Molecular mechanisms of repeated social defeat-induced glucocorticoid resistance: Role of microRNA.
Glucocorticoid (GC) resistance is a severe problem associated with various inflammatory diseases. Previous studies have shown that repeated social stress induces GC resistance in innate immune cells, but the underlying molecular mechanisms have not been fully elucidated. Therefore, the purpose of this study was to examine potential underlying molecular mechanism(s) of repeated social defeat (RSD) stress on GC resistance in splenic macrophages. It was hypothesized that mRNA expression of receptors for GC and nuclear translocating-associated regulators in splenic macrophages would be affected by RSD, and that these changes would be associated with epigenetic modification. The data showed that the mRNA expression of GC and mineralocorticoid receptors were significantly decreased in splenic macrophages by RSD. RSD also induced a significantly decreased mRNA expression in FK506-binding protein 52 (FKBP52), consequently resulting in a significantly increased ratio of FKBP51 to FKBP52. Moreover, DNA methyltransferases 3a and 3b showed a significant decrease in their mRNA expression in the RSD group as did mRNA expression of histone deacetyltransferase 2. The RSD group also showed a significantly reduced quantity of methylated DNA in splenic macrophages. Based on microRNA (miRNA) profiling data, it was determined that RSD induced significantly increased expression of 9 different miRNAs that were predicted to interact with mRNAs of the GC receptor (6 miRNAs), mineralocorticoid receptor (3 miRNAs) and FKBP52 (2 miRNAs). Spearman correlation analysis revealed significantly strong correlations between the expression of 2 miRNAs and their target mRNA expression for GC receptors. Among these miRNAs, we verified direct effects of miRNA-29b and -340 overexpression on mRNA expression of GC receptors in L929 cells. The overexpression of miRNA-29b or -340 in L929 cells significantly reduced LPS-induced overexpression of GC receptors. In conclusion, this study provides evidence that epigenetic regulation, such as DNA methylation and miRNA expression, may play a role in the RSD-induced GC resistance that we have observed in splenic macrophages.


The cytomegaloviral protein pUL138 acts as potentiator of tumor necrosis factor (TNF) receptor 1 surface density to enhance ULb'-encoded modulation of TNF-α signaling.
Human cytomegalovirus is a ubiquitous herpesvirus that establishes lifelong latent infection. Changes in immune homeostasis induce the reactivation of lytic infection, which is mostly inapparent in healthy individuals but often causes overt disease in immunocompromised hosts. Based on discrepant tumor necrosis factor receptor 1 surface disposition between human cytomegalovirus AD169 variants differing in the ULb' region, we identified the latency-associated gene product pUL138, which also is expressed during productive infection, as a selective potentiator of tumor necrosis factor receptor 1, one of the key receptors of innate immunity. Ectopically expressed pUL138 coprecipitated with tumor necrosis factor receptor 1, extended the protein half-life, and enhanced its signaling responses, thus leading to tumor necrosis factor receptor 1 hyperresponsiveness. Conversely, the targeted deletion of UL138 from the human cytomegaloviral genome strongly reduced tumor necrosis factor receptor 1 surface densities of infected cells. Remarkably, the comparison of UL138 deficiency to ULb' deficiency revealed the presence of further positive modulators of tumor necrosis factor alpha signal transduction encoded within the human cytomegalovirus ULb' region, identifying this region as a hub for multilayered tumor necrosis factor alpha signaling regulation.


Subangstrom profile imaging of relaxed ZnO(10 ̅10) surfaces.
Relaxation is a most basic structural behavior of free surfaces, however, direct observation of surface relaxation remains challenging in atomic-scale. Herein, single-crystalline nanoislands formed in situ on ZnO nanowires and nanobelts are characterized using aberration-corrected transmission electron microscopy combined with ab initio calculations. For the first time, displacements of both Zn and O atoms in the fresh (10 ̅10) facets are quantified to accuracies of several picometers and the under-surface distributions of contractions and rotations of Zn-O bonds are directly measured, which unambiguously verify the theoretically predicted relaxation of ZnO (10 ̅10) free surfaces. Finally, the surface relaxation is directly correlated with the size effects of electromechanical properties (e.g., elastic modulus and spontaneous polarization) in ZnO nanowires.


Effect of Sarcostemma acidum stem extract on spermatogenesis in male albino rats.
To evaluate the possible antifertility activity of Sarcostemma acidum (Roxb) Voigt. stem extract in male rats. Male rats were given 70% methanol extract of S. acidum stem orally at dose levels of 50 and 100 mg/kg/day for 60 days. Fertility was evaluated with mating test. Sperm motility and sperm density in cauda epididymides were also assessed. Biochemical and histological analyses were performed on blood samples and on the reproductive organs. S. acidum stem extract resulted in an arrest of spermatogenesis without any systemic side effect. Sperm motility as well as sperm density was reduced significantly. Treatment caused a 80% reduction in fertility at the 50 mg dose and complete suppression of fertility at the 100 mg dose. There was no significant change in RBC and WBC count, hemoglobin, haematocrit, sugar and urea in the whole blood and cholesterol, protein and phospholipid in the serum. The protein and glycogen content of the testes, fructose in the seminal vesicle and protein in epididymides were significantly decreased. Cholesterol in the testes was elevated. Treatment at both of the doses caused a marked reduction in the number of primary spermatocytes (preleptotene and pachytene), secondary spermatocytes and spermatids. The number of mature Leydig cells was decreased, and degenerating Leydig cells was increased proportionately. S. acidum stem extract arrests spermatogenesis in male rats without noticable side effects.


Functional genomics of the social amoebae, Dictyostelium discoideum.
Dictyostelium discoideum is one of the simplest organisms to form a multicellular structure, and it offers several advantages as a model. In order to understand the genetic basis of the multicellular development, a comprehensive analysis of cDNAs is being performed. To date, about 75,000 ESTs have been collected at different stages of development. They have been assembled into about 6,400 independent sequences that represent 70-80% of all of the expected genes in D. discoideum. The results are available on the Internet. In addition to structural analyses, functional analyses of the temporal and spatial expression patterns and gene targeting are being carried out. Furthermore, there are plans to combine the information that is obtained from the cDNA, Genome, and Proteome Projects, as well as the published results, into an integrated database, DictyBase.


Transcriptome Patterns of BRCA1- and BRCA2- Mutated Breast and Ovarian Cancers.
Mutations in the BRCA1 and BRCA2 genes are known risk factors and drivers of breast and ovarian cancers. So far, few studies have been focused on understanding the differences in transcriptome and functional landscapes associated with the disease (breast vs. ovarian cancers), gene (BRCA1 vs. BRCA2), and mutation type (germline vs. somatic). In this study, we were aimed at systemic evaluation of the association of BRCA1 and BRCA2 germline and somatic mutations with gene expression, disease clinical features, outcome, and treatment. We performed BRCA1/2 mutation centered RNA-seq data analysis of breast and ovarian cancers from the TCGA repository using transcriptome and phenotype "portrayal" with multi-layer self-organizing maps and functional annotation. The results revealed considerable differences in BRCA1- and BRCA2-dependent transcriptome landscapes in the studied cancers. Furthermore, our data indicated that somatic and germline mutations for both genes are characterized by deregulation of different biological functions and differential associations with phenotype characteristics and poly(ADP-ribose) polymerase (PARP)-inhibitor gene signatures. Overall, this study demonstrates considerable variation in transcriptomic landscapes of breast and ovarian cancers associated with the affected gene (BRCA1 vs. BRCA2), as well as the mutation type (somatic vs. germline). These results warrant further investigations with larger groups of mutation carriers aimed at refining the understanding of molecular mechanisms of breast and ovarian cancers.


Post-basic nursing students' access to and attitudes toward the use of information technology in practice: a descriptive analysis.
Nurses are exposed to the changing demands in technology as they execute their patient-related duties in the workplace. Integration of Information Technology (IT) in healthcare systems improves the quality of care provided. Nursing students with prior exposure to computers tend to have a positive influence IT. A descriptive study design using a quantitative approach and structured questionnaire was used to measure the nurses' attitudes towards computer usage. A census of 45 post-basic first year nursing management students were participated in this study. The students demonstrated a positive attitude towards the use of a computer. But access to and use of a computer and IT was limited and nurses in clinics had no access to IT. A lack of computer skills was identified as a factor that hinders access to IT. Nursing students agreed that computer literacy should be included in the curriculum to allow them to become independent computer users. The Department of Health should have IT in all health-care facilities and also train all health-care workers to use IT. With the positive attitudes expressed by the students, nurse managers need to create a conducive environment to ensure such a positive attitude continues to excel.


Unexpected high incidence of severe toxicities associated with alpha interferon, low-dose cytosine arabinoside and all-trans retinoic acid in patients with chronic myelogenous leukemia.
Preclinical data have shown that all-trans retinoic acid (ATRA) with interferon-alpha (IFN-alpha) can exert significant suppressive effects on Philadelphia-chromosome (Ph)-positive cells. The aim of this study combining IFN-alpha, low-dose cytosine arabinoside (ara-C) and ATRA was to increase the proportion of patients achieving a major cytogenetic response, in comparison with a group of 140 patients previously treated with IFN-alpha plus low-dose ara-C. Forty three patients with Ph-positive CML in early chronic phase were treated with IFN-alpha 5 MU/m2 s.c. daily, low-dose ara-C 10 mg s.c. daily and ATRA 45 mg/m2 orally daily, for 7 consecutive days every other week. Overall, 76% of patients achieved a complete hematologic response (CHR). A cytogenetic response was in observed 59% (major in 38% and complete in 17%). Compared with patients treated with IFN-alpha and low-dose ara-C, those receiving additional ATRA had a lower CHR rate (p. 014), but other response rates were similar. Severe toxicities were common with the triple regimen (64%), mostly related to ATRA therapy. Two patients experienced pseudotumor cerebri; two patients had leukocytosis during the week on ATRA treatment, decreasing during the week off (one suffered a severe asthma-like reaction followed by pulmonary edema, resembling ATRA syndrome). Six patients had other unusual side-effects: aseptic necrosis of the hip (1 patient), ataxic syndrome (1 patient), paranoid syndrome (2 patients), syncopal episodes (1 patient), pure red cell aplasia (1 patient). In conclusion the results of IFN-alpha and low-dose ara-C combined with ATRA in patients with early CML-chronic phase were disappointing, due to excessive toxicity. Whether different ATRA dose schedules may result in fewer side-effects and improve hematologic and cytogenetic response remains to be determined.


Urinary retention following lower limb arthroplasty: analysis of predictive factors and review of literature.
Acute urinary retention is a common complication after lower limb arthroplasty. The aim of our study was to assess whether the International Prostate Symptom Score (IPSS) and other patient related factors could predict the likelihood of patients developing urinary retention after lower limb arthroplasty. We have also reviewed the literature on this subject. This is a prospective study of 102 male patients undergoing hip or knee arthroplasty. Data collected included age, IPSS, type of operation, type of anaesthesia and development of acute urinary retention in the immediate postoperative period. Thirty-one patients (30.4%) developed acute urinary retention. Of all the parameters studied, age was the only factor that correlated significantly with development of urinary retention. The risk factors for progression of benign prostatic hyperplasia could all be considered as factors for the development of this complication. However, apart from age more than 70 years, it is not practical to use the other parameters.


[Atopic keratoconjunctivitis in patients of the pediatric dermatology ambulatory in a reference center].
To evaluate the frequency of atopic keratoconjunctivitis, its symptoms and changes in patients of Pediatric Dermatology Service of 'Santa Casa de Misericordia de São Paulo' Hospital with a previous diagnosis of atopic dermatitis. Fifty-two patients with atopic dermatitis under 16 years old (mean age 8.9 +/- 4.1 between 2 and 16 years old) were evaluated through a protocol of questions and assessment of signs and symptoms. The signs and symptoms were graded from 0 (absent) to 4 (highest intensity), and in some cases only as present or not. The analysis was descriptive and statistical, with a 5% significance level. The frequency of atopic keratoconjunctivitis was 76.9% among the 52 patients with atopic dermatitis, including atopic conjunctivitis (26.7%) and atopic blepharitis (50.2%). Atopic dermatitis is more frequent in female patients and atopic conjunctivitis in male. Age was practically the same in both groups. The most frequent symptoms were red eye and itching, especially in the atopic conjunctivitis group. Itching was the most intense symptom and was present in all patients of the atopic conjunctivitis group. Blepharitis and papillae were the most common signs. Other signs were less frequent. The tear break-up time was changed in most patients. The prevalence of atopic keratoconjunctivitis was 76.9% in patients with atopic dermatitis. Itching was the most frequent symptom, followed by red eye, in patients with atopic conjunctivitis. Blepharitis and papillae were the most frequent signs in patients with atopic conjunctivitis. Due to the increasing prevalence of atopic dermatitis in children, it would be prudent to perform a routine ophthalmologic evaluation of these patients. From the patients evaluated in this study, none had been previously monitored with ophthalmological exams.


Mechanistic insights into an unprecedented C-C bond activation on a Rh/Ga bimetallic complex: a combined experimental/computational approach.
The unusual rearrangement of [RhCp(GaCp)(CH(3))(2)] (1c) to [RhCp(C(5)Me(4)Ga(CH(3))(3))] (2) is presented and its mechanism is discussed in detail. (13)C MAS NMR spectroscopy revealed that the title reaction proceeds cleanly not only in solution but also in solid state, which supports a unimolecular reaction pathway. On the basis of (1)H, (13)C, and ROESY NMR spectroscopy as well as isolation and structural elucidation of the hydrolysis product, the compound [RhCp(endo-eta(4)-C(5)Me(5)GaMe(2))] (3a) was identified as a crucial reaction intermediate. DFT calculations on the B3LYP level of theory support this assignment and suggest a concerted C-C bond activation mechanism that topologically takes place at the gallium center. Furthermore, two fluxional processes of the reaction intermediate 3a were studied experimentally as well as by computational methods. First, a mechanism takes place similar to a ring-slipping process that exchanges a GaMe(2) group between adjacent ring carbon atoms within the same Cp ring. This process proceeds at a rate comparable to the NMR time scale and indeed is calculated to be energetically very favorable. Second, a unimolecular exchange process of the GaMe(2) group between the two Cp rings of 3a could be experimentally proven by the introduction of phenyl substituents as a label into the Cp ligands at both sites, the rhodium as well as the gallium center. A series of experiments including deuteration studies and competition reactions was performed to substantiate the suggested mechanism being in accordance with DFT calculations on possible transition states.


On the origin of human adipocytes and the contribution of bone marrow-derived cells.
In the last decade, results in both animal models and humans have demonstrated that white adipocytes are generated over the entire life-span. This adds to the plasticity of adipose tissue and alterations in adipocyte turnover are linked to metabolic dysfunction. Adipocytes are derived from precursors present primarily in the perivascular areas of adipose tissue but their precise origin remains unclear. The multipotent differentiation capacity of bone marrow-derived cells (BMDC) has prompted the suggestion that BMDC may contribute to different cell tissue pools, including adipocytes. However, data in murine transplantation models have been conflicting and it has been a matter of debate whether BMDC actually differentiate into adipocytes or just fuse with resident fat cells. To resolve this controversy in humans, we recently performed a study in 65 subjects that had undergone bone marrow transplantation. Using a set of newly developed assays including single cell genome-wide analyses of mature adipocytes, we demonstrated that bone marrow contributes with approximately 10 % to the adipocyte pool. This proportion was more than doubled in obesity, suggesting that BMDC may constitute a reserve pool for adipogenesis, particularly upon weight gain. This commentary discusses the possible relevance of these and other recent findings for human pathophysiology.


Risk factors for cervical cancer development: what do women think?
The current cervical cancer prevention strategy is exclusively directed towards screening, without taking into account any relationship with sexual risk factors. The introduction of human papillomavirus (HPV) detection into the screening procedure implicates that we should give attention to this relationship. The aim of this study was to investigate what knowledge women have of the relation between HPV and cervical cancer. Rather than asking about HPV specifically, we suggested 20 risk factors for the development of cervical cancer, including viral infection, and asked 73 women visiting their general practitioner, 67 women visiting a lecture on risk factors for cervical cancer and 28 female students in biomedical sciences to rate the importance of these risk factors on a scale of 1-5. Genetic factors were rated highest with a mean score of 4.5. Bacterial infection ranked second highest with a mean score of 3.8. Smoking ranked fourth at a mean score of 3.6, whereas viral infection shared the sixth place with number of sexual partners with a mean score of 3.4. The presence of high voltage power lines and physical activity appropriately scored the last two places at 2.4 and 2.2, respectively. Twenty-one women suggested a role for sexually transmitted agents, but only five women (3.1%) could actually pinpoint HPV. This enquiry indicates that the risk factor 'genetic factors' was over-rated, while knowledge of the most important risk factors, i.e. smoking and sexual habits and (sexually transmitted) infections, would appear to be present to a moderate level in our population. However, knowledge of the role of HPV in cervical cancer development is lacking.


Recent trends of biomedical offprint distribution.
The total number of substantive articles published in a random group of U. S. biomedical journals increased 34 percent from 1957 through 1962 and 52 percent from 1952 through 1962. Likewise, the total number of subscriptions increased 28 percent from 1957 through 1962 and 47 percent from 1952 through 1962. On the other hand, the rise in the number of preprints and reprints distributed reached its peak from 1952 to 1957 (37 percent); by 1962 the rate had declined, with an increase of only 4 percent from 1957 to 1962 and thus of only 43 percent for the entire period, 1952 through 1962. Replies from publishers indicate that at present the provision of preprints and reprints is merely a service in the case of almost 90 percent of the journal titles and not an enterprise undertaken for significant profit. The cause of the decline in offprint distribution should be investigated.


Breath hydrogen excretion or plasma acetate levels during the lactulose tolerance test?
Since both acetate and hydrogen are produced by colonic bacterial fermentation, the clinical utility of the measurement of either parameter in nine subjects for the lactulose tolerance test was tested. The fasting plasma acetate concentration (mean +/- s.d., mmol/l) of 0.11 +/- 0.06 increased to peak levels between 150 min (0.23 +/- 0.12) and 180 min (0.23 +/- 0.09), both P less than 0.01, after ingesting 20 g lactulose. In one subject with previous gastrectomy and intestinal hurry, the peak was at 30 min. Mean post-lactulose acetate levels (0.21 +/- 0.09) were higher than fasting levels (P less than 0.03). Breath hydrogen excretion exhibited a similar trend. Indeed, a significant correlation (rs 0.39, P less than 0.01) was demonstrated between the acetate and hydrogen values. It is therefore concluded that patients for the lactulose breath test show fairly similar changes in plasma acetate and breath hydrogen excretion after lactulose ingestion. Either measurement could thus be used in assessing colonic fermentation in humans.


The urinary sodium/potassium ratio in children from southern Italy living in Cimitile: a case for concern.
The urinary sodium/potassium (Na/K) ratio was evaluated in 220 children aged 3-16 years living in Cimitile, a small town near Naples in Southern Italy by utilizing 24 hour urinary collections. The Na/K ratio averaged 3.79 +/- 1.68 and correlated significantly (p less than 0.001) with age, body weight and height but not with Body Mass Index (BMI). No difference was seen when data were analyzed by sex. Mean daily sodium excretion averaged 3.91 +/- 1.52 mM/Kg while potassium excretion averaged 1.17 +/- 0.54 mM.Kg. The Na/K ratio was higher than that observed in children studied in Israel, United Kingdom, USA, and the Federal Republic of Germany and is of the same magnitude of that previously reported in children born in Japan. This high Na/K ratio is a case for concern because of the risks connected with high Na/K ratio in urine.


[Akin moyamoya disease in children].
Moyamoya disease is characterized by bilateral involvement of the internal carotid arteries. The etiology of this involvement is unknown. However, we previously reported two pediatric cases of moyamoya disease that progressed from unilateral to bilateral involvement. Some cases of unilateral occlusion in the carotid fork seem to have occurred at an early stage of definite moyamoya disease. In the present study, we examined five pediatric patients showing bilateral and/or unilateral occlusion of the internal carotid artery. In each case, the etiology was known. They included Apert syndrome, radiation therapy for pilocytic astrocytoma, systemic lupus erythematosis, von Recklinghausen disease and Down syndrome. The clinical manifestations, EEG, CT, MRI, PET, and angiographic findings in these patients were presented in comparison with those of definite moyamoya disease. This comparison led us to suggest that definite moyamoya disease might be included in these cases, and we emphasize the importance of precise examination in each case.


Promotion of exclusive breastfeeding among HIV-positive mothers: an exploratory qualitative study.
Exclusive breastfeeding has the potential to reduce infant and under-five mortality, but research shows the practice is not widespread in resource-poor settings of sub-Saharan Africa. We explored factors influencing the decision to exclusively breastfeed among HIV-positive mothers accessing interventions for prevention of mother-to-child transmission of HIV in selected sites of Zambia. This exploratory qualitative study was embedded in research conducted on: HIV and infant feeding; choices and decision-outcomes in the context of prevention of mother-to-child transmission among HIV-positive mothers in Zambia. Thirty HIV-positive mothers and six key informants were recruited from two health facilities providing mother-to-child HIV transmission prevention services. A semi-structured guide was used to conduct interviews, which were digitally recorded and simultaneously transcribed. Data coding and analysis was done with the support of QRS Nvivo 10 version software. Despite the known benefits of exclusive breastfeeding, gaps in understanding and potential for behaviour change remained. We found that information promoting exclusive breastfeeding may have been understood by mothers as instructions from the health care workers indicating how to feed their HIV-exposed babies rather than as an option for the mothers' own informed-decision. This understanding influenced a mother's perceptions of breast milk safety while on antiretroviral medicine, of the formula feeding option, and of the baby crying after breastfeeding. The meanings mothers attached to exclusive breastfeeding thus influenced their understanding of breast milk insufficiency, abrupt weaning and mixed feeding in the context of preventing mother-to-child transmission of HIV. In order to enhance feeding practices for HIV-exposed infants, our study suggests a broader health campaign supporting all mothers to exclusively breastfeed.


Influence of temperature and gas atmosphere on in-vitro fertilization and embryo development in domestic cats.
The influence of culture temperature and gas atmosphere on in-vitro fertilization and embryo development was examined in the domestic cat. In Exp. 1, eggs were fertilized and cultured in 5% CO2 in air at 37, 38 or 39 degrees C. Experiment 2 evaluated the effects of 5% CO2 in air; 5% CO2, 5% O2 and 90% N2; and 10% CO2 in air. Fertilization (cleavage) and development to the morula/blastocyst stage were not influenced (P greater than 0.05) by variations in temperature and gas composition. Despite changing these culture conditions, egg cleavage averaged approximately 75% and greater than 80% of the 2-cell embryos proceeded to morulae in vitro. However, the partial in-vitro morula-to-blastocyst developmental block normally observed in this species was not removed.


Rapid maxillary expansion screws on the test bench--a pilot study.
In order to apply high, short-term forces during rapid maxillary expansion (RME) to the sutures of the maxilla with minimum loss of force and without causing unwanted side-effects (dentoalveolar tipping, etc.), the appliance should be as rigid as possible. The retention arms of the RME screws, representing a particularly vulnerable and stressed weak point of RME appliances, were the focus of this laboratory technical study. Retention arms of 16 types of RME screws comprising four arms and one with eight arms were examined using a three-point bending test. According to their ability to absorb the applied bending loads, the screws were classified in product groups from 1 (highest) to 6 (lowest). Fifteen of the tested retention arms (stainless steel), despite having the same diameter (1.48-1.49 mm), differed up to 69.81 per cent between the highest (288.0 N) and lowest (169.6 N) maximum force parameters and up to 66.40 per cent between the highest (3325.9 N/mm(2)) and lowest (1998.7 N/mm(2)) maximum bending stress parameters. Due to optimum formability, though reduced rigidity, a titanium screw for nickel-sensitive patients (group 6) displayed the lowest force and bending tension values. The stainless steel double arms of the eight-arm screw device welded on both ends displayed the highest force data. The mean ductilities of the groups with the most and least rigid single steel arms differed by 22.77 per cent. Statistical analysis using the Pearson correlation coefficient revealed a significant indirect correlation between ductility and both maximum force (r = -0.780, P < 0.001) and maximum bending stress (r = -0.778, P < 0.001). The SUPERscrews, the Tiger Dental four-arm screw (group 1), and the eight-arm screw displayed the highest capacity to absorb an applied bending load. The screws in groups 3-6 appear acceptable for RME during the pre-pubertal period, whereas in the pubertal and post-pubertal period, groups 1 and 2 are sufficient. In early adulthood only the screws in group 1 and especially the eight-arm screw seem advisable, as mechanical demands increase with age.


High pressure cell for Raman scattering at low temperatures.
An optical cell suitable for Raman studies and for absorption studies of gases, liquids, and solids is described. The cell has been used at temperatures down to 4.2 K and pressures up to 10 kilobars. It contains a sample chamber with special scattering geometry and a ruby manometer for in situ pressure measurements. Typical results are given for the impurity induced one phonon Raman spectra of doped alkali halides and for the fundamental vibrational Raman spectra of matrix-isolated molecules under pressure.


Exacerbation of indomethacin-induced gastric ulceration by systemically administered GABA in rats: possible involvement of peripheral GABA receptors.
Effects of systemically administered gamma-aminobutyric acid (GABA) on indomethacin-induced gastric ulceration were studied in rats. Orally administered GABA significantly exacerbated the ulceration in a dose-dependent manner, although GABA per se had no ulcerogenic activity. The exacerbation was restored by GABA receptor antagonists, bicuculline methiodide, picrotoxin and pentylenetetrazol. Pretreatment with atropine sulfate antagonized the exacerbating effect of GABA on indomethacin-induced ulceration. 3-Amino-1-propanesulfonic acid, but not glycine, taurine or beta-alanine, mimicked the effect of GABA on the ulceration, which was inhibited by picrotoxin. Muscimol and (-)-baclofen could not potentiate the ulceration. However, sodium pentobarbital and diazepam caused synergistic exacerbation of the ulcer when combined with GABA. Since it is known that systemically administered GABA can not penetrate into the brain, these results suggest that systemically administered GABA may stimulate the cholinergic transmission mediating the activation of peripheral GABA receptors, resulting in the exacerbation of indomethacin-induced ulceration.


Clinical usefulness of macrophage colony-stimulating factor for ovarian cancers: Long-term prognosis after five years.
We performed a randomized double blind study between 1992 and 1995 in which 214 patients with FIGO stage I to III ovarian cancers received administration of 10(6) units (low dose group) or 8x10(6) units (high dose group) of macrophage colony-stimulating factor (M-CSF) after cyclophosphamide/adriamycin/cisplatin (CAP) therapy. The period required to finish a set of intensive chemotherapy, which was the primary endpoint, was significantly shortened (p=0.0004), and the incidence of febrile neutropenia significantly decreased (p=0.04). In this study, we followed the patients for a prolonged period. The patients were divided into two groups: patients with complete tumor excision and those with incomplete excision, then the relapse rate and survival rate 5 years after initiation of the clinical study were compared. The relapse rate tended to be lower in the high dose group than in the low dose group in patients with no residual tumor (p=0.0750). However, there was no difference in the relapse rate between the two dose groups in patients with residual tumor. Although there were no significant differences in the survival rate between the high and low dose groups in patients with or without residual tumor, the survival rate in mucinous adenocarcinoma patients with no residual tumor was 64.3% in the low dose group (n=14) and 92.3% in the high dose group (n=14), showing a significantly higher rate (p=0.0436), and the survival rate tended to be higher in the high dose group in patients with serous adenocarcinoma (p=0.0786). Furthermore, in patients aged 40 years or younger with no residual tumor, the survival rates were 73.9 and 100% in the low and high dose groups, respectively, showing a significantly higher rate in the high dose group (p=0.0310). Our results suggest that administration of M-CSF can improve the long-term prognosis of ovarian cancer patients with no residual tumor, but further prospective randomized trials with a primary endpoint of relapse-preventing effect are needed.


Physiological Genetics Reformed: Bridging the Genome-to-Phenome Gap by Coherent Chemical Fingerprints - the Global Coordinator.
Forward-focused molecular genetics is successfully framing DNA diversity and mapping primary gene functions. However, abandoning the classic Linnaean fingerprint link between the phenome and genome by suppressing gene interaction (pleiotropy), has resulted in a genome-to-phenome gap and poor utilization of molecular data. We demonstrate how to bridge this gap by using an example of a barley mutant seed model, where pleiotropy is observed as covarying global molecular patterns that define each endosperm. Global coherence was discovered as a covariate coordinator within and between local genotype specific fingerprints. This implies that any of these fingerprints can select its recombinant global phenotype variant, including composition. Introducing the law of coherence, and the movement of gene complexes by chemical fingerprint traits as selectors, introduces a revolution in understanding physiological molecular genetics and plant-breeding.


Efficiency transfer and coincidence summing corrections for gamma-ray spectrometry
ETNA (Efficiency Transfer for Nuclide Activity measurements) is a new computer program providing both detector efficiency transfer for various types of sources for coaxial source-detector geometries and coincidence summing corrections. This program, available for use on PCs, has a direct link to the computerised database NUCLEIDE in order to automatically import the necessary radionuclide decay data. The specific features and facilities are outlined and examples are given.


Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase. Steps toward novel drugs for treating Alzheimer's disease.
We report highly potent, selective, and low cost bifunctional acetylcholinesterase (AChE) inhibitors developed by our two-step prototype optimization strategy utilizing computer modeling of ligand docking with target proteins: 1) identify low affinity sites normally missed by x-ray crystallography; and 2) design bifunctional analogs capable of simultaneous binding at the computer-determined low affinity site and the x-ray-identified high affinity site. Applying this strategy to 9-amino-1,2,3,4-tetrahydroacridine (THA), a drug for Alzheimer's disease, we obtained alkylene linked bis-THA analogs. These analogs were up to 10,000-fold more selective and 1,000-fold more potent than THA in inhibiting rat AChE and yet required one simple reaction to synthesize. Additionally, alkylene linked benzyl-THA analogs were developed to examine the specificity of the docking-derived low affinity THA peripheral site in AChE. The present work and our previous computational studies strongly suggest that a low affinity THA peripheral site exists in AChE. This peripheral site provides a structural basis for design of improved cholinesterase ligands for treating Alzheimer's disease and for other health-related purposes.


Extracellular glutamate: functional compartments operate in different concentration ranges.
Extracellular glutamate of glial origin modulates glial and neuronal glutamate release and synaptic plasticity. Estimates of the tonic basal concentration of extracellular glutamate range over three orders of magnitude (0.02-20 μM) depending on the technology employed to make the measurement. Based upon binding constants for glutamate receptors and transporters, this range of concentrations translates into distinct physiological and pathophysiological roles for extracellular glutamate. Here we speculate that the difference in glutamate measurements can be explained if there is patterned membrane surface expression of glutamate release and transporter sites creating extracellular subcompartments that vary in glutamate concentration and are preferentially sampled by different technologies.


Transplantation in rare lymphoproliferative and histiocytic disorders.
Some uncommon lymphoproliferative and histiocytic disorders may present with an aggressive course and require hematopoietic stem cell transplantation (HSCT) as part of the therapeutic approach. Published research on the use of HSCT for the treatment of these disorders was reviewed and summarized. Allogeneic HSCT may be indicated in patients with blastic plasmacytoid dendritic cell neoplasia, familial or secondary recurrent hemophagocytic lymphohistiocytosis, and resistant Langerhans cell histiocytosis. Autologous HSCT may be considered in patients with Castleman disease resistant to treatment. No role has been established for the use of HSCT for dendritic cell sarcoma. HSCT has an evolving role in the treatment of select aggressive lymphoproliferative and histiocytic disorders.


Surgery for non-Covid-19 patients during the pandemic.
In the early phase of the Covid-19 pandemic, mainly data related to the burden of care required by infected patients were reported. The aim of this study was to illustrate the timeline of actions taken and to measure and analyze their impact on surgical patients. This is a retrospective review of actions to limit Covid-19 spread and their impact on surgical activity in a Swiss tertiary referral center. Data on patient care, human resources and hospital logistics were collected. Impact on surgical activity was measured by comparing 6-week periods before and after the first measures were taken. After the first Swiss Covid-19 case appeared on February 25, progressively restrictive measures were taken over a period of 23 days. Covid-19 positive inpatients increased from 5 to 131, and ICU patients from 2 to 31, between days 10 and 30, respectively, without ever overloading resources. A 43% decrease of elective visceral surgical procedures was observed after Covid-19 (295 vs 165, p<0.01), while the urgent operations (all specialties) decreased by 39% (1476 vs 897, p<0.01). Fifty-two and 38 major oncological surgeries were performed, respectively, representing a 27% decrease (p = 0.316). Outpatient consultations dropped by 59%, from 728 to 296 (p<0.01). While allowing for maximal care of Covid-19 patients during the pandemic, the shift of resources limited the access to elective surgical care, with less impact on cancer care.


Escherichia fergusonii, an Underrated Repository for Antimicrobial Resistance in Food Animals.
A total of 1,400 samples of food animals (pigs, chickens, and ducks) were collected between July and September 2019 in China to uncover the prevalence of E. fergusonii and its potential role in the evolution of antimicrobial resistance (AMR). An isolation of E. fergusonii was performed and pulsed-field gel electrophoresis (PFGE) was used to uncover the genetic relationship. The AMR of E. fergusonii isolates was comprehensively characterized using broth microdilution-based antimicrobial susceptibility testing, S1-PFGE, southern hybridization, whole-genome sequencing, and in-depth bioinformatics analysis. As a result, a total of 133 E. fergusonii isolates were obtained. These isolates could be grouped into 41 PFGE subclades, suggesting a diverse genetic relationship. The resistance phenotypes of sulfafurazole (97.74%) and tetracycline (94.74%) were the most frequently found. Of the E. fergusonii isolates, 51.88% were extended spectrum beta-lactamase (ESBL)-positive. Forty-three different AMR genes were revealed based on 25 genome sequences harboring mcr-1. Briefly, aph(6)-Id, aph(3'')-Ib and tet(A) genes were the most frequently observed, with the highest rate being 76.00% (19/25). Three mcr-1-harboring plasmids were identified after Nanopore sequencing, including pTB31P1 (IncHI2-IncHI2A, 184,652 bp), pTB44P3 (IncI2, 62,882 bp), and pTB91P1 (IncHI2-IncHI2A, 255,882 bp). Additionally, 25 E. fergusonii isolates harboring mcr-1 were clustered together with other E. fergusonii isolates from different regions and sources available in GenBank, suggesting a possible random process of mcr-1 transmission in E. fergusonii. In conclusion, E. fergusonii is widespread in food animals in China and might be an important reservoir of AMR genes, especially mcr-1, and facilitate the evolution of AMR. IMPORTANCEE. fergusonii, a member of the genus Escherichia, has been reported to transmit via the food chain and cause diseases in humans. However, the prevalence of multidrug-resistant E. fergusonii, especially mcr-1-positive E. fergusonii isolates, has rarely been reported. Here, we collected 1,400 samples from food animals in three provinces of China and obtained 133 E. fergusonii isolates (9.5%). We found that the prevalence of E. fergusonii isolates was diverse, with high levels of antimicrobial resistance. Among them, 18.8% E. fergusonii isolates carried the colistin resistance gene mcr-1. Thus, E. fergusonii may facilitate the evolution of colistin resistance as a reservoir of mcr-1. As far as we know, the prevalence and AMR of E. fergusonii in the food animals in this study was first reported in China. These findings increase our understanding of the role of E. fergusonii in public health and the evolution of antibiotic resistance.


Safety considerations of polyunsaturated fatty acids.
The n-6 and n-3 polyunsaturated fatty acids (PUFAs) are essential nutrients; intake of relatively small amounts of these fatty acids prevents nutritional deficiencies. Replacing dietary saturated fat with PUFAs may confer health gains. Experimental data support the notion that high intake of n-6 PUFAs may increase in vivo lipid peroxidation. This effect may be counteracted by dietary antioxidant supplementation. The influence of a high n-3 PUFA intake on measures of lipid peroxidation has been equivocal. In clinical trials, subjects who consumed diets rich in n-6 or n-3 PUFAs had fewer atherothrombotic endpoints than did control groups. In this report, data regarding the influence of PUFAs on lipid peroxidation as well as on cholesterol and glucose metabolism, hemostasis, and other aspects of interest are reviewed and discussed. Currently, daily intake of PUFAs as >10% of total energy is not recommended. Below this ceiling there is little evidence that high dietary intake of n-6 or n-3 PUFAs implies health risks.


Minimal impairment in a rat model of duration discrimination following excitotoxic lesions of primary auditory and prefrontal cortices.
We present a behavioral paradigm for the study of duration perception in the rat, and report the result of neurotoxic lesions that have the goal of identifying sites that mediate duration perception. Using a two-alternative forced-choice paradigm, rats were either trained to discriminate durations of pure tones (range = [200,500] ms; boundary = 316 ms; Weber fraction after training = 0.24 ± 0.04), or were trained to discriminate frequencies of pure tones (range = [8,16] kHz; boundary = 11.3 kHz; Weber = 0.16 ± 0.11); the latter task is a control for non-timing-specific aspects of the former. Both groups discriminate the same class of sensory stimuli, use the same motions to indicate decisions, have identical trial structures, and are trained to psychophysical threshold; the tasks are thus matched in a number of sensorimotor and cognitive demands. We made neurotoxic lesions of candidate timing-perception areas in the cerebral cortex of both groups. Following extensive bilateral lesions of the auditory cortex, the performance of the frequency discrimination group was significantly more impaired than that of the duration discrimination group. We also found that extensive bilateral lesions of the medial prefrontal cortex resulted in little to no impairment of both groups. The behavioral framework presented here provides an audition-based approach to study the neural mechanisms of time estimation and memory for durations.


The role of oxybutynin in spinal cord injured patients with indwelling catheters.
The long-term benefits of oral oxybutynin in spinal cord injured patients with indwelling catheters is unknown. We reviewed our experience with this population of men and present the results of our analysis. A total of 109 male spinal cord injured patients at the Houston Veterans Affairs Medical Center have been treated with chronic indwelling catheters (80 transurethral and 29 suprapubic). Thirty-eight patients (35%) were identified as using oxybutynin on a regular basis. These patients were compared to those not using oxybutynin with regard to urodynamic parameters and upper tract deterioration. Specifically examined were bladder compliance, bladder leak point pressure, vesicoureteral reflux, hydronephrosis, urolithiasis, febrile urinary tract infections and serum creatinine greater than 2 mg./dl. The mean duration of indwelling catheter use was 11.9 years (12.4 without oxybutynin and 10.9 on oral oxybutynin). Of the 31 patients with normal compliance (greater than 20 ml./cm. water), 24 (77%) were using oxybutynin (p = 0.001). Bladder leak point pressures were abnormal (greater than 35 cm. water) in 5 of 32 patients (16%) on oxybutynin versus 34 of 60 (57%) without it (p <0.001). Hydronephrosis was present in 15 of 66 patients (23%) without oxybutynin versus 1 of 36 (3%) with oxybutynin (p = 0.009). Febrile urinary tract infections occurred in 4 of 35 patients (11%) versus 17 of 62 patients (27%) with or without oxybutynin, respectively (p = 0.077). No significant differences were found between the 2 groups with regard to reflux, renal scars, stones or elevated serum creatinine. It appears that regular use of oxybutynin may be beneficial in spinal cord injured patients who require chronic indwelling catheters for bladder management. Our analysis reveals that patients who take oxybutynin regularly have better bladder compliance, lower bladder leak point pressures and less hydronephrosis. Until a prospective, randomized trial reveals contradicting outcomes, empiric use of oxybutynin in all spinal cord injured patients requiring chronic indwelling catheters seems justified.


Postpartum thyroiditis in India: prevalence of postpartum thyroiditis in Kashmir Valley of Indian sub-continent.
Various studies have reported a spectrum of thyroid dysfunction in the postpartum period. Postpartum thyroiditis is a syndrome of thyroid dysfunction that occurs in the first year after parturition. Prevalence of postpartum thyroiditis has been reported to vary from 3 to 6 percent in different regions of the world. Kashmir Valley is inhabited by a relatively homogeneous racial group and the Valley has been documented to have significant iodine deficiency. We studied the prevalence and pattern of postpartum thyroiditis in an urban region of this Valley. 120 women were registered within first month of postpartum period for the study along with one hundred controls. Of these 120 women, 104 reported for follow-up at 3 months postpartum and 106 reported for follow-up at 6 months postpartum. Initial and subsequent clinical details at follow-up were recorded on a pre-determined questionnaire. Overall, postpartum thyroiditis (PPT) was seen in 8 (7%) study subjects. Of these 8 patients with PPT, 4 had biochemical evidence of thyrotoxicosis at first month, 3 developed biochemical thyrotoxicosis at 3-month follow-up while as one study subject developed thyrotoxicosis at 6 months. Most of these subjects were antithyroid antibodies (anti-microsomal and anti-thyroglobulin) positive. We conclude that iodine deficient status of the community doesn't seem to influence the incidence of PPT.


Theoretical study of the ammonia-hypochlorous acid reaction mechanism.
A mechanism for the oxidation of ammonia by hypochlorous acid to form nitrogen gas has been developed at the B3LYP/6-31G(d,p) level of theory using the Gaussian 03 software package. The formation of NH(2)Cl, NHCl(2), and NCl(3) was studied in the gas phase, with explicit water molecules included to examine the transition state energy in aqueous solution. The inclusion of explicit water molecules in the transition state dramatically reduced the reaction barrier in reactions involving transfer of a hydrogen atom between molecules, effects that were not taken into account through use of a solvation model alone. Three mechanisms were identified for the decomposition of chloramine species to form N(2), involving the combination of two chloramine species to form hydrazine, dichlorohydrazine and tetrachlorohydrazine intermediates. The highest barrier in each pathway was found to be the formation of the hydrazine derivative.


Macrophage metalloelastase-12 is detectable in human seminal plasma and represents a predictor for inflammatory processes in the male genital tract.
Macrophage metalloelastase-12 (MMP-12), a protein of the matrix metalloproteinase family, is involved in the breakdown of extracellular matrix in normal physiological processes as well as in disease processes. MMP-12 is almost exclusively produced by macrophages and is associated with inflammatory disorders. Giving the fact that inflammation negatively influences ejaculate parameters, we investigated a possible presence and correlation of MMP-12 in seminal plasma with parameters of the ejaculate, especially in leucocytospermic ejaculates. Forty-two patients who presented for semen analysis were assigned into four groups depending on the result of semen analysis according to the WHO guidelines 2010: normozoospermia (n = 11), OAT (n = 10), azoospermia (n = 10) and leucocytospermia (>1 mio. peroxidase-positive cells per ml) (n = 11). MMP-12 was detected by ELISA and was measurable in nearly all seminal plasma samples. Generally, MMP-12 concentrations were significantly higher in leucocytospermic samples than in nonleucocytospermic ones (P = 0.001). The MMP-12 levels between the latter nonleucocytospermic groups did not differ. Moreover, MMP-12 levels correlated with the presence of peroxidase-positive leucocytes. No correlation with CD 14 positive monocytes/macrophages was detected. In this study, we demonstrate that MMP-12 is present in seminal plasma and is correlated with inflammatory conditions in human semen and therefore may serve as predictor of ongoing inflammatory processes.


Endoscopic treatment of the benign and malignant esophageal stenosis.
Gastrointestinal endoscopy was born almost 40 years ago as diagnostic modality, but in last two decades with gradually developing of therapeutic possibilities gastroenterologists have taken an increasing role in the iinterventional treatment of many upper gastrointestinal problems. Modalities of treatment for esophageal stenoses were explained. Endoscopists should be aware that all of these methods has their limitations and they must be able to balance technological enthusiasm with full consideration of the patients qualities of life. All of this treatments are palliative, risky and only partially effective at best. They often need to be repeated. Even achieving a large lumen will not restore normal swallowing. The goal must be to restore "adequate but not perfect" swallowing, at lowest risk, cost and inconvenience to the patient.


Multi-scale locally low-rank noise reduction for high-resolution dynamic quantitative cardiac MRI.
Evaluation of myocardial T1 times is conventionally limited to a single temporal snapshot of the cardiac cycle, leaving the dependence between functional and tissue characterization unexplored. We recently proposed a technique that alleviates this limitation by acquiring dynamic quantitative myocardial T1 maps. However, tradeoffs between temporal resolution, scan duration and SNR limit the spatial resolution. In this work, we propose a multi-scale locally low rank noise reduction approach without parameter-tuning to enable high acceleration rates in the acquisition, facilitating superior spatial and temporal resolutions in dynamic myocardial T1 mapping.


The Association Between African American Parent-Child Sex Communication and Adolescent Condomless Sex.
African American adolescents are at elevated risk for HIV and sexually transmitted infections. Risk reduction efforts have focused on parent-child communications, despite inconsistent findings regarding their association with adolescent sexual risk behaviors. The present study included sexually active African American adolescents and their parents/guardians (N = 125 dyads). All participants reported on frequency of sexual health conversations and adolescents reported recent occasions of protected and condomless sex. Analyses examined the congruence between parent-child communication reports and the association between this congruence and adolescent condomless sex. Parents and adolescents disagreed on the frequency of sexual health communication: 30% of parents reported such conversations as frequent, whereas only 2% of adolescents did. Parent-reported sex communication was negatively associated with adolescent condomless sex, while adolescent-reported communication was not. The moderation hypothesis was supported in that adolescent-reported sex communication was negatively associated with adolescent condomless sex only among parent-child dyads high in agreement on sexual health communication. Promoting parent-child conversations regarding sexual health, with attention to relational characteristics of the conversations, offers a promising approach to sexual health promotion and disease prevention for African American youth.


Ovarian susceptibility to benzo[a]pyrene: tissue burden of metabolites and DNA adducts in F-344 rats.
Exposure to environmental toxicants has been implicated as one of the causative factors for infertility in mammals. The objective of this study was to determine the amount of ingested benzo[a]pyrene (BaP), an environmental toxicant that reaches the reproductive tissues (internal dose) subsequent to a single acute exposure. Toward this end, the concentrations of BaP reactive metabolites and BaP-DNA adducts were measured throughout the course of BaP's residence in the body. Ten-week-old female Fischer-344 rats weighing approximately 220 g were administered 5 mg BaP/kg body weight orally. 1, 7, 14, 2,1 and 28 d post BaP exposure, BaP parent compound and metabolites from plasma, ovaries, and liver tissues were extracted using liquid-liquid extraction. The extracts were analyzed by reverse-phase highperformance liquid chromatography (HPLC). DNA was isolated and analyzed for BaP-induced DNA adducts by (32)P-postlabeling method. The BaP total metabolite concentrations in plasma, ovaries, and liver showed a gradual decrease from d 1 to 28 post BaP administration. The BaP-DNA adducts concentrations in ovaries and liver tissues from the treatment group demonstrated a trend similar to that observed for metabolites. Ovaries showed greater concentrations of DNA adducts compared to liver. However, with an increase in time post cessation of exposure, the adduct concentrations in liver tissue started declining rapidly, from d 1 to 28. For ovaries, the adduct concentrations demonstrated a significant decline from d 1 to 7 and a gradual fall thereafter. A concordance between BaP reactive metabolite levels and adduct concentrations indicates that the bioavailability of reactive metabolites determines the binding with DNA and consequently the formation and persistence of adducts in an acute exposure regimen.


Levels of specific antigen (gp43), specific antibodies, and antigen-antibody complexes in saliva and serum of paracoccidioidomycosis patients.
The present study analyses human immunoglobulin G (IgG) antibodies directed against the Paracoccidioides brasiliensis exoantigen, gp43, as well as the presence of gp43-IgG immune complexes (ICs) in 31 samples of saliva and serum from 19 patients with paracoccidioidomycosis (PCM) and 12 normal donors. Additional analysis of secretory IgA (sIgA) was performed on the same saliva samples. Consistent with previous findings, a significant increased specific IgG level was observed in PCM patients' saliva and serum (P < 0.05). The analysis of serum gp43 and gp43-IgG IC demonstrated a higher level in patients with PCM (P < 0.05); however, this difference was not statistically significant with regard to gp43 and gp43-IgG in saliva when compared to the healthy donors. A high level of sIgA in saliva of PCM patients compared to that of normal donors was also observed (P < 0.05). Patients exhibiting low levels of serum IgG but with high titres of IC were observed, thus strengthening the idea of the necessity to use more than one marker for diagnosis and treatment monitoring of PCM. This is the first report of sIgA in PCM patients' saliva and may be indicative of a protective role in neutralizing antigens on mucosal surfaces.


The emerging concept of antigen-driven lymphomas: epidemiology and treatment implications.
Dramatic increases in the incidence of lymphomas worldwide have stimulated considerable efforts to identify factors that contribute to the etiology of this heterogeneous group of malignancies. The treatment and, ultimately, the prevention of lymphoma depend on our understanding of the complex interaction of exogenous agents with the molecular milieu which initiates and sustains a lymphoid malignancy. This review discusses the current evidence for the role of foreign or self antigens in the initiation of lymphomagenesis. Recent data have demonstrated an increased risk of lymphoma among individuals with chronic inflammatory conditions, persistent infections or immunodeficient states. Common to these clinical conditions is antigenic stimulation leading to an inflammatory cascade of cellular and cytokine reactions that may tax the host immune response, provoke tissue injury and eventually result in lymphoid neoplasia. Efforts to detect and suppress chronic, antigen-driven inflammation have suggested that neoplastic progression may often be interrupted and controlled. Elucidation of the etiologic mechanisms critical to the survival of these malignancies would provide promising alternatives for the prevention and treatment of some lymphomas.


Functional Supported ZnO/Bi2MoO6 Heterojunction Photocatalysts with 3D-Printed Fractal Polymer Substrates and Produced by Innovative Plasma-Based Immobilization Methods.
Inorganic photocatalysts became an essential and powerful tool for the remediation of polluted water. However, important limitations of photocatalysts in their colloidal form, especially nanosized, remain. For instance, their separation from water after use and recovery, which can be particularly demanding, time- and energy-wise. Considering such aspects, supported catalysts bear significant advantages. However, efforts still have to be made to develop processes that allow the permanent and efficient immobilization of inorganic photocatalysts in sustainable conditions, in order to maintain the advantages of supported catalysts over colloidal ones. Herein, we report the use of an aqueous-phase plasma-aided grafting (APPAG) process to produce functional and efficient hybrid photocatalysts. More specifically, based on cold plasma discharge (CPD), ZnO/Bi2MoO6 heterojunctions were permanently immobilized on polymer supports generated by 3D-printing, with fractal-inspired designs. Three different approaches of the APPAG process have been successfully used for the immobilization of the inorganic phase, that is core-shell-assisted direct grafting, indirect grafting and in situ complexation-assisted precipitation (ISCAP). Noticeably, the latter technique has never been reported before to our knowledge. These three immobilization routes rely on different strategies and yield to distinct morphological specificities, but all allow using mild synthesis conditions and producing stable, active, permanently immobilized coatings of photocatalysts. Regarding the preparation of the organic supports, two sorts of additive manufacturing (AM) technologies were employed, namely fused-deposition modeling (FDM) and liquid crystal diode (LCD)-based SLA (stereolithography). The use of fractal geometries combined with AM permits the production of supports with relatively high surface areas, in a single processing step. Overall, the three plasma-based immobilization methods revealed to be efficient and the performance of the different hybrid photocatalysts have later been assessed through the photodegradation of Rhodamine B dye under simulated sunlight irradiation and visible light only, with promising results.


Endothelial cell loss after small incision cataract surgery.
The corneal endothelium plays an important role in maintaining the dehydrated state and the transparency of the cornea. Some degree of endothelial cell loss invariably occurs in all types of cataract surgery but the amount of endothelial cell loss varies with the surgical technique. To evaluate the density of the central corneal endothelial cells before and after small incision cataract surgery (SICS) with posterior chamber intraocular lens (PC IOL) implantation. A total of 100 eyes of 100 patients undergoing SICS with PC IOL were included in the study. Endothelial cell density was measured with non-contact specular microscope pre-operatively and post-operatively on Day 1, Day 7 and at one month. The mean endothelial cell count pre-operatively was 2673 ± 358.85 cells / sq mm while post-operatively at 1 month it was 2249.77 ± 354.04 cells / sq mm. There is 15.83 % reduction in endothelial cell count after SICS with PC IOL implantation, which is comparable with other modes of cataract surgery like extra-capsular cataract extraction and phacoemulsification.


Multifunctional Polymer Nanoparticles for Dual Drug Release and Cancer Cell Targeting.
Multifunctional polymer nanoparticles have been developed for cancer treatment because they could be easily designed to target cancer cells and to enhance therapeutic efficacy according to cancer hallmarks. In this study, we synthesized a pH-sensitive polymer, poly(methacrylic acid-co-histidine/doxorubicin/biotin) (HBD) in which doxorubicin (DOX) was conjugated by a hydrazone bond to encapsulate an immunotherapy drug, imiquimod (IMQ), to form dual cancer-targeting and dual drug-loaded nanoparticles. At low pH, polymeric nanoparticles could disrupt and simultaneously release DOX and IMQ. Our experimental results show that the nanoparticles exhibited pH-dependent drug release behavior and had an ability to target cancer cells via biotin and protonated histidine.


Identification of varicella-zoster virus-specific CD8 T cells in patients after T-cell-depleted allogeneic stem cell transplantation.
To study the role of CD8 T cells in the control of varicella-zoster virus (VZV) reactivation, we developed multimeric major histocompatibility complexes to identify VZV-specific CD8 T cells. Potential HLA-A2 binding peptides from the putative immediate-early 62 protein (IE62) of VZV were tested for binding, and peptides with sufficient binding capacity were used to generate pentamers. Patients with VZV reactivation following stem cell transplantation were screened with these pentamers, leading to the identification of the first validated class I-restricted epitope of VZV. In 42% of HLA-A2 patients following VZV reactivation, these IE62-ALW-A2 T cells could be detected ex vivo.


Demographic characteristics of the population of FR Yugoslavia by nationality.
Changes in the ethnic composition of Yugoslavia as a whole are analyzed using data from censuses carried out between 1948 and 1991. "The subject matter of the analysis [was] the differences in natural movements (birth rate, death rate, natural increase) and migrations by nationalities, as well as marriages and divorces of people of different nationalities." Problems concerning the various ways of identifying ethnic groups by nationality or language are also reviewed.


A bacterial artificial chromosome-based genetic linkage map of the nematode Pristionchus pacificus.
To understand the evolution of developmental processes, nonmodel organisms in the nematodes, insects, and vertebrates are compared with established model systems. Often, these comparisons suffer from the inability to apply sophisticated technologies to these nonmodel species. In the nematode Pristionchus pacificus, cellular and genetic analyses are used to compare vulva development to that of Caenorhabditis elegans. However, substantial changes in gene function between P. pacificus and C. elegans limit the use of candidate gene approaches in studying P. pacificus mutations. To facilitate map-based cloning of mutations in P. pacificus, we constructed a BAC-based genetic linkage map. A BAC library of 13,440 clones was generated and completely end sequenced. By comparing BAC end and EST sequences between the "wild-type" strain P. pacificus var. California and the polymorphic strain P. pacificus var. Washington, 133 single-stranded conformational polymorphisms were identified. These markers were tested on a meiotic mapping panel of 46 randomly picked F(2) animals after a cross of the two strains, providing the first genetic linkage map of P. pacificus. A mapping strategy using two selected markers per chromosome was devised and the efficiency of this approach was illustrated by the mapping of the Ppa-unc-1/Twitchin gene.


The Brugmann Fatigue Scale: An Analogue to the Epworth Sleepiness Scale to Measure Behavioral Rest Propensity.
Background: While often confused, fatigue (as opposed to sleepiness) mostly requires rest, not sleep, to recover from. Clinical evaluations of fatigue mainly rely on assessments of symptom intensity, however without taking into account the need to engage in behavioral countermeasures. We therefore developed an 8-item 4-point Likert scale (the Brugmann Fatigue Scale; BFS) sharing a similar conceptual background with the Epworth Sleepiness Scale (ESS), assessing mental and physical fatigue and focusing specifically on rest propensity. Methods: Out of 496 consecutive patients addressed to the sleep unit of an academic hospital, we selected a sample of 295 hypnotic-free subjects (122 females). The present study examines (a) the psychometric properties of the BFS and (b) measurement invariance regarding perceived sleep quality, in parallel with common sleepiness and fatigue scales (ESS and Fatigue Severity Scale; FSS). In addition, (c) correlations of the BFS with clinical scales and polysomnographic variables were explored descriptively. Results: Rasch analyses revealed that the BFS possesses sound psychometric characteristics (rating scale functioning, item fit, dimensionality and measurement invariance) allowing for valid, reliable, linear and unidimensional measurement of mental and physical rest propensity, irrespective of perceived sleep quality, age, or gender. In addition, the BFS was significantly correlated to periodic limb movements during sleep and inversely to REM sleep duration. For both mental and physical subscales, scores above 6 are proposed as cutoff values. Conclusion: In analogy to the ESS, the BFS shows to be a unique and precise instrument assessing symptomatic fatigue with respect to rest propensity.


Findings of unique small muscle fibers at the superficial portion of the orbicularis oculi in the lateral canthal region of Japanese adult cadavers.
This study reports the existence of previously unknown muscle fascicles in Japanese adult cadavers. A bundle of these muscle fascicles diverged from the pretarsal portion of the orbicularis oculi muscle and coursed in a lateral direction superficial to this muscle. When observed with the naked eye, the bundle seemed to originate at the medial canthus and run along or near the edge of the upper eyelid. However, its boundary with the orbicularis oculi muscle was indistinguishable until it crossed superficial to this muscle. Throughout our observations, the thin muscle bundle was identified with high frequency (94%, 49 of 52 individual cadavers), and is thus unlikely to be an artifact. Light microscopy revealed that, in sagittal sections, the thin muscle bundle was located on the superficial side of the lateral portion of the orbicularis oculi muscle, while in horizontal sections, it ran in a superficial plane to the orbicularis oculi muscle in a medial to lateral direction. Despite having some similarity to a muscular raphe, the lateral canthal band, and to one of the previously known inferior muscles of the orbicularis oculi muscle, the results of our anatomical study suggest that the bundle is none of these. Rather, it is a previously unreported muscle that likely contributes to the surface morphology at the lateral canthus.


The increasing trend in Japan of müllerian mixed tumor of endometrium.
An increasing trend in Japan of Müllerian mixed tumor (MMT) of the endometrium has been suspected from both the Annual Pathological Autopsy Records in Japan (APARJ) and an analysis of surgical cases from the National Cancer Center Hospital (NCCH). One hundred and four MMT cases were recorded in APARJ during the period, 1965-1984, which constituted 1.1% of all malignant uterine tumors. The number of MMT cases in the past 10 years (87 cases during the period, 1975-1984) increased more than fivefold over that of the previous 10 years (17 cases during the period, 1965-1974). The proportion among malignant uterine tumors also increased from 0.5 to 1.5%. Eighteen patients with MMT underwent surgery in the NCCH during the period, 1963-1986, which accounted for 4.3% of endometrial malignant tumor cases. Of these only one was resected during the 12-year period, 1963-1974, while there were 17 surgically resected cases during the 12 years from 1975 to 1986. These represented 0.8 and 5.7%, respectively of malignant tumors of the endometrium during the two periods. In five out of 18 cases, MMT occurred as a second primary malignancy, and in all cases the histology was one of mesodermal mixed tumor. It was suggested that its occurrence as a second primary malignancy would be contributing to the recent increase of MMT in Japan.


Use of locally weighted scatterplot smoothing (LOWESS) regression to study selection signatures in Piedmontese and Italian Brown cattle breeds.
Selection is the major force affecting local levels of genetic variation in species. The availability of dense marker maps offers new opportunities for a detailed understanding of genetic diversity distribution across the animal genome. Over the last 50 years, cattle breeds have been subjected to intense artificial selection. Consequently, regions controlling traits of economic importance are expected to exhibit selection signatures. The fixation index (Fst ) is an estimate of population differentiation, based on genetic polymorphism data, and it is calculated using the relationship between inbreeding and heterozygosity. In the present study, locally weighted scatterplot smoothing (LOWESS) regression and a control chart approach were used to investigate selection signatures in two cattle breeds with different production aptitudes (dairy and beef). Fst was calculated for 42 514 SNP marker loci distributed across the genome in 749 Italian Brown and 364 Piedmontese bulls. The statistical significance of Fst values was assessed using a control chart. The LOWESS technique was efficient in removing noise from the raw data and was able to highlight selection signatures in chromosomes known to harbour genes affecting dairy and beef traits. Examples include the peaks detected for BTA2 in the region where the myostatin gene is located and for BTA6 in the region harbouring the ABCG2 locus. Moreover, several loci not previously reported in cattle studies were detected.


Categorization of fragrance contact allergens for prioritization of preventive measures: clinical and experimental data and consideration of structure-activity relationships.
Contact allergy to fragrances is still relatively common, affecting ∼ 16% of patients patch tested for suspected allergic contact dermatitis, considering all current screening allergens. The objective of the review is to systematically retrieve, evaluate and classify evidence on contact allergy to fragrances, in order to arrive at recommendations for targeting of primary and secondary prevention. Besides published evidence on contact allergy in humans, animal data (local lymph node assay), annual use volumes and structure-activity relationships (SARs) were considered for an algorithmic categorization of substances as contact allergens. A total of 54 individual chemicals and 28 natural extracts (essential oils) can be categorized as established contact allergens in humans, including all 26 substances previously identified as contact allergens (SCCNFP/0017/98). Twelve of the 54 individual chemicals are considered to be of special concern, owing to the high absolute number of reported cases of contact allergy (>100). Additionally, 18 single substances and one natural mixture are categorized as established contact allergens in animals. SARs, combined with limited human evidence, contributed to the categorization of a further 26 substances as likely contact allergens. In conclusion, the presence of 127 single fragrance substances and natural mixtures should, owing to their skin sensitizing properties, be disclosed, for example on the label. As an additional preventive measure, the maximum use concentration of 11 substances of special concern should be limited to 100 ppm. The substance hydroxyisohexyl 3-cyclohexene carboxaldehyde and the two ingredients chloroatranol and atranol in the natural extracts Evernia prunastri and Evernia furfuracea should not be present in cosmetic products.


Choice-matching preference reversals in health outcome assessments.
Health outcome utility assessments generally assume procedural invariance. Preference reversals violating procedural invariance occur in economic scenarios when the assessment process shifts from a choice to a fill-in-the-blank task. To determine if similar reversals occur in utility assessments. One hundred thirty-six volunteer subjects completed 6 preference assessments of 4 personal health scenarios. Patients responded to otherwise identical tasks using either choice or fill-in-the-blank processes in a randomized crossover design. The authors determined the percentage of subjects preferring, or inferred to prefer, a given choice. Preference reversals occurred in all assessment scenarios. These preference reversals are a potential source of confusion for utility assessment and informed consent. They could be manipulated to achieve ends other than the best interest of patients. Anchoring or the prominence hypothesis may explain these findings.


COVID-19 Vaccination Behavior of People Living with HIV: The Mediating Role of Perceived Risk and Vaccination Intention.
The COVID-19 vaccination behavior of people living with HIV (PLWH) was examined via a cross-sectional web-based survey of PLWH aged 18 years and older. The survey was conducted from l May to 20 June 2021. The survey included social demographic information; vaccination behavior (B); and questions related to perceived usefulness (PU), perceived risk (PR), subjective norms (SNs), perceived behavior control (PBC), and behavior intention (BI). The associations between the questionnaire variables and COVID-19 vaccination behavior were assessed by calculating the descriptive data, correlation analysis, and structural equation modeling. In total, 43.71% of the 350 eligible respondents had received a COVID-19 vaccine. The differences in COVID-19 vaccination behavior according to age, gender, religious belief, marital status, income, education level, and occupation were not obvious (p > 0.05). PU had a significantly negative effect on PR (p < 0.05). PR had a significantly negative effect on BI (p < 0.05). SNs had a significantly positive effect on BI (p < 0.05). BI had a significantly positive effect on B (p < 0.05). PR fully mediated the effects of PU on BI, BI fully mediated the effects of PR on B, and BI fully mediated the effects of SNs on B (p < 0.05). Health policymakers and medical workers should provide more information about the risks of vaccine application to improve the vaccination behavior of PLWH.


Intrathecal clonidine and tizanidine in conscious dogs: comparison of analgesic and hemodynamic effects.
Intrathecal delivery of alpha(2)-adrenergic agonists produces an analgesic effect. However, hemodynamic side effects limit their clinical usage. To more fully characterize the effects on heart rate and arterial blood pressure of alpha(2)-adrenergic agonists, clonidine and tizanidine were injected intrathecally in conscious dogs. Both compounds produced a potent inhibition of thermal foot-withdrawal latencies at 1000 micrograms, which was blocked by the alpha(2)-adrenergic antagonist yohimbine. Tizanidine (250-500 micrograms) did not change heart rate. Clonidine (500 -2000 micrograms) and tizanidine (1000-2000 micrograms) decreased heart rate. The tizanidine effect was inhibited by yohimbine and the alpha(2)/imidazoline antagonist idazoxan, as well as the parasympathetic blocker glycopyrrolate. No drug completely inhibited the clonidine-induced bradycardia. Clonidine had a biphasic effect on arterial blood pressure, a decrease at 500 micrograms and an increase at 2000 micrograms. Tizanidine decreased arterial blood pressure at all doses. The results indicate that, while the analgesic effects of both drugs are similar, the hemodynamic responses differ. While the decrease in heart rate with tizanidine is consistent with alpha(2)-adrenergic binding and vagal action, the bradycardia induced by clonidine is more complex. In addition, the increased arterial blood pressure with high doses of clonidine, which is suggestive of a peripheral vasoconstrictive effect, does not occur with tizanidine.


Will they fit? Development of a measurement device to assess body habitus compatibility with MRI bore diameter for emergency trauma imaging.
Excessive obesity poses a significant limitation to radiographic magnetic resonance imaging (MRI), particularly related to aperture or bore diameter due to the patient's girth. Determination of whether a patient will fit into the bore of the MRI scanner is currently accomplished using patient height, weight, and MRI technician experience. These simple methods have proven unreliable. We sought to develop a device and method which could accurately determine whether a patient would fit into the MRI scanner. We developed an MRI template prototype which was tested against the standard radiology methods in a pilot study (n = 6). We then performed a prospective validation study in adult human volunteers (n = 100) to assess the accuracy of the MRI template. We collected height, weight, shoulder and pelvis girth/diameter for each study participant to evaluate the body dimension measurements that would assist in determination of whether a patient would fit into the MRI scanner. Using the MRI template, we determined that 11 of the 100 study participants would not fit in the MRI scanner and 10 were confirmed to not fit into the MRI aperture [positive predictive value (PPV) 0.91 (0.58-0.99); negative predictive value (NPV) 1.00 (0.95-1.00), sensitivity 1.00 (0.69-1.00), specificity 0.99 (0.93-0.99), likelihood ratio positive test 90 (12.81-632), likelihood ratio negative test 0, accuracy 99%]. In comparison, the body measurement method did not perform as well [PPV 0.66 (0.34-0.90), NPV 0.97 (0.92-0.99), sensitivity 0.80 (0.44-0.97), specificity 0.95 (0.89-0.98), likelihood ratio positive test 17.97 (6.56-49.2), likelihood ratio negative test 0.209 (0.06-0.72), accuracy 94%]. This study confirmed that the use of an MRI template is an accurate tool in determining whether an obese patient can fit through the MRI bore and be accommodated in the MRI scanner.


The beginning of a decline in breast cancer incidence in Italy?
The incidence of invasive breast cancer in Turin, Italy, showed a statistically significant decrease during 1999-2003 overall (estimated annual percent change -2.6; 95% CL -8.52; -0.78) and in women aged over 50, similar to the recently documented trend in American data. This represents the first demonstration of a decline in breast cancer incidence in the early years of this decade outside the United States. In our population, the drop in the usage of hormone replacement therapy which occurred after 2002 is unlikely to be at the origin of this declining incidence trend, which is largely explained by a screening effect. This observation may be relevant to other geographical areas where organized or spontaneous screening reached a plateau after an increase in the preceding years.


Self-help and long-term behavior therapy for obesity.
The Trevose Behavior Modification Program, a self-help group offering continuing care for obesity, has recently been shown to produce large long-term weight losses. The present study aimed to replicate this finding across different settings and participants, assessing the weight losses and attrition rates of 128 participants in three Trevose program satellite groups that used the same treatment procedures and manual as the central Trevose group. The satellite groups' results closely paralleled those of the Central Group. Mean intent-to-treat weight loss, or final losses recorded for all participants regardless of their treatment termination date, was 13.7 +/- 0.7% of initial body weight (1.8 +/- 0.7 kg). At two years, 43.8% of participants remained in treatment, having lost a mean of 19.0 +/- 0.8% of their body weight (16.2 +/- 1.0 kg); at five years, 23.4% remained, having lost 18.4 +/- 1.1% of body weight (15.6 +/- 1.5 kg). These results demonstrate that the Trevose model of weight control, combining self-help and continuing care, can be extended and disseminated to other settings, with potentially significant public health consequences.


Association between the intake of plant and animal proteins and the serum fibroblast growth factor-23 level in patients with chronic kidney disease analyzed by the isocaloric substitution model.
Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by the bone in response to dietary phosphate intake. Since the phosphate content in the diet correlates with the protein content, both plant- and animal-based protein intake can increase the serum FGF23 level. However, a higher percentage of energy from plant protein than from animal protein is associated with a lower serum FGF23 level in patients with chronic kidney disease (CKD) in the United States. Since dietary habits differ between Asian and Western populations, we performed a cross-sectional study to determine the association between the percentages of energy from plant and animal proteins and the serum FGF23 level in Japanese CKD patients. In 107 non-dialysis CKD patients (age: 66 ± 9 years; estimated glomerular filtration rate: 56 ± 21 mL/min/1.73 m2), the percentages of energy from plant and animal proteins were assessed using a food frequency questionnaire based on food groups. Venous blood samples were used to measure the serum FGF23, phosphate, 1,25-dihydroxyvitamin D, and intact parathyroid hormone levels. The percentages of energy from plant and animal proteins showed a negative and positive association, respectively, with the serum FGF23 level. Furthermore, isocaloric substitution modeling showed that replacing animal protein with plant protein was associated with a low serum FGF23 level. Our findings suggest that encouraging diets with high plant protein level may prevent an increase in the serum FGF23 level in Japanese CKD patients.


Comparison of plant families in a greenhouse phytoremediation study on an aged polycyclic aromatic hydrocarbon-contaminated soil.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, recalcitrant, and potentially carcinogenic pollutants. Plants and their associated rhizosphere microbes can promote PAH dissipation, offering an economic and ecologically attractive remediation technique. This study focused on the effects of different types of vegetation on PAH removal and on the interaction between the plants and their associated microorganisms. Aged PAH-polluted soil with a total PAH level of 753 mg kg(-1) soil dry weight was planted with 18 plant species representing eight families. The levels of 17 soil PAHs were monitored over 14 mo. The size of soil microbial populations of PAH degraders was also monitored. Planting significantly enhanced the dissipation rates of all PAHs within the first 7 mo, but this effect was not significant after 14 mo. Although the extent of removal of lower-molecular-weight PAHs was similar for planted and unplanted control soils after 14 mo, the total mass of five- and six-ring PAHs removed was significantly greater in planted soils at the 7- and 14-mo sampling points. Poaceae (grasses) were the most effective of the families tested, and perennial ryegrass was the most effective species; after 14 mo, soils planted with perennial ryegrass contained 30% of the initial total PAH concentration (compared with 51% of the initial concentrations in unplanted control soil). Although the presence of some plant species led to higher populations of PAH degraders, there was no correlation across plant species between PAH dissipation and the size of the PAH-degrading population. Research is needed to understand differences among plant families for stimulating PAH dissipation.


Hydatidiform mole and HLA. II. Compatibility between patient and conceptus.
In 52 conceptuses with known genomic origin, the HLA types expressed on whole villi and/or stromal cell cultures were compared with the HLA types of the patients. No preference for either HLA compatibility or incompatibility was found for androgenetic and paternally derived triploid conceptuses as a whole. Heterozygous, androgenetic, conceptuses, however, showed a trend towards preferential incompatibility, which may be of importance for their apparent greater risk for trophoblastic tumour. HLA antibodies were found in 19.2% of the women, i.e. in the range reported for molar as well as non-molar pregnancies. Non-HLA antibodies reacting with lymphocytes of the spouse and/or cells from the conceptus were observed.


A new hope in the treatment of coronary vasospasm: bosentan.
Atherosclerosis is the most important cause of acute coronary syndromes. The mediators that trigger vasospasm, including endothelin and serotonin, are synthesized and secreted into circulation from atherosclerotic plaques and surrounding tissues. A 68-year-old man was hospitalized due to acute coronary syndrome four times in a one-year period. The patient presented to emergency service again with heartburn and a pressure-like pain in his upper abdomen in February 2012. He was admitted to the coronary care unit with the detection of a more than three-fold increase in troponin values and ischemic changes on electrocardiography. By decision of the cardiology council, the endothelin receptor antagonist, bosentan was added to the treatment. There were no contraindications to this medication according to his blood and hepatic indicators. After confirmation of the Social Security Institution, bosentan was started as 62.5 mg twice a day. After the first month, the dose was increased to 125 mg b.i.d. As of completion of the eighth month of treatment with bosentan, the patient had not been hospitalized due to angina attack or acute coronary syndrome.


Insulin resistance in familial and nonfamilial hypercholesterolemia.
High levels of very low density lipoprotein triglycerides and low levels of high density lipoprotein cholesterol have been found to be associated with insulin resistance measured by the euglycemic clamp technique. In contrast, the association of isolated hypercholesterolemia with insulin resistance has not been systematically studied. Therefore, we performed two separate studies designed to investigate the degree of insulin resistance in familial hypercholesterolemia (FH) (study 1) and nonfamilial hypercholesterolemia (non-FH) (study 2). Study 1 included eight young adults with FH and 13 corresponding control subjects. Fasting blood glucose, insulin, and C-peptide levels were similar in FH patients and control subjects during an oral glucose tolerance test. During the euglycemic hyperinsulinemic (1,200-1,300 pmol/l) clamp studies, FH patients and control subjects had similar rates of whole-body glucose uptake (73 +/- 6 versus 70 +/- 3 mumol/kg per minute, respectively; p = NS). Glucose oxidation, glucose nonoxidation, lipid oxidation, suppression of free fatty acid levels, and potassium disposal were similar in both groups. Study 2 included 25 middle-aged non-FH patients and 18 corresponding control subjects. Glucose, insulin, and C-peptide responses in an oral glucose tolerance test were similar in both groups. During the euglycemic hyperglycemic clamp studies, non-FH patients and control subjects had similar rates of whole-body glucose uptake (61 +/- 3 versus 58 +/- 3 mumol/kg per minute, p = NS). In addition, glucose oxidation, glucose nonoxidation, lipid oxidation, and suppression of free fatty acid levels as well as potassium disposal were similar in non-FH patients and control subjects. We conclude that FH and non-FH are not insulin-resistant states.


Postoperative delirium in the elderly.
Older patients are at a higher risk for postoperative delirium. Symptoms of delirium are flucuating sensorium, altered perception and attention levels, and increased confusion. The incidence of delirium after surgery does not correlate with a specific anesthetic agent or the route of administration.


Role of aquaporin-4 in airspace-to-capillary water permeability in intact mouse lung measured by a novel gravimetric method.
The mammalian peripheral lung contains at least three aquaporin (AQP) water channels: AQP1 in microvascular endothelia, AQP4 in airway epithelia, and AQP5 in alveolar epithelia. In this study, we determined the role of AQP4 in airspace-to-capillary water transport by comparing water permeability in wild-type mice and transgenic null mice lacking AQP1, AQP4, or AQP1/AQP4 together. An apparatus was constructed to measure lung weight continuously during pulmonary artery perfusion of isolated mouse lungs. Osmotically induced water flux (J(v)) between the airspace and capillary compartments was measured from the kinetics of lung weight change in saline-filled lungs in response to changes in perfusate osmolality. J(v) in wild-type mice varied linearly with osmotic gradient size (4.4 x 10(-5) cm(3) s(-1) mOsm(-1)) and was symmetric, independent of perfusate osmolyte size, weakly temperature dependent, and decreased 11-fold by AQP1 deletion. Transcapillary osmotic water permeability was greatly reduced by AQP1 deletion, as measured by the same method except that the airspace saline was replaced by an inert perfluorocarbon. Hydrostatically induced lung edema was characterized by lung weight changes in response to changes in pulmonary arterial inflow or pulmonary venous outflow pressure. At 5 cm H(2)O outflow pressure, the filtration coefficient was 4.7 cm(3) s(-1) mOsm(-1) and reduced 1.4-fold by AQP1 deletion. To study the role of AQP4 in lung water transport, AQP1/AQP4 double knockout mice were generated by crossbreeding of AQP1 and AQP4 null mice. J(v) were (cm(3) s(-1) mOsm(-1) x 10(-5), SEM, n = 7-12 mice): 3.8 +/- 0. 4 (wild type), 0.35 +/- 0.02 (AQP1 null), 3.7 +/- 0.4 (AQP4 null), and 0.25 +/- 0.01 (AQP1/AQP4 null). The significant reduction in P(f) in AQP1 vs. AQP1/AQP4 null mice was confirmed by an independent pleural surface fluorescence method showing a 1.6 +/- 0.2-fold (SEM, five mice) reduced P(f) in the AQP1/AQP4 double knockout mice vs. AQP1 null mice. These results establish a simple gravimetric method to quantify osmosis and filtration in intact mouse lung and provide direct evidence for a contribution of the distal airways to airspace-to-capillary water transport.


Development of functional LH Receptors on pig cumulus-oocyte complexes cultured in vitro by a novel two-step culture system.
We show in the present study that freshly isolated pig cumulus-oocyte complexes (COCs) display a limited response to LH, as assessed by the expression of hyaluronan synthase 2 (Has2) mRNA, activation of protein kinase A (PKA), production of hyaluronic acid (HA) and progesterone, cumulus cell expansion and resumption of meiosis. These data indicate that freshly isolated COCs do not possess a sufficient number of functional LH receptors (LHR). However, the expression of Lhr significantly increased during the culture of COCs in vitro in a medium supplemented with FSH. Assuming that the effect of FSH on LHR induction is mediated via cAMP signaling pathways, we developed a new culture system, in which the COCs were pre-cultured for 72 hr in a medium supplemented with dbcAMP. The pre-cultured COCs remained in the germinal vesicle stage, their cumulus investment underwent a dramatic increase in size and gap junctions between the cumulus cells were preserved. The stimulation of such COCs with either FSH or LH led to the resumption and completion of meiosis, activation of PKA, expression of Has2, synthesis of large amounts of HA and progesterone, and extensive expansion of cumulus cells. We conclude that the formation of functional LHR is stimulated in cumulus cells during the culture in vitro in a cAMP-dependent pathway. The dbcAMP-treated COCs thus represent a new model in which the resumption of meiosis and cumulus expansion can be induced exclusively by the action of recombinant LH.


Large-Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis.
To provide a large-scale assessment of serum protein dysregulation in diffuse cutaneous systemic sclerosis (dcSSc) and to investigate serum protein correlates of SSc fibrotic features. We investigated serum protein profiles of 66 participants with dcSSc at baseline who were enrolled in the Scleroderma: Cyclophosphamide or Transplant Trial and 66 age- and sex-matched healthy control subjects. A panel of 230 proteins, including several cytokines and chemokines, was investigated. Whole blood gene expression profiling in concomitantly collected samples was performed. Among the participants with dcSSc, the mean disease duration was 2.3 years. All had interstitial lung disease (ILD), and none were being treated with immunosuppressive agents at baseline. Ninety proteins were differentially expressed in participants with dcSSc compared to healthy control subjects. Similar to previous global skin transcript results, hepatic fibrosis, granulocyte and agranulocyte adhesion, and diapedesis were the top overrepresented pathways. Eighteen proteins correlated with the modified Rodnan skin thickness score (MRSS). Soluble epidermal growth factor receptor was significantly down-regulated in dcSSc and showed the strongest negative correlation with the MRSS, being predictive of the score's course over time, whereas α1 -antichymotrypsin was significantly up-regulated in dcSSc and showed the strongest positive correlation with the MRSS. Furthermore, higher levels of cancer antigen 15-3 correlated with more severe ILD, based on findings of reduced forced vital capacity and higher scores of disease activity on high-resolution computed tomography. Only 14 genes showed significant differential expression in the same direction in serum protein and whole blood RNA gene expression analyses. Diffuse cutaneous SSc has a distinct serum protein profile with prominent dysregulation of proteins related to fibrosis and immune cell adhesion/diapedesis. The differential expression for most serum proteins in SSc is likely to originate outside the peripheral blood cells.


[Effects of omeprazole and famotidine on (H+-K+) ATPase and acid secretion in rabbit gastric glands].
Effects of omeprazole, an anti-ulcer drug, on (H+-K+) ATPase activity and gastric acid secretion in a gastric mucosal gland preparation from rabbits were investigated. The mode of action of the substance was compared with famotidine, and H2 antagonist, by examining the effects of both drugs on the (H+-K+) ATPase of the rabbit gastric mucosa and on gastric acid secretion from the isolated rabbit gastric glands. Optimal assay conditions for (H+-K+) ATPase activity differed slightly from that reported for pig gastric mucosa, and they were pH 7.0, 2 mM of MgCl2 and 50 mM of KCl. Omeprazole dose-dependently inhibited the enzyme activity with an IC50 of 4.2 microM, whereas famotidine was not inhibitory even at the highest concentration of 100 microM. Acid secretion in the glands was determined by measuring accumulation of 14C-aminopyrine. Omeprazole and famotidine showed almost the same inhibitory effect against histamine-stimulated gastric secretion, and their IC50 values were 0.35 microM. Omeprazole inhibited dibutyryl cyclic AMP-stimulated gastric acid secretion, but famotidine was not inhibitory even at the highest concentration of 100 microM. The reason for this difference was that (H+-K+) ATPase activity is linked to the final step of acid secretion. From these results, omeprazole can be expected to be useful for the treatment of peptic ulcer disease.