged bilateral TKA using data from the Australian Orthopaedic Association National Joint Replacement Registry.

Quality underlies diverse efforts to repair the troubled health care system, yet the many abstract definitions offered are not particularly useful. A better approach is to evaluate quality in an applied or situational context. This article offers six propositions that establish such a context and explain why the current health care environment is so volatile. Some parallels between health care and the emerging field of science called chaos theory are drawn as a possible future basis for recognizing order in the health care system.

The conservative approach in the treatment of maxillofacial trauma in children has been widely adopted. The type of fracture and its presence within the growing facial skeleton along with the presence of tooth buds may result in different management strategies to that employed in adults. An understanding of conservative treatment options is essential to make informed choices which will best manage these injuries, and an example is presented in this paper. This case report describes a 14-year-old boy who sustained trauma to the chin as a result of a fall, causing a mandibular symphyseal fracture. He was successfully treated by the means of applying direct interdental wiring combined with an acrylic splint.

The aim of the study was to improve the pre-operative diagnosis of mammary mucinous lesions. All mucinous lesions detected by fine needle aspiration (FNA) and confirmed by histological examination were reviewed by cytological findings, mammographic appearances and sonographic findings. Twenty aspirates had corresponding pathology, including 12 mucinous carcinomas, two mucocele-like lesions (MLL) with atypical ductal hyperplasia, three MLL with ductal hyperplasia and three simple MLL. Simple MLL and mucocele-like with ductal hyperplasia showed scant cellularity, no or rare intact single tumour cells, monolayered arrangement and absence of nuclear atypia. In contrast, most mucinous carcinomas showed higher cellularity, more single tumour cells, three-dimensional clusters, and mild to marked nuclear atypia. However, MLL with atypical ductal hyperplasia showed cytological features overlapping with mucinous carcinoma. MLL had a non-specific mammographic appearance and showed a cystic lesion on sonography. Mucinous carcinoma appeared as a solid mass on sonography and as a distinct nodule on mammography. Based on the combination of FNA cytology and image findings, benign MLL can be correctly distinguished from mucinous carcinoma before surgery.

Women aged 45-64 in 78 general practices in the city of Edinburgh were followed up for five to seven years and all cause mortality noted. Standardised mortality ratios were calculated for the individual practices. Postcodes were available for a 20% sample of these women and were used to retrieve relevant measures of social class and deprivation from the 1981 census for the smallest division, the enumeration district. Weighted averages gave socioeconomic variables at the level of the general practice. High positive correlations were found between standardised mortality ratios and the socioeconomic variables, with the highest being for percentage overcrowding. This study established that the relation between deprivation and excess mortality can be shown in general practices in one large city and gave a direct relation for women without reference to their husbands' occupations, thus obviating problems of assigning social class. The data also partially refute the "social drift" hypothesis as an explanation of the association between mortality and social class.

We have previously shown a marked diurnal variation in the excretion of cortisol and 6 beta-hydroxycortisol at 36-38 weeks pregnancy with no variation in estrogen excretion. Since others have shown a reciprocal relationship between plasma levels of estriol and cortisol at 30-35 weeks of pregnancy, we decided to determine whether a similar relationship was present in urinary concentrations of cortisol, 6 beta-hydroxycortisol and estriol at this gestational age. A significant variation in excretion of both cortisol and 6 beta-hydroxycortisol was found. The variation in urinary levels of estriol was less than that of the corticosteroids but followed the same pattern.

In the racemic title compound, C16H14O3, the ring of the 4-hy-droxy-benzyl substituent group forms a dihedral angle of 80.12 (12)° with the benzene ring of the chromanone system. Two C atoms of the pyran-one ring and the H atoms on the benzyl α-C atom are disordered over two sites, with site-occupation factors of 0.818 (8) and 0.182 (8). The crystal structure is stabilized by O-H⋯O hydrogen bonds, which form parallel one-dimensional zigzag chains down the c axis and are inter-connected by both methine C-H⋯O hydrogen bonds and weak aromatic C-H⋯π inter-actions, giving a sheet structure lying parallel to [011].

Neutrophils accumulate in many types of human and murine tumors and represent a significant portion of tumor-infiltrating myeloid cells. Our current understanding of the role of neutrophils in tumor development has depended primarily on murine models of cancer. However, there are crucial species differences in the evolution of tumors, genetic diversity, immune and inflammatory responses, and intrinsic biology of neutrophils that might have a profound impact on the tumor development and function of neutrophils in mouse versus human tumors. To date, the majority of experimental approaches to study neutrophils in cancer patients have been limited to the examination of circulating blood neutrophils. The phenotype and function of tumor-associated neutrophils (TANs) in humans, particularly in the early stages of tumor development, have not been extensively investigated. Thus, the long-term goal of our work has been to characterize human TANs and determine their specific role in tumor development. Here, we summarize our findings on human TANs obtained from human early stage lung cancer patients. We will describe the phenotypes of different TAN subsets identified in early stage lung tumors, as well as their functional dialog with T cells.

We describe a multiple alignment program named MAP2 based on a generalized pairwise global alignment algorithm for handling long, different intergenic and intragenic regions in genomic sequences. The MAP2 program produces an ordered list of local multiple alignments of similar regions among sequences, where different regions between local alignments are indicated by reporting only similar regions. We propose two similarity measures for the evaluation of the performance of MAP2 and existing multiple alignment programs. Experimental results produced by MAP2 on four real sets of orthologous genomic sequences show that MAP2 rarely missed a block of transitively similar regions and that MAP2 never produced a block of regions that are not transitively similar. Experimental results by MAP2 on six simulated data sets show that MAP2 found the boundaries between similar and different regions precisely. This feature is useful for finding conserved functional elements in genomic sequences. The MAP2 program is freely available in source code form at http://bioinformatics.iastate.edu/aat/sas.html for academic use.

We review the scientific evidence concerning the relation between power and social information processing. Does having or obtaining power affect how we perceive and judge our social interaction partners and how accurately we do this? High power individuals perceive others as more agentic and tend to project characteristics of themselves onto others. People in power tend to stereotype others more and see them as less human and generally in a more negative way. Powerholders are not more or less accurate in assessing others; rather, the way they understand their power (as responsibility or opportunity) seems to make the difference: Power as responsibility results in better interpersonal accuracy. Our analysis shows that it is not so much being high or low in power that explains how we perceive others, but rather how we understand our power, whether our high power position is stable, and what our current interaction goals are.

New molecular approaches are rapidly yielding information about the composition of bone marrow and culture studies suggest possible functions for many molecules in that organ. However, the marrow is extraordinarily complex with respect to interactions between cells and their behaviour may not be adequately modeled in culture. It is becoming apparent that post-translational modifications and function of proteins can be highly influenced by the cellular and extracellular environment. Therefore, in vivo studies will continue to be important for understanding this remarkable organ.

A new and convenient spectroscopic method for measuring monovalent cation flux in cells is described. The technique is based on fluorescence quenching of an entrapped fluorophore (anthracene-1,5-dicarboxylic acid) by Cs+. A conventional fluorescence microscope can be used to measure the Cs+ flux. The usefulness of the technique is illustrated by measurement of acetylcholine receptor-mediated Cs+ flux in PC-12 cells, a sympathetic neuronal cell line. The results are the same as those obtained when radioactive tracer ions were used. The technique is applicable to any transmembrane process in which Cs+ can substitute for either Na+ or K+. The method has been developed to identify the different neurotransmitter receptors that control the translocation of monovalent cations and to locate the cells in central nervous system cell preparations that contain these receptors. The advantage of an optical method over tracer ion methods for biochemical and pharmacological studies of transmembrane processes in cells is described.

Head-down tilted bedrest is a ground-based microgravity simulation model. Since in this position the influence of chief external determinants of circadian blood pressure variation, i.e. activity and posture, are reduced, it may reveal endogenous oscillatory factors. The effects of 42 days of 6 degrees head-down tilt on the circadian profiles of continuous finger blood pressure, heart rate, stroke volume, cardiac output and total peripheral resistance were analysed. In seven healthy volunteers (25-31 years) twelve 22 h Portapres registrations were performed: two in an ambulatory baseline period, eight during 42 days of head-down tilt, and two during recovery. Stroke volume was estimated by a pulse contour method ('Modelflow') from the finger arterial blood pressure tracing. Head-down tilt rapidly reduced circadian BP variation, especially for diastolic blood pressure. No effect of long-term head-down tilt on blood pressure level was observed. The day-night difference in heart rate was essentially unaffected. Cardiac output was maintained through an increase of heart rate and simultaneous decline of stroke volume. Our observations confirm the overriding importance of physical activity and orthostatic load on the diurnal variation of BP. The time-frame of the changes in stroke volume and heart rate during head-down tilt might point to a contribution of other factors besides a reduction of circulating blood volume affecting cardiovascular performance under these conditions.

Etodolac, a new anti-inflammatory analgesic drug found to be effective in treating arthritis in a dose range of 100 to 300 mg bid, has been shown to induce significantly less gastrointestinal microbleeding in normal men than several other NSAIDs. In this study, the effect on gastrointestinal blood loss of high-dose etodolac, 300 and 500 mg bid, versus piroxicam at its normal therapeutic dose of 20 mg qd, was investigated by the 51Cr method in 23 men with osteo- or rheumatoid arthritis. Placebo periods preceded and followed 28 days of active drug treatment. Blood and stool analyses were performed by an analyst not aware of drug assignment or study design. Patients receiving piroxicam, but not those receiving either dose of etodolac, had a significantly higher mean level of fecal blood loss in the active treatment phase compared with the pretreatment placebo level (p less than 0.01). Further, microbleeding was significantly greater for the piroxicam group during treatment than for either of the etodolac groups (p less than 0.01). There were no significant differences in fecal blood loss between the two groups receiving etodolac compared with pretreatment. Even at doses two to three times those found effective in the treatment of arthritis, etodolac produces no increase in fecal blood loss, in contrast to blood loss seen with the recommended dose of piroxicam. Fecal blood loss in osteoarthritic patients, not receiving an NSAID, was similar to normal subjects in previous studies.

Quercetin, the major flavonol found in several fruits and vegetables, is a natural antioxidant with potential anticancer and antiaging activities. In this paper, the effect of quercetin in Sacharomyces cerevisiae cells submitted to oxidative stress was studied. Hydrogen peroxide resistance increased in cells pretreated with quercetin. Cellular protection was correlated with a decrease in oxidative stress markers, namely, levels of reactive oxygen species, glutathione oxidation, protein carbonylation, and lipid peroxidation. The acquisition of H2O2 resistance was not associated with the induction of antioxidant defenses or with iron chelation. Oxidative stress is a limiting factor for longevity. In agreement, quercetin also increased 60% chronological life span. These results support the utilization of yeast as a useful model to screen in vivo for natural antioxidants with putative health beneficial effects.

Micro- and nanopatterning of metal oxide materials is an important process to develop electronic or optoelectronic devices. ZnO is a material of choice for its semiconducting and photoluminescence properties. In the frame of the nanoarchitectonics concept, we have developed and investigated a new process that relies on direct writing laser patterning in the Deep-UV (DUV) range to prepare photoluminescent microstructures of ZnO at room temperature, under air. This process is based on a synthesis of colloidal ZnO nanocrystals (NCs) with a careful choice of the ligands on the surface to obtain an optimal (i) stability of the colloids, (ii) redissolution of the non-insolated parts and (iii) cross-linking of the DUV-insolated parts. The mechanisms of photocrosslinking are studied by different spectroscopic methods. This room temperature process preserves the photoluminescence properties of the NCs and the wavelength used in DUV allows to reach a sub-micrometer resolution, which opens new perspectives for the integration of microstructures on flexible substrates for optoelectronic applications.

The occurrence of large taurine pool sizes in the crystalline lens was further elucidated by studying the in vitro synthesis and uptake of taurine in the rat lens. It was observed that a time- and concentration-dependent synthesis of taurine from methionine occurred in the rat lens. The time curve for uptake was linear up to 4 hr and was not saturated up to 40 mM concentration of taurine. The uptake was inhibited by ouabain, cyanide, Ca2+, GTP and cGMP but was not affected by ATP and cAMP. It is suggested that a dual mechanism exists for maintenance of high concentrations of taurine in the lens. Moreover, the uptake mechanism is energy-dependent.

Hypertension detection and follow-up programs have recently received increased attention. The authors studied the effect of screening for hypertension in a geriatric screening program for a large ambulatory elderly population in Dunedin, Florida, over a three-year period. Of the 4,247 participants initially screened, 39 percent had some form of hypertension, and 15.6 percent of these had not received any form of treatment. At the time of the first year follow-up, the proportion of participants with treated, controlled hypertension had increased from 14.7 to 21 percent. These data lend support to the value of hypertension screening among persons over 65 years of age.

With the clinical promotion of precision medicine and individualized medical care, molecular targeted medicine has been used to treat non-small cell lung cancer (NSCLC) patients and proved to be significantly effective. Anaplastic lymphoma kinase (ALK) inhibitor is one of the most important specific therapeutic agents for patients with ALK-positive NSCLC. It can extend the survival of patients. However, resistance to the ALK inhibitor inevitably develops in the application process. So, the real-time resistance surveillance is particularly important, and liquid biopsy is one of the most potential inspection methods. Circulating tumor cells, circulating free tumor DNA and exosome in body fluid are used as the main detection biomarkers to reflect the occurrence of resistance in real time through sequencing or counting and then to guide the follow-up treatment.

Since April 2010, domesticated ducks in China have been suffering from an emerging infectious disease characterized by retarded growth, high fever, loss of appetite, decline in egg production, and death. The causative agent was identified as a duck Tembusu virus (DTMUV), a member of the Ntaya virus (NTAV) group within the genus Flavivirus, family Flaviviridae. DTMUV is highly contagious and spreads rapidly in many species of ducks. More than 10 million shelducks have been infected and approximately 1 million died in 2010. The disease remains a constant threat to the duck industry; however, it is not known whether DTMUV can infect humans or other mammalians, despite the fact that the virus has spread widely in southeast China, one of the most densely populated areas in the world. The lack of reliable methods to detect the serum antibodies against DTMUV has limited our ability to conduct epidemiological investigations in various natural hosts and to evaluate the efficiency of vaccines to DTMUV.

In recent years, several assistive devices have been proposed to reconstruct arm and hand movements from electromyographic (EMG) activity. Although simple to implement and potentially useful to augment many functions, such myoelectric devices still need improvement before they become practical. Here we considered the problem of reconstruction of handwriting from multichannel EMG activity. Previously, linear regression methods (e.g., the Wiener filter) have been utilized for this purpose with some success. To improve reconstruction accuracy, we implemented the Kalman filter, which allows to fuse two information sources: the physical characteristics of handwriting and the activity of the leading hand muscles, registered by the EMG. Applying the Kalman filter, we were able to convert eight channels of EMG activity recorded from the forearm and the hand muscles into smooth reconstructions of handwritten traces. The filter operates in a causal manner and acts as a true predictor utilizing the EMGs from the past only, which makes the approach suitable for real-time operations. Our algorithm is appropriate for clinical neuroprosthetic applications and computer peripherals. Moreover, it is applicable to a broader class of tasks where predictive myoelectric control is needed.

Duodenal cluster designation 3 positive (CD3+) intraepithelial T lymphocytes (IELs) are increased in gluten-sensitive enteropathy (GSE) and, because of the dispersed nature of the gut immune system, might also be increased in mucosa distant from the duodenum. Conversely, little is known about their frequency in the duodenum during inflammatory conditions of the stomach and esophagus. This study assessed whether CD3+ IELs are increased in duodenal biopsies in patients with esophagitis or gastritis relative to normal control subjects.

The pharmacokinetics of the enantiomers of indoprofen were determined after intravenous administration of the racemate to 10 surgical patients. The mean volume of distribution was 8.97 +/- 2.21 (s.d.) 1 for the pharmacologically active S(+)-enantiomer and 12.60 +/- 4.21 1 for the R(-)-enantiomer (P less than 0.001). The corresponding values for clearance were 32.2 +/- 11.1 ml min-1 and 48.8 +/- 15.5 ml min-1 (P less than 0.001). There was no significant difference in mean terminal half-life between the enantiomers.

A laser-based angle resolved photoemission (ARPES) system utilizing 6 eV photons from the fourth harmonic of a mode-locked Ti:sapphire oscillator is described. This light source greatly increases the momentum resolution and photoelectron count rate, while reducing extrinsic background and surface sensitivity relative to higher energy light sources. In this review, the optical system is described, and special experimental considerations for low-energy ARPES are discussed. The calibration of the hemispherical electron analyzer for good low-energy angle-mode performance is also described. Finally, data from the heavily studied high T(c) superconductor Bi(2)Sr(2)CaCu(2)O(8+delta) (Bi2212) is compared to the results from higher photon energies.

Heating at slowly rising temperatures is suspected to enhance thermotolerance in Listeria monocytogenes and, since anaerobic environments have been shown to facilitate resuscitation of heat-injured cells of this micro-organism, concern may arise about the possibility of L. monocytogenes surviving in minimally preserved products. The effect of rapid ( > 10 degrees C min-1) and slow (0.3 and 0.6 degrees C min-1) heating on survival of L. monocytogenes in sous vide cooked beef was therefore examined at mild processing temperatures of 56 degrees, 60 degrees and 64 degrees C. No statistically significant difference (P = 0.70) was observed between the tested heating regimes. Since the average pH of beef was low (5.6), and little or no effect was observed, a pH-dependency of heat shock-induced thermotolerance in L. monocytogenes is suggested to account for this result.

Spx, an ArsC (arsenate reductase) family member, is a global transcriptional regulator of the microbial stress response and is highly conserved amongst Gram-positive bacteria. Bacillus subtilis Spx protein exerts positive and negative control of transcription through its interaction with the C-terminal domain of the RNA polymerase (RNAP) alpha subunit (alphaCTD). Spx activates trxA (thioredoxin) and trxB (thioredoxin reductase) in response to thiol stress, and bears an N-terminal C10XXC13 redox disulfide center that is oxidized in active Spx.

O'Brien and Fleming (1979, Biometrics 35, 549-556) proposed a procedure for multiple testing in clinical trials for acute disease. We evaluated their procedure for chronic-disease models and found that it can be used without modification. Type I errors are unaltered and no loss of power is seen in comparison with single-sample procedures. However, average savings in sample size are less for the chronic-disease models than for the acute model. Finally, it is shown that for any specific disease model and fixed maximum number of inspections of the data, the percentage reduction in sample size can be readily predicted from the power.

Perovskite solar cells (PSCs) are one of the promising photovoltaic technologies for solar electricity generation. NiO <i>_x</i> is an inorganic p-type semiconductor widely used to address the stability issue of PSCs. Although high efficiency is obtained for the devices employing NiO <i>_x</i> as the hole transport layer, the fabrication methods have yet to be demonstrated for industrially relevant manufacturing of large-area and high-performance devices. Here, it is shown that these requirements can be satisfied by using the magnetron sputtering, which is well established in the industry. The limitations of low fill factor and short-circuit current commonly observed in sputtered NiO <i>_x</i> -derived PSCs can be overcome through magnesium doping and low oxygen partial pressure deposition. The fabricated PSCs show a high power conversion efficiency of up to 18.5%, along with negligible hysteresis, improved ambient stability, and high reproducibility. In addition, good uniformity is also demonstrated over an area of 100 cm². The simple and well-established approach constitutes a reliable and scale method paving the way for the commercialization of PSCs.

Structural optimization of a series of 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidinyl compounds, potential new irreversible EGFR inhibitors, was performed to improve pharmacokinetic properties of the compounds. This led to compound 2v with improved aqueous solubility and good pharmacokinetic properties which at the nanomolar level potently inhibits gefitinib-resistant EGFR(L858R/T790M) kinase and displays strong antiproliferative activity against H1975 nonsmall cell lung cancer cells. The new inhibitor also shows promising antitumor efficacy in a murine EGFR(L858R/T790M)-driven H1975 xenograft model without effect on body weight. These studies provide new lead compounds for further development of drugs for treatment of gefitinib-resistant nonsmall cell lung cancer patients.

Shewanella putrefaciens can use trimethylamine oxide (TMAO) as electron acceptor under anoxic conditions. The associated cytochromes induced during growth under various respiratory conditions have been separated by liquid chromatography (DEAE Sepharose CL6b) and SDS-PAGE and characterized spectrophotometrically and by redox potentiometry. Two major low potential cytochromes and at least three minor low potential cytochromes, likely to be involved in TMAO reduction, were found. No cytochrome specific for TMAO reductase was found.

The paper describes a cross-sectional household survey conducted in randomly-selected villages in rural Ethiopia to assess strategies of households for coping with financial and time costs of illness. Results of the survey showed that the average monthly household health expenditure was 32.87 Birr (about 4.1 US dollars [1 US dollar = 8 Birr at the time of study]). In addition, the average time lost due to illness was 9.23 days for the sick and 7.38 days for their caretakers. Monetary price was a significant (p<0.05) deterrent from visiting health facilities among households with no land or house, the divorced or widowed, and those with annual income less than 500 Birr (62.5 US dollars). The main strategies to cope with the financial costs of illness were waiver privileges, selling household assets, and using savings. Division of labour among household members was used for compensating for the loss of working time due to sickness. The findings of the study indicate that financial and time costs of illness seem to significantly contribute to the impoverishment of rural households.

By using inverse PCR and DNA sequencing, 13 sul3-associated mutational integrons, 2 defective class 1 integrons, and 1 qnrB2-associated complex sul1-type class 1 integrons were identified in Salmonella enterica serovar Choleraesuis, Pseudomonas aeruginosa, and Enterobacter cloacae, respectively. In addition, conjugation and Southern hybridization demonstrated that unusual class 1 integrons were located on plasmids or integrated into chromosomal DNA. Thus, an inverse PCR assay can be a valuable tool for the analysis of unusual structures of the 3' conserved region of class 1 integrons.

Explicit memory and two forms of implicit memory, repetition priming and cognitive skill learning, were examined in twenty-four schizophrenic patients and twenty-four normal control subjects previously matched for sex, age, and educational level. Two explicit tasks, free recall and frequency monitoring, and two implicit tasks, word completion and the Tower of Toronto puzzle, a variant of the Tower of Hanoi puzzle, were selected. The performance of schizophrenic patients was impaired in both explicit tasks, whereas repetition priming was intact; in the Tower of Toronto puzzle, a deficit was observed in problem solving, but not in skill learning. This dissociation between explicit and implicit memory is not entirely consistent with the hypothesis of a deficiency in effort-demanding information processing. It could be better accommodated by a model of a disturbance in the internal representation of context.

A new method for shockless compression and acceleration of solid materials is presented. A plasma reservoir pressurized by a laser-driven shock unloads across a vacuum gap and piles up against an Al sample thus providing the drive. The rear surface velocity of the Al was measured with a line VISAR, and used to infer load histories. These peaked between approximately 0.14 and 0.5 Mbar with strain rates approximately 10(6)-10(8) s(-1). Detailed simulations suggest that apart from surface layers the samples can remain close to the room temperature isentrope. The experiments, analysis, and future prospects are discussed.

The product of the Lap locus in the marine bivalve Mytilus edulis is a neutral, membrane-associated aminopeptidase that is primarily localized on intestinal microvilli and in digestive cell lysosomes. Natural populations are genetically differentiated at the Lap locus between areas of differing salinity. A steep (0.55-0.15) allele frequency cline connects differentiated populations between the Atlantic Ocean and Long Island Sound. We demonstrate an annual gene flow/mortality cycle in cline populations whereby gene frequencies after mortality are correlated with salinity and enzyme activity. The cline is spatially and temporally unstable in immigrants, but stable in residents after mortality. Mortality is nonrandom with regard to the Lap locus; genotype-dependent properties of the aminopeptidase enzyme apparently led to a differential rate of the utilizaiton of nutrient reserves because selected genotypes exhibited an increased rate of tissue weight loss. Aminopeptidase genotypes are differentially adapted to different temperatures and salinities, which provides a mechanism for the relationship among biochemical, physiological, and population phenotypes.

Cognitive-behavioral therapy (CBT) has been strongly identified as a time-limited treatment approach for Axis-I disorders, but CBT models for addressing personality disorders - enduring patterns of relational and emotional difficulties - are gaining greater attention. This review touches on three influential models: Beck's cognitive therapy (CT), Young's schema focused therapy (SFT), and Linehan's dialectical behavior therapy (DBT), presenting the rationale for their development, main theoretical components, and a brief discussion of their goals and means, along with a review of the growing evidence base supporting their effectiveness. The need for integrative models for treatment of this population is noted.

In the beginning of 2020, the novel Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus, became a public health emergency in the U.S. and rapidly escalated into a global pandemic. Because the SARS-CoV-2 virus is highly contagious, physical distancing was enforced and indoor public spaces, including schools and educational institutions, were abruptly closed and evacuated to ensure civilian safety. Accordingly, educational institutions rapidly transitioned to remote learning. We investigated the impacts of the COVID-19 pandemic on domestic U.S. college students, ages 18-24 years.

The levels of 11 essential minerals in food commodity groups and total diets of adult males, infants, and toddlers were summarized from the Selected Minerals in Foods Survey, Fiscal Years (FY) 1974 through mid-1982, of the Food and Drug Administration (FDA) to evaluate the sources and adequacy of those minerals in the diets. The three diets were adequate in calcium, phosphorus, magnesium, potassium, manganese, and selenium; low in copper; and elevated in sodium and iodine. Iron was adequate in adult male but not in infant or toddler diets, and zinc was adequate in infant but somewhat low in adult male and toddler diets. Dairy products; meat, fish, and poultry; grain and cereal products; and fruits and vegetables were the major sources of the 11 minerals. Some statistically significant differences in mineral levels were found among years for total diets and food commodity groups. Regression analysis indicated several linear trends in the mineral content of food commodity groups but no linear trends in the mineral levels of total diets. FDA continues to monitor the levels of minerals in food and diets through the revised Total Diet Study program, which began in mid-FY82.

We reviewed the clinical and radiologic results of 47 cementless acetabular revisions performed by a single surgeon. The mean follow-up period was 58 months. The American Academy of Orthopaedic Surgeons (AAOS) acetabular defect classification was type I in 4 hips, type II in 9 hips, and type III in 32 hips. All patients received AML (Depuy, Warsaw, IN) Duraloc cup implants. Morcellized allograft was used in 23 hips (49%), and screw augmentation in 22 hips (47%). The Harris Hip score improved from 72 to 90 points. No revisions were performed for aseptic loosening. Nonprogressive thin radiolucent lines were found in a single zone in 10 hips (21%) and in all 3 zones in 5 hips (11%). No migration was found in any cups with radiolucent lines, and the presence of a radiolucent line was considered clinically unimportant. Progressive loosening with migration of the cup was found in 1 hip (2%). Kaplan-Meier survivorship using revision for aseptic loosening or radiologic loosening as end points was 92% at 72 months. No statistically significant difference was found in the survival of the cups fixed with or without screws. These encouraging midterm results confirm the role of cementless acetabular revision.

Status epilepticus (SE) has attracted renewed interest lately, and efforts are made to optimize every treatment stage. For refractory SE, optimal supporting care involves mechanical ventilation and intensive care unit (ICU) admission. Infections often complicate SE and recently a single-centre observational study demonstrated an association between infections and poor short-term outcome of SE in a cohort of severely ill patients. We have here attempted to replicate those findings in a different cohort.

The case of a twelve years old boy with unilateral medullary carcinoma of the thyroid gland, whose main symptoms were cough, hemoptisis, fever and weight loss is reported. The diagnosis was made by lymph node biopsy, high levels of serum calcitonin and a positive skin test for histaminase. The main clinical, anatomical and genetic features of this tumor are discussed. The familial study did not show any other affected member. Therefore, it was considered as a sporadic case. Emphasis is made on the diagnostic methodolgy.

Laboratory studies were conducted in solid-phase reactors on a silty loam contaminated with bis-(2-ethylhexyl) phthalate (BEHP) to determine the conditions under which calcium peroxide (CaO(2)) would promote the aerobic bioremediation of water-saturated soil. Closed 500 ml solid-phase reactors were operated to determine whether CaO(2) stimulated the biodegradation of BEHP in saturated soil. Ex situ bioremediation conditions were then simulated by mixing water-saturated soil for 6 h before placing the soil in three vented, 2 l solid-phase reactors for 50 days. Biodegradation of BEHP was quantified using four different measurements of microbial activity: (1) oxygen concentrations in the reactor gas; (2) bacterial colony-forming units (CFU); (3) fungal CFU; and (4) 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride dehydrogenase activity (INT-DHA). CaO(2) released molecular O(2), which retarded dewatering but substantially enhanced BEHP biodegradation. After 20 days, BEHP in the amended reactor was reduced from 20.3 to roughly 5 g kg(-1) vs. 15 g kg(-1) in the reactor without CaO(2). Bacterial growth was favored over fungal growth at elevated moisture and BEHP levels.

A microwave-induced, steam/Ar/O2, plasma "torch" was operated at atmospheric pressure to determine the feasibility of destroying volatile organic compounds (VOCs) of concern. The plasma process can be coupled with adsorbent technology by providing steam as the fluid carrier for desorbing the VOCs from an adsorbent. Hence, N2 can be excluded by using a relatively inexpensive carrier gas, and thermal formation of oxides of nitrogen (NOx) is avoided in the plasma. The objectives of the study were to evaluate the technical feasibility of destroying VOCs from gas streams by using a commercially available microwave plasma torch and to examine whether significant byproducts were produced. Trichloroethene (TCE) and toluene (TOL) were added as representative VOCs of interest to a flow that contained Ar as a carrier gas in addition to O2 and steam. The O2 was necessary to ensure that undesirable byproducts were not formed in the process. Microwave power applied at 500-600 W was found to be sufficient to achieve the destruction of the test compounds, down to the detection limits of the gas chromatograph that was used in the analysis. Samples of the postmicrowave gases were collected on sorbent tubes for the analysis of dioxins and other byproducts. No hazardous byproducts were detected when sufficient O2 was added to the flow. The destruction efficiency at a fixed microwave power improved with the addition of steam to the flow that passed through the torch.

Long-term treatment with 6-thioguanine (6-TG) for pediatric acute lymphoblastic leukemia (ALL) is associated with high rates of hepatic sinusoidal obstruction syndrome (SOS). Nevertheless, current treatment continues to use short-term applications of 6-TG with only sparse information on toxicity. 6-TG is metabolized by thiopurine methyltransferase (TPMT) which underlies clinically relevant genetic polymorphism. We analyzed the association between hepatic SOS reported as a serious adverse event (SAE) and short-term 6-TG application in 3983 pediatric ALL patients treated on trial AIEOP-BFM ALL 2000 (derivation cohort) and defined the role of TPMT genotype in this relationship. We identified 17 patients (0.43%) with hepatic SOS, 13 of which with short-term exposure to 6-TG (P < 0.0001). Eight of the 13 patients were heterozygous for low-activity TPMT variants, resulting in a 22.4-fold (95% confidence interval 7.1-70.7; P ≤ 0.0001) increased risk of hepatic SOS for heterozygotes in comparison to TPMT wild-type patients. Results were supported by independent replication analysis. All patients with hepatic SOS after short-term 6-TG recovered and did not demonstrate residual symptoms. Thus, hepatic SOS is associated with short-term exposure to 6-TG during treatment of pediatric ALL and SOS risk is increased for patients with low-activity TPMT genotypes.

Germ-line stem cells are unique because they either self-renew through mitosis or, at a certain frequency, switch to meiosis and produce gametes. The switch from proliferation to meiosis is tightly regulated, and aberrations in switching result in either too little or too much proliferation. To understand the genetic basis of this regulation, we characterized loss-of-function mutations and a novel tumorous allele of Caenorhabditis elegans mett-10, which encodes a conserved putative methyltransferase. We show that METT-10 is a nuclear protein that acts in the germ line to inhibit the specification of germ-cell proliferative fate. METT-10 also promotes vulva, somatic gonad, and embryo development and ensures meiotic development of those germ cells that do differentiate. In addition, phenotypic analysis of a mett-10 null allele reveals that METT-10 enables mitotic cell cycle progression. The finding that METT-10 functions to inhibit germ-cell proliferative fate, despite promoting mitotic cell cycle progression of those germ cells that do proliferate, separates the specification of proliferative fate from its execution.

Alpha-dystroglycan is a cell surface peripheral membrane protein which binds to the extracellular matrix, while beta-dystroglycan is a type I integral membrane protein which anchors alpha-dystroglycan to the cell membrane via the N-terminal extracellular domain. The complex composed of alpha- and beta-dystroglycan is called the dystroglycan complex. Although defects of the dystroglycan gene have not been identified as the primary causes of hereditary diseases in humans, secondary but significant abnormalities of the dystroglycan complex have been revealed in severe muscular dystrophies, including sarcoglycanopathy (LGMD2C, D, E and F). In this study, we investigated proteolytic processing of beta-dystroglycan and its effect on the extracellular matrix-cell membrane linkage in cardiomyopathic hamsters, the model animals of LGMD2F. Compared to normal controls, proteolytic processing of beta-dystroglycan was activated in the skeletal, cardiac and smooth muscles of cardiomyopathic hamsters and this resulted in the partial disruption of the dystroglycan complex in these tissues. These phenomena were observed from the early phase of muscle degeneration process. Our results suggest that proteolytic processing of beta-dystroglycan disrupts the extracellular matrix-cell membrane linkage via the dystroglycan complex and this may play a role in the molecular pathogenesis of muscle degeneration in cardiomyopathic hamsters.

It has been long known that uremia and RDT could alter the optical fibers of the Central Nervous System: we also previously demonstrated the persistence of a delayed P100 wave evoked by Visual Potentials (VEPs) in RDT patients. Our present study evaluates changes in IOP during RDT and possible correlations between electrophysiological and tonometrical modifications. In twenty patients undergoing RDT (12 hrs/weekly, mean age 42.05 +/- 10.80 yrs) we performed, just before and immediately after the dialytic session the tonographic recordings and serum osmolality. The pre-dialysis IOP of all 20 patients ranged from 9.00 to 27.19 mmHg with a mean of 16.40 +/- 7.20. Serum osmolality predialysis was 326.10 +/- 5.72 mOsm/l and post-dialysis 290.33 +/- 2.95 mOsm/l. Our studies suggest a correlation between decrease in plasma osmolality and increase in IOP during dialysis. The effect of RDT on IOP depends on the balance between the rise in IOP with the reduction of the concentrations of "waste products" and the extracellular volume reduction associated with ultrafiltration. The elevation of IOP may be due to a decrease in post-dialysis outflow facility inducing an osmotic influx of water into the eye because of hyperosmolality of intraocular fluids. These continuous modifications may be partially responsible for the defective propagation and the delayed transmission documented by VEPs.

The basic structural characterization of complex I is still not trivial due to its complexity, not only in the number of its protein constituents but especially because of the different properties of the several subunits. Bacterial complex I generally contains 14 subunits: 7 hydrophilic proteins located in the peripheral arm and 7 hydrophobic proteins present in the membrane arm. It is the identification of the hydrophobic proteins that makes the characterization of complex I, and of membrane proteins in general, very difficult. In this article, we report the identification of the subunits of complex I from Rhodothermus marinus. The original approach, presented here, combined several protein and peptides separation strategies (different reversed phase materials, high-performance liquid chromatography, and gel electrophoresis) with different identification methods (electrospray ionization-tandem mass spectrometry, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, and Edman degradation analysis) and represents a step forward in the characterization of membrane proteins that studies are still technically highly challenging. The combination of the different methodologies allowed the identification of complex I canonical subunits and also a possible novel subunit, namely a pterin-4α-carbinolamine dehydratase (PCD). This was the first time that a PCD was suggested to be part of complex I, and its possible regulatory role is discussed.

An open study of 47 patients with cancer pain treated with repeated doses of a controlled-release oral morphine tablet was conducted to assess the acceptability of this drug and develop guidelines for its use. Each patient kept a detailed record of pain, analgesic intake, side effects, and other medications. A nurse observer/clinician followed these patients on a daily basis and kept similar records. Of 47 patients who began the study, 37 were successfully stabilized with standard morphine sulfate tablets and then switched to controlled-release morphine (CRM). Twenty-one patients who completed the study took CRM every 12 h, and 16 patients received a dose every 8 h. Doses of the CRM ranged from 30 mg every 12 h to 360 mg every 8 h. Less frequent doses and uninterrupted sleep were reported advantages. All of the patients completing the study chose to continue this method of pain management and extended care data were obtained from each patient poststudy through continued monitoring.

Experience in managing 33 lower limb fractures in 25 chronic spinal injured patients is described. An increased awareness among patients and medical staff is required to avoid misdiagnosis. Effort should be made to ensure bone union in satisfactory position, recognising the different requirements of ambulant and non-ambulant patients. 'Soft pillow splints' were found to give the best results in all fractures other than those of the femoral neck. Operative treatment with antibiotic prophylaxis is only indicated to correct important deformity.

The sensitivity and specificity of enzyme immunofiltration and DNA hybridization were compared in human cytomegalovirus (HCMV) (AD 169)-infected MRC-5 cells. The enzyme immunofiltration was carried out on glass fiber filters in microplates, using an HCMV (AD 169) monoclonal antibody and a peroxidase conjugate. The DNA hybridization was carried out with a microfiltration apparatus, using a 32P-labelled HCMV (AD 169) Eco R1 D fragment probe. The sensitivities of enzyme immunofiltration and DNA hybridization were 1.82 X 10(3) and 1.13 X 10(3) infected cells, respectively. Both methods were highly specific, but enzyme immunofiltration was faster and simpler.

Understanding mechanisms underlying titin regulation in cardiac muscle function is of critical importance given recent compelling evidence that highlight titin mutations as major determinants of human cardiomyopathy. We previously identified a cardiac biomechanical stress-regulated complex at the cardiac-specific N2B region of titin that includes four-and-a-half LIM domain protein-1 (Fhl1) and components of the mitogen-activated protein signaling cascade, which impacted muscle compliance in Fhl1 knock-out cardiac muscle. However, direct regulation of these molecular components in mediating titin N2B function remained unresolved. Here we identify Fhl1 as a novel negative regulator of titin N2B levels and phosphorylation-mediated mechanics. We specifically identify titin N2B as a novel substrate of extracellular signal regulated-kinase-2 (Erk2) and demonstrate that Fhl1 directly interferes with Erk2-mediated titin-N2B phosphorylation. We highlight the critical region in titin-N2B that interacts with Fhl1 and residues that are dependent on Erk2-mediated phosphorylation in situ. We also propose a potential mechanism for a known titin-N2B cardiomyopathy-causing mutation that involves this regulatory complex. These studies shed light on a novel mechanism regulating titin-N2B mechano-signaling as well as suggest that dysfunction of these pathways could be important in cardiac disease states affecting muscle compliance.

In the title compound, C(12)H(10)N(2)O(4)S, the conformation of the N-H bond in the -SO(2)-NH- fragment is syn to the ortho-nitro group in the sulfonyl-benzene ring. The mol-ecule is twisted at the S-N bond, the C-N-S-C torsion angle being -72.83 (15)°. The dihedral angle between the benzene rings is 59.55 (7)°. The amide H atom and the nitro group O atom form an intra-molecular hydrogen bond, generating an S(7) motif. In the crystal, C-H⋯O hydrogen-bond inter-actions link the mol-ecules into S(2) (2)(10) networks.

Displaced retinal ganglion cells in birds are the sole source of the retinal projection onto the nucleus of the basal optic root, the main component of the accessory optic system. This nucleus has direct bilateral axonal projections onto the oculomotor nuclear complex, the trochlear nucleus- and folia IXc,d and paraflocculus of the vestibulocerebellum. The cerebellar projection terminates within a superficial band of the granule cell layer adjacent to the Purkinje cell layer as a mossy fiber system. This bisynaptic projection onto oculomotor neurons and the cerebellum may play a functionally distinct and specific role in oculomotor reflexes.

The hearing organ contains sensory hair cells, which convert sound-evoked vibration into action potentials in the auditory nerve. This process is greatly enhanced by molecular motors that reside within the outer hair cells, but the performance also depends on passive mechanical properties, such as the stiffness, mass, and friction of the structures within the organ of Corti. We used resampled confocal imaging to study the mechanical properties of the low-frequency regions of the cochlea. The data allowed us to estimate an important mechanical parameter, the radial strain, which was found to be 0.1% near the inner hair cells and 0.3% near the third row of outer hair cells during moderate-level sound stimulation. The strain was caused by differences in the motion trajectories of inner and outer hair cells. Motion perpendicular to the reticular lamina was greater at the outer hair cells, but inner hair cells showed greater radial vibration. These differences led to deformation of the reticular lamina, which connects the apex of the outer and inner hair cells. These results are important for understanding how the molecular motors of the outer hair cells can so profoundly affect auditory sensitivity.

We have determined that two infants with perinatal lethal osteogenesis imperfecta in one family had the same new dominant point mutation. Although not detected in his dermal fibroblast DNA, the mutation was detected in somatic DNA from the father's hair root bulbs and lymphocytes. The mutation was also detected in the father's sperm, demonstrating that mosaicism in the father's germ line explains recurrence. The presence of both germ-line and somatic mosaicism indicates that the mutation occurred prior to segregation of the germ-line and somatic cell progenitors. About one in eight sperm carry the mutation, which implies that at least four progenitor cells populate the germ line in human males. The observation that the mosaic individual is clinically normal suggests that genetic diseases can have both qualitative and quantitative components.

AIM:To determine whether incorporation of the pH dependent bacterial toxin listeriolysin O (LLO) into the DNA carrier system could increase the endosomal escape of internalized DNA and result gene expression.METHODS:A multi component delivery system was prepared consisting of asialoglycoprotein (ASG), poly L-lysine(PL), and LLO.Two marker genes, luciferase and beta galactosidase in plasmids were complexed and administered in vitro to Huh7(ASG receptor (+) and SK Hep1(ASG receptor (-) cells. Purity, hemolytic activity, gene expression, specificity, and toxicity were evaluated.RESULTS:An LLO containing conjugate retained cell target-ing specificity and membranolytic activity. In ASG receptor (+) cells,luciferase gene expression was enhanced by more than 7 fold over that of conjugates without the incorporation of listeriolysin O. No significant expression occurred in ASG receptor (-) cells. Enhancement of betagalactosidase gene expression was less, but still significantly increased over controls. There was no detectable toxicity at concentrations shown to be effective in transfection studies.CONCLUSIONS:ASOR-PL can be coupled to LLO using disulfide bonds, and successfully target and increase the gene expression of foreign DNA.

We report on vibrational dynamics of water near the surface of AOT reverse micelles studied by narrow-band excitation, mid-IR pump-probe spectroscopy. Evidence of OH-stretch frequency splitting into the symmetric and asymmetric modes is clearly observed for the interfacial H(2)O molecules. The polarization memory of interfacial waters is preserved over an exceptionally extended >10 ps timescale which is a factor of 100 longer than in bulk water. These observations point towards negligibly small intermolecular vibrational coupling between the water molecules as well as strongly reduced water rotational mobility within the interfacial water layer.

The taxon Paraleptophlebia Lestage 1917 is accepted here in generic rank, so rank of Neoleptophlebia Kluge 1997 is also raised from subgenus to genus, and the following new combinations are proposed: Neoleptophlebia adoptiva (McDunnough 1929) comb. n., N. assimilis (Banks 1914) comb. n., N. erratica (Kang & Yang 1994) comb. n., N. heteronea (McDunnough 1924) comb. n., N. japonica (Matsumura 1931) comb. n. (= Paraleptophlebia chocolata Imanishi 1937), N. mollis (Eaton 1871) comb. n., N. memorialis (Eaton 1884) comb. n., N. spina (Kang & Yang 1994) comb. n., N. swannanoa (Traver 1932) comb. n., N. temporalis (McDunnough 1926) comb. n., N. vladivostokica (Kluge 1982) comb. n. Larvae, male and female imagoes and eggs of Paraleptophlebia falcula Traver 1934 are described based on reared specimens from Siberia and Russian Far East; larvae and eggs are described for the first time. Characters of this species agree with diagnosis of Paraleptophlebia in the restricted sense; comparison of larva of P. falcula with other known larvae of Paraleptophlebia is given. Formerly this species was known as imagoes from limited area in Western Nearctic. According to the new data, it is widely distributed in northern part of Amphipacific Sector of Holarctic, and its area includes Polar Urals (Komi Republic), Siberia (Transbaikal Kray, Sakha Yakutia and Amurskaya Oblast' of Russia) and west of North America (Oregon, Idaho and Washington states of USA).

Unique amino acid substitutions occur in D. lebanonensis ADH. They are found within the putative NAD(+)-binding domain and affect residues that are otherwise highly conserved in all other species of the genus. To restore the consensus amino acids, we have constructed an expression system for this enzyme in E. coli, and engineered two mutants, Ala13Gly and Asn56Thr. The biochemical and kinetic features of these retromutants are consistent with increased catalytic efficiency and thermal stability. Thus, results show that wild-type D. lebanonensis ADH can be improved by site-directed mutagenesis.

Due to ethical and logistical concerns it is common for data monitoring committees to periodically monitor accruing clinical trial data to assess the safety, and possibly efficacy, of a new experimental treatment. When formalized, monitoring is typically implemented using group sequential methods. In some cases regulatory agencies have required that primary trial analyses should be based solely on the judgment of an independent review committee (IRC). The IRC assessments can produce difficulties for trial monitoring given the time lag typically associated with receiving assessments from the IRC. This results in a missing data problem wherein a surrogate measure of response may provide useful information for interim decisions and future monitoring strategies. In this paper, we present statistical tools that are helpful for monitoring a group sequential clinical trial with missing IRC data. We illustrate the proposed methodology in the case of binary endpoints under various missingness mechanisms including missing completely at random assessments and when missingness depends on the IRC's measurement.

The aggregation of crystals is a common phenomenon during the crystallization process. However, the formation mechanism of the aggregates remains elusive. In this work, we combine experiments with molecular simulations to investigate the attachment behavior of an organic compound photoinitiator bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (XBPO) in different solvents. The simulation results were highly in line with the experimental results. The results indicate that the aggregation behavior occurs on the high-energy surface (1 0 0) and the attachment angle is 0° during the solvothermal process. Meanwhile, solvents play the critical role in the formation of aggregated particles. It was found that the solvents with high Kamlet-Taft dipolarity/polarizability can promote the aggregation behavior of photoinitiator XBPO crystals. Furthermore, a solvent-mediated growth mechanism assisted by "oriented attachment"-like and Ostwald ripening mechanisms was proposed to elucidate the growth and aggregation of particles. We anticipate that this study will provide a comprehensive understanding of the attachment behavior and be helpful to control the aggregation of crystals.

The present study was undertaken to estimate bio-availability and biological half-life of fluoride and accumulation of fluoride in bone in the domestic pig. Eight animals receiving 2 mg F-/kg b.w. per day from age 8 to 14 months were compared with eight controls. Plasma fluoride concentrations just prior to the daily oral dose were measured at regular intervals. After 112 days post-dose, plasma fluoride levels were measured over a 48-hour period following the daily oral dose or a single intravenous dose. Mean bio-availability factor for the oral dose was 0.3 (range 0.2-0.4), and mean biological half-life was 59 days (range 49-72). Bone fluoride content calculated from the pharmacokinetic parameters derived from plasma data was similar to the content of fluoride measured in the bone at slaughter. The study showed that accumulation of fluoride in bone influences plasma fluoride levels during chronic administration of fluoride to growing pigs. The long biological half-life found showed that it was not possible to achieve steady-state plasma levels within the six-month experimental period used. This means that, for dose-response studies of dental fluorosis in this animal, it is not possible to achieve steady-state plasma concentrations as a basis for correlations to the degrees of pathological change observed in the teeth.

Ninety-nine patients with premature rupture of the membranes (PROM) before 36 weeks' gestation and documented fetal pulmonary maturity were studied prospectively. Fifty-two patients in labor were allowed to deliver. The remaining 47 were randomly assigned to either prompt delivery (N = 26) or conservative management (N = 21). The overall corrected perinatal survival was excellent (96%). Only one death in the entire series clearly was due to prematurity. Expectant management prolonged gestation greater than one week in only four of 21 patients (19%), and was associated with a significantly increased risk of maternal infections. There were no failed inductions of labor, and 22 of 24 induced patients (92%) delivered vaginally. Neonatal morbidity was similar in each group. These findings in an indigent, largely black population suggest that when pulmonary maturity is present, the maternal risks of conservative management may exceed the potential benefit to the fetus and newborn. The findings of this study may be specific to the population studied, and extrapolation to dissimilar populations may not be warranted.

Medical records are an integral part of patient care. Information loss during the handover from Emergency Care Providers to hospital staff is common and has a significant impact on patient care. Information loss can be prevented with medical documentation that is accurate, complete and contains the relevant information regarding patient management. Patient report Forms (PRF's) are used by Emergency Care Providers to record the details of their patient care and they form part of the patients' medical records. Quality assuring of PRF's is required to determine if the required information has been recorded on the PRF. Checklists are one the means of quality assuring PRF, by comparing the points on the checklist to the content of the PRF.

Systemic lupus erythematosus (SLE) patients are at high risk of developing osteonecrosis. This study utilized MRI to document the long-term natural history of asymptomatic osteonecrosis associated with corticosteroid therapy in SLE patients. Two hundred and one SLE patients treated with high-dose corticosteroids were prospectively observed from 1986 to 1997. The inclusion criterion was that patients had received periodic MRI examinations of all their hip and knee joints for ≥10 years. Joints that were already collapsed and symptomatic at the first examination were excluded. Five hundred and thirty-seven joints (251 hips and 286 knees) were identified in 144 patients, with a mean follow-up period of 13.6 years (range, 10-20 years) and a follow-up rate of 73%. Mean age of SLE onset was 26 years, and the mean highest oral corticosteroid dosage was 57 mg/day. Osteonecrosis developed in 238 (44%) of 537 joints. At final follow-up, 117 (49%) of these 238 joints demonstrated spontaneous repair in the necrotic area. Osteonecrosis completely disappeared in 21 joints. Enlargement of osteonecrosis was noted in 35 joints (15%) following increased steroid dosage because of SLE recurrence. Finally, 52 joints (22%) were collapsed. Spontaneous repair of asymptomatic osteonecrosis was observed, whereas enlargement occurred only after corticosteroid dosage increases.

RNA interference (RNAi) mediated by microRNA (miRNA) is an evolutionarily conserved mechanism of posttranscriptional gene regulation in all eukaryotes, involving in natural antiviral immunity. The RNAase III Drosha is a key component for miRNA maturation. To date, however, the roles of Drosha in virus infection remain to be addressed. In this study, the Drosha was characterized in Marsupenaeus japonicus shrimp. The sequence analysis revealed that the shrimp Drosha gene encoded a 1081-amino-acid peptide, which comprised two tandem ribonuclease III C terminal domains and a double-stranded RNA binding motif. The shrimp Drosha was homologous with those of other animal species. The quantitative RT-PCR analysis revealed that the Drosha gene was highly expressed in lymphoid organ and was significantly up-regulated in response to WSSV challenge, suggesting that the Drosha was involved in the antiviral immunity of shrimp. The results showed that the knock down of Drosha gene led to the defect of miRNA maturation, and subsequent higher virus loads in shrimp. Our study presented that Drosha played important roles in the antiviral defense of shrimp.

In North America, until recently, all cases of anuran myiasis were attributed to Lucilia silvarum (Meigen) or Lucilia elongata Shannon. The latter species is exceedingly rare and its life history is unknown, but L. silvarum is common and was thought to be capable of being either parasitic or saprophytic in North America. Until recently, the anuran parasite Lucilia bufonivora Moniez was thought to be strictly Palearctic, but a study in 2014 has determined this species is established throughout southern Canada. In 2019, a study demonstrated, with molecular and morphological evidence, that two adult flies formerly identified as L. silvarum and reared from amphibian myiasis cases from Canada, are actually L. bufonivora. Although the mentioned study detected relatively high genetic distances with European L. bufonivora, the lack of evident morphological differentiation suggest that they are the same species. The current study examined 12 adult males and eleven adult females morphologically from three additional North American studies. Specimens were examined which had been identified as L. silvarum or L. elongata, and they all proved to be L. bufonivora. We now suspect L. silvarum is strictly saprophagous in North America like they are in the Palearctic Region. We also provide evidence that the pattern of myiasis differs between European and North American specimens.

Neuropathic pain encompasses a diverse array of clinical entities affecting 7-10% of the population, which is challenging to adequately treat. Several promising therapeutics derived from molecular discoveries in animal models of neuropathic pain have failed to translate following unsuccessful clinical trials suggesting the possibility of important cellular-level and molecular differences between animals and humans. Establishing the extent of potential differences between laboratory animals and humans, through direct study of human tissues and/or cells, is likely important in facilitating translation of preclinical discoveries to meaningful treatments. Patch-clamp electrophysiology and RNA-sequencing was performed on dorsal root ganglia taken from patients with variable presence of radicular/neuropathic pain. Findings establish that spontaneous action potential generation in dorsal root ganglion neurons is associated with radicular/neuropathic pain and radiographic nerve root compression. Transcriptome analysis suggests presence of sex-specific differences and reveals gene modules and signalling pathways in immune response and neuronal plasticity related to radicular/neuropathic pain that may suggest therapeutic avenues and that has the potential to predict neuropathic pain in future cohorts.

Due to their high degree of polymorphism, microsatellites are considered useful tools for studying population genetics. Nevertheless, studies of genetic diversity in stingless bees by means of these primers have revealed a low level of polymorphism, possibly the consequence of the heterologous primers used, since in most cases these were not specifically designed for the species under consideration. Herein we compared the number of polymorphic loci and alleles per locus, as well as observed heterozygosity in Melipona rufiventris and M. mondury populations, using specific and heterologous primers. The use of specific primers placed in evidence the greater frequency of polymorphic loci and alleles per locus, besides an expressive increase in observed heterozygosity in M. rufiventris and M. mondury, thereby reinforcing the idea that populational studies should be undertaken by preferably using species-specific microsatellite primers.

Metagenomic DNA (gDNA) is an important research topic because uncultivated microorganisms represent an interesting reservoir of genes with potential biotechnological applications. Here we describe a novel Si-C-N chromatography approach of gDNA extraction from environmental samples. Amorphous Si-C-N ceramic was obtained by the pyrolysis of a polymer precursor (polycarbosilazane) at 1350 degrees C in Ar. The purified gDNA fragments were at least 12 kilo base pairs in size and were sufficiently free of contaminants, thus were applicable to both restriction enzyme digestion using five different enzymes and polymerase chain reaction amplification for detecting phylogenetic groups of native microorganisms in environmental samples. This Si-C-N material produces pure gDNA that can be utilized in some of the most common molecular biological procedures applied in the purification step.

Noninvasive diagnosis of the malignant potential of colon polyps can improve prevention of colorectal cancer without the need for time-consuming and expensive biopsies. This study examines the use of spectroscopic optical coherence tomography (OCT) to classify tissue from genetically engineered mouse models of early-stage adenoma (APC) and advanced adenocarcinoma (AKP) in which tumors are induced in the distal colon. The optical tissue properties of scattering power and scattering attenuation coefficient are evaluated by analyzing the imaging data collected from tissues. Classifications are generated using 2D linear discriminant analysis with high levels of discrimination obtained. The overall classification accuracy obtained was 91.5%, with 100% sensitivity and 96.7% specificity in separating tumors from benign tissue, and 77.8% sensitivity and 99.4% specificity in separating adenocarcinoma from nonmalignant tissue. Thus, this study demonstrates the clinical potential of using spectroscopic OCT for rapid detection of colon adenoma and colorectal cancer.

Colloidal interactions in nematic liquid crystals can be described as interactions between elastic multipoles that depend on particle shape, topology, chirality, boundary conditions and induced topological defects. Here, we describe a nematic colloidal system consisting of mesostructures of gold capable of inducing elastic multipoles of different order. Elastic monopoles are formed by relatively large asymmetric mesoflower particles, for which gravity and elastic torque balancing yields monopole-type interactions. High-order multipoles are instead formed by smaller mesoflowers with a myriad of shapes corresponding to multipoles of different orders, consistent with our computer simulations based on free energy minimization. We reveal unexpected many-body interactions in this colloidal system, ranging from de-mixing of elastic monopoles to a zoo of unusual colloidal crystals formed by high-order multipoles like hexadecapoles. Our findings show that gold mesoflowers may serve as a designer toolkit for engineering colloidal interaction and self-assembly, potentially exceeding that in atomic and molecular systems.

During this study, 134 samples have been examined for the detection of the viruses associated with neonatal calf diarrhea. The presence of Nebraska viruses (rotavirus and coronavirus) has been demonstrated by using the electron microscope and the fluorescent antibody techniques while the presence of other viruses has been detected by the observation of a cytopathic effect on monolayer cells of calf testis. The Nebraska viruses have been demonstrated in 107 (80%) out of 134 field case specimens. An association of rotaviruses and coronaviruses was found in 58 cases (54%) whilst the coronaviruses and the rotavirus were found singly in 34 cases (53%) and in 15 cases (14%) respectively. Four bovine virus diarrhea viruses, two infectious bovine rhinotracheitis viruses and two enteroviruses have also been isolated in the preceding 107 Nebraska positive specimens. For the detection of the Nebraska viruses, the fluorescent antibody techniques were more sensitive than the electron microscopy. However, those two techniques must be used simultaneously for a better detection of a greatest possible number of cases.

Bullous pemphigoid (BP) is described as a subepidermal blistering disorder, which is commonly reported among the elderly, particularly those older than 60 years of age. In this report, we present the case of a 41-year-old female patient with BP lesions that were initially detected at the site of Hijama therapy with a subsequent generalized spread. Punch biopsy from the lesions and perilesional direct immunofluorescence (DIF) demonstrated features of BP. The anti-BP180 level was 178 RU/mL, and the anti-BP230 level was negative. BP antigens at the site of Hijama caused an antibody response, which led to widespread blistering over the trunk due to epitope spreading. In a comprehensive review of the literature, a total of 22 BP patients with lesions due to physical trauma were studied, and clinical, immunological, and epidemiological information was gathered. This article is the first report on the occurrence of BP induced by Hijama therapy.

Only recently novel high-throughput binary interaction data in E. coli became available that allowed us to compare experimentally obtained protein-protein interaction networks of prokaryotes and eukaryotes (i.e. E. coli and S. cerevisiae). Utilizing binary-Y2H, co-complex and binary literature curated interaction sets in both organisms we found that characteristics of interaction sets that were determined with the same experimental methods were strikingly similar. While essentiality is frequently considered a question of a protein's increasing number of interactions, we found that binary-Y2H interactions failed to show such a trend in both organisms. Furthermore, essential genes are enriched in protein complexes in both organisms. In turn, binary-Y2H interactions hold more bottleneck interactions than co-complex interactions while both binary-Y2H and co-complex interactions are strongly enriched among co-regulated proteins and transcription factors. We discuss if such similarities are a consequence of the underlying methodology or rather reflect truly different biological patterns.

The Sixth Eilat Conference on New Antiepileptic Drugs (AEDs) took place in Taormina, Sicily, Italy from 7th to 11th April, 2002. Basic scientists, clinical pharmacologists and neurologists from 27 countries attended the conference, whose main themes included dose-response relationships with conventional and recent AEDs, teratogenic effects of conventional and recent AEDs, update on clinical implications of AED metabolism, prevention of epileptogesis, and seizure aggravation by AEDs. According to tradition, the central part of the conference was devoted to a review of AEDs in development, as well to updates on AEDs, which have been marketed in recent years. This article summarizes the information presented on drugs in preclinical and clinical development, including carabersat (SB-204269), CGX-1007 (Conantokin-G), pregabalin, retigabine (D-23129), safinamide, SPD421 (DP-VPA), SPM 927, talampanel and valrocemide (TV 1901). Updates on fosphenytoin, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin, zonisamide, new formulations of valproic acid, and the antiepileptic vagal stimulator device are also presented.

Herbicides are well known for unintended effects on freshwater periphyton communities. Large knowledge gaps, however, exist regarding indirect herbicide impacts on primary consumers through changes in the quality of periphyton as a food source (i.e., diet-related effects). To address this gap, the grazer <i>Physella acuta</i> (Gastropoda) was fed for 21 days with periphyton that grew for 15 days in the presence or absence of the herbicide diuron (8 &#956;g/L) to quantify changes in the feeding rate, growth rate, and energy storage (neutral lipid fatty acids; NLFAs) of <i>P. acuta</i>. Periphyton biomass, cell viability, community structure, and FAs served as proxies for food quality that support a mechanistic interpretation of the grazers' responses. Diuron changed the algae periphyton community and fatty acid profiles, indicating alterations in the food quality, which could explain differences in the snails' feeding rate compared to the control. While the snails' growth rate was, despite an effect size of 55%, not statistically significantly changed, NLFA profiles of <i>P. acuta</i> were altered. These results indicate that herbicides can change the food quality of periphyton by shifts in the algae composition, which may affect the physiology of grazers.

In this paper, I examine the importance of class, ethnicity and gender in the causation and meaning of somatization for Greek women in Montreal. I argue that nevra--a form of psychosocial distress experienced by many of the women--is a phenomenon of the poor working conditions, low wages and gender relations in the Greek community. Data is based on interviews with 100 Greek families in Montreal and 45 patients in two different clinical settings. Comparing results with material on nervios and nerves from Latin America and the United States, I concur with Low (1985) that nerves should be viewed as a 'culturally-interpreted symptom' rather than a 'culture bound syndrome'. It is further suggested that the importance of social and material conditions and gender relations in mediating the cultural interpretation must be stressed. Failure to do so often results in the medicalization of nevra and the creation of a chronic sick role for the patient.

The COVID-19 crisis has forced a sudden and dramatic shift in the way that clinicians interact with their patients, from outpatient encounters to telehealth visits utilizing a variety of internet-based videoconferencing applications. Although many aspects of pre-COVID-19 outpatient sports medicine care will ultimately resume, it is likely that telehealth will persist because of its practicality and because of patient demand for access to efficient and convenient health care. Physical examination is widely considered a critical obstacle to a thorough evaluation of sports medicine patients during telehealth visits. However, a closer reflection suggests that a majority of the examination maneuvers are possible virtually with limited, if any, modifications. Thus, we provide a comprehensive shoulder and knee physical examination for sports medicine telehealth visits, including (1) verbal instructions in layman's terms that can be provided to the patient before or read verbatim during the visit, (2) multimedia options (narrated videos and annotated presentations) of the shoulder and knee examination that can be provided to patients via screen-share options, and (3) a corresponding checklist to aid in documentation.

Limb salvage for management of osteosarcoma of the lower extremity has become the mainstay of treatment for patients with malignant bony and soft tissue tumors. The knee has become a special area of concern for the reconstructive surgeon due to the high rate of wound complications and difficulties of soft tissue reconstruction. With the availability of new prosthetic implants, the advancement of surgical soft tissue techniques and introduction of adjuvant and neoadjuvant chemotherapy, resection and reconstruction has become the standard approach for patients presenting to St. Jude Children's Research Hospital. The pediatric plastic surgeon's role usually requires handling of wound complications in these reconstructive procedures. This article will discuss the authors' approach to dealing with wound complications in this difficult patient population and their interaction with the orthopedic oncologic service in obtaining primary resection and soft tissue coverage.

A 3-year-old Filipino-American child with recurrent fever, splenomegaly, anemia, and thrombocytopenia, was found to have a hemoglobin F level of 76.9%. His reticulocyte count was elevated (4.3%), and erythroblasts were present in his peripheral blood. The child's erythrocytes were microcytic (MCV 66.9 fl) but his serum ferritin level was normal. His bone marrow at initial presentation demonstrated normal cellularity without an increase in blast cells. The disease progressed with worsening anemia, leukocytosis, and thrombocytopenia, with increased blasts in his marrow and the appearance of a mediastinal mass. His liver, spleen, and lymph nodes were found to be infiltrated with myeloblasts, supporting a diagnosis of juvenile myelomonocytic leukemia (JMML). Analysis of the child's Hb F showed a Ggamma/Agamma ratio of 2.2, which was within the characteristic range for JMML. A globin synthesis study using blood reticulocytes showed an alpha/non-alpha globin synthesis ratio of 2.24, typical of severe homozygous beta thalassemia. Southern blot analysis of blood-leukocyte DNA from the patient and his parents demonstrated no apparent abnormality in the beta-globin gene promoter or coding regions. The elevated level of Hb F in this child with JMML appeared to be part of an acquired Cooley's anemia-like hematologic phenotype.

A natural groundwater system modified by pollutant phenols and agricultural nitrate has been modelled in the laboratory by a series of sacrificial microcosm experiments. Samples of aquifer sediment and groundwater from the margin of the phenol plume were used to inoculate anaerobic microcosms enriched in nitrate and pollutant phenols. Rapid degradation of phenol and p-cresol was observed over a 35-day period leading to the generation of inorganic carbon and a number of transient intermediates. O-cresol proved to be recalcitrant on the experimental time-scale. A mass balance calculation shows that, during degradation, carbon was conserved in the aqueous phase. Groundwater-sediment interactions were monitored using carbon stable isotope data. A mass balance for solution TIC indicates thatp-cresol degradation stimulated the dissolution of sedimentary carbonate phases due to the formation of carbonic acid. Compound-specific carbon isotope analysis (GC-IRMS) was used to search for 13C enrichment in residual p-cresol. A slight enrichment trend (epsilon = -2.5/1000) was tentatively identified. The potential of this fractionation effect for obtaining in situ degradation rates is discussed. Results from the microcosm experiments help to explain the observed distribution of nitrate and phenols within the polluted aquifer.

Mitochondria are the major site of cellular oxidation. Metabolism and oxidative stress have been implicated as possible mechanisms for postoperative atrial fibrillation (POAF) after cardiac operations. Establishing the precise nature of mitochondrial dysfunction as an etiologic factor for oxidative stress-related cell death and apoptosis could further the understanding of POAF. To establish this relationship, mitochondrial function was studied in patients undergoing cardiac operations that developed POAF and compared it with patients without POAF.

Chlorpromazine (CPZ) is a phenothiazine acting as dopamine antagonist. Aside from application in schizophrenia therapy, chlorpromazine is found to be a putative inhibitor of proteins involved in cancers, heritable autism disorder and prion diseases. Four new &#946;-lactoglobulin variants with double or triple substitutions: I56F/L39A, F105L/L39A, I56F/L39A/M107F or F105L/L39A/M107F changing the shape of the binding pocket were produced and their chlorpromazine binding properties have been investigated by X-ray crystallography, circular dichroism, isothermal titration calorimetry and thermophoresis. The CD spectra and crystal structures revealed that mutations do not affect the protein overall structure but in comparison to WT protein, variants possessing I56F substitution had lower stability while mutation F105L increased melting temperature of the protein. The new variants showed affinity to chlorpromazine in the range 4.2-15.4&#8239;&#215;&#8239;10³&#8239;M^-1. The CD spectra and crystal structures revealed complementarity of the binding pocket shape, to only one chlorpromazine chiral conformer. The (aR)-CPZ was bonded to variants containing I56F substitution while variants with F105L substitution preferred (aS)-CPZ.

Most portable electronic devices are power-limited by battery capacity, and recharging these batteries often interrupts the user's experience with the device. The product presented in this paper provides an alternative to powering portables by converting regular human walking motion to electricity. The device harvests electric power using air bulbs, distributed in the sole of a shoe to drive a series of micro-turbines connected to small DC motors. The number and position of air bulbs is optimized to harvest the maximum airflow from each foot-strike. The system is designed to continuously drive the micro-turbines by utilizing both outflow and inflow from the air bulbs. A prototype combat boot was fitted on the right foot of a 75 kg test subject, and produced an average continuous power on the order of 10 s of mW over a 22 Ω load during walking at 3.0 mph. This combat boot provides enough electric power to a passive GPS tracker that periodically relays geographical coordinates to a smartphone via satellite without battery replacement.

TRAF family member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) serves as hub molecule at the crossroad of multiple signaling pathways of type I interferon (IFN) induction. The importance of TBK1 in innate immunity has been demonstrated in mammalian, however the characterization and function of TBK1 in avian remains largely unknown. In this study, we cloned duck TBK1 (duTBK1) from duck embryo fibroblasts (DEFs) for the first time, which encoded 729 amino acids and had a high amino acid identity with goose and cormorant TBK1s. The duTBK1 showed a diffuse cytoplasmic localization in DEFs and was extensively expressed in all tested tissues. Overexpression of duTBK1 induced IFN-β production through the activation of IRF1 and NF-κB in DEFs. The N-terminal kinase domain and the ubiquitin-like domain in middle of duTBK1 played pivotal roles in IFN-β induction as well as in IRF1 and NF-κB activation. Furthermore, knockdown of duTBK1 by small interfering RNA significantly decreased poly(I:C)- or Sendai virus (SeV)-induced IFN-β expression. In addition, duTBK1 expression dramatically reduced the replication of both duck reovirus (DRV) and duck Tembusu virus (DTMUV) in DEFs. These results suggested that the duTBK1 played a pivotal role in mediating duck antiviral innate immunity.

In order to analyse the regional and age-related variations of primate condyles, immunohistochemical techniques were used to examine the localization of types I, II and III collagen and a variety of glycosaminoglycans in distinct anteroposterior regions of the mandibular condyle of two growing female rhesus monkeys (Macaca mulatta). In the juvenile monkey staining for types I and III collagen was weak in the fibrous tissue layer, intense in the pre-cartilaginous tissue layer and faint in the cartilaginous tissue layer; staining was significantly more intense in the posterosuperior and posterior regions than in the anterior region. Similarly, staining for cartilage-characteristic extracellular matrices, including type II collagen and keratan sulfate, was intense in the cartilaginous tissue layer of the posterior condyle. In contrast, in the late-adolescent monkey staining for the extracellular matrices was more intense in the anterior half of the condyle (i.e. from the anterior to the posterosuperior region) than in the posterior region, and most intense in the posterosuperior region. The results demonstrate that marked regional differences exist in the phenotypic expression of the extracellular matrices in the mandibular condyles of growing monkeys and that these differences vary between different developmental stages. The variations probably reflect the predominance of competing growth and articulatory functions in the mandibular condyles.

In 1916 patients with primary malignant melanoma of the skin (excluding palms, soles, and nailbeds) the primary lesions were reviewed microscopically and classified according to Clark's system into lentigo maligna melanoma (85), superficial spreading melanoma (1234), and nodular melanoma (513). Differentiation between the types was not possible in 84 melanomas (4%). By correlating type of melanoma with various clinical and histological features, it was found that the 3 types differed significantly from one another with regard to growth rate of tumor, antecedent nevus, dominant type of invasive tumor cell, and prognosis. The study thus supported the basic principle of the classification employed, that the 3 histological types represent distinct entities of cutaneous melanoma with different clinical, cellular, and behavioral characteristics. As originally described by Clark, the growth rate was greatest for nodular melanoma, followed by superficial spreading melanoma, and least for lentigo maligna melanoma. It is recommended that this classification be employed in the histological typing of cutaneous melanoma as 1) it is readily applied to the vast majority of melanomas, and 2) it seems to delineate separate clinico-pathologic entities of cutaneous melanoma, which might be correlated with aetiological differences.

Routinely used procedures for chemical fixation often fail to preserve delicate membrane-bounded tubular structures in a variety of cell types. Fixation procedures commonly employed in immunocytochemical studies for localization of structural proteins, such as those found in cytoskeletal elements, may also degrade these tubular structures. Here we describe a procedure that preserves the elaborate tubular lysosome system found in stimulated macrophages and allows the subsequent immunofluorescence localization of microtubules in the same cells. Use of this methodology permits the assessment of the spatial relationship between tubular lysosomes and microtubules in macrophages.

Respiratory medicine is an underdeveloped subspecialty in veterinary medicine, and there are relatively few sophisticated tests that are available to the clinician that actually diagnose specific pulmonary disorders. Instead, most of the commonly available tests are most helpful if used to point the veterinarian in the right direction and to rule out the presence of other potentially confounding disorders. This article reviews the diagnostic tests that are available to evaluate dogs and cats with signs of respiratory disease, including the advantages, disadvantages, and current controversies regarding many of the tests used to evaluate animals with signs of pulmonary impairment.

The activity of the cII protein of phage lambda is probably the critical controlling factor in the choice of the lytic or lysogenic pathway by an infecting virus. Previous work has established that cII activity is regulated through the turnover of cII protein; the products of the hflA and hflB loci of Escherichia coli are needed for a degradative reaction, and lambda cIII functions in stabilizing cII. By using the cloned hflA locus, we have purified a cII-cleaving enzyme that we term HflA. Purified HflA contains three polypeptides; at least two of the subunits are products of the hflA region, and the third is probably a cleavage product of the larger of these two hflA-encoded polypeptides. The HflA protease activity cleaves cII to small fragments. We conclude that the switch between lambda developmental pathways involves regulated cleavage of cII by the specific protease HflA.

Axolotl limb stumps with dorsal-ventral confrontations between digits 2 and 3 but with a normal anterior-posterior pattern were created by grafting between contralateral limbs. Graft and host differed in ploidy to permit a determination of the origin of cells in the regenerated limb. After regeneration, limbs were analysed for skeletal and muscle patterns and for the distribution of marked cells in the regenerate. Regenerated limbs showed varying degrees of abnormality in their dorsal-ventral organization. Following regeneration, the original dorsal-ventral discontinuities were in some cases maintained and in others resolved. The maintenance or resolution of pattern discontinuities occurred in a position-dependent manner. Cell marker analysis indicates a relationship between the resolution of discontinuities and the extent to which cells become displaced across the original graft-host interface. These data lend support to the suggestion that circumferential intercalation is directionally biased.

Disulfide-bond formation, mediated by the Dsb family of proteins, is important in the correct folding of secreted or extracellular proteins in bacteria. In Gram-negative bacteria, disulfide bonds are introduced into the folding proteins in the periplasm by DsbA. DsbE from Escherichia coli has been implicated in the reduction of disulfide bonds in the maturation of cytochrome c. The Gram-positive bacterium Mycobacterium tuberculosis encodes DsbE and its homologue DsbF, the structures of which have been determined. However, the two mycobacterial proteins are able to oxidatively fold a protein in vitro, unlike DsbE from E. coli. In this study, the crystal structure of a DsbE or DsbF homologue protein from Corynebacterium diphtheriae has been determined, which revealed a thioredoxin-like domain with a typical CXXC active site. Structural comparison with M. tuberculosis DsbF would help in understanding the function of the C. diphtheriae protein.

p63 is a known homologue of p53. In contrast to p53, however, p63 mutations are rarely seen in tumours. There have been several reports that p63 plays a regulatory role in the normal differentiation of cells, whereas its role in tumour biology must still be elucidated. The main aim of this study was to compare p63 and p53 expression in tissue microarrays of malignant melanomas and to establish any prognostic significance. p63 expression was found in 2 out of 59 tumours, both pT4. The p63 index did not exceed 30%. p53 expression was found in 27 out of 59 melanomas, with maximal expression in up to 80% of tumour cells. There were no correlations observed between the two markers. Multivariate analysis confirmed the prognostically independent role of p53. This study also confirmed that tissue microarrays can be used effectively for evaluation of the expression of certain tumour markers.

Tissue factor (TF)/FVIIa initiates coagulation by activating factor IX (FIX) and factor X (FX). Tissue factor pathway inhibitor (TFPI)-FXa complexes form and inhibit TF/FVIIa. Blocking of TFPI may facilitate haemostasis initiated by FVIIa/TF thereby compensating for impaired FIX/FVIII-dependent coagulation. This hypothesis was tested in a study using rabbits made temporarily haemophilic by the injection of antibodies against FVIII. These rabbits were given i.v. injections of anti-TFPI IgG antibodies and 40 min later bleeding was initiated by cutting the nail including the apex of the cuticle. Injection of anti-TFPI IgG shortened the bleeding time significantly from 26 min to 11 min (normal mean bleeding time in non-haemophilia rabbits: 5 min). Treatment with anti-TFPI IgG also resulted in a shortening of the haemophilic aPTT to a level slightly longer than the normal aPTT. In addition, the prolonged dilute TF clotting time was shortened by the anti-TFPI IgG treatment. Thus, both bleeding and coagulation parameters indicated that blocking of TFPI may be potentially haemostatic in haemophilia.