Calciphylaxis and Martorell Hypertensive Ischemic Leg Ulcer: Same Pattern - One Pathophysiology.
This review presents a closer look at four diseases which are probably closely related to one another pathophysiologically: (a) calciphylaxis (distal pattern); (b) calciphylaxis (proximal pattern); (c) Martorell hypertensive ischemic leg ulcer; (d) calciphylaxis with normal renal and parathyroid function (synonym: eutrophication). The four diseases have largely the same risk factors: (1) arterial hypertension, (2) diabetes mellitus (types 1 and 2), (3) secondary or tertiary hyperparathyroidism (in end-stage kidney disease) and (4) oral anticoagulation with vitamin K antagonists. They share the same clinical patterns: necrotizing livedo, skin infarctions at typical locations and acral gangrene in calciphylaxis. They also share the same histopathology: ischemic subcutaneous arteriolosclerosis and small-artery disease and 'miniaturizing' Mönckeberg medial calcinosis. The treatment concept for the acute phase of the diseases is also broadly similar. In addition to an optimized control of the cardiovascular risk factors, a proactive wound approach (necrosectomy, negative pressure wound treatment with vacuum dressings, and early skin grafts supported by systemic antibiotic therapy) leads most rapidly and effectively to a reduction of the initially severe wound pain, and finally to complete healing of the wound. Oral anticoagulation with vitamin K antagonists should be stopped. In extensive cases, the use of intravenous sodium thiosulfate is recommended. All four diagnoses are little known in the medical schools of most countries. The need to improve familiarity with these four closely related disorders is therefore great. In particular, the risk of confusion with pyoderma gangrenosum is a major diagnostic problem which can lead to false and even damaging treatment.


FMS-like tyrosine kinase 3 internal tandem duplication and the patterns of its gene sequence in 207 Chinese patients with de novo acute myeloid leukemia.
Constitutive activation of the FMS-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase by internal tandem duplication (ITD) has been researched in patients with de novo acute myeloid leukemia (AML). To study the patterns of FLT3-ITD in Chinese patients with AML. A total of 207 patients with de novo AML were enrolled in the study. Genomic DNA was extracted from peripheral blood and polymerase chain reaction was performed. GeneScan was used to analyze the mutant to wild-type ratio. The sequencing of mutated genes was performed to confirm the mutation types and exclude false positives. A total of 42 cases (20.3%) were associated with mutations. FLT3-ITD was found equally in AML subtypes M1 to M6. The level of the ITD allele was heterogeneous. GeneScan showed that the mutant to wild-type ratio ranged from 0.03 to 3.78 (median, 0.43). Patients with a high ratio had significantly lower cancer remission rates and shorter survival. They also showed distinct clinical features including higher white blood cell counts and higher CD7 and CD56 expression. The length of the duplicated fragment was 26 to 57 bp (median, 43 bp). Twenty-two cases (52%) had simple tandem duplications, while 20 other cases (48%) had an extra interval of 12 to 30 bp before the tandem duplications. A hexanucleotide consisting of GAAAAG was found exclusively in the intervals. Patients with this GAAAAG interval showed better survival. The ITD to wild-type ratio, gene pattern, and CD7 expression status appear to be independent prognostic indices for patients with AML. Detection of FLT3 mutation is fast, easy, and inexpensive. The mutant to wild-type ratio is helpful for performing detailed risk stratification. DNA sequence analysis is more precise for confirming and evaluating the mutation pattern.


Transcriptome-based SNP discovery by GBS and the construction of a genetic map for olive.
Molecular markers located in the genic regions of plants are valuable tools for the identification of candidate genes of economically important traits and consequent use in marker-assisted selection (MAS). In the past, simple sequence repeat markers (SSRs) and single-nucleotide polymorphisms (SNPs) located in expressed sequence tags (ESTs) were developed by sequencing RNA derived from different plant tissues, which involves laborious RNA extraction, mRNA isolation, and cDNA synthesis. In order to develop SNP markers located in olive transcriptomes, we used the recently developed genotyping-by-sequencing (GBS) technique. An analysis was done for 125 olive DNA samples (123 DNA samples from a cross-pollinated F1 mapping population, and two samples from parents). From 45 to 66% of Illumina reads from GBS analysis were aligned to the olive transcriptome. A total of 22,033 transcriptome-based SNP markers were identified, and 3384 of these were mapped in the olive genome. The genetic linkage map constructed in this study consists of 1 cleaved amplified polymorphic sequence (CAPS), 19 SSR, and 3384 transcriptome-based SNP markers. The map covers 3340.8 cM of the olive genome in 23 linkage groups, with the length of the linkage groups ranging from 55.6 to 248.7 cM. Average map distance between flanking markers was 0.98 cM. This genetic linkage map is a saturated genetic map and will be a useful tool for the localization of quantitative trait loci (QTLs) and gene(s) of interest and for the identification of candidate genes for economically important traits.


Sulfur Induces Resistance against Canker Caused by Pseudomonas syringae pv. actinidae via Phenolic Components Increase and Morphological Structure Modification in the Kiwifruit Stems.
Bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has led to considerable losses in all major kiwifruit-growing areas. There are no commercial products in the market to effectively control this disease. Therefore, the defense resistance of host plants is a prospective option. In our previous study, sulfur could improve the resistance of kiwifruit to Psa infection. However, the mechanisms of inducing resistance remain largely unclear. In this study, disease severity and protection efficiency were tested after applying sulfur, with different concentrations in the field. The results indicated that sulfur could reduce the disease index by 30.26 and 31.6 and recorded high protection efficiency of 76.67% and 77.00% after one and two years, respectively, when the concentration of induction treatments was 2.0 kg/m3. Ultrastructural changes in kiwifruit stems after induction were demonstrated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and the activities of phenylalanine ammonia-lyase (PAL), peroxidase (POD) and polyphenol oxidase (PPO), and the accumulation of lignin were determined by biochemical analyses. Our results showed that the morphological characteristics of trichomes and lenticels of kiwifruit stem were in the best defensive state respectively when the sulfur concentration was 3.0 kg/m3 and 1.5 kg/m3. Meanwhile, in the range of 0.5 to 2.0 kg/m3, the sulfur could promote the chloroplast and mitochondria of kiwifruit stems infected with Psa to gradually return to health status, increasing the thickness of the cell wall. In addition, sulfur increased the activities of PAL, POD and PPO, and promoted the accumulation of lignin in kiwifruit stems. Moreover, the sulfur protection efficiency was positively correlated with PPO activity (p < 0.05) and lignin content (p < 0.01), which revealed that the synergistic effect of protective enzyme activity and the phenolic metabolism pathway was the physiological effect of sulfur-induced kiwifruit resistance to Psa. This evidence highlights the importance of lignin content in kiwifruit stems as a defense mechanism in sulfur-induced resistance. These results suggest that sulfur enhances kiwifruit canker resistance via an increase in phenolic components and morphology structure modification in the kiwifruit stems. Therefore, this study could provide insights into sulfur to control kiwifruit canker caused by Psa.


LncRNA ADAMTS9-AS2 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Lung Adenocarcinoma.
The role of long noncoding RNA (LncRNA) ADAMTS9 antisense RNA 2 (ADAMTS9-AS2) is unclear in lung adenocarcinoma (LUAD). The aim of this study was to explore the relationship between ADAMTS9-AS2 and LUAD, based on The Cancer Genome Atlas (TCGA) database and bioinformatics analysis. Various statistical methods, Kaplan-Meier method, Cox regression analysis, GSEA, and immune infiltration analysis were used to evaluate the relationship between clinical features and ADAMTS9-AS2 expression, prognostic factors, and the significant involvement of ADAMTS9-AS2 in function. In LUAD patients, low expression of ADAMTS9-AS2 was associated with N stage (P=0.011), gender (P=0.002), number of packs smoked (P=0.024) and smoker (P<0.001). Low ADAMTS9-AS2 expression predicted a poorer overall survival (OS) (HR: 0.68; 95% CI: 0.51-0.91; P=0.01). And ADAMTS9-AS2 expression (HR: 0.626; 95% CI: 0.397-0.986; P=0.043) was independently correlated with OS in LUAD patients. Unwinding of DNA, extrinsic pathway, polo-like kinase-mediated events, cori cycle, MCM pathway, proteasome pathway, lagging strand synthesis and PCNA-dependent long patch base excision repair were differentially enriched in ADAMTS9-AS2 high expression phenotype. ADAMTS9-AS2 expression was correlated with certain immune infiltrating cells. In LUAD patients, ADAMTS9-AS2 expression was significantly associated with poor survival and immune infiltration. ADAMTS9-AS2 may be a promising biomarker of prognosis and response to immunotherapy for LUAD.


Pharmacokinetics of cefotetan in elderly subjects after intramuscular administration.
The pharmacokinetics of cefotetan were studied in 10 healthy male subjects 65-75 years of age with normal liver function and a creatinine clearance of greater than 80 ml/min after single 2 g intramuscular doses. The mean plasma level at 0.5 h was 52.50 +/- 9.16 micrograms/ml. Peak concentrations were 91.78 +/- 12.02 micrograms/ml at 3 h, declining to 10.33 +/- 2.18 micrograms/ml at 18 h, 4.0 +/- 1.12 micrograms/ml at 24 h after the start injection. The percentage of the dose recovered in urine (0 to 24 h) was 60.3%. Cefotetan plasma clearance showed a statistically significant correlation (r = 0.956, p less than 0.001) with measured creatinine clearance and the positive intercept ordinate confirmed a nonrenal clearance of the drug (biliary excretion). The normal age-related changes in cefotetan kinetics were relatively small and dosage adjustment was not necessary for normal elderly subjects requiring cefotetan.


Storytelling and the interpretation of meaning in qualitative research.
This paper reviews literature on narrative analysis and illustrates the meaning-making function of stories of chronic illness through analysis and discussion of two case studies from a study of acute episodes of chronic obstructive pulmonary disease (COPD). Individuals living with COPD experience acute exacerbations characterized by extreme dyspnea, but there has been little research to provide understanding of these events from the perspectives of individuals with COPD, family caregivers, and nurses. Narrative analysis -- considered in the context of the aims of qualitative research -- illuminates how these people make sense of acute exacerbation events by telling stories. In an ethnographic study, 10 patient-family nurse units in two Canadian general hospitals participated in interviews concerning acute episodes of COPD. Narrative analysis enabled identification of several story forms and their functions. Examples were found of a story told twice with different meanings, and of a patient's 'death story' used to communicate distrust of the nurse's ability to recognize the seriousness of distress and implications for its potential course. These examples are presented, and interpreted with respect to issues of meaning. The analysis indicates that stories told by patients in the context of nurse-client interactions inform understanding of the individual's acute exacerbation events beyond the biophysical.


Characteristics of the Electrocardiogram in Japanese Fabry Patients Under Long-Term Enzyme Replacement Therapy.
Objective: An electrocardiogram (ECG) is an important tool for demonstrating cardiac manifestations in various heart diseases. The present study clarified the characteristics of ECG parameters in Japanese Fabry patients under long-term enzyme replacement therapy (ERT). Methods: We analyzed the ECGs of 40 Fabry patients (male, n = 17; female, n = 23) before and after treatment with ERT. To evaluate the atrio-ventricular conduction, the PQ interval, corrected PQ and PQ minus P-wave in lead II (Pend-Q) were calculated. The QRS duration, QTc, Sokolow-Lyon index, and strain pattern were also examined. Results: At the baseline, the shortening of the PQ interval, corrected PQ and Pend-Q was identified in 7.5, 25.0, and 47.5% of cases, respectively. The prolongation of QRS duration and QTc was found in 7.5 and 40.0% of cases, respectively. The strain pattern was mainly identified in female patients, irrespective of left ventricular hypertrophy (LVH). During long-term ERT, the PQ interval, corrected PQ and Pend-Q did not change significantly. The QRS duration was significantly prolonged in both genders, whereas the QTc was significantly prolonged only in male patients. A subgroup analysis revealed that the prolongation of the QRS duration and QTc only occurred in male patients with LVH and only occurred in female patients with the classical type mutation. The prevalence of the strain was significantly increased only in male patients with LVH. Conclusions: These results suggest that the shortening of the Pend-Q is a specific finding in Japanese Fabry patients, and the strain pattern without LVH in female patients can be considered Fabry disease. During long-term ERT, prolongation of the QRS duration and QTc can indicate the progression of myocardial damage in male patients with LVH and in female patients with the classical type mutation.


Rational Design of Conjugated Acetylenic Polymers Enables a Two-Electron Water Oxidation Pathway for Enhanced Photosynthetic Hydrogen Peroxide Generation.
Herein, the design of conjugated acetylenic polymers (CAPs) featuring diverse spatial arrangements and intramolecular spacers of diacetylene moieties (─C≡C─C≡C─) for photocatalytic hydrogen peroxide (H2 O2 ) production from water and O2 , without the need for sacrificial agents, is presented. It is shown that the linear configuration of diacetylene moieties within conjugated acetylenic polymers (CAPs) induces a pronounced polarization of electron distribution, which imparts enhanced charge-carrier mobility when compared to CAPs' networks featuring cross-linked arrangements. Moreover, optimizing the intramolecular spacer between diacetylene moieties within the linear structure leads to the exceptional modulation of the band structures, specifically resulting in a downshifted valence band (VB) and rendering the two-electron water oxidation pathway thermodynamically feasible for H2 O2 production. Consequently, the optimized CAPs with a linear configuration (LCAP-2), featuring spatially separated reduction centers (benzene rings) and oxidation centers (diacetylene moieties), exhibit a remarkable H2 O2 yield rate of 920.1 µmol g-1 h-1 , superior than that of the linear LCAP-1 (593.2 µmol g-1 h-1 ) and the cross-linked CCAP (433.4 µmol g-1 h-1 ). The apparent quantum efficiency (AQE) and solar-to-chemical energy conversion (SCC) efficiency of LCAP-2 are calculated to be 9.1% (λ = 420 nm) and 0.59%, respectively, surpassing the performance of most previously reported conjugated polymers.


Effects of inhaled nitric oxide 10 ppm in spontaneously breathing horses anaesthetized with halothane.
Inhaled nitric oxide, a selective pulmonary vasodilator, is known to improve arterial oxygenation after cardiopulmonary bypass and during acute respiratory distress syndrome in humans. During general anaesthesia with spontaneous ventilation, healthy adult horses develop large alveolar-arterial oxygen tension differences. In this study, we have determined the effects of inhaled nitric oxide (10 parts per million (ppm)) on venous admixture and pulmonary haemodynamics in horses anaesthetized with halothane. Seven adult horses were studied twice in random sequence. After premedication with romifidine 100 micrograms kg-1, anaesthesia was induced with ketamine 2.2 mg kg-1 and maintained with 1.1 MAC (0.95%) of halothane in oxygen. Horses breathed spontaneously. After 65 min, each horse had nitric oxide 10 ppm added to the inspired gas for 20 min (procedure HA + NO) or anaesthesia was continued with halothane in oxygen (procedure HA). Cardiac output, minute ventilation, arterial and mixed venous oxygen and carbon dioxide tensions, and mean pulmonary and carotid arterial pressures were measured for 100 min. Shunt fraction and pulmonary and systemic vascular resistances were calculated. Shunt fraction (SF) and mean pulmonary artery pressure (PPA mean) were not different between the two groups after 65 min of general anaesthesia (HA: SF 0.20 (SD 0.06), PPA mean 45 (8) mm Hg; HA + NO: SF 0.21 (0.04), PPA mean 44 (7) mm Hg) or after 85 min (HA: SF 0.22 (0.07), PPA mean 45 (8) mm Hg; HA + NO: SF 0.20 (0.03), PPA mean 43 (7) mm Hg). There were no significant effects of time or nitric oxide inhalation on any other variable. There was a significant correlation (r = 0.80, P < 0.05) between calculated shunt fraction 65 min after induction of anaesthesia and body weight.


Case mix, quality, and cost relationships in Colorado nursing homes.
The analyses reported in this article assessed the cost, case mix, and quality interrelationships among Colorado nursing homes. A unique set of patient-level data was collected specifically to measure case mix and quality. Case mix was found to be strongly associated with cost, accounting for up to 45 percent of the variation in cost per patient day. The relationship between quality and cost was weaker; quality variables accounted for only about 10 percent of the cost per day variation. Case mix was also associated with several facility characteristics found to be significant in other cost studies, suggesting that such facility characteristics serve as partial proxy measures for case mix. The cost-case mix relationships appear to be strong enough to justify incorporating case mix directly in nursing home reimbursement systems. In contrast, the weaker cost-quality association implies that it may not (yet) be appropriate to incorporate quality directly in reimbursement.


Modeling the development of acquired clinical immunity to Plasmodium falciparum malaria.
Individuals living in regions where malaria is endemic develop an acquired immunity to malaria which enables them to remain asymptomatic while still carrying parasites. Field studies indicate that cumulative exposure to a variety of diverse Plasmodium parasites is required for the transition from symptomatic to asymptomatic malaria. This study used a simulation model of the within-host dynamics of P. falciparum to investigate the development of acquired clinical immunity under different transmission conditions and levels of parasite diversity. Antibodies developed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), a clonally variant molecule, were assumed to be a key human immunological response to P. falciparum infection, along with responses to clonally conserved but polymorphic antigens. The time to the development of clinical immunity was found to be proportional to parasite diversity and inversely proportional to transmission intensity. The effect of early termination of symptomatic infections by chemotherapy was investigated and found not to inhibit the host's ability to develop acquired immunity. However, the time required to achieve this state was approximately double that compared to when no treatment was administered. This study demonstrates that an immune response primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of infections irrespective of whether treatment is administered, supporting its role in the development of acquired clinical immunity. The results also illustrate a novel use for simulation models of P. falciparum infections, investigation of the influence of intervention strategies on the development of naturally acquired clinical immunity.


You've Got to Hand It to Them: Assessing Final Year Medical Students Knowledge of Hand Anatomy and Pathology.
Knowledge of hand anatomy and pathology is important for final year medical students as it frequently appears in examinations as a short case or in a written paper. Studies have shown that doctors in the Emergency Department have a deficient grasp of musculoskeletal anatomy secondary to a lack of dedicated teaching in medical school. A questionnaire was handed out to 111 final year medical students. Students were asked to fill it out before and after dedicated upper limb teaching sessions during their rotation. The questionnaire consisted of an anatomical and pathological component. Students were tested on basic anatomy and pathology of several common upper limb conditions. There was a significant improvement in the medical students knowledge after the dedicated hand teaching. The identification of the carpal bones showed the most improvement overall. Basic musculoskeletal knowledge is essential to the practice of medicine. The majority of medical students gravitate towards a career in general practice or emergency medicine and good knowledge of upper limb anatomy is important. We have piloted a new interactive dedicated upper limb teaching module and have shown that there has been a significant improvement in students knowledge.


Tardive dyskinesia and neurotransmitters: effects of sodium valproate, cyproheptadine, oxypertine, hydroxyzine pamoate and Ca-hopantenate on monoamine metabolites, cyclic nucleotides and gamma-aminobutyric acid in human cerebrospinal fluid.
Lumbar cerebrospinal fluid (CSF) homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), cyclic AMP (cAMP) and cyclic GMP (cGMP) were measured in chronic schizophrenics with tardive dyskinesia before and three weeks after the initial treatment with sodium valproate (VPA), cyproheptadine, oxypertine or hydroxyzine pamoate. HVA levels significantly decreased after the administration of VPA, cyproheptadine or oxypertine. Cyclic GMP levels significantly increased after the administration of VPA or cyproheptadine. Elevation of the cAMP level was observed after the administration of VPA, cyproheptadine or oxypertine. An elevation of the MHPG level was observed during oxypertine treatment and a reduction of the 5-HIAA level was observed during hydroxyzine pamoate treatment. Decreases in HVA and increases in cGMP levels during treatment might be indicative of normalization of the dopaminergic-cholinergic imbalance in the brain. Lumbar CSF HVA and gamma-aminobutyric acid (GABA) were also measured in patients with tardive dyskinesia before and eight weeks after Ca-hopantenate treatment. No significant changes were observed before or after this treatment. The hypothesis is discussed that the pathogenesis of tardive dyskinesia may involve functional disorders not only of the dopaminergic or cholinergic system but also of the norepinephrinergic, serotoninergic and GABA-ergic systems.


[Master of Chinese medicine: the career life of Professor HE Pu-Ren].
With his unique comprehension, theoretical contribution and technique of acupuncture, Professor HE Pu-ren has devoted himself into the career of Chinese Medicine for 70 years. Besides the professional contributions, his academic spirit and idea of humanities are also handed down to the next generation. And it is held that his success rests with the spirit of both imitation of the ancients and innovation as well as the practical idea and insistence.


Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid.
Self-assembling peptides (SAPs) are promising vehicles for the delivery of hydrophobic therapeutics for clinical applications; their amphipathic properties allow them to dissolve hydrophobic compounds in the aqueous environment of the human body. However, self-assembling peptide solutions have poor blood compatibility (e.g., low osmolarity), hindering their clinical application through intravenous administrations. We have recently developed a generalized platform for hydrophobic drug delivery, which combines SAPs with amino acid solutions (SAP-AA) to enhance drug solubility and increase formulation osmolarity to reach the requirements for clinical uses. This formulation strategy was thoroughly tested in the context of three structurally different hydrophobic compounds - PP2, rottlerin, and curcumin - in order to demonstrate its versatility. Furthermore, we examined effects of changing formulation components by analyzing 6 different SAPs, 20 naturally existing amino acids at low and high concentrations, and two different co-solvents dimethyl sulfoxide (DMSO) and ethanol. Our strategy proved to be effective in optimizing components for a given hydrophobic drug, and therapeutic function of the formulated inhibitor, PP2, was observed both in vitro and in vivo. This manuscript outlines our generalized formulation method using SAP-AA combinations for hydrophobic compounds, and analysis of solubility as a first step towards potential use of these formulations in more functional studies. We include representative solubility results for formulation of the hydrophobic compound, curcumin, and discuss how our methodology serves as a platform for future biological studies and disease models.


Nuclear forward scattering of synchrotron radiation by 99Ru.
We measured nuclear forward scattering spectra utilizing the (99)Ru transition, 89.571(3) keV, with a notably mixed E2/M1 multipolarity. The extension of the standard evaluation routines to include mixed multipolarity allows us to extract electric and magnetic hyperfine interactions from (99)Ru-containing compounds. This paves the way for several other high-energy Mössbauer transitions, E ∼ 90 keV. The high energy of such transitions allows for operando nuclear forward scattering studies in real devices.


Time-dependent pseudo Jahn-Teller effect: phonon-mediated long-time nonadiabatic relaxation.
Our system under theoretical consideration is an impurity center in a solid. We are considering the time evolution of the center in a quasi-degenerate electronic state. Strict quantum mechanical treatment of non-adiabadicity of the state is used. The phonon continuum is taken into account in addition to the vibration responsible for the main vibronic interaction. To describe the dynamics of the excited state a master equation has been used. The theoretical considerations are illustrated by the calculations of the long-time evolution of vibrations of the center, influenced by the emission of phonons to the bulk.


OKT3 monoclonal antibody in cardiac transplant patients.
The nurse's role in caring for cardiac transplant patients involves attention to many details, including assessment of organ function, provision of care, and administration of immunosuppressive medications. OKT3 monoclonal antibody, an immunosuppressive agent under investigational use in the cardiac transplant population, requires special nursing considerations.


Bistability and nonlinearity in optically addressed ferroelectric liquid-crystal spatial light modulators: applications to neurocomputing.
We report the characteristics of a truly bistable optically addressed ferroelectric liquid-crystal spatial light modulator that is capable of storing binary images. We show that, in addition to this bistability, a nonlinear response and gray scales can be observed under certain operating conditions. We then report on how these capabilities can be used in implementing optical neurocomputing architectures.


Infectivity of Hymenolepis diminuta for the jird, Meriones unguiculatus, and utility of this model for anthelmintic studies.
The jird (Meriones unguiculatus) has been shown to be a useful model host for the cestodes Taenia crassiceps and Echinococcus multilocularis. This report outlines a novel model in which hydrocortisone-treated jirds (0.02% in the feed) are infected with another cestode, Hymenolepis diminuta. Jirds were inoculated with 5 freshly harvested cysticercoids of H. diminuta prior to (day 0, -1, or -5) or after (day 1 or 5) switching to medicated feed; in some cases, jirds were never medicated. On days 7, 14, 21, or 28 postinoculation (PI), jirds were killed by CO2 inhalation and their small intestines were examined for tapeworms. Hymenolepis diminuta established, grew, and developed to the gravid adult state in jirds. They persisted longer in medicated (21 days) than in nonmedicated (7 days) animals, and generally higher levels of infection were obtained when jirds were inoculated immediately prior to switching to medicated feed. Treatment of infected jirds on day 4 or days 4, 5, and 6 PI with selected anthelmintics followed by necropsy on day 7 PI discriminated drugs with known activity against tapeworms from those with little or no activity. This rodent in vivo model should provide a useful adjunct for anthelmintic studies.


Dementia in elderly inpatients admitted to medical wards in Brazil: diagnosis and comorbidity with other clinical diseases.
Specific comorbidities affect older patients with dementia admitted to general hospitals and may complicate the recognition of dementia. The aim of the present study was to estimate the prevalence of dementia among elderly inpatients admitted to hospital medical wards and to identify its distribution across clinical and sociodemographic conditions. From June 2011 to May 2012, a sample of elderly inpatients (≥60 years old) were screened for dementia with the Mini-Mental State Examination and the Bayer Activities of Daily Living Scale to identify cognitive and functional impairment (CFI). Subjects with CFI underwent a diagnostic procedure for dementia using the Cambridge Mental Disorders of the Elderly Examination and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The elderly inpatients also completed a standard questionnaire to investigate sociodemographic and clinical variables and a screening procedure for depression and delirium. The data obtained were submitted to univariate and multivariate analyses. The sample of 224 subjects had a mean age of 71.5 years and was mostly men (62.2%), poorly educated (≤4 years of schooling: 74.6%), and married (53.4%). CFI was observed in 84 subjects (prevalence: 37.4%; 95% confidence interval: 31.1-43.7), and dementia was observed in 31 subjects (prevalence: 17.2%; 95% confidence interval: 12.3-22.1). Dementia was related to older age and the presence of delirium, stroke, and pneumonia. The prevalence of CFI and dementia was high among the elderly inpatients examined. The identification of medical and sociodemographic conditions associated with a dementia diagnosis in a general hospital may be useful in the development of preventative actions.


Calibration of a portable intrinsic Ge gamma-ray detector using point sources and testing for field applications.
A simple procedure using point sources is described for the calibration of portable high-resolution gamma-ray detectors used in field surveys. The point source data are fitted by empirical equations that are used to calculate efficiency for field applications. Two models for the distribution of radionuclides are treated: a thin surface-film model and a vertically homogeneous model. The success of the procedure has been demonstrated by field applications in plots where the levels of contamination are known.


[Assessing bioaccumulation and bioavailability of PAHs and OCPs in water using sediment, rare minnow and biomimetic sampler].
Accumulation of polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in different phases in water was assessed in a wetland in Guanting, Beijing, China, by analyzing their concentrations in sediment, 30 d-exposed caged Chinese rare minnow (Gobiocypris rarus) and triolein embedded cellulose acetate membrane (TECAM). The applicability of TECAM to bioavailability assessment of PAHs and OCPs for aquatic organisms was also examined. The results showed that there were great differences of both bio-sediment accumulation factors (BSAFs) and TECAM-sediment accumulation factors (TSAFs) for target analytes between experiment sites with variation coefficients of 10%-70% and 20%-50%, respectively. The BSAFs and TSAFs were independent of relevant Kow. For the target pollutants especially PAHs, BSAFs for rare minnow were lower about one order of magnitude than those (1-4) predicted by equilibrium partitioning theory (EPT). However, TSAFs of PAHs and OCPs for TECAM were almost consistent with the EPT. Meanwhile, good correlations were found between the BSAFs and TSAFs for OCPs at 5 experiment sites (r = 0.80, 0.87, 0.83, 0.85 and 0.84, p < 0.01), but not good for PAHs (p > 0.1). It can be concluded that it is more reliable and accurate to assess the pollution status jointly using sediment, fish and TECAM, and that TECAM can be used as a biomimetic sampler to predict bioaccumulation potential of poorly biodegradable organic compounds like OCPs in fish.


Inheritance of cancer.
Extract: A single inherited mutant gene may be enough to cause a very high cancer risk. Single-mutation cases have provided much insight into the genetic basis of carcinogenesis, but they are relatively rare and account for only a small fraction of all cancers. Examples include mutation to the APC gene, causing early onset colon cancer in the syndrome familial adenomatous polyposis (tumorous polyp-tissue in the colon); mutation to either the BRCA1 or BRCA2 genes, causing an increased risk of breast cancer; and mutation to the TP53 gene, causing Li-Fraumeni syndrome with various early onset cancers such as bone or soft tissue sarcoma. Cancers sometimes cluster in families, but do not follow the rigid inheritance pattern characteristic of a mutation to a single gene. Males with a brother or father who has suffered prostate cancer are more likely to develop the disease. Similarly, females with a sister or mother who has suffered breast cancer are more likely to get a breast tumor. Some of the clustering may arise from the common diet and environment shared by families. Recently, however, researchers have begun to assign a significant fraction of cancer risk to the particular genetic variants that individuals inherit.


Assembly of live micro-organisms on microstructured PDMS stamps by convective/capillary deposition for AFM bio-experiments.
Immobilization of live micro-organisms on solid substrates is an important prerequisite for atomic force microscopy (AFM) bio-experiments. The method employed must immobilize the cells firmly enough to enable them to withstand the lateral friction forces exerted by the tip during scanning but without denaturing the cell interface. In this work, a generic method for the assembly of living cells on specific areas of substrates is proposed. It consists in assembling the living cells within the patterns of microstructured, functionalized poly-dimethylsiloxane (PDMS) stamps using convective/capillary deposition. This versatile approach is validated by applying it to two systems of foremost importance in biotechnology and medicine: Saccharomyces cerevisiae yeasts and Aspergillus fumigatus fungal spores. We show that this method allows multiplexing AFM nanomechanical measurements by force spectroscopy on S. cerevisiae yeasts and high-resolution AFM imaging of germinated Aspergillus conidia in buffer medium. These two examples clearly demonstrate the immense potential of micro-organism assembly on functionalized, microstructured PDMS stamps by convective/capillary deposition for performing rigorous AFM bio-experiments on living cells.


Functional KCa3.1 channels regulate steroid insensitivity in bronchial smooth muscle cells.
Identifying the factors responsible for relative glucocorticosteroid (GC) resistance present in patients with severe asthma and finding tools to reverse it are of paramount importance. In asthma we see in vivo evidence of GC-resistant pathways in airway smooth muscle (ASM) bundles that can be modeled in vitro by exposing cultured ASM cells to TNF-α/IFN-γ. This action drives GC insensitivity via protein phosphatase 5-dependent impairment of GC receptor phosphorylation. In this study, we investigated whether KCa3.1 ion channels modulate the activity of GC-resistant pathways using our ASM model of GC insensitivity. Immunohistochemical staining of endobronchial biopsies revealed that KCa3.1 channels are localized to the plasma membrane and nucleus of ASM in both healthy controls and asthmatic patients, irrespective of disease severity. Western blot assays and immunofluorescence staining confirmed the nuclear localization of KCa3.1 channels in ASM cells. The functional importance of KCa3.1 channels in the regulation of GC-resistant chemokines induced by TNF-α/IFN-γ was assessed using complementary inhibitory strategies, including KCa3.1 blockers (TRAM-34 and ICA-17043) or KCa3.1-specific small hairpin RNA delivered by adenoviruses. KCa3.1 channel blockade led to a significant reduction of fluticasone-resistant CX3CL1, CCL5, and CCL11 gene and protein expression. KCa3.1 channel blockade also restored fluticasone-induced GC receptor-α phosphorylation at Ser(211) and transactivation properties via the suppression of cytokine-induced protein phosphatase 5 expression. The effect of KCa3.1 blockade was evident in ASM cells from both healthy controls and asthmatic subjects. In summary, KCa3.1 channels contribute to the regulation of GC-resistant inflammatory pathways in ASM cells: blocking KCa3.1 channels may enhance corticosteroid activity in severe asthma.


Effects of Fish Oil Supplementation on Oxidative Stress Biomarkers and Liver Damage in Hypercholesterolemic Rats.
Metabolic syndrome, especially its component related to dyslipidemia, is related to the development of nonalcoholic fatty liver disease (NAFLD), which is a disease with a significant global prevalence. Supplementation with omega-3 polyunsaturated fatty acids emerged as a complementary therapeutic possibility for dyslipidemia, but its benefits are questioned. This paper aims at evaluating the effects of fish oil supplementation in rats with hypercholesterolemia induced by hypercholesterolemic diet (HD). The study design is based on an experimental model in which the animals were randomly divided into 3 groups: G1 (standard commercial feed + saline solution); G2 (hypercholesterolemic diet + saline solution) and G3 (hypercholesterolemic diet + fish oil) over a period of 16 weeks. Metabolic control parameters and oxidative stress biomarkers were evaluated according to standardized methodologies. The G3 group showed significantly lower values of plasma concentrations of TG, and hepatic myeloperoxidase as well as higher erythrocyte superoxide dismutase activity (p < 0.05). Regarding histopathological analysis, there was lipid accumulation in the liver of animals from group G2; meanwhile, hepatocytes reorganization and expressive reduction of lipid vacuoles and hepatic TG content was observed in group G3. This study demonstrated how fish oil supplementation reduced the plasma concentration and hepatic content of triglycerides, as well as liver tissue damage in histopathological analysis.


Novel insights into chorioretinal and juxtapapillary colobomas by optical coherence tomography.
The purpose was to describe the in vivo microanatomy of typical and atypical chorioretinal and juxtapapillary colobomas in the dog. Three cross-breed dogs were found to be affected with colobomas. Two of the cases were NEHJ1 homozygous and Collie Eye Anomaly (CEA) affected and had the typical optic nerve head colobomas seen with the disease. The third case had an unexpected atypical coloboma. In vivo retinal photography and non-invasive retinal imaging by confocal scanning laser ophthalmoscope (cSLO) and optical coherence tomography (OCT) were done, and the eye affected with the atypical coloboma was collected and processed for histopathological evaluation. The majority of the defining features within the CEA defects were similar, with the extent of change to the choroid being of note. Similar to the first two cases, the atypical coloboma demonstrated absent normal retina, RPE, and choroid within the coloboma. Prominent intercalary membranes and vitreal strands attached to the depth of the coloboma were also apparent in all affected eyes. However, unlike the CEA-associated colobomas, the atypical coloboma possessed normal choroid surrounding the lesion and the depth of the lesion was apparent throughout. Advanced retinal imaging enables the appreciation of microanatomical changes that occur in the living eye. The ability of OCT to enhance visualization of abnormal retinal structures and detect subtle neurosensory retinal defects has allowed for the in vivo characterization of features observed in typical and atypical colobomas, as well as the appreciation of some of the resulting structural changes not visible by ophthalmoscopy alone.


Esophageal ulceration following doxycycline ingestion.
Esophageal ulceration occasionally occurs in patients taking doxycycline capsules or tablets. In the case described here, examination of biopsy specimens obtained at endoscopy showed polarizable matrix material in the ulcer bed, thus confirming the diagnosis.


Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis.
Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. The role of MAGL was assessed in vivo by using the xenograft and the azoxymethane models of colon carcinogenesis; MAGL expression was evaluated by RT-PCR and immunohistochemistry; 2-AG levels were measured by liquid chromatography mass spectrometry; angiogenesis was evaluated in tumor tissues [by microvessel counting and by investigating the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) proteins] as well as in human umbilical vein endothelial cells (HUVEC); cyclin D1 was evaluated by RT-PCR. MAGL and 2-AG were strongly expressed in tumor tissues. The MAGL inhibitor URB602 reduced xenograft tumor volume, this effect being associated to down-regulation of VEGF and FGF-2, reduction in the number of vessels and down-regulation of cyclin D1. In HUVEC, URB602 exerted a direct antiangiogenic effect by inhibiting FGF-2 induced proliferation and migration, and by modulating pro/anti-angiogenic agents. In experiments aiming at investigating the role of MAGL in chemoprevention, URB602 attenuated azoxymethane-induced preneoplastic lesions, polyps and tumors. MAGL, possibly through modulation of angiogenesis, plays a pivotal role in experimental colon carcinogenesis. Pharmacological inhibition of MAGL could represent an innovative therapeutic approach to reduce colorectal tumor progression.


The heart as a target for xenobiotic toxicity: the cardiac susceptibility to oxidative stress.
The heart is a target organ for oxidative stress-related injuries. Because of its very high energetic metabolic demand, the heart has the highest rate of production of reactive oxygen species, namely, hydrogen peroxide (H2O2), per gram of tissue. Additionally, the heart has lower levels of antioxidants and total activity of antioxidant enzymes when compared to other organs. Furthermore, drugs that have relevant antioxidant activity and that are used in the treatment of oxidative stress related cardiac diseases demonstrate better clinical cardiac outcomes than other drugs with similar receptor affinity but with no antioxidant activity. Several xenobiotics particularly target the heart and promote toxicity. Anticancer drugs, like anthracyclines, cyclophosphamide, mitoxantrone, and more recently tyrosine kinase targeting drugs, are well-known cardiac toxicants whose therapeutic application has been associated to a high prevalence of heart failure. High levels of catecholamines or drugs of abuse, namely, amphetamines, cocaine, and even the consumption of alcohol for long periods of time, are linked to cardiovascular abnormalities. Oxidative stress may be one common link for the cardiac toxicity elicited by these compounds. We aim to revise the mechanisms involved in cardiac lesions caused by the above-mentioned substances specially focusing in oxidative stress related pathways. Oxidative stress biomarkers can be useful in the early recognition of cardiotoxicity in patients treated with these drugs and aid to minimize the setting of cardiac irreversible events.


Nitroglycerin facilitates calcitonin gene-related peptide-induced behavior.
Nitric oxide and calcitonin gene-related peptide (CGRP) have been implicated in craniofacial pain including migraine headache, and CGRP induces face-grooming indicative of nocifensive behavior in animals. The aim of this study was to test whether systemic administration of nitroglycerin (NTG) influences the CGRP-induced behavior in awake rats and whether sumatriptan, a 5-HT1B/1D receptor agonist, can block the effects of NTG. CGRP was not significantly different from normal saline in inducing face-grooming behavior but NTG facilitated the effect of CGRP. Furthermore, sumatriptan was found to block the effect of NTG. These data suggest that facilitatory processes involving nitric oxide may be necessary for CGRP to play a role in some craniofacial pain conditions including possibly migraine headache.


Appendicitis after laparoscopic ovarian cystectomy-coincidence or complication.
Diagnosis of appendicitis, particularly in young women, may be challenging. In case of abdominal pain in the postoperative period of laparoscopic surgery, one should not only think of complications such as bleeding and injury of the bowel but also such as acute appendicitis. We report a case of a 26-year-old female patient with a post-laparoscopic acute appendicitis with appendicolithiasis 3 days after a laparoscopic ovarian cystectomy during which the appendix appeared inconspicuous. Appendicitis after gynecologic laparoscopy is a rare but potentially dangerous condition. One should consider the possibility of a postoperative appendicitis in case of an acute abdomen after laparoscopic surgery. Further studies might be of value to re-evaluate incidental appendectomy especially in cases of appendicolithiasis.


Undisplaced Intraoperative Fracture Presenting as Early Dislocation with Tapered Wedge Stems in Total Hip Arthroplasty - Case Series and Review of Literature.
Periprosthetic fractures and dislocation in the early post-operative period can be disastrous both for the surgeon and the patient. However, undisplaced periprosthetic fractures presenting with dislocation is uncommon. We describe successful management of two cases (one bilateral dislocation and one unilateral dislocation) of undisplaced iatrogenic fractures in total hip arthroplasty (THA) presenting as early dislocation. Case 1 was a 45-year-old female with osteoarthritis of hip secondary to developmental dysplasia of the hip with bilateral early nontraumatic dislocation with bilateral identical periprosthetic fracture. It was managed by revision to long stem and encirclage wiring. Case 2 presented with early dislocation in the 2nd week post THA. We found an intertrochanteric fracture intra-operatively with unstable implant. Acetabular component and femoral component revision were done with reconstruction of the greater trochanter. These fractures could be occult iatrogenic fractures characteristic of taper wedge stems which presented as early nontraumatic dislocation in the post-operative period. The prosthesis subsidence, loss of muscle tension and change of version might be the factors leading to dislocation. Unrecognized incomplete intraoperative fracture can occur with tapered wedge uncemented stems which can present as a dislocation in the immediate post-operative period. This will require early revision of the femoral component.


Cardiac Resynchronization Therapy Guided by Echocardiography, MRI, and CT Imaging: A Randomized Controlled Study.
This study evaluated if selecting the left ventricular (LV) target segment by echocardiography-derived late mechanical activation, with access to multimodality imaging for scar and venous anatomy, could help to increase responder rates to cardiac resynchronization therapy (CRT). LV lead placement is important for clinical outcome, but the optimal strategy for LV lead placement in CRT is still debated. This study conducted a prospective, blinded randomized controlled trial on 102 patients with indication for CRT (27% women, 46% with ischemic cardiomyopathy, 63% in New York Heart Association functional class III, 74% with left bundle branch block, and with mean ejection fraction of 23%). Optimal LV lead location was defined as the latest mechanically activated available segment (free of transmural scar), determined by radial strain echocardiography, cardiac computed tomography, and cardiac magnetic resonance (n = 70). The primary endpoint was reduction of LV end-systolic volume by ≥15% at 6 months post-implantation. Patients were followed for 47 ± 21 months. Based on imaging, optimal or adjacent lead placement was feasible in 96% of all cases and was obtained in 83% of the intervention group versus 80% of the control group. Fifty-six percent of the patients were LV end-systolic volume responders compared with the control group (55%) (p = 0.96), and 71% improved ≥1 New York Heart Association functional class (74% vs. 67%; p = 0.43). Death or heart failure hospitalization within 2 years occurred in 6% (2% of the intervention group vs. 10% of the control group; p = 0.07). Radial strain-guided LV lead placement, in combination with multimodality imaging, did not result in increased clinical or echocardiographic response, nor in a significant reduction of death or heart failure hospitalization. (Combining Myocardial Strain and Cardiac CT to Optimize Left Ventricular Lead Placement in CRT Treatment [CRT Clinic]; NCT01426321).


Radiating leg pain in the older patient.
Failure to recognize the presentation frequently leads to misdiagnoses and treatment errors. To avoid such pitfalls, guidelines on seven prominent etiologies are provided. With careful attention to the history and physical examination, an understanding of how those etiologies present will lead to accurate diagnosis and appropriate treatment.


Constitutively elevated levels of ornithine and polyamines in mouse epidermal papillomas.
Epidermal papillomas were induced in CD-1 mice by a single topical application of 7,12-dimethylbenzanthracene (DMBA) followed by twice weekly applications of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in acetone. Control groups consisted of mice treated singly or chronically with acetone or TPA. TPA induced a rapid, yet transient 500- to 1000-fold increase in ornithine decarboxylase (ODC) activity which resulted in a 2- to 8.4-fold elevation of putrescine in both singly or chronically TPA-treated mouse epidermis 4-6 h after its application. After 24 h, levels of spermidine, but not spermine, were also elevated. The ODC and arginase activities in the 11 individual papillomas studied averaged 400- and 26-fold higher respectively than basal levels in epidermis. The activity of ODC in most papillomas, unlike ODC in epidermis, could be stimulated by guanosine 5'-triphosphate (GTP). Putrescine and spermidine levels in papillomas, especially those exhibiting highly GTP-stimulated ODC, were substantially higher compared to either normal or TPA-treated epidermis. Although epidermis contains a relatively high ornithine content, its level is even further elevated in papillomas, in some cases as much as 70-fold. The consequences of the constitutively elevated polyamine levels in papillomas caused by the loss of control over the normally tightly regulated polyamine biosynthetic pathway are not known, but could be important in regulating the balance between proliferation and differentiation in this self-renewing epithelial tissue.


The scintigraphic diagnosis of osteomyelitis.
Osteomyelitis is a serious health problem that results in multiple limb amputations annually. This article reviews the current scintigraphic procedures used in the diagnosis of osteomyelitis and discusses some of the newer radiopharmaceuticals now being developed. The goal is to understand the strengths and weaknesses of each method so that the procedure most effective for specific clinical settings can be selected. In general, the three-phase bone scan is the procedure of choice if the suspected osteomyelitis is not superimposed on another disease that causes increased bone remodeling (i.e., findings on the radiograph are normal). If the suspected osteomyelitis is superimposed on a disease that causes increased bone remodeling, the combined 111In-labeled leukocyte-99mTc bone scan is the procedure of choice in the non-marrow-containing skeleton and the 111In-labeled leukocyte and 99mTc bone marrow scans are the procedures of choice in the marrow-containing skeleton.


The chemical components of Coreopsis tinctoria Nutt. and their antioxidant, antidiabetic and antibacterial activities.
Seventeen compounds were isolated from the capitula of Coreopsis tinctoria Nutt. with various column chromatographic methods and semi-preparative HPLC. Their structures were identified by the spectroscopic data and comparison with literatures as 2'-hydroxy-4,4'-dimethoxy-chalcone; (1), isoliquiritigenin (2), eriodictyol (3), naringenin (4), maritimetin (5), butin (6), taxifolin (7), luteolin (8), 7,3',4'-trihydroxyflavone (9), 8,3',4'-trihydroxyflavone-7-O-β-d-glucoside (10), quercetin (11), quercetagitin-7-O-β-d-glucoside (12), quercetin-7-O-β-d-glucoside (13), 3,4-dihydroxybenzoic acid (14), caffeic acid (15), coreoside B (16), and myo-inositol (17). Compounds 1, 4, 9, 10 and 17 were isolated from C. tinctoria Nutt. for the first time. Compounds 7 and 12 possessed the highest antioxidant activity (IC50 = 64.37 and 32.86 µg/ml, respectively) among the tested compounds (IC50 value of positive control was 5.34 µg/ml). Compound 7 exhibited potent PTP1B enzymatic inhibition with an IC50 value of 7.73 μg/ml (IC50 value of positive control is 1.46 µg/ml). Furthermore, compound 5 showed strong antibacterial activity against the Gram-positive bacterium, S. aureus.


Health Management Occupations During COVID-19: Experiences of Older African Americans With Multimorbidity.
Older African Americans with multimorbidity are at an especially high risk of adverse outcomes due to synergistic risks conferred by age, chronic disease burden and social determinants of health. Chronic condition self-management is one way older African Americans can use health management occupations and exercise agency to reduce their risk of becoming severely ill, and during the ongoing pandemic, of COVID-19 infection. The objective of this study was to understand how the COVID-19 pandemic shaped health management occupations of older African Americans. In-depth qualitative interviews were conducted with 30 African Americans aged 65 and older who reported having two or more chronic conditions. Data were analyzed using thematic analysis. Data suggest how key health management occupations (accessing care; managing medications, nutrition, and physical activity; and social and emotional health promotion and maintenance) were utilized and also shaped by the pandemic. Another key finding was perceived benefits of the pandemic on health and well-being.


Lipoprotein profile and cholesteryl ester transfer protein in neonates.
Undernourishment in utero appears to be associated with persisting changes in the metabolic, endocrine, and immune functions. In this study, we determined the influence of birth weight on the lipoprotein profile and cholesteryl ester transfer protein (CETP), which promotes a proatherogenic lipoprotein profile in plasma by determining the chemical, physical, and biologic properties of the respective lipoprotein particles. Triglyceride (TG) concentrations were highest and high-density lipoprotein (HDL)(2)-cholesterol levels were lowest in small for gestational age (SGA) neonates. CETP-mass was determined by enzyme-linked immunosorbent assay (ELISA) and CETP-activity by using exogenous lipoproteins. Cholesteryl ester transfer was determined as transfer of radiolabeled cholesteryl esters (CE) from HDL to apolipoprotein B-containing lipoproteins. CETP mass was lowest and cholesteryl ester transfer was highest in SGA neonates. CETP-activity did not differ among the neonates. Our results suggest that increased and decreased nourishment in utero affects the lipoprotein profile and CETP in neonates. High TG and low HDL(2) levels in SGA neonates might result from increased cholesteryl ester transfer and, may in part, explain the increased risk of coronary heart disease (CHD) of small for gestational age neonates in later life.


Development of a SOD ELISA to determine the immunological relatedness among mycobacteria.
This study reports on the standardization of an enzyme-linked immunosorbent assay (ELISA) system for the measurement of immunological distances (ImDs) of the superoxide dismutase (SOD) molecule among the cultivable mycobacteria, namely, Mycobacterium vaccae, M. phlei, M. smegmatis, M. avium, M. scrofulaceum, M. tuberculosis H37Ra, M. tuberculosis H37Rv, and M. bovis BCG, and M. leprae. SODs from cultivable mycobacteria were purified, antibodies were raised against these molecules, and ImDs between these anti-SOD antibodies and antigen (SODs) were determined by an immunoprecipitation technique standardized earlier and by the ELISA technique developed in this study. The ELISA system developed in this study showed higher sensitivity and consistent and reproducible ImDs among various mycobacteria, including pathogens such as M. tuberculosis, M. leprae and M. avium. These values were comparable with the values derived by the immunoprecipitation technique. Our ELISA technique appears to be a sensitive and rapidly reproducible method with the additional advantage of the stability of reagents, and holds promise in the taxonomy as well as in the development of diagnostics for leprosy and other mycobacterial infections.


Glial cell line-derived neurotrophic factor signals through the RET receptor and activates mitogen-activated protein kinase.
Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta family of growth factors, was first identified by its ability to promote the survival of midbrain dopaminergic neurons in culture. We demonstrate that GDNF treatment of several neuroblastoma cell lines leads to dose-dependent tyrosine phosphorylation of the RET receptor and that other transforming growth factor-beta family members are not able to activate the RET receptor. GDNF treatment of neuroblastoma cells also results in increased transcription of an Elk luciferase reporter gene, suggesting that GDNF activates the mitogen-activated protein kinase signal transduction pathway.


Intentional and unintentional nonadherence in patients prescribed HAART treatment regimens.
The objective was to investigate intentional and unintentional nonadherence to anti-HIV treatment regimens from a decision-making perspective. The participants (n = 117) being treated with anti-HIV medication completed a questionnaire asking about nonadherence; reasons for and against taking the medication; and medical consultation style. Thirty-three participants (29%) reported intentionally missing or altering doses of medication at least 5% of the time; 59 participants (50%) reported forgetting to take medication at least 5% of the time. Intentional nonadherence was associated with the balance of the perceived benefits and losses of taking medication, and extent to which participants were 'prepared for the effects of the medication'. Unintentional nonadherence was associated with demographic and clinical variables. The research highlights the importance of (i) treating intentional and unintentional nonadherence as separate entities; (ii) assessing individuals' idiosyncratic beliefs and internal logic when considering intentional nonadherence; and (iii) ensuring that individuals feel prepared for the effects of their medications.


Bone-Targeted Therapy.
Bisphosphonates and denosumab are well established components of the therapy for osteoporosis and osseous metastases. Their relevance in the adjuvant situation for breast cancer patients is being discussed in part controversially due to the heterogeneous nature of the available data. In particular, it appears that post-menopausal women benefit from an adjuvant therapy with bisphosphonates. In the present contribution we discuss the clinical relevance of osteoprotective therapy in the metastatic and adjuvant settings. Above all the current AGO guidelines on osteo-oncology and bone health have been taken into consideration for recommendations to implement the available data.


Measurement of antinuclear antibodies: assessment of different test systems.
The performance of rat liver and HEp-2 in the detection of antinuclear antibodies (ANA) was studied by two independent sites and compared against an ANA enzyme immunoassay (EIA) screen and EIA systems for the measurement of antibodies to double-stranded DNA (dsDNA) and ENA. Sixty-two sera from patients with connective tissue disease (CTD) and 398 from controls suffering from other disorders were included. The level of agreement was, for HEp-2 and rat liver (within one site), 82.0% (ANA positive/ANA negative) and 51.0% (ANA pattern); and for HEp2- and HEp-2 (between sites), 71.8 and 86.5%. On sera with the ANA homogeneous pattern, the measurement of anti-ENA EIA added little to the detection rate with anti-dsDNA EIA alone. On ANA speckled sera, the EIA reactivity depended on the reaction of the mitotic cells: while sera with positive mitoses reacted similarly to ANA homogeneous sera, in those with negative mitoses the measurement of anti-ENA added about 10% to the detection rate achieved with anti-dsDNA alone. The measurement of anti-Scl-70 and anti-Jo-1 did not markedly improve the positive rate with classical ENA (anti-SSA, -SSB, -Sm, and -RNP) alone, raising doubts about the cost efficiency of including these measurements in unselected sera. The ANA EIA identified patients with CTD at a rate similar to that for rat liver and HEp-2. However, up to 98% of the sera found to be negative by ANA EIA but positive by use of rat liver and HEp-2 were from controls. Thus, the ANA EIA may possible be used as an alternative screen, particularly in laboratories with a high frequency of sera from patients not suffering from CTD.


Not all germ cells are created equal: aspects of sexual dimorphism in mammalian meiosis.
The study of mammalian meiosis is complicated by the timing of meiotic events in females and by the intermingling of meiotic sub-stages with somatic cells in the gonad of both sexes. In addition, studies of mouse mutants for different meiotic regulators have revealed significant differences in the stringency of meiotic events in males versus females. This sexual dimorphism implies that the processes of recombination and homologous chromosome pairing, while being controlled by similar genetic pathways, are subject to different levels of checkpoint control in males and females. This review is focused on the emerging picture of sexual dimorphism exhibited by mammalian germ cells using evidence from the broad range of meiotic mutants now available in the mouse. Many of these mouse mutants display distinct differences in meiotic progression and/or dysfunction in males versus females, and their continued study will allow us to understand the molecular basis for the sex-specific differences observed during prophase I progression.


Comparing exponentially weighted moving average and run rules in process control of semiquantitative immunogenicity immunoassays.
The immunogenicity immunoassay validation process ensures development of a robust, reproducible method. However, no matter how well developed, validated, and maintained a method is, in the course of running a large number of samples over time, it is not uncommon to see bad reagents, poorly calibrated equipment, personnel errors, or other unknown and unpredictable factors that have an impact in the performance of the method and quality of the sample results. The immunogenicity immunoassay thus needs to be closely monitored with an internal statistical quality control process overtime to ensure a consistent and reliable output. The statistical process control has been widely applied to monitor manufacturing processes and in clinical laboratories. Its application to immunogenicity immunoassays is relatively novel. Limited guidance is available to implement the process to monitor semiquantitative immunogenicity immunoassay performance. Here, we have performed a suitability evaluation for process control charts with actual laboratory data from three immunogenicity immunoassay methods each utilizing a different technology platform. Additionally, a panel of prepared samples designed to assess long-term method performance were periodically evaluated for over a year. Finally, we make recommendations for an internal quality control process based on the results of these evaluations.


Hemophagocytic lymphohistiocytosis in the premature neonate.
Hemophagocytic lymphohistiocytosis (HLH), a rare disease, results in pathological findings secondary to an abnormal proliferation of activated lymphocytes and histiocytes (tissue macrophages) and is lethal unless identified and adequately treated. Clinical features of HLH include fever, hepatosplenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, elevated blood levels of ferritin, lymphadenopathy, skin rash, jaundice, and edema. Often, the symptoms of HLH are misinterpreted as infection, resulting in inadequate treatment and death. Several case studies of premature neonates with HLH have recently been published. Therapeutic guidelines for HLH exist and, when identified, HLH in the premature infant can be successfully treated resulting in resolution of symptoms.


Nebivolol for the treatment of heart failure.
Heart failure (HF) is a common and disabling disease with a high prevalence in the elderly. Beta-blockers are among the mainstay therapies of HF because they antagonize the deleterious effects of the chronic activation of sympathetic nervous system. In large randomized clinical trials, bisoprolol, carvedilol and metoprolol reduced mortality and cardiovascular hospital admission and, hence, are included in current guidelines for HF treatment. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenoceptors selectivity and vasodilating effects. It also shows antioxidant, antiproliferative and antithrombotic properties. Nebivolol is generally well tolerated. Typical β-blocker-related adverse events are same as that with placebo, except for bradycardia. In addition, it shows no negative effects on chronic obstructive pulmonary disease, erectile function, and glucose and lipid metabolism. The benefits of nebivolol for HF treatment have been evaluated in the SENIORS trial, where it reduced the composite endpoint of mortality and cardiovascular hospital admission. Nebivolol is a β-blocker with distinctive characteristics. Initiated at 1.25 mg and titrated up to 10 mg/day, it has shown safety and efficacy in one large outcome trial, when added to standard medical therapy, in elderly patients (≥ 70 years) affected by HF.


Role of nociceptin and opioid receptor like 1 on entrainment function in the rat suprachiasmatic nucleus.
The suprachiasmatic nucleus of the hypothalamus is the master circadian clock in mammals. Phase shifts in circadian locomotor activity occur when an animal is exposed to light during the subjective night. An endogenous ligand of opioid receptor like 1, nociceptin is reported to inhibit light-induced phase shifts in locomotor activity rhythm. However, little is known about the role of opioid receptor like 1 receptors in the entrainment. Therefore, we investigated the involvement opioid receptor like 1 and its endogenous ligand, intnociceptin, in the suprachiasmatic nucleus and in the entrainment of circadian rhythms in rats. In an in vitro experiment, glutamate (1 microM) -induced phase delay of suprachiasmatic nucleus neuronal activity rhythms was inhibited by nociceptin during the early subjective night. An opioid receptor like 1 antagonist, compound B (10 microM), induced a phase delay, and this effect was blocked by nociceptin (10 microM). Moreover, compound B (10 microM) potentiated the glutamate (1 microM) -induced phase delay. Fos expression in the suprachiasmatic nucleus of rats induced by photic stimulation (50 lux, 30 min) during the early subjective night was inhibited by treatment with nociceptin (0.5-10 nM, i.c.v.). The effect of nociceptin (10nM, i.c.v.) was blocked by pretreatment with compound B (30 mg/kg, i.p). In an in vivo experiment, nociceptin significantly inhibited a light-induced (300 lux, 1 h) phase delay of locomotor activity rhythms, and this effect was inhibited by Compound B. Compound B (30 mg/kg, i.p.) significantly potentiated the light-induced phase delay. Nociceptin induced a neuronal firing phase advance (in vitro) and locomotor activity rhythms (in vivo) in the daytime and this effect was blocked by Compound B. These results suggest that opioid receptor like 1 receptors have an inhibitory effect at night, and a facilitative effect in the day, on phase changes.


Psychosocial adjustment of adolescent siblings of hematopoietic stem cell transplant patients.
Hematopoietic stem cell transplantation (HSCT) is a widely practiced therapy for many life-threatening childhood disorders. The authors investigated the psychosocial effects of HSCT on siblings of pediatric HSCT patients (n = 44; 21 donors, 23 nondonors, ages 6 to 18 years). Donor siblings reported significantly more anxiety and lower self-esteem than did nondonors. Nondonors showed significantly more school problems. Approximately one third of all siblings reported moderate to severe posttraumatic stress. The study drew on the developmental theory of Erik Erikson and the psychosocial model of posttraumatic stress. As part of the study, the authors used the Measures of Psychosocial Development (MPD), a self-report measure based on Eriksonian constructs. The MPD was used to assess the psychosocial adjustment of 12 siblings who were adolescents (> or =13 years) at the time the study was conducted. In this article, findings are presented from the MPD as well as salient findings from the larger study.


Endoscopic treatment can be a viable therapeutic option for esophageal gastrointestinal stromal tumors.
Esophageal gastrointestinal stromal tumors(GISTs) are extremely rare. We sought to determine whether endoscopic treatment can be a viable therapeutic option for esophageal GISTs. A total of 20 cases with histological diagnosis of esophageal GISTs were obtained from our center between 2008 and 2020. Data on the clinicopathological features and treatment were recorded. There were 9 males (45%) and 11 females (55%) in this study, with a median age of 56 years. The tumors preferentially occurred in the middle and lower parts of the thoracic esophagus (45 and 40%, respectively). The mean size of the tumors was 2.27 cm and mitotic index was no more than 5/50 high power field (HPF) in all patients. In this study, 11 patients received endoscopic treatment and nine patients underwent surgical resection. Tumors ranged from 0.6 to 4 cm in the endoscopic treatment patients and 0.5 to 7 cm in the surgical patients. There were no significant differences in gender, age, symptoms, tumor location, tumor size, mitotic index, and adjuvant imatinib therapy between the endoscopic treatment group and the surgery group (all p > .05). The Kaplan-Meier curve suggested that there was also no significant difference in disease-free survival between the two groups (p = .264). Endoscopic treatment may be an option for the treatment of esophageal GISTs smaller than 5 cm with a mitotic index no more than 5/50 HPF.


Effects of zinc sulfate concentration and feeding frequency on ruminal protozoal numbers, fermentation patterns and amino acid passage in steers.
Effects of zinc sulfate (0 vs 1,142 ppm supplemental zinc from zinc sulfate) and feeding frequency (1 x vs 12x daily) on ruminal protozoa numbers, fermentation patterns and amino acid passage were investigated using four ruminally and abomasally cannulated mature Jersey steers in a 4 x 4 Latin square experiment. Steers (530 kg) were fed a 50:50 roughage:concentrate diet at 1.5 times their NEm requirement. Experimental periods were 14 d in duration; ruminal, abomasal and fecal samples were collected at 6-h intervals during the last 3 d of each period. Protozoa numbers tended to be lowest (1.82 x 10(6)/ml) in steers fed zinc 1 x and tended to be highest (3.83 x 10(6)/ml) in steers fed zinc 12 x daily (P less than .10). Frequent feeding decreased ruminal pH .24 units and increased total VFA 20.7%, ammonia 22.7% and ruminal digestion of dietary amino acids (AA) 61.6% (P less than .05). Zinc supplementation decreased ruminal digestion of dietary AA 35.8% (P less than .05) and the abomasal passage of bacterial OM and AA 21.2% (P less than .05) and increased ruminal output of amino acids as a percentage of intake 15.1% (P less than .05). Although it increased escape of dietary AA, zinc sulfate decreased postruminal passage of bacterial AA and resulted in a net negative effect on total postruminal AA passage as a percentage of intake. The effects of zinc on ruminal AA digestion may be more closely related to an interaction of zinc with dietary CP rather than to an effect of Zn on ruminal microbial populations.


Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet.
Little is known about the comparative effect of weight-loss diets on metabolic profiles during dieting. The purpose of this study was to compare the effect of a low-carbohydrate diet (< or =20 g/d) with a high-carbohydrate diet (55% of total energy intake) on fasting and hourly metabolic variables during active weight loss. Healthy, obese adults (n = 32; 22 women, 10 men) were randomly assigned to receive either a carbohydrate-restricted diet [High Fat; mean +/- SD body mass index (BMI; in kg/m(2)): 35.8 +/- 2.9] or a calorie-restricted, low-fat diet (High Carb; BMI: 36.7 +/- 4.6) for 6 wk. A 24-h in-patient feeding study was performed at baseline and after 6 wk. Glucose, insulin, free fatty acids (FFAs), and triglycerides were measured hourly during meals, at regimented times. Remnant lipoprotein cholesterol was measured every 4 h. Patients lost a similar amount of weight in both groups (P = 0.57). There was an absence of any diet treatment effect between groups on fasting triglycerides or on remnant lipoprotein cholesterol, which was the main outcome. Fasting insulin decreased (P = 0.03), and both fasting (P = 0.040) and 24-h FFAs (P < 0.0001) increased within the High Fat group. Twenty-four-hour insulin decreased (P < 0.05 for both groups). Fasting LDL cholesterol decreased in the High Carb group only (P = 0.003). In both groups, the differences in fasting and 24-h FFAs at 6 wk were significantly correlated with the change in LDL cholesterol (fasting FFA: r = 0.41, P = 0.02; 24-h FFA: r = 0.52, P = 0.002). Weight loss was similar between diets, but only the high-fat diet increased LDL-cholesterol concentrations. This effect was related to the lack of suppression of both fasting and 24-h FFAs.


[Effect of native and oxidation-modified LDL, VLDL and HDL on the morphological appearance and phenotype of cultured human arterial smooth muscle cells].
The arterial smooth muscle cells (SMC) are the predominant type of cells in atherosclerotic lesions, and their proliferation plays an important role in the process of AS genesis. We established the primary culture and sub-culture method for human arterial SMC and observed the effects of LDL, VLDL, HDL, OX-LDL, OX-VLDL and OX-HDL on the morphological appearance and phenotype of cultured human arterial SMC. The results revealed that the cells cultured in the medium containing OX-LDL, OX-VLDL and OX-HDL (25 micrograms/ml) became more irregular with long finger-like projects and lacked a bipolar shape, and the characteristic "hills" and "valleys" disappeared. LDL and VLDL also had the influence but in smaller degrees. HDL did not have any effect. The SMC cultured in the presence of OX-LDL (25 micrograms/ml) had less myofilaments and more endoplasmic reticulua, Golgi and mitochondria in cytoplasm compared with the cells in control group under electronmicroscope. These results suggest that the atherogenic role of LDL, VLDL, OX-LDL, OX-HDL, and OX-VLDL are closely related to their stimulating effects on the modulation of phenotype of arterial SMCs from "contractile" towards "synthetic".


The decline of official language minorities in Quebec and English Canada.
"This paper considers the evolution of French outside of Quebec and the English in Quebec.... The total historical set of national data on ethnicity, mother tongue, knowledge of official languages and home language [is first presented]. The 120 year stability showing French at around 30 percent of the national total is a function of compensating factors including high French fertility and high English immigration. During the 1960s both of these demographic supports disappeared and thus mobility across linguistic lines has become a particularly sensitive issue. "The picture with regard to French outside of Quebec has changed rather radically in the last thirty-five years. For instance, there was one French child to every nine in 1941 and one to every twenty-one children in 1976. While the English of Quebec were once represented in various parts of the province, their strength is now largely limited to the Montreal metropolitan area which includes 76 percent of the English mother tongue group. Outside of Montreal, the English amounted to 7.9 percent of Quebec's population in 1941 and 5.6 percent in 1976. The paper concludes with a discussion of the social factors that underlie these trends and their relevance to the models of institutional and territorial bilingualism." (summary in FRE)


[An evaluation of the incidence of hyperparathyroidism after 131I treatment for Basedow disease (Part II)].
The authors reported in a previous paper that 131I treatment for Basedow disease tends to increase in development of hyperparathyroidism (HPT) after therapy, from results showing that the measurement of levels of parathyroid hormone and calcium in the blood showed higher levels in the 131I-treated (RI) group than in the anti-thyroid drugs (ATD) group after therapy for Basedow disease. In the present work, the incidence of HPT was studied in patients with HPT that developed after treatment with 131I and/or ATD for Basedow disease at Ito Hospital. Fifteen of nineteen HPT patients had been treated with 131I and the other four had been treated with ATD. Basedow patients of the same age and sex with HPT and treated in the same year at Ito Hospital were selected as the control population for this study. The populations were 223 cases treated with 131I and 199 cases with ATD. The incidence of HPT in the RI and ATD groups was 6.7 percent and 2.0 percent, respectively. The incidence in the RI group was apparently higher than that in the ATD group. The average latent periods in the RI group and in the ATD group were 13.5 years and 4.1 years respectively. In the RI group 11 cases underwent follow-up periods of more than 10 years and 4 cases were followed up for less than 10 years. For the ATD group 3 of 4 HPT cases were followed up for less than 3 years. In the population the average follow-up periods for the RI group and the ATD group were 5.9 years and 5.3 years respectively. A relationship between radiation dose and development of HPT was demonstrated in these 15 cases of HPT. These findings suggest that 131I treatments for Basedow disease may result in development of hyperparathyroidism but the length of the follow-up period may also be an important factor in the incidence.


Remarkable alkali cation template effect in 1,5-bridged calix[8]arenes.
Treatment of 1,5-bridged calix[8]arenes 2-4 with alkali metal carbonates produces salts in which an included cation acts as a conformational template. This induces the folding of calix[8]arene skeleton in a conformation in which the triads of contiguous OH-bearing rings adopt a 3/4-cone conformation with all hydroxyls converging toward the same center. The template effect requires the presence of short bridges (ethylene, tetramethylene, diethylene glycol) and became stronger by increasing the cation dimension up to that of Cs(+).


Public Health: years of leadership and vision.
From its work in immigration and rural health to its fight against smoking and AIDS, the U.S. Public Health Service has stood on the cusp of science and politics. As the PHS looks forward to the year 2000, a new book details its two centuries of service and its ongoing role in the health of the nation.


[Selective catalytic reduction of NO on Ag, Co and Cu/Al2O3 in excess oxygen].
The catalytic activities of alumina-supported Ag, Co and Cu for selective reduction of NO with propene as reductant in the presence of excess oxygen were investigated. The catalytic performances of single-component catalysts with different metal loadings and of samples prepared by various methods such as mechanical mixing, one-step impregnation, two-step impregnation, etc. were studied. The experimental results showed that the Ag exhibited the highest conversion of NO to N2 (approximately 89% with 2% loading, wt.) among single-component catalysts, the lower was Co, and the lowest was Cu. The sequence of the temperature for the maximum conversion was on the order of Cu < Co < Ag. For Ag catalysts, the activities between samples of identical loadings prepared by one-step and two-step impregnation were almost the same. The activities of mixed samples were not the simple sum of the single-component catalysts. The mixed Ag-Co sample possessed the highest activity (80% above). The activities of the combinatorial samples declined comparatively to some extent. The activities of one-step impregnation samples descended more markedly and the highest conversion was only over 30%.


Autochthonous mouse models for prostate cancer: past, present and future.
Prostate cancer continues to be the second leading cancer related death among men. In order to more fully develop effective prevention and intervention strategies for this prevalent disease, the underlying molecular mechanisms of initiation, progression and metastatic spread must be understood. To this end mouse models have an essential role in prostate cancer research in that they can closely mimic the pathological and biochemical features of the disease. In this review we discuss the history of autochthonous murine models of prostate cancer, the essentials of the idealized mouse model for prostate cancer and speculate on approaches towards this goal.


Structure of the murine fifth complement component (C5) gene. A large, highly interrupted gene with a variant donor splice site and organizational homology with the third and fourth complement component genes.
To understand fifth complement component (C5) gene regulation, splicing, and C5 protein deficiency at the molecular level, the organization of the murine C5 gene was determined. The C5 structural gene is present as a single copy in the mouse genome as demonstrated by Southern blot analysis. Accordingly, three cosmid clones were isolated from a genomic library that was prepared from mouse strain B10.D2/nSnJ. These clones overlapped and contained the structural gene encoding the complete C5 alpha-chain and 90% of the beta-chain. The 5'-flanking region of the C5 gene was obtained from a clone isolated from a genomic lambda-MOPC-41 library. Unique restriction fragments were prepared from the genomic clones and subcloned, and the exons were sequenced. All introns were sized by sequencing or Southern analysis. The C5 structural gene was found to be a highly interrupted gene of approximately 78 kilobases containing 42 exons and 41 introns. The exons ranged in length from 58 to 247 base pairs, with an average length of 131 base pairs. The introns ranged in size from 100 base pairs to 4 kilobases with an average length of 1.5 kilobases. The C5 alpha-chain was encoded by 49 kilobases containing 26 exons; the beta-chain was encoded by 29 kilobases containing 16 exons. The C5a coding sequence was split between two exons. All intron/exon junctions followed the normal consensus rule except at intron 35 in which the 5'-donor GT was substituted by GC. The 2-base-pair gene deletion and HindIII and PvuII restriction fragment length polymorphisms associated with murine C5 deficiency were localized to exon 7, exon 16, and intron 20, respectively. Comparison of the intron-exon junctions of the murine C5, human C3, and mouse C4 genes indicated that these genes are nearly identical in structural organization. However, the rat alpha 2-macroglobulin gene showed only moderate genomic organizational similarity to the murine C5 gene. A major and a minor transcriptional initiation site in the C5 gene were identified by primer extensions and confirmed by RNase protection assays. Sequence analysis of the 5'-flanking region (760 base pairs) revealed a TATA-like and CAAT box upstream of the major transcriptional initiation site at positions -274 and -303, respectively, suggesting an atypical promoter. The 5'-flanking region also contained sequences identical with several cis-acting motifs known to bind the liver-specific nuclear protein LF-A1 and the nuclear protein NF-kappa B.(ABSTRACT TRUNCATED AT 250 WORDS)


Properties of single fast chloride channels from rat cerebral cortex neurons.
1. Properties of Cl- channels from surface membranes of acutely dissociated rat cerebral cortical neurons were studied with the patch clamp technique. These channels were present in the majority of excised inside-out membrane patches. 2. Cl- channels were rarely observed in cell-attached membrane patches, and usually several minutes elapsed following excision of the patch before Cl- channels became active. 3. Under asymmetric ionic conditions (1000 mM-KCli, 140 mM-KClo), neuronal Cl- channels are fairly selective for Cl- over K+ and Na+, with permeability ratios, determined by reversal potential shifts of 4.8 for both PCl/PK and PCl/PNa. 4. Neuronal Cl- channel kinetic activity remained stable over periods of time long enough to collect up to 500,000 open and closed intervals. Occasionally, the channels entered altered modes of activity. In the 'buzz mode' the open and closed interval durations became much shorter than normal for several hundreds of intervals. In the 'subconductance mode' the channel opened to a current level about two-thirds of the normal level. 5. Using the method of maximum likelihood, sums of exponentials were fitted to the distributions of open and closed interval durations. Open interval distributions required at least two exponential components with time constants of less than 1 ms. At least six or seven exponential components were required to fit the closed interval distributions with time constants ranging from 30 microseconds to several hundreds of milliseconds. This suggests that neuronal Cl- channels enter at least two open and six or seven closed kinetic states during normal activity. 6. Cl- channels often entered long-duration closed states of several minutes which could not be accounted for by the sums of exponentials fitted to the distribution of closed interval durations. 7. Neuronal Cl- channels exhibit a marked voltage dependence with the percentage of time the channels are open increasing with depolarization. Most of the observed voltage dependence can be accounted for by a decrease in the mean closed interval duration with depolarization. The mean open interval was relatively independent of voltage. 8. These results suggest a high degree of similarity in kinetic behaviour and conductance properties between the fast Cl- channels of tissue-cultured rat skeletal muscle and fast Cl- channels in acutely dissociated rat cerebral cortical neurons.


Longer Participation in the Special Supplemental Nutrition Program for Women, Infants, and Children Is Not Associated with Reduced Sugar-Sweetened Beverage Intake among Black Participants.
This study assessed relationships of duration of family Special Supplemental Nutrition Program for Women, Infants and Children (WIC) participation with racial/ethnic disparities in child sugar-sweetened beverage (SSB) and water intake. Child beverage intake and family duration on WIC were collected during three cross-sectional surveys of WIC-participating families in Los Angeles County, California (2014, 2017 and 2020; n = 11,482). The associations of family duration of WIC participation, a proxy for the amount of WIC services received, with daily intake of total SSBs, fruit-flavored SSBs and water were assessed in race/ethnicity strata with multivariable negative binomial and Poisson regression models. Among English-speaking Hispanic children, those of families reporting 10 years of WIC participation consumed 33% and 27% fewer servings of total and fruit-flavored SSBs compared to those of families reporting 1 year on WIC. Among Black children, those from families reporting 5 and 10 years of participation in WIC consumed 33% and 45% more daily servings of fruit-flavored SSBs than those from families reporting 1 year on WIC. Disparities in daily total and fruit-flavored SSB intake between Black and White children increased with longer family duration on WIC. Duration of family WIC participation is associated with healthier beverage choices for infants and children, but does not appear to be equally beneficial across racial/ethnic groups in Los Angeles County.


[[(Ethoxycarbonyl)difluoromethyl]thio]phthalimide: A Shelf-Stable, Electrophilic Reagent with a Convertible Group for the Synthesis of Diversified Fluoroalkylthiolated Compounds.
A shelf-stable and easily convertible reagent for the preparation of diversified fluoroalkylthiolated compounds, [[(ethoxycarbonyl)difluoromethyl]thio]phthalimide, was developed. [[(Ethoxycarbonyl)difluoromethyl]thio]phthalimide is an efficient electrophilic fluoroallylthiolating reagent that reacted with electron-rich heteroarenes/arenes, β-ketoesters, oxindoles, benzofuranones, and thiols. More importantly, the ethoxycarbonyl group of the resulting fluoroalkylthiolated compounds could be easily converted into various other functional groups such as chloride, alkynyl, hydrocarbonyl, carbomoyl, hydromethyl, or heteroaryl groups.


GABAergic pathways in the rat subcortical visual system: a comparative study in vivo and in vitro.
Inhibitory pathways project from the pretectal nuclear complex to the ipsilateral superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN). Both pathways arise from GABAergic neurones that are located in the dorsal pretectal nuclear complex. In the present experiments, we compared the anatomy and physiology of these two pathways with the objective of determining whether they have similar functions. First, we injected retrograde axonal tracers that fluoresce at different wavelengths in the dLGN and SC of single animals to determine if individual GABAergic neurones in the pretectum project to both structures. The results showed that the dLGN and SC receive input from different cell groups. Next, morphological reconstructions of cells labelled after in-vitro whole-cell patch-clamp recordings demonstrated that the pretectal-recipient cells in the dLGN are GABAergic interneurones, whereas those in the SC are projection cells. Finally, with in-vitro whole-cell patch-clamp recordings we showed that inhibitory currents generated by both pathways are mediated by GABA(A) receptors. Taken together, these results suggest that these inhibitory projections may function to facilitate the relay of information from the dLGN to the visual cortex by suppressing the activity of dLGN interneurones, and to reduce the level of activity leaving the SC by inhibiting the projection neurones. These hypotheses will be discussed in the context of the known functions of the pretectal complex.


Bioavailability of alpha-linolenic acid in subjects after ingestion of three different forms of flaxseed.
Dietary flaxseed may have significant health-related benefits due to its high content of the omega-3 fatty acid, alpha-linolenic acid (ALA). However, before extensive work can be undertaken in clinical populations to determine its efficacy, basic information on ALA bioavailability from flaxseed and the physiological effects of its ingestion need to be examined. The purpose of this study, therefore, was to determine the bioavailability of ALA when the flaxseed was ingested in the form of whole seed, milled seed or as flaxseed oil. The flaxseed components (30 g of seed or 6 g of ALA in the oil) were baked into muffins for delivery over a 3 month test period in healthy male and female subjects. Flaxseed ingestion over a 1 month period resulted in significant (P = 0.005) increases in plasma ALA levels in the flaxseed oil and the milled flaxseed supplemented groups. The former group had significantly (P = 0.004) higher ALA levels than the milled flaxseed group. The subjects supplemented with whole flaxseed did not achieve a significant (P > 0.05) increase in plasma ALA levels. An additional two months of flaxseed ingestion did not achieve significantly higher levels of plasma ALA in any of the groups. However, no significant increase was detected in plasma eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) levels in any of the flax-fed groups. There were no changes in plasma cholesterol or triglycerides or in platelet aggregation at any time point in any of the groups. Subjects in all of the groups exhibited some symptoms of gastro-intestinal discomfort during the early stages of the study but these disappeared in the oil and milled seed groups. However, compliance was a problem in the whole flaxseed group. In summary, ingestion of flax oil and milled flaxseed delivered significant levels of ALA to the plasma whereas whole flaxseed did not. Whole seed and oil preparations induced adverse gastrointestinal effects within 4 weeks and these were severe enough to induce the withdrawal of some subjects from these two groups. No one withdrew from the group that ingested milled flaxseed and, therefore, may represent a good form of flaxseed to avoid serious side-effects and still provide significant increases in ALA to the body.


Flavor components in tobacco capsules identified through non-targeted quantitative analysis.
Tobacco flavors increase the attractiveness of a tobacco brand and ultimately promote addiction. Information about what flavor and how much flavor is in flavor capsules can provide an effective way to regulate tobacco flavor. In this study, 128 flavor chemicals were identified and quantified by gas chromatography-mass spectrometry using libraries and authentic standards. Validation of the developed method was performed for interference, detection limits, calibration curves, accuracy, and precision. Menthol was the main ingredient in all capsules, and the carcinogenic pulegone was detected. Detected menthofuran, benzyl alcohol, geraniol, and eugenol cause toxic or severe irritation, and detected lactones can increase nicotine addiction by inhibiting nicotine metabolism in smokers. Margin of exposures for carcinogenic pulegone and non-carcinogenic menthol were well below safety thresholds, indicating a significant risk of inhalation exposure. It is desirable to prohibit the use of flavor capsules in consideration of human risk.


A conservative mutation in a class I MHC molecule outside the peptide binding groove stimulates responses to self peptides.
A transgenic mouse has been made that expresses a mutant MHC class I H-2Kb molecule with glutamic acid at position 65 (E65) in place of glutamine. The side chain at position 65, on the outward face of the alpha-helix of the alpha 1 domain of the class I molecule, interacts with the TCR, and not with the peptide binding groove. The transgenic mouse, on a DBA/2 background, mounts Kb,E65-restricted Ag-specific responses to conventional Kb-restricted Ag such as OVA and vesicular stomatitis virus, and shows strong alloreactivity to wild-type Kb. The transgenic mouse also mounts a primary in vitro alloreactive response directed to a mutant molecule with aspartic acid at position 65 (D65). This response is relatively weak, probably because of the structural similarities between aspartic and glutamic acid side chains; both have carboxylic termini, and the aspartic acid side chain is shorter by a single secondary carbon. The alloreactive CTL lines elicited by this conservative change are cross-reactive among several position-65 variants of H-2Kb. Individual CTL clones are specific for self peptides that can be extracted from cells expressing Kb,E65, and from purified wild-type Kb molecules, and that are recognized in the context of the D65 residue. Thus, the smallest variance from self in a class I molecule, even outside the peptide binding groove, can be antigenic.