Functional analysis of genes implicated in Down syndrome: 1. Cognitive abilities in mice transpolygenic for Down Syndrome Chromosomal Region-1 (DCR-1).
Down syndrome occurs every 1/1000 births and is the most frequent genetic cause of mental retardation. The genetic substrate of Down syndrome, an extra chromosome 21, was discovered by Lejeune, half-a-century ago, and the chromosome has been fully sequenced, although the gene(s) implicated in the mental retardation observed with the syndrome are still unknown. Observations of patients with partial trisomy of the 21q22.2 fragment suggest that most of the signs of the syndrome, including mental retardation, could be influenced by the region referred to as the Down Minimal Chromosomal Region-1 (DCR-1) for that reason. Using the extensive syntenies between human chromosome 21 and murine chromosome 16, Smith et al. (1995, 1997) developed transpolygenic mice with human chromosome 21 fragments covering the DCR-1. Here, we explored cognitive performances in mice over-expressing the genes carried by these fragments with the Morris water-maze and fear-conditioning procedures. The 152F7 transpolygenic mice had lower performance levels, compared to non-transgenic and other transgenic mice on most measurements in the water-maze. In fear-conditioning, all transgenic mice recorded lower performance levels compared to controls in the altered context stage. The 230E8, 141G6 and 285E6 mice failed to learn or react when the sound used as the conditional stimulus was added. These results showed that the 152F7 region played a crucial role in cognitive impairment, supporting the hypothesis of DYRK-1A gene involvement. However, the data presented here also suggest that other chromosomal regions within the DCR-1 may be involved in specific cognitive functions.


Teleost Mauthner cap cells: intimate contact by gap junctions.
In rainbow trout the glial cap cells ensheating the Mauthner cell axon cap form a more or less double-layered arrangement consisting of fibrous astrocytes, sometimes intermingled with an oligodendrocyte. All cells of the glial wall are linked together by many gap junctions. Especially the somata of the astrocytes are connected to each other by large symmetrical gap junctions. For this reason the glial cap cells might act as an (electro-) physiological unity. Morphologically, the high axon cap resistance above all results from the densely packed glial elements. Regarding their function the astro-astrocytic gap junctions might contribute to the formation of this barrier.


Time Series Modeling of Nano-Gold Immunochromatographic Assay via Expectation Maximization Algorithm.
In this paper, the expectation maximization (EM) algorithm is applied to the modeling of the nano-gold immunochromatographic assay (nano-GICA) via available time series of the measured signal intensities of the test and control lines. The model for the nano-GICA is developed as the stochastic dynamic model that consists of a first-order autoregressive stochastic dynamic process and a noisy measurement. By using the EM algorithm, the model parameters, the actual signal intensities of the test and control lines, as well as the noise intensity can be identified simultaneously. Three different time series data sets concerning the target concentrations are employed to demonstrate the effectiveness of the introduced algorithm. Several indices are also proposed to evaluate the inferred models. It is shown that the model fits the data very well.


[Influence of hot environment on body temperature, heart rate and blood pressure of pregnant rats].
Twenty-six out of fifty pregnant rats died on days 18-20 of gestation at 33 degrees C environment. The death generally occurred in the dark period around 1-5 a.m. Shortly prior to the death, very high body temperature of 42.0-43.7 degrees C were recorded and the blood pressure was undetectably low. In autopsy, the finding in the main was the congestion in lungs and liver. In temporal changes of body temperature and heart rate, influences of hot environment were observed, but there was no significant difference between dead pregnant group and delivered pregnant group at 33 degrees C environment. At 23 degrees C, the blood pressure of pregnant rats starting at about 140 mmHg level, reached 160-168 mmHg on day 12 of gestation and maintained the level to day 16. On day 18, the pressure returned to 140-145 mmHg and unchanged to term. At 33 degrees C, significant differences were obviously observed between dead group and delivered group in temporal changes of blood pressure. The blood pressure of rats delivered sharply increased to 170 mmHg or more in the middle stage of pregnancy and decreased to about 140 mmHg in the final stage. However, these of dead group increased to 160 mmHg or less in the middle stage of pregnancy, and maintained the level until the final stage.


Influence of Estrogenic Metabolic Pathway Genes Polymorphisms on Postmenopausal Breast Cancer Risk.
Estrogen metabolism plays an important role in tumor initiation and development. Lifetime exposure to high estrogens levels and deregulation of enzymes involved in estrogen biosynthetic and metabolic pathway are considered risk factors for breast cancer. The present study aimed to evaluate the impact of mutations acquisition during the lifetime in low penetrance genes that codify enzymes responsible for estrogen detoxification. Genotype analysis of GSTM1 and GSTT1 null polymorphisms, CYP1B1 Val432Leu and MTHFR C677T polymorphisms was performed in 157 samples of women with hormone-dependent breast cancer and correlated with the age at diagnosis. The majority of patients with GSTT1 null genotype and with both GSTM1 and GSTT1 null genotypes were 50 years old or more at the diagnosis (p-value = 0.021 and 0.018, respectively). Older women with GSTM1 null genotype were also carriers of the CYP1B1Val allele (p-value = 0.012). As well, GSTT1 null and CYP1B1Val genotypes were correlated with diagnosis at later ages (p-value = 0.022). Similar results were found associating MTHFR C677T and GSTT1 null polymorphism (p-value = 0.034). Our results suggest that estrogen metabolic pathway polymorphisms constitute a factor to be considered simultaneously with models for breast cancer risk assessment.


[Molecular ecology of microalgal viruses].
A great amount of virus particles exist in natural waters. Each virion is considered to have its own ecological role, affecting the maintenance and fluctuation of aquatic ecosystems. We have been studying viruses infectious to micro-plankton, especially those infecting phytoplankton. Red tides are caused by drastic increase in abundance of plankton. We succeeded in elucidating that viral infection is one of the most important factors determining the dynamics and termination of algal blooms by means of field survey and molecular experiments. In addition, we demonstrated that the interrelationship between viruses and their hosts are highly complicated, and might be determined by the molecular-structural difference of viral capsids among distinct virus ecotypes. Furthermore, in the process of our investigation on various aquatic algal viruses, their importance as genetic sources has also been suggested. In order to deeply understand the mechanism of aquatic ecosystem, more intensive studies as for aquatic viruses are urgently required.


Frequent paracetamol use and asthma in adults.
The pulmonary antioxidant glutathione may limit airway inflammation in asthma. Since paracetamol (acetaminophen) depletes the lung of glutathione in animals, a study was undertaken to investigate whether frequent use in humans was associated with asthma. Information was collected on the use of analgesics as part of a population based case-control study of dietary antioxidants and asthma in adults aged 16-49 years registered with 40 general practices in Greenwich, South London. The frequency of use of paracetamol and aspirin was compared in 664 individuals with asthma and in 910 without asthma. Asthma was defined by positive responses to questions about asthma attacks, asthma medication, or waking at night with shortness of breath. The association between analgesic use and severity of disease amongst asthma cases, as measured by a quality of life score, was also examined. Paracetamol use was positively associated with asthma. After controlling for potential confounding factors the odds ratio for asthma, compared with never users, was 1.06 (95% CI 0.77 to 1.45) in infrequent users (<monthly), 1.22 (0.87 to 1.72) in monthly users, 1. 79 (1.21 to 2.65) in weekly users, and 2.38 (1.22 to 4.64) in daily users (p (trend) = 0.0002). This association was present in users and non-users of aspirin and was stronger when cases with more severe disease were compared with controls; amongst cases increasing paracetamol use was associated with more severe disease. Frequency of aspirin use was not associated with asthma when cases as a whole were compared with controls, nor with severity of asthma amongst cases. Frequent paracetamol use was positively associated with rhinitis, but aspirin use was not. Frequent use of paracetamol may contribute to asthma morbidity and rhinitis in adults.


Acute stress disorder among parents of infants in the neonatal intensive care nursery.
The authors examined the prevalence of acute stress disorder (ASD) in parents of infants hospitalized in the neonatal intensive care unit (NICU). Forty parents were assessed after the birth of their infants. Parents completed self-report measures of ASD, parental stress, family environment, and coping style: 28% of parents developed symptoms of ASD. ASD was associated with female gender, alteration in parental role, family cohesiveness, and emotional restraint. Family environment and parental coping style are significantly associated with the development of trauma symptoms. Results from this study suggest potential interventions to help minimize psychological distress in parents.


Characterization of egg white antibacterial properties during the first half of incubation: A comparative study between embryonated and unfertilized eggs.
Egg white is an important contributor to the protection of eggs against bacterial contaminations during the first half of incubation (day zero to 12), prior to the egg white transfer into the amniotic fluid to be orally absorbed by the embryo. This protective system relies on an arsenal of antimicrobial proteins and on intrinsic physicochemical properties that are generally unfavorable for bacterial multiplication and dissemination. Some changes in these parameters can be observed in egg white during egg storage and incubation. The aim of this work was to characterize changes in the antibacterial potential of egg white in embryonated eggs (FE) during the first half of incubation using unfertilized eggs (UF) as controls. Egg white samples were collected at day zero, 4, 8, and 12 and analyzed for pH, protein concentration, and protein profile. Antibacterial properties of egg white proteins were evaluated against Listeria monocytogenes, Streptococcus uberis, Staphylococcus aureus, Escherichia coli, and Salmonella Enteritidis. During incubation, differential variations of egg white pH and protein concentrations were observed between UF and FE. At equal protein concentrations, similar activities against L. monocytogenes and S. uberis were observed for FE and UF egg white proteins. A progressive decline in these activities, however, was observed over incubation time, regardless of the egg group (UF or FE). SDS-PAGE analysis of egg white proteins during incubation revealed discrete changes in the profile of major proteins, whereas the stability of some less abundant antimicrobial proteins seemed more affected. To conclude, the antibacterial activity of egg white proteins progressively decreased during the first half of egg incubation, possibly resulting from the alteration of specific antimicrobial proteins. This apparent decline may be partly counterbalanced in embryonated eggs by the increase in egg white protein concentration. The antibacterial potential of egg white is very effective during early stages of embryonic development but its alteration during incubation suggests that extra-embryonic structures could then progressively ensure protective functions.


Double minute chromosomes and homogeneously staining regions in tumors taken directly from patients versus in human tumor cell lines.
There is increasing evidence that copies of amplified oncogenes or drug-resistant genes located on extrachromosomal DNA (e.g. double minutes and/or episomes) can be eliminated from mammalian tumor cell lines by treatment of the cells with low concentrations of hydroxyurea. However, amplified oncogenes or drug-resistant genes located in an intrachromosomal site (such as in a homogeneously staining region (HSR)) cannot be eliminated from the cells. A question which arises is do primary human tumors have extrachromosomal DNA present often enough to make elimination of that extrachromosomal DNA a potentially important therapeutic strategy? To address that question we have reviewed published cytogenetic analyses of 200 tumors taken directly from patients to determine the percentage of primary human tumors which have amplified genes present on extrachromosomal DNA (present in the form of double minutes [DMs]) vs the percentage of tumors which have amplified genes located on an intrachromosomal site (in the form of HSRs). Of the 200 primary human tumors reviewed, 91% contained DMs only, 6.5% contained HSRs, and 2.5% contained both. Of interest, in a parallel review of 109 cell lines with cytogenetic and/or molecular evidence of gene amplification, 60.6% contained DMs, 26.6% contained HSRs, and 12.8% contained both. These data indicate that DMs are the predominant cytogenetic marker for gene amplification in patients, but are present less frequently in established cell lines. These findings indicate that ongoing efforts to eliminate amplified drug-resistant genes or oncogenes contained on DMs (or precursors of DMs) from tumor cells may be relevant for in vivo situations.


Kisspeptin neurons mediate reflex ovulation in the musk shrew (Suncus murinus).
The present study investigated whether kisspeptin-G protein-coupled receptor 54 (GPR54) signaling plays a role in mediating mating-induced ovulation in the musk shrew (Suncus murinus), a reflex ovulator. For this purpose, we cloned suncus Kiss1 and Gpr54 cDNA from the hypothalamus and found that suncus kisspeptin (sKp) consists of 29 amino acid residues (sKp-29). Injection of exogenous sKp-29 mimicked the mating stimulus to induce follicular maturation and ovulation. Administration of several kisspeptins and GPR54 agonists also induced presumed ovulation in a dose-dependent manner, and Gpr54 mRNA was distributed in the hypothalamus, showing that kisspeptins induce ovulation through binding to GPR54. The sKp-29-induced ovulation was blocked completely by pretreatment with a gonadotropin-releasing hormone (GnRH) antagonist, suggesting that kisspeptin activates GnRH neurons to induce ovulation in the musk shrew. In addition, in situ hybridization revealed that Kiss1-expressing cells are located in the medial preoptic area (POA) and arcuate nucleus in the musk shrew hypothalamus. The number of Kiss1-expressing cells in the POA or arcuate nucleus was up-regulated or down-regulated by estradiol, suggesting that kisspeptin neurons in these regions were the targets of the estrogen feedback action. Finally, mating stimulus largely induced c-Fos expression in Kiss1-positive cells in the POA, indicating that the mating stimulus activates POA kisspeptin neurons to induce ovulation. Taken together, these results indicate that kisspeptin-GPR54 signaling plays a role in the induction of ovulation in the musk shrew, a reflex ovulator, as it does in spontaneous ovulators.


Chrysin ameliorates ANTU-induced pulmonary edema and pulmonary arterial hypertension via modulation of VEGF and eNOs.
Alpha-naphthylthiourea (ANTU), a rodenticide induces lung toxicity. Chrysin a flavonoid possesses antioxidant, anti-inflammatory, and antihypertensive potential. The aim of this study was to evaluate the efficacy of chrysin against ANTU-induced pulmonary edema (PE) and pulmonary arterial hypertension (PAH) in laboratory rats. Sprague-Dawley rats were used to induce PE (ANTU, 10 mg/kg, ip) and PAH (ANTU, 5 mg/kg, ip, 4 weeks). Animals were treated with chrysin (10, 20, and 40 mg/kg) and various biochemical, molecular, and histological parameters were evaluated. Acute administration of ANTU induces PE revealed by significant (P < 0.05) increase in relative lung weight, pleural effusion volume, lung edema, bronchoalveolar lavage fluid cell counts, total protein, 5-hydroxytryptamine (5-HT), lactate dehydrogenase (LDH), and γ-glutamyl transferase (GGT), whereas pretreatment with chrysin (20 and 40 mg/kg, ip) significantly (P < 0.05) attenuated these ANTU-induced biochemical and histological alterations. Repeated administration of ANTU caused induction of PAH evaluated by significant (P < 0.05) alterations in electrocardiographic, hemodynamic changes, and left ventricular function, whereas chrysin (20 and 40 mg/kg, p.o.) treatment significantly (P < 0.05) attenuated these alterations. ANTU-induced hematological and serum biochemical (aspartate transaminase, alanine transaminase, LDH, and creatinine kinase MB) alterations were significantly (P < 0.05) inhibited by chrysin. It also significantly (P < 0.05) decreased elevated levels of oxido-nitrosative stress in the right ventricle (RV) and lung. Chrysin significantly (P < 0.05) attenuated downregulated endothelial nitric oxide synthase and upregulated vascular endothelial growth factor messenger RNA and protein expressions both in the RV and pulmonary artery. Chrysin inhibited ANTU-induced PE and PAH via modulation of inflammatory responses (5-HT, LDH, and GGT), oxido-nitrosative stress, and VEGF and eNOs levels.


Phorbol esters cause preferential secretion of norepinephrine from bovine chromaffin cells.
Differential secretion of norepinephrine and epinephrine was studied in cultured bovine chromaffin cells. Nicotinic agonists and 55 mM K+ evoked a slightly greater release of norepinephrine than of epinephrine: The percentage of norepinephrine secreted was 1.5 to two times greater than the percentage of epinephrine secreted. In contrast, when the cells were treated with phorbol 12,13-dibutyrate, the percentage of norepinephrine released was six to eight times greater than that of epinephrine released. Similar results were obtained in experiments with cultures highly enriched in either norepinephrine-containing cells or epinephrine-containing cells. In response to 55 mM K+, catecholamine release from norepinephrine-containing cells was two times greater than that from epinephrine-containing cells. In response to phorbol 12,13-dibutyrate, secretion from norepinephrine-containing cells was 13 times greater than that from epinephrine-containing cells. These results suggest that protein kinase C plays a specific role in the regulation of catecholamine secretion from norepinephrine-containing cells.


Early tracheostomy: on the cutting edge, some benefit more than others.
The decision to undergo early tracheostomy in critically ill patients has been the subject of multiple studies in recent years, including several meta-analyses and a large-scale examination of the National in-patient Sampling (NIS) database. The research has focused on different patient populations, and identified common outcomes measures related to ventilation. At the crux of the new research is the decision to undergo an additional invasive procedure, mainly tracheostomy, rather than attempt endotracheal tube ventilation with or without early extubation. Notably, recent research indicates that neurological and SARS-CoV-2 (COVID-19) patients seem to have an exaggerated benefit from early tracheostomy. Recent studies of patients undergoing early tracheostomy have shown decreases in ventilator associated pneumonia, ventilator duration and duration of ICU stay. However, these studies have shown mixed data with respect to mortality and length of hospitalization. Such advantages only become apparent with large-scale examination. Confounding the overall discussion is that the research has focused on heterogeneous groups, including neurosurgical ICU patients, general ICU patients, and most recently, intubated COVID-19 patients. Specific populations such as neurosurgical and COVID-19 patients have clearly defined benefits following early tracheostomy. Although the benefit is less pronounced, there does seem to be an advantage in general ICU patients with regards to ventilator-free days and lower incidence of ventilator-associated pneumonia. In these patients, large-scale examination points to a clear mortality benefit.


Control of stability of cyclin D1 by quinone reductase 2 in CWR22Rv1 prostate cancer cells.
Aberrant expression of cyclin D1, frequently observed in human malignant disorders, has been linked to the control of G(1)→S cell cycle phase transition and development and progression in carcinogenesis. Cyclin D1 level changes are partially controlled by GSK-3β-dependent phosphorylation at threonine-286 (Thr286), which targets cyclin D1 for ubiquitination and proteolytic degradation. In our continuing studies on the mechanism of prostate cancer prevention by resveratrol, focusing on the role of its recently discovered target protein, quinone reductase 2 (NQO2), we generated NQO2 knockdown CWR22Rv1 using short hairpin RNA (shRNA)-mediated gene silencing approach. We found that, compared with cells expressing NQO2 (shRNA08), NQO2 knockdown cells (shRNA25) displayed slower proliferation and G(1) phase cell accumulation. Immunoblot analyses revealed a significant decrease in phosphorylation of retinoblastoma Rb and cyclin D1 in shRNA25 compared with shRNA08. Moreover, shRNA25 cells showed a 37% decrease in chymotrypsin-like proteasome activity. An increase in AKT activity was also observed in shRNA25, supported by a ∼1.5-fold elevation in phosphorylation and ∼50% reduction/deactivation of GSK-3α/β at Ser21/9, which were accompanied by a decrease in phosphorylation of cyclin D1 at T286. NQO2 knockdown cells also showed attenuation of resveratrol-induced downregulation of cyclin D1. Our results indicate a hitherto unreported role of NQO2 in the control of AKT/GSK-3β/cyclin D1 and highlight the involvement of NQO2 in degradation of cyclin D1, as part of mechanism of chemoprevention by resveratrol.


Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells.
In diabetic patients, medial vascular calcification is common and associated with increased cardiovascular mortality. Excessive glucose concentrations can activate the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and trigger pro-calcific effects in vascular smooth muscle cells (VSMCs), which may actively augment vascular calcification. Zinc is able to mitigate phosphate-induced VSMC calcification. Reduced serum zinc levels have been reported in diabetes mellitus. Therefore, in this study the effects of zinc supplementation were investigated in primary human aortic VSMCs exposed to excessive glucose concentrations. Zinc treatment was found to abrogate the stimulating effects of high glucose on VSMC calcification. Furthermore, zinc was found to blunt the increased expression of osteogenic and chondrogenic markers in high glucose-treated VSMCs. High glucose exposure was shown to activate NF-kB in VSMCs, an effect that was blunted by additional zinc treatment. Zinc was further found to increase the expression of TNFα-induced protein 3 (TNFAIP3) in high glucose-treated VSMCs. The silencing of TNFAIP3 was shown to abolish the protective effects of zinc on high glucose-induced NF-kB-dependent transcriptional activation, osteogenic marker expression, and the calcification of VSMCs. Silencing of the zinc-sensing receptor G protein-coupled receptor 39 (GPR39) was shown to abolish zinc-induced TNFAIP3 expression and the effects of zinc on high glucose-induced osteogenic marker expression. These observations indicate that zinc may be a protective factor during vascular calcification in hyperglycemic conditions.


Exposure to ACEI/ARB and β-Blockers Is Associated with Improved Survival and Decreased Tumor Progression and Hospitalizations in Patients with Advanced Colon Cancer.
Advanced colon cancer is associated with weight loss and decreased survival. Studies suggest that angiotensin and β-adrenergic blockade decrease colon cancer progression and ameliorate weight loss. This study aims to determine whether exposure to β-adrenoceptor blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) is associated with decreased mortality, tumor progression, number of hospitalizations, or weight loss in colorectal cancer. Retrospective chart review included patients with advanced colorectal cancer. Survival, stage, hospitalization, cancer progression, cancer treatment, and body weight history were collected. Two hundred sixty-two of 425 new stage III to IV colorectal cancer cases reviewed met the study criteria. Those exposed to ACEI/ARB, BB, or both were more likely to have diabetes, hypertension, and stage III colorectal cancer. Adjusting for age, presence of hypertension and diabetes, and stage, ACEI/ARB + BB exposure was associated with decreased mortality compared to unexposed individuals [hazard ratio (HR) = 0.5, confidence interval (CI) = 0.29-0.85; Cox regression, P = .01]. Fewer total and cancer-related hospitalizations and decreased cancer progression in the ACEI/ARB + BB group versus the unexposed group (HR = 0.59, CI = 0.36-0.99, P = .047) were seen. Exposure did not affect weight changes; furthermore, body weight changes from both prediagnosis and at diagnosis to 6, 12, 18, and 24 months postdiagnosis predicted survival. We have observed an association between exposure to a combination of ACEI/ARB + BB and increased survival, decreased hospitalizations, and decreased tumor progression in advanced colorectal cancer. Future studies will be needed to replicate these results and generalize them to broader populations. Determination of causality will require a randomized controlled trial.


The Baby Steps Web Program for the Well-Being of New Parents: Randomized Controlled Trial.
New parents face increased risks of emotional distress and relationship dissatisfaction. Digital interventions increase support access, but few preventive programs are optimized for both parents. This study aims to conduct the first randomized controlled trial on universal self-guided digital programs to support positive perinatal adjustment of both mothers and fathers. Effects of childcare information (Baby Care) and information plus an interactive program (Baby Steps Wellbeing) were compared from the third trimester baseline to 3 and 6 months subsequently. The study recruited 388 co-parenting male-female adult couples expecting their first single child (26-38 weeks' gestation), using web-based registration. Most (337/388, 86.8%) were obtained from prenatal hospital classes. Couples' randomization was automated and stratified by Edinburgh Postnatal Depression Scale (EPDS) scores (50% couples scored high if either mother >7, father >5). All assessments were web-based self-reports: the EPDS and psychosocial quality of life were primary outcomes; relationship satisfaction, social support, and self-efficacy for parenting and support provision were secondary. Linear mixed models provided intention-to-treat analyses, with linear and quadratic effects for time and random intercepts for participants and couples. Selection criteria were met by 63.9% (248/388) of couples, who were all randomized. Most participants were married (400/496, 80.6%), tertiary educated (324/496, 65.3%), employed full time (407/496, 82%), and born in Australia (337/496, 67.9%). Their mean age was 32.2 years, and average gestation was 30.8 weeks. Using an EPDS cutoff score of 13, 6.9% (18/248) of men, and 16.1% (40/248) of women screened positive for depression at some time during the 6 months. Retention of both partners was 80.6% (201/248) at the 6-month assessments, and satisfaction with both programs was strong (92% ≥50). Only 37.3% (185/496) of participants accessed their program more than once, with higher rates for mothers (133/248, 53.6%) than fathers (52/248, 20.9%; P<.001). The EPDS, quality of life, and social support did not show differential improvements between programs, but Baby Steps Wellbeing gave a greater linear increase in self-efficacy for support provision (P=.01; Cohen d=0.26) and lower reduction in relationship satisfaction (P=.03; Cohen d=0.20) than Baby Care alone. Mothers had greater linear benefits in parenting self-efficacy over time than fathers after receiving Baby Steps Wellbeing rather than Baby Care (P=.01; Cohen d=0.51). However, the inclusion of program type in analyses on parenting self-efficacy and relationship satisfaction did not improve model fit above analyses with only parent gender and time. Three secondary outcomes showed differential benefits from Baby Steps Wellbeing, but for one (parenting self-efficacy), the effect only occurred for mothers, perhaps reflecting their greater program use. Increased engagement will be needed for more definitive testing of the potential benefits of Baby StepsWellbeing for perinatal adjustment. Australian New Zealand Clinical Trials Registry ACTRN12614001256662; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367277.


Decontamination of industrial wastewater from sugarcane crops by combining solar photo-Fenton and biological treatments.
The department of Valle del Cauca is the region with the largest sugarcane production in Colombia. This agricultural activity uses high quantities of herbicides, mainly Diuron and 2,4-Dichlorophenoxyacetic acid. Wastewater generated in the washing process of spray equipment and empty pesticide containers must be treated to keep natural water sources from being polluted with these pesticides when these effluents are disposed off. Conventional biological treatments are not able to remove recalcitrant substances like Diuron and 2,4-Dichlorophenoxyacetic acid; therefore, it is essential to have alternative treatment systems. In recent years, photocatalytic processes have been proven efficient methods in treating polluted water with recalcitrant organic substances. This study sought to evaluate the efficiency of a coupled treatment constituted for a solar photo-Fenton treatment and a biological system like an immobilized biological reactor to treat industrial wastewater containing pesticides (2,4-Dichlorophenoxyacetic acid and Diuron). The mineralization and degradation of pesticides were followed by measuring the dissolved organic carbon and pesticide concentrations. The results revealed that industrial wastewaters with high Diuron and 2,4-Dichlorophenoxyacetic acid concentrations can be successfully treated by a combined solar photo-Fenton-biological system, achieving mineralization of 79.8% in prepared wastewater and 82.5% in real industrial wastewater by using low Fe(2+) and H(2)O(2) concentrations.


Quantitative model for gene regulation by lambda phage repressor.
A statistical thermodynamic model has been developed to account for the cooperative interactions of the bacteriophage lambda repressor with the lambda right operator. The model incorporates a general theory for quantitatively interpreting cooperative site-specific equilibrium binding data. Values for all interaction parameters of the model have been evaluated at 37 degrees C, 0.2 M KCl, from results of DNase protection experiments in vitro [A. D. Johnson, B. J. Meyer, & M. Ptashne, Proc. Natl. Acad. Sci. USA (1979) 76, 5061-5065]. With these values, the model predicts repression curves at the divergent promoters PR and PRM that control transcription of genes coding for the regulatory proteins cro and repressor, respectively. At physiological repressor concentrations, repression at PR is predicted to be nearly complete whereas PRM is predicted to remain highly active. The results demonstrate the importance of cooperative interactions between repressor dimers bound to the adjacent operator sites OR1 and OR2 in maintaining a stable lysogenic state and in allowing efficient switchover to the lytic state during induction.


[Cystic meningioma simulating glioblastoma in x-ray computed tomography].
Seven cases of supratentorial meningiomas are reported. CT-Scan showed irregular hypo-hyperdense zones and features of intratumoral cysts. At surgery a well circumscribed tumor has always been found and easily removed "en bloc". In two cases stereotaxic biopsy was performed previously. CT-Scan findings of meningiomas with microcystic structure and/or necrotic areas may mimic a malignant glioma and lead to an incorrect presumptive diagnosis: then, both therapy and prognosis will be very different. It comes that stereotaxic biopsy is mandatory in all suspected cases of cerebral tumors, in the absence of classical angiographic patterns.


White matter network damage mediates association between cerebrovascular disease and cognition.
To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores.Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers.Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.


Dose-time response in mouse skin tumor induction by 7, 12-dimethylbenz[a]anthracene and 12-O-tetradecanoyl-phorbol-13-acetate.
The question was addressed whether the dose-response relationship derived from a carcinogenicity study can be used for mechanistic interpretation and to what extent the shape of the curve is dependent on the duration of the bioassay and the time of analysis. The mouse skin tumor model was used. It allows recording of the time of tumor appearance without interim sacrifice. Groups of 16 female NMRI mice were treated twice weekly by dermal administration with combinations of (a) 2.5 nmol 12-O-tetradecanoyl-phorbol-13-acetate (TPA) plus 0, 0.3, 1, 3, or 10 nmol 7,12-dimethylbenz[a]anthracene (DMBA) or with (b) 2.5 nmol DMBA plus 0, 0.1, 0.3, 1, 3, or 10 nmol TPA. The appearance of the first papilloma was recorded for each animal and the cumulative incidence data were analyzed in two ways: (i) With the usual dose-prevalence representation at a fixed time point, the dose response for TPA was sigmoidal, while it was linear-superlinear for DMBA. This was observed at all time points, indicating that the dose-response information may be used for a distinction between DNA-reactive and tumor-promoting mechanisms of action. (ii) When time-to-tumor and loss of tumor-free lifetime was analyzed as a function of dose, there was again a marked difference between DMBA and TPA. The tumor-free lifetime increased with each step of dose reduction but the slope was about four times larger for TPA compared with that for DMBA. Further reduction of the TPA dose could result in a situation in which the natural life span sets a limit to an observable effect. Under the conditions of this bioassay for mouse skin papilloma induction by a combination treatment with DMBA plus TPA, the findings support the idea of a no-effect low-dose threshold for the tumor-promoting agent.


Modulatory effects of the GABAergic basal ganglia neurons on the PPN and the muscle tone inhibitory system in cats.
Pedunculopontine tegmental nucleus (PPN) contributes to the control muscle tone by modulating the activities of pontomedullary reticulospinal systems during wakefulness and rapid eye movement (REM) sleep. The PPN receives GABAergic projection from the substantia nigra pars reticulata (SNr), an output nucleus of the basal ganglia. Here we examined how GABAergic SNr-PPN projection controls the activity of the pontomedullary reticulospinal tract that constitutes muscle tone inhibitory system. Intracellular recording was made from 121 motoneurons in the lumbosacral segments in decerebrate cats (n=14). Short train pulses of stimuli (3 pulses with 5 ms intervals, 10-40 mA) applied to the PPN, where cholinergic neurons were densely distributed, evoked eye movements toward to the contralateral direction and bilaterally suppressed extensor muscle activities. The identical PPN stimulation induced IPSPs, which had a peak latency of 40-50 ms with a duration of 40-50 ms, in extensor and flexor motoneurons. The late-latency IPSPs were mediated by chloride ions. Microinjection of atropine sulfate (20 mM, 0.25 ml) into the pontine reticular formation (PRF) reduced the amplitude of the IPSPs. Although conditioning stimuli applied to the SNr (40-60 mA and 100 Hz) alone did not induce any postsynaptic effects on motoneurons, it reduced the amplitude of the PPN-induced IPSPs. Subsequent injection of bicuculline (5 mM, 0.25 ml) into the PPN blocked the SNr effects. Microinjections of NMDA (5 mM, 0.25 ml) and muscimol (5 mM, 0.25 ml) into the SNr reduced and increased the amplitude of the PPN-induced IPSPs, respectively. These results suggest that GABAergic basal ganglia output controls postural muscle tone by modulating the activity of cholinergic PPN neurons which activate the muscle tone inhibitory system. The SNr-PPN projection may contribute to not only control of muscle tone during movements in wakefulness but also modulation of muscular atonia of REM sleep. Dysfunction of the SNr-PPN projection may therefore be involved in sleep disturbances in basal ganglia disorders.


Cobalt, iron co-incorporated Ni(OH)2 multiphase for superior multifunctional electrocatalytic oxidation.
The cobalt, iron co-incorporated Ni(OH)2 multiphase displays superior catalytic activity and stability for multifunctional electrocatalytic oxidation, ascribed to the multiphase synergy, enhanced charge transfer and well-exposed active sites.


The neurovascular couplings between electrophysiological and hemodynamic activities in anticipatory selective attention.
Selective attention is thought to involve target enhancement and distractor inhibition processes. Here, we recorded simultaneous electroencephalographic (EEG) and functional near-infrared spectroscopy (fNIRS) data from human adults when they were pre-cued by the visual field of coming target, distractor, or both of them. From the EEG data, we found alpha power relatively decreased contralaterally to the to-be-attended target, as reflected by the positive-going alpha modulation index. Late alpha power relatively increased contralaterally to the to-be-suppressed distractor, as reflected by the negative-going alpha modulation index. From the fNIRS data, we found enhancements of hemodynamic activity over the contralateral hemisphere in response to both the target and the distractor anticipation but within nonoverlapping posterior brain regions. More importantly, we described the specific neurovascular modulation between alpha power and oxygenated hemoglobin signal, which showed a positive coupling effect during target anticipation and a negative coupling effect during distractor anticipation. Such flexible neurovascular couplings between EEG oscillation and hemodynamic activity seem to play an essential role in the final behavioral outcomes. These results provide unique neurovascular evidence for the dissociation of the mechanisms of target enhancement and distractor inhibition. Individual behavioral differences can be related to individual differences in neurovascular coupling.


Genotypic heterogeneity among strains of Mycoplasma gallinarum.
Seven field strains of Mycoplasma gallinarum isolated from chickens on three local farms and the type strain PG 16 were compared by restriction endomiclease DNA analysis using EcoRI, HindIII, BamHI, PstI and Xhol. The restriction patterns generated by the first four enzymes indicated considerable DNA polymorphisms among M. gallinarum strains. Field strains revealed 3 distinct patterns of the genomic DNA which differed from that of the PG 16 strain. BamHI enabled easy distinguishing between related and unrelated strains due to the fragments being characteristic for certain strains. Interestingly, the characteristic patterns were associated with the corresponding chicken selection and this suggests that DNA analysis has a potential use for studying the epidemiology of M. gallinarum.


Crossover effects of estrogen receptor status on breast cancer-specific hazard rates by age and race.
Previous studies found that the risk of breast cancer-related death is greater in estrogen receptor (ER)-negative disease than in ER-positive disease within 5 years of diagnosis, but greater for ER-positive disease than for ER-negative disease more than 5 years after diagnosis. This phenomenon is referred to as ER-positive and -negative crossover. Our aim was to evaluate this crossover by determining the timing of the hazard of breast cancer death by patient, clinical, and tumor factors. Patients with breast cancer diagnosed between 1990 and 2005 were identified from the Surveillance, Epidemiology, and End Results database. The cohort was evaluated by age at diagnosis, race, tumor ER status, tumor and nodal stage, and tumor grade. Disease-specific (DS) hazard rates were calculated. Of the 439,444 patients identified, 77.5% had ER-positive disease. Overall, ER-negative to ER-positive DS hazard rates crossed between the years 7 and 8 after diagnosis. Earlier crossover was linked to black or Hispanic race, young age (<40 years), or tumors that were larger, higher grade, or affected the nodes. Young black (<40 years) patients who had a T3/T4 tumor with positive nodes, grade III or undifferentiated, had the earliest crossover, in year 4. The timing of crossover of death hazard for ER-positive and ER-negative disease varies by clinical and tumor factors. These findings may help guide recommendations regarding the duration of endocrine therapy for patients with ER-positive cancer.


Determination of fluoroquinolones in chicken feces - a new liquid-liquid extraction method combined with LC-MS/MS.
The application of antibiotics including fluoroquinolones to farming animals is widespread and may lead to the development of antibiotic resistance and other environmental effects. To calculate environmental loads and for a proper risk assessment it is necessary to determine the antibiotic concentration in feces. Therefore, a new liquid-liquid extraction method combined with HPLC-MS/MS for the detection of marbofloxacin, ciprofloxacin, enrofloxacin and difloxacin in chicken feces was developed. Recoveries ranged from 51.0% to 83.5%. LOQs were between 0.10 and 1.09μg/kg. Feces of chickens treated with an enrofloxacin dosage of 10mg/kg bodyweight revealed maximum enrofloxacin and ciprofloxacin concentrations of 61.3 and 18.8mg/kg. Both antibiotics could be detected in feces up to two days after the last application in notable amounts (∼1mg/kg). Thus, feces of recently medicated chickens should not be used as a fertilizer without any further processing.


[Expression of myeloid-derived suppressor cells in the peripheral blood and its clinical significance in renal carcinoma].
To investigate the expression of CD33⁺ HLA-DR⁻ myeloid-derived suppressor cells (MDSCs) in the peripheral blood of patients with renal carcinoma and its correlation with the clinicopathological features of renal cancer. Forty-four patients with renal carcinoma treated in our hospital between June, 2011 and October, 2012 and 18 healthy volunteers were enrolled in this study. Flow cytometry was performed to detect CD33⁺ HLA-DR⁻ MDSCs in the peripheral blood, and its correlation with the clinicopathological features of the patients were analyzed. The positivity rate of CD33⁺ HLA-DR⁻ MDSCs in the peripheral blood was significantly higher in the cancer patients than in the healthy controls [(1.91 ± 0.66)% vs (0.62 ± 0.22)%, P<0.001]. The expression levels of CD33⁺ HLA-DR⁻ MDSCs in patients with renal carcinoma showed significant differences between stage I+II [(1.46 ± 0.44)%] and stage III [(2.04 ± 0.35)%] patients (P<0.01) and between stage III and stage IV patients [(2.50 ± 0.64)%] (P<0.05), but did not differ significantly in respect of age or gender. CD33⁺ HLA-DR⁻ MDSCs expression in the peripheral blood is associated with tumor stage and differentiation in renal carcinoma and may play an important role in predicting the prognosis and tumor immunology of renal carcinoma.


The grasping response in rats: interaction between gamma-type endorphins and haloperidol.
gamma-Type endorphins mimic neuroleptics in inducing a grasping response in rats. It was studied whether the haloperidol-induced grasping response was altered after blockade of gamma-type endorphin activity in the rat brain. To achieve this blockade rats were injected i.c.v. with gamma-endorphin antiserum or with a monoclonal anti-idiotype desenkephalin-gamma-endorphin antibody, which may bio-inactivate the gamma-type endorphins or block the putative receptors for gamma-type endorphins, respectively. The results showed that both treatments attenuated the haloperidol-induced grasping response, particularly 3 h after haloperidol treatment. The influence of these antibodies appeared to be specific, since other sera were without effect. Thus there may be an interaction between the endogenous gamma-type endorphin activity and the haloperidol-induced grasping response.


[Analysis of delay in diagnosis of extrahepatic biliary atresia].
Prognosis of extrahepatic biliary atresia depends on an early surgical treatment. This survey studied the delay to surgery of infants treated for biliary atresia and analysed the causes of late diagnosis and referral. Medical files of 21 infants treated for biliary atresia between 1988 and 1998 were retrospectively analysed. Median age at biliary operation was 57 days and did not change during time. In only 3/21 cases, surgery was performed before 45 days of age. The first clinical or biological sign of cholestasis was noted at a median age of 12 days. In eight cases, the first medical visit for cholestasis (median age of 21 days) was not followed by a blood test. In 11 cases, infants presenting with biological cholestasis were referred to hospital more than seven days later. False diagnosis was noted in seven cases and delayed significantly the operation. The delay to surgical treatment is too long and does not decrease whereas a majority of infants visit their physician early. Medical information is mandatory for all physicians taking care of infants.


Small-scale module of the rat granular retrosplenial cortex: an example of the minicolumn-like structure of the cerebral cortex.
Structures associated with the small-scale module called "minicolumn" can be observed frequently in the cerebral cortex. However, the description of functional characteristics remains obscure. A significant confounding factor is the marked variability both in the definition of a minicolumn and in the diagnostic markers for identifying a minicolumn (see for review, Jones, 2000; DeFelipe et al., 2002; Rockland and Ichinohe, 2004). Within a minicolumn, cell columns are easily visualized by conventional Nissl staining. Dendritic bundles were first discovered with Golgi methods, but are more easily seen with microtubule-associated protein 2 immunohistochemistry. Myelinated axon bundles can be seen by Tau immunohistochemistry or myelin staining. Axon bundles of double bouquet cell can be seen by calbindin immunohistochemistry. The spatial interrelationship among these morphological elements is more complex than expected and is neither clear nor unanimously agreed upon. In this review, I would like to focus first on the minicolumnar structure found in layers 1 and 2 of the rat granular retrosplenial cortex. This modular structure was first discovered as a combination of prominent apical dendritic bundles from layer 2 pyramidal neurons and spatially matched thalamocortical patchy inputs (Wyss et al., 1990). Further examination showed more intricate components of this modular structure, which will be reviewed in this paper. Second, the postnatal development of this structure and potential molecular players for its formation will be reviewed. Thirdly, I will discuss how this modular organization is transformed in mutant rodents with a disorganized layer structure in the cerebral cortex (i.e., reeler mouse and shaking rat Kawasaki). Lastly, the potential significance of this type of module will be discussed.


Unilateral Scissor Bite Managed with Prefabricated Functional Appliances in Primary Dentition-A New Interceptive Orthodontic Protocol.
A unilateral scissor bite is a type of severe malocclusion in primary dentition that can influence the development of the mandible and face. The present case report describes an interceptive treatment on a 4-year-old girl with a unilateral scissor bite combined with an anterior crossbite, increased reverse overjet, and overbite on a skeletal Class III base. The patient was treated with a new Prefabricated Functional Appliance (PFA) which was modified from a Frankel-III appliance to induce a mandible to move backwards and relieve an occlusion discrepancy of the dental arch, and a functional dental rehabilitation with resin and myofunctional exercises with a PFA which was modified from an oral screen appliance were performed during the treatment. The total treatment time was 11 months and a satisfactory improvement of occlusion and facial esthetics was achieved. This case report presents a new PFA system and treatment protocol in primary dentition which results in a favorable outcome, and the clinical effectiveness of this appliance system warrants further investigation.


The Impact of COVID-19 on Otolaryngology Community Practice in Massachusetts.
Coronavirus disease 2019 (COVID-19) significantly affected many health care specialties, including otolaryngology. In response to governmental policy changes, many hospitals and private practices in Massachusetts canceled or postponed nonurgent office visits and elective surgeries. The objective of this study was to quantify the impact of COVID-19 on the provision and practice trends of otolaryngology services for 10 private practices in Massachusetts. Retrospective review. Multipractice study for community practices in Massachusetts. Electronic billing records from 10 private otolaryngology practices in Massachusetts were obtained for the first 4 months of 2019 and 2020. Questionnaires from these otolaryngology practices were collected to assess financial and staffing impact of COVID-19. The local onset of the COVID-19 pandemic had a significant decrease of 63% of visits in comparison to equivalent weeks in 2019. Virtual visits overtook in-person visits over time. A greater decline in operating room (OR) procedures than for office procedures was recorded. Ninety percent of practices reduced working hours, and 80% furloughed personnel. Seventy percent of practices applied for the Paycheck Protection Program (PPP). COVID-19 has had a multifaceted impact on private otolaryngology practices in Massachusetts. A significant decline in provision of otolaryngology services aligned with the Massachusetts government's public health policy changes. The combination of limited personnel and personal protective equipment, as well as suspension of nonessential office visits and surgeries, led to decrease in total office visits and even higher decrease in OR procedures.


Quantifying relative within-host replication fitness in influenza virus competition experiments.
Through accumulation of genetic mutations in the neuraminidase gene, the influenza virus can become resistant to antiviral drugs such as oseltamivir. Quantifying the fitness of emergent drug-resistant influenza viruses, relative to contemporary circulating viruses, provides valuable information to complement existing efforts in the surveillance of drug-resistance. We have previously developed a co-infection based method for the assessment of the relative in vivo fitness of two competing viruses. We have also introduced a model of within-host co-infection dynamics that enables relative within-host fitness to be quantified in these competitive-mixtures experiments. The model assumed that fitness differences between co-infecting strains were mediated by strain-dependent viral production rates from infected epithelial cells. Here we extend the model to enable a more complete exploration of biological processes that may differ between virus pairs and hence generate fitness differences. We use the extended model to re-analyse data from competitive-mixtures experiments that investigated the fitness of oseltamivir-resistant (OR) H1N1 pandemic 2009 ("H1N1pdm09") viruses that emerged during a community outbreak in Australia in 2011. Results are consistent with those of our previous analysis, suggesting that the within-host replication fitness of these OR viruses is not compromised relative to that of related oseltamivir-susceptible (OS) strains, and that potentially permissive mutations in the neuraminidase gene (V241I and N369K) significantly enhance the fitness of H1N1pdm09 OR viruses. These results are consistent regardless of the hypothesised biological cause of fitness difference.


["I tried to be as defiant as possible". Case histories with autobiographical diaries: relationship with the custodial parent during childhood as recalled by young adults].
The predominant structural orientation of divorce research which either ignores or under represents to a great extent the child's perspective and his/her agency is criticized. As a consequence of these methodological shortcomings not only the production of scientific knowledge but also professional practice working with children from divorced families might be negatively affected--especially the regulation of custody and visiting issues. Therefore, the aim of this article is to give children a voice in describing their own experiences of visits and relationships with the non-residential father or mother during childhood and adolescence (sometimes until adulthood). By presenting numerous detailed autobiographical narratives from children of divorced parents, the study revealed a great diversity of visiting patterns as well as different relationship qualities ranging from loving to negative. In addition, visiting patterns and relationship qualities were not always static but were dynamic and changed over time, whereby the child's personality and agency contributed to this diversity and these processes. Finally, methodological recommendations are offered and it is suggested that the child's perspective and agency should be included in research about children of divorce.


Behavioral Activation Contributed to the Total Reduction of Depression Symptoms in the Smartphone-based Cognitive Behavioral Therapy: A Secondary Analysis of a Randomized, Controlled Trial.
Objective: The contribution of components in cognitive behavior therapy (CBT) to the total reduction of depression symptoms has not been well elucidated, and previous studies couldn't exclude the human factors in the therapy. Design: This is a secondary analysis of a randomized, controlled trial comparing automated smartphone CBT without human factors plus antidepressant switch against antidepressant switch alone among patients with antidepressant-resistant depression. The present CBT consisted of self-monitoring, behavioral activation, and cognitive restructuring. We used linear regression to predict the overall pre- to post-symptom improvement based on improvement achieved by sessions teaching each cognitive or behavioral skill. The overall improvement was measured with the Beck Depression Inventory-II and the session-to-session improvement with K6. Results: Of the 164 participants originally enrolled in the study, 94 participants who completed all K6 evaluation were included in the primary analyses. The results indicated that K6 score reduction in the first half of behavioral activation significantly predicted BDI-II score reduction. The sensitivity analysis including 162 participants did not change the result. K6 score reductions after other CBT sessions did not significantly predict BDI-II score reduction. Conclusion: The behavioral activation seems to contribute to the total reduction of depressive symptoms even if human factors are excluded by using automated smartphone CBT.


Successful Treatment with 5-fluorouracil and Levofolinate Calcium in Advanced Gastric Cancer Patient with Disseminated Intravascular Coagulation.
A 32-year-old woman was found to have a gastric adenocarcinoma with multiple bone metastases. Chemotherapy in the first, second and third-line was not effective. Blood examinations showed disseminated intravascular coagulation(DIC)at the end of the second-line chemotherapy. The fourth-line chemotherapy, infusional 5-fluorouracil and levofolinate calcium was performed. This resulted in a good response for DIC. This palliative therapy was effective and safety.


High rate of complications associated with extrafocal kirschner wire pinning for distal radius fractures.
Kirschner wire (K-wire) fixation is a common technique aimed at treating unstable distal radius fractures. We report our experience with extrafocal K-wire fixation in the treatment of unstable distal radius fractures in 34 patients (AO classification: 10 A2, 5 A3, 14 C1, and 5 C2). The patients' median age was 63 years (range, 16-87 years). K-wires remained in place for a median duration period of 42 days, and a splint was applied during 44 days in median. The median follow-up was 2.5 years (range, 1.3-5 years). At the final follow-up examination, all patients were assessed clinically and bilateral radiographs were taken. The median final range of motion was 69 degrees /64 degrees for extension/flexion, 88 degrees/82 degrees for pronation/supination and 36 degrees/21 degrees for ulnar/radial deviation. Grip strength was 81% of the contralateral side. Using the Gartland-Werley score, 12 patients (35%) had excellent results, 17 (50%) good, and five patients (15%) had fair results. The median final radiographic dorsal tilt was 4.5 degrees (range, 0-14 degrees) and 79% of patients had a loss of volar reduction (median 8 degrees). Radial inclination was in median 20 degrees (range, 10-32 degrees) with 82% of the patients with loss of reduction (median 5 degrees). Radial shortening was in median 0.9 mm (range, -2 to +5 mm) and 62% of patients had median loss of radial length of 1.1mm. Radial shortening was the major source of pain due to ulnar impingement. We found a high complication rate, with 15 patients (44%) suffering from at least one of the 30 reported complications. We did not find any direct correlation between radiographic results and mobility. Although good clinical outcome may be obtained, K-wire fixation cannot be routinely recommended.


The Effect of Environmental Stressors on Tinnitus: A Prospective Longitudinal Study on the Impact of the COVID-19 Pandemic.
Tinnitus, the perception of sound in the absence of a corresponding sound, and the distress caused by it, is rarely a static phenomenon. It rather fluctuates over time depending on endogenous and exogenous factors. The COVID-19 pandemic is a potential environmental stressor that might influence the individually perceived tinnitus distress. Since not all people are affected by the pandemic in the same way, the situation allows one to identify environmental factors and personality traits that impact tinnitus distress differently. In our study, 122 tinnitus patients were included at two time points: in the year 2018 and during the German lockdown in April 2020. We assessed tinnitus-related distress, depressive symptoms, personality characteristics and the individual perception of the pandemic situation. On average, there was only a small increase of tinnitus distress with heterogeneous changes during the lockdown. People perceiving the situation as generally stressful with increased grief, frustration, stress and nervousness reported the worsening of tinnitus distress. People with high values in neuroticism also reported the worsening of tinnitus distress, while the personality traits extraversion, conscientiousness and openness seemed to be a protection factor. The study identifies factors that influence tinnitus distress change during a pandemic and spots those patients that need specific help in the pandemic situation.


Medullary carcinoma of thyroid. Biologic behavior of the sporadic and familial neoplasm.
Three groups of patients with medullary thyroid carcinoma treated for cure from an institution under standardized tumor stage were compared. For sporadic cases and all cases across groups, the observed survival rates at 10 years were significantly lower than expected based on persons from the West North Central region of the US of like age and sex born in the same calendar year. They were not different for patients with multiple endocrine neoplasia (MEN), type 2a and 2b. Mean ages were significantly different among the three groups: they were 48.5 years for sporadic, 37.7 for MEN 2a, and 23.4 for MEN 2b. Tumor-free survival rate after surgical treatment of MEN 2b was 36.6% at 5 years and 27.3% at 10 years, and was significantly lower in comparison with that of sporadic cases. Medullary carcinoma in patients with MEN 2b appeared to develop at an earlier mean age, with a higher frequency of nodal metastasis and a higher rate of tumor recurrence.


Interlaboratory development and validation of a HRM method applied to the detection of JAK2 exon 12 mutations in polycythemia vera patients.
Myeloproliferative disorders are characterized by clonal expansion of normal mature blood cells. Acquired mutations giving rise to constitutive activation of the JAK2 tyrosine kinase has been shown to be present in the majority of patients. Since the demonstration that the V617F mutation in the exon 14 of the JAK2 gene is present in about 90% of patients with Polycythemia Vera (PV), the detection of this mutation has become a key tool for the diagnosis of these patients. More recently, additional mutations in the exon 12 of the JAK2 gene have been described in 5 to 10% of the patients with erythrocytosis. According to the updated WHO criteria the presence of these mutations should be looked for in PV patients with no JAK2 V617F mutation. Reliable and accurate methods dedicated to the detection of these highly variable mutations are therefore necessary. For these reasons we have defined the conditions of a High Resolution DNA Melting curve analysis (HRM) method able to detect JAK2 exon 12 mutations. After having validated that the method was able to detect mutated patients, we have verified that it gave reproducible results in repeated experiments, on DNA extracted from either total blood or purified granulocytes. This HRM assay was further validated using 8 samples bearing different mutant sequences in 4 different laboratories, on 3 different instruments. The assay we have developed is thus a valid method, adapted to routine detection of JAK2 exon 12 mutations with highly reproducible results.


[Malignant rhabdoid tumor of the kidney in the adult].
Presentation of a malignant rhabdoid renal tumour. This type of sarcoma which occurs commonly during the paediatric age is exceptional in the adult, this being the reason for reviewing this clinical case and its management. The term rhabdoid includes several types of morphologically similar tumours which make analysis and pathological categorization difficult. A description of the classification criteria and likely origin of the tumour is included.


Role of the multipolar electrostatic interaction energy components in strong and weak cation-π interactions.
Density functional and Møller-Plesset second-order perturbation (MP2) calculations have been carried out on various model cation-π complexes formed through the interactions of Mg(2+), Ca(2+), and NH4(+) cations with benzene, p-methylphenol, and 3-methylindole. Partial hydration of the metal cations was also considered in these model studies to monitor the effect of hydration of cations in cation-π interactions. The binding energies of these complexes were computed from the fully optimized structures using coupled cluster calculations including triple excitations (CCSD(T)) and Gaussian-G4-MP2 (G4MP2) techniques. An analysis of the charge sharing between the donor (the π-systems) and the acceptors (the cations) together with the partitioning of total interaction energies revealed that the strong and weak cation-π interactions have similar electrostatic interaction properties. Further decomposition of such electrostatic terms into their multipolar components showed the importance of the charge-dipole, charge-quadrupole, and charge-octopole terms in shaping the electrostatic forces in such interactions. The computed vibrational spectra of the complexes were analyzed for the specific cation-π interaction modes and have been shown to contain the signature of higher order electrostatic interaction energy components (quadrupole and octopole) in such interactions.


Rule-makers who establish infection control standards.
Standards of care and regulations of employment have been instituted to guard the safety of patients, employees, and employers. The evolution of many rules is mystifying because the sources and the enforcers are diverse. This article identifies authoritative agents that influence or create rules that guide infection control practice.


Hypophosphataemia in patients undergoing bone marrow transplantation.
We studied the prevalence of hypophosphataemia (< 0.80 mmol/l) in seventeen patients who had undergone bone marrow transplantation (BMT). Thirteen (77%) of the seventeen patients had hypophosphataemia at some stage during the conditioning phase or after their BMT. Seven (41%) of the seventeen patients had hypophosphataemia in the peri-BMT period that is during the conditioning phase or within one week thereafter. Two of the patients showed severe hypophosphataemia (< 0.30 mmol/l). We suggest that plasma phosphate should be monitored in patients with a bone marrow transplant.


Spatiotemporal properties of magnetic fields induced by auditory speech sound imagery and perception.
Brain computer interface (BCI) technologies, which enable direct communication between the brain and external devices, have been developed. BCI technology can be utilized in neural prosthetics to restore impaired movement, including speech production. However, most of the BCI systems that have been developed are the "P300-speller" type, which can only detect objects that users direct his/her attention at. To develop more versatile BCI systems that can detect a user's intention or thoughts, the brain responses associated with verbal imagery need to be clarified. In this study, the brain magnetic fields associated with auditory verbal imagery and speech hearing were recorded using magnetoencephalography (MEG) carried out on 8 healthy adults. Although the magnetic fields lagged slightly and were long-lasting, significant deflections were observed even for verbal imagery, in the temporal regions, as well as for actual speech hearing. Also, sources for the deflections were localized in the association auditory cortices. Cross-correlations were calculated between envelopes of the imagined/presented speech sound and the evoked brain responses in the temporal areas. Measurable correlations were obtained for the presented speech sound; however, no significant correlations were observed for the imagined speech sound. These results indicate that auditory verbal imagery undoubtedly activates the auditory cortex, at least, and generates some observable neural responses.


Effect of dietary polyphenols from hop (Humulus lupulus L.) pomace on adipose tissue mass, fasting blood glucose, hemoglobin A1c, and plasma monocyte chemotactic protein-1 levels in OLETF rats.
Hop (Humulus lupulus L.) pomace contains procyanidin-rich polyphenols, which are large oligomeric compounds of catechin. We studied the effect of high dose (1%) of dietary hop pomace polyphenols (HPs) in Otsuka Long-EvansTokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. By 70 days, the rats fed HPs tended to have a lower body weight and reduced mesenteric white adipose tissue weight than the rats fed a control diet. Triglyceride levels in both plasma and liver tended to be lower in the HPs-fed group than in the control group. Dietary HPs substantially suppressed the activities of hepatic fatty acid synthetase, glucose-6-phosphate dehydrogenase, and malic enzyme, through the suppression of SREBP1c mRNA expression in OLETF rats. Moreover, in the HPs-fed group, monocyte chemotactic protein-1 (MCP-1) expression and fasting blood glucose levels at 40 days, and hemoglobin A1c (HbA1c) levels at 70 days were significantly lower than those in the control group. Thus, dietary HPs may exert an ameliorative function on hepatic fatty acid metabolism, glucose metabolism, and inflammatory response accompanying the increase of the adipose tissue mass in OLETF rats.


Reducing PICU-to-Floor Time-to-Transfer Decision in Critically Ill Bronchiolitis Patients using Quality Improvement Methodology.
Specific criteria for de-escalation from the PICU are often not included in viral bronchiolitis institutional pathways. Variability of transfer preferences can prolong PICU length of stay. We aimed to decrease the time from reaching floor-appropriate heated high flow nasal cannula (HHF) settings to the transfer decision by 20% through standardizing PICU-to-floor transfer assessment in a PICU bronchiolitis cohort. We included PICU bronchiolitis admissions from October 2019 to April 2020, who were 6-months to 2-years-old with no comorbidities nor intubation during their encounter. Our intervention bundle included introduction of transfer criteria and standardization of transfer-readiness assessment. The primary outcome was time from reaching floor-appropriate HHF settings [8 L per minutes (Lpm)] to placement of the transfer order ("time-to-transfer decision"). The secondary outcome was PICU length of stay. The main process measure was the proportion of patients transferred on ≥6 Lpm HHF. Balancing measures included Rapid Response Team activation and unplanned PICU readmission. We assessed admissions meeting inclusion criteria from December, 2018-March, 2019 for the preintervention baseline. Special cause variation indicated improvement in our primary outcome and process measures. Comparison of baseline to postintervention revealed a reduction in median time-to-transfer decision (14.4-7.8 hours; P < 0.001) and increase in children transferred on ≥6 Lpm (51%-72%; P < 0.001). We observed no change in PICU length of stay or balancing measures. Standardizing de-escalation criteria and transfer-readiness assessment reduced the time-to-transfer decision out of the PICU and increased the proportion transferred on ≥6 Lpm HHF for children with viral bronchiolitis without increasing PICU readmissions.


Postmodernity and the new breastfeeding culture.
The purpose of this article is to outline the impact of culture in relation to breastfeeding promotion--culture as a pervading worldview and culture as a geographical trend. It is hoped that the information provided will enable health professionals to move toward using culture as a facilitator rather than an inhibitor of breastfeeding promotion.


Avoiding detrimental human immune response against Mammalian extracellular matrix implants.
This review describes the antibodies formed against mammalian extracellular matrix (ECM) implants in humans and proposes methods for avoiding the detrimental effects of these antibodies. There are two types of antibodies against ECM implants: (i) The natural anti-Gal antibody constituting ∼1% of immunoglobulins in humans. This antibody binds to a carbohydrate antigen called the α-gal epitope with the structure Galα1-3Galβ1-4GlcNAc-R. The α-gal epitope is abundant in nonprimate mammals, including on ECM proteins and proteoglycans. Moreover, anti-Gal antibody titers increase within 2-4 weeks by 10- to 100-folds in human recipients of mammalian implants or xenografts expressing α-gal epitopes. (ii) Anti-non gal antibodies formed against ECM peptide sequences differing from those in homologous proteins in humans. Most homologous proteins in mammals contain immunogenic peptides that elicit anti-non gal antibody production when introduced into humans. Formation of anti-non gal antibodies is much slower than that of elicited anti-Gal antibodies. Both anti-Gal and anti-non gal antibodies are detrimental to ECM implant regeneration in humans by binding to the ECM and directing extensive macrophage-mediated degradation of the implant. In addition, antibodies binding to ECM proteins/proteoglycans may hinder stem cells interaction with the ECM, which is required for directing stem cell differentiation. The anti-Gal immunological barrier can be avoided by using mammalian ECM implants lacking α-gal epitopes. Such implants can be engineered by enzymatic destruction of α-gal epitopes with recombinant α-galactosidase. Alternatively, implants may be obtained from α1,3galactosyltransferase knockout donor species that lack α-gal epitopes. Since postimplantation production of anti-non gal antibodies is a slow process, the detrimental effects of these antibodies may be avoided by accelerating stem cells recruitment into implants, thus accelerating the regeneration process. Acceleration of stem cell recruitment may be achieved by introducing α-gal nanoparticles into the implant. α-Gal nanoparticles present multiple α-gal epitopes, which bind anti-Gal and induce recruitment of macrophages by generating complement chemotactic factors. Fc/Fcγ receptor interaction between anti-Gal coating α-gal nanoparticles and recruited macrophages activates the macrophages to secrete "pro-healing" cytokines/growth factors that recruit stem cells. These recruited cells are instructed by the implanted ECM to regenerate the implant before anti-non gal antibodies can reach detrimental titers.


Long-term results in hairy cell leukemia treated with 2-chlorodeoxyadenosine.
We treated 19 patients with hairy cell leukemia (HCL) with 2-chlorodeoxyadenosine. 15 patients followed up at least 6 months were evaluated. The follow up period varied between 6 months and 37 months (median, 19 months). 8 patients were previously treated. The overall response in 15 evaluable HCL patients was 100%, with 87% complete hematological remissions including three patients with retroperitoneal and mediastinal lymphadenopathy and one patient with leukemic infiltrates of the cornea: 13% of patients achieved partial hematological remission. Soluble interleukin-2 receptor (sIL-2R) considered as a reliable non-invasive marker of HCL tumor burden dropped from the median of 1350 pM/ml (range 188 to 9000 pM/ml) to the median of 84.3 pM/ml (range 37 to 382 pM/ml) RdW which reflects the anisocytosis of red cells decreased after therapy from the median of 20.6% (range 13.1-25.0%) to the median of 13.7% (range 12.4-16.3%).


Testicular Mineralization in KK-A(y) Mice Treated with an Oxovanadium Complex.
Vanadium has potential for use in diabetes therapy. Many investigators have reported toxic effects of inorganic vanadium salts; however, there are few reports on toxic effects of oxovanadium(VO(2+)) complexes. Therefore, we studied VO(2+) toxicity by examining histological changes and measuring the vanadium concentration in the testis after repeated oral administration of bis(1-oxy-2-pyridine-thiolato)oxovanadium(VO(2+)) (VO(opt)2) for 2 or 4 weeks in KK-A(y) mice. Severe mineralization and degeneration/necrosis of the seminiferous tubules were detected after either 2 or 4 weeks of administration. Vacuolar changes in Sertoli cells and the seminiferous epithelia, and hyperplasia of Leydig cells were observed in the testes of some animals. Vanadium concentrations in the mineralized testis were much higher than those in the testis of untreated KK-A(y) mice. These results represent the first report of the possibility for seminiferous tubules mineralization induced by VO(opt)2 administration. Therefore, our research provides important information about the potentially toxic effects of VO(2+) complexes.


Fabrication and investigation of quaternary Ag-In-Zn-S quantum dots-based memristors with ultralow power and multiple resistive switching behaviors.
Quaternary Ag-In-Zn-S (AIZS) quantum dots (QDs) play critical roles in various applications since they have advantages of combining superior optical and electrical features, such as tunable fluorescence emission and high carrier mobilities. However, the application of semiconductor AIZS QDs in brain-inspired devices (e.g. memristor) has been rarely reported. In this work, the tunable volatile threshold switching (TS) and non-volatile memory switching (MS) behaviors have been obtained in a memristor composed of AIZS QDs by regulating the magnitude of compliance current. Additionally, the innovative Ag/AIZS structure devices without traditional oxide layer exhibit low operation voltage (∼0.25 V) and programming current (100 nA) under the TS mode. Moreover, the devices achieve reproducible bipolar resistive switching (RS) behaviors with large ON/OFF ratio of ∼105, ultralow power consumption of ∼10-10 W, and good device-to-device uniformity under the MS mode. Furthermore, the charge transport mechanisms of the high- and low-resistance states under the positive and negative bias have been analyzed with space-charge-limited-current and filament conduction models, respectively. This work not only validates the potential of AIZS QDs acting as dielectric layer in RS devices but also provides a new guideline for designing ultralow power and multiple RS characteristics devices.


Imprint cytology of axillary lymph nodes in breast carcinoma following neoadjuvant chemotherapy.
To evaluate the efficacy of imprint cytology (IC) in detecting residual axillary metastasis following neoadjuvant chemotherapy (NACT) in order to check its feasibility on sentinel nodes in the posttherapy setting in patients with breast carcinoma Thirty women on NACT for locally advanced breast cancer were subjected to total mastectomy with axillary node dissection. Routinely stained imprints from 172 resected nodes were studied to detect residual metastasis and therapy-induced changes, adopting a semiquantitative grading system for assessing the cell yield. Sensitivity and specificity tests were performed. The effect of cellularity in detecting malignancy was statistically determined by the McNemar test. Of the 172 nodes, 58 (33.7%) and 64 (37.2%) were positive by IC and histopathologic examination, respectively. Sparse, moderate and high cell yield was observed in 27 (15.2%), 33 (19.4%) and 112 (66.4%) nodes, respectively. No statistically significant difference was found with respect to the cellularity of imprints. Sensitivity, specificity and diagnostic accuracy were 89.1%, 99.1% and 95.4%, respectively. The false positive and negative rates were 0.6% and 4.1%, respectively. The positive and negative predictive values were 98.3% and 93.9%, respectively. IC is a sensitive, specific and accurate method of detecting axillary metastasis in patients with down-staged tumors following chemotherapy. The fact that therapy did not affect the cell yield on IC makes the technique very applicable for assessing the sentinel nodes following NACT.


Characteristics of hearing-impaired children in the public schools: part I--demographic data.
Survey questionnaires eliciting incidence information about degree and type of hearing loss, educational placement, use of amplification, and other demographic data were completed by audiologists in 13 of the 15 Area Education Agencies in Iowa in an attempt to describe the characteristics of hearing-impaired children in public-school settings. The information revealed patterns of hearing loss related to age and sex, use of hearing aids, and classroom placement that may be useful in planning support services for this population.


Age differences between brides and grooms in Australia.
This one-page article analyzes changes in the age differences between spouses in Australia over the period from 1921 to 1995 using data from official sources. "Over seven decades, the mean age difference between brides and grooms for all marriages in Australia has declined by one year from 3.6 years (grooms 3.6 years older than brides on average) in 1921 to 2.6 years in 1995."


Diagnosis of carriers of haemophilia A by RFLP analysis: Austrian results.
RFLP analysis with extragenic and intragenic probes was performed in 25 Austrian families with haemophilia A for the purpose of carrier diagnosis. Diagnosis could be established in 22 families, in 7 families with intragenic and extragenic probes, in 15 families with extragenic probes only. The remaining 3 families were not informative. During routine diagnosis we found three interesting cases which are described in the following paper. Firstly, we identified one deletion with Bcl I/p 114.12. Secondly, we observed an additional polymorphic band (5.2 kb) with Xba I/probe A. Thirdly, we saw one case where Bcl I/p 114.12 and Bgl I/1.8 were not in linkage disequilibrium.


Improved neonatal seizure detection using adaptive learning.
In neonatal intensive care units performing continuous EEG monitoring, there is an unmet need for around-the-clock interpretation of EEG, especially for recognizing seizures. In recent years, a few automated seizure detection algorithms have been proposed. However, these are suboptimal in detecting brief-duration seizures (<; 30s), which frequently occur in neonates with severe neurological problems. Recently, a multi-stage neonatal seizure detector, composed of a heuristic and a data-driven classifier was proposed by our group and showed improved detection of brief seizures. In the present work, we propose to add a third stage to the detector in order to use feedback of the Clinical Neurophysiologist and adaptively retune a threshold of the second stage to improve the performance of detection of brief seizures. As a result, the false alarm rate (FAR) of the brief seizure detections decreased by 50% and the positive predictive value (PPV) increased by 18%. At the same time, for all detections, the FAR decreased by 35% and PPV increased by 5% while the good detection rate remained unchanged.


Rivaroxaban Treatment in Two Breastfeeding Mothers: A Case Series.
Background: Rivaroxaban (Xarelto) is a reversible direct factor Xa inhibitor used for the treatment and prevention of coagulation in numerous syndromes. There is very limited information available on the transfer of rivaroxaban into human breast milk. Case Report: This study determined the drug concentration-time profile of rivaroxaban in milk samples collected from two lactating mothers consuming 15 mg twice daily. After 21 days, each mother transitioned to 20 mg once daily. Levels in milk were measured using liquid chromatography mass spectrometry and analysis was done for both dosages. The maximum concentration of rivaroxaban observed for the 15 mg dose was 0.3 ± 0.02 μg/mL and that for the 20 mg dose was 0.26 ± 0.01 μg/mL. The relative infant dose (RID) was calculated to be 5% and 4%, respectively. Discussion: This relatively low infant dose is probably explained by the high plasma protein binding of rivaroxaban and its subsequent poor penetration into human milk. The results indicate that rivaroxaban receded to minimum concentration over a period of 12 hours. Conclusions: In these two cases, we found the levels of rivaroxaban in milk to be quite low, and the RID to be 5% of the maternal dose. Although the levels detected were low, rivaroxaban does transfer into breast milk. Caution should be exercised until further studies are conducted and report the safety profile of rivaroxaban in breastfeeding infants.


Characterization of the chicken and quail homologues of the human gene responsible for the X-linked Kallmann syndrome.
The human KAL gene, responsible for the X-linked Kallmann syndrome, was isolated previously. Southern blot analysis using human cDNA probes detected cross-hybridization with DNA from several organisms, including chicken and quail. The entire coding sequences of chicken and quail KAL cDNAs were determined. A comparison of these cDNAs with the human KAL cDNA reveals an overall identity of 73 and 72%, respectively. This results in 76 and 75% identity at the protein level. The highest conservation was found in the WAP four-disulfide core motif and in two of the four fibronectin type III repeats reported in the human protein. These results further support the hypothesis that the KAL protein is an extracellular matrix component with anti-protease and adhesion functions.


The insE open reading frame of IS1 is not required for formation of cointegrates.
The role of the insE open reading frame in transposition of IS1 was reexamined by using an insE nonsense mutation that does not alter the amino acid sequence of InsA inhibitor or InsAB transposase. The mutant was active in all strains tested, showing that insE is not essential for formation of cointegrates.


Patient satisfaction with the colonoscopy procedure: endoscopists overestimate the importance of adverse physical symptoms.
Colonoscopy is a frequently performed procedure associated with a substantial burden for the patient. Most of what is known about patient satisfaction stems from surveys that target issues doctors believe to be important. It has been noticed that patients often focus on different aspects. To have patients and endoscopists rate the extent to which each of a list of patient-generated issues-of-concern contributes to patient satisfaction with the colonoscopy procedure. A sample of consecutive patients undergoing colonoscopy in a Dutch tertiary teaching hospital and a convenience sample of endoscopists. Colonoscopy patients and endoscopists were asked to rate on a five-point Likert scale the importance of 55 items concerning the colonoscopy procedure for patient satisfaction. Items were derived from focus group sessions with colonoscopy patients. Endoscopists were invited to rate the importance of the same set of items from a patient perspective. An analysis was carried out of whether patients and endoscopists rated the importance of items differently. 69 patients and 34 endoscopists completed the questionnaire. The ratings of the endoscopists were significantly different from those of patients (p<0.0001). Endoscopists underestimated the importance of involving patients in decisions, discussing risks and complications, providing the opportunity for substantive questions and offering a comfortable temperature in the examination room. Endoscopists overestimated the importance of adverse physical symptoms, such as pain and abdominal cramps, and the role of the treating doctor. Endoscopists do not have a good perception of the items that contribute most to patient satisfaction with the colonoscopy procedure. Overcoming this gap may be an essential step towards improving patient satisfaction by targeting those concerns most relevant to patients.


[Measurement of cerebral blood flow using phase-contrast MRI].
The development of phase-contrast magnetic resonance imaging(P-C MRI) provides a noninvasive method for measurement of volumetric blood flow(VFR). The VFR of the left and right internal carotid arteries and basilar artery were measured using P-C MRI, and total cerebral blood flow(tCBF) was calculated by summing up the VFR values in three vessels. We investigated the changes in these blood flows as influenced from age, head size, height, weight, body surface area and handedness. Moreover, regional CBF(rCBF) was measured by combining with the single photon emission computed tomography(SPECT) of 123I. The blood flows were 142 +/- 58 mL/ min(mean +/- SD) in the basilar artery, 229 +/- 86 mL/min in the left, 223 +/- 58 mL/min in the right internal carotid artery, and tCBF was 617 +/- 128 mL/min(Ref. Magn Resn Imaging 14:P. 1143, 1996). Significant increases were observed in head-size-related change of VFR in the basilar artery and height-related change of tCBF. The value of rCBF was easily acquired in combination with SPECT. Phase-contrast MRI is useful for a noninvasive and rapid analysis of cerebral VFR and has potential for clinical use.


Role of interleukin 6 and transforming growth factor-beta in the induction of depressed splenocyte responses following sepsis.
We examined whether (1) there is an association between elevated circulating levels of transforming growth factor-beta (TGF-beta) and splenocyte dysfunction during sepsis, and (2) administration of monoclonal antibodies to interleukin 6 (an inducer of TGF-beta release) or TGF-beta could ablate these changes. Blood and splenocytes were obtained from C3H/HeN mice at 1, 4, or 24 hours following cecal ligation and puncture or sham operation. Only at 24 hours after cecal ligation and puncture was there an association between elevated blood TGF-beta value and depressed splenocyte interleukin 2 release. Administration of monoclonal antibodies against interleukin 6, but not against TGF-beta (intraperitoneally immediately following cecal ligation and puncture), significantly decreased the blood levels of TGF-beta at 24 hours following cecal ligation and puncture and improved splenocyte interleukin 2 release. Thus, the judicious use of monoclonal antibodies against interleukin 6 may block the subsequent elevation of TGF-beta, thereby attenuating host immunosuppression during sepsis.


Healthcare utilization among women with physical disabilities.
Current published data indicate barriers and deficiencies in healthcare for women with physical disabilities. Yet, information regarding the influence of secondary conditions and demographic variables on the actual utilization of general health and rehabilitative services is limited. This research examined this issue. Survey research Metropolitan Philadelphia region 170 women between 21 and 65 years of age with physical disabilities Most (96%) women had seen a general healthcare provider (eg, personal physician or gynecologist) in the past 6 months, with 60% reporting seeing such a provider 3 or more times. Despite this high frequency, many women had not had routine preventive gynecologic cancer screening services in the past 5 years. Additionally, respondents reported experiencing on average 12 secondary complications in the past year that moderately impaired their functioning. Many of these complications (fatigue, spasticity, deconditioning, joint pain, depression, social isolation) are preventable. Despite these complications, only about half of the women had seen a rehabilitative service provider (eg, physical therapist, mental health worker) in the past 6 months. Women who saw their general healthcare provider most frequently were more likely to also be receiving services from a rehabilitative service provider. General healthcare providers are frequently seeing women with physical disabilities. Healthcare providers have the ability and opportunity to enhance the health and wellness of this population. Particular attention should be focused on providing preventive healthcare services, including gynecologic cancer screenings and prevention and management of secondary conditions that accompany disability.


Biomagnetic noninvasive localization of accessory pathways in Wolff-Parkinson-White syndrome.
It was our purpose to assess the clinical relevance of noninvasive magnetocardiographic localization of accessory pathways. Nine patients with Wolff-Parkinson-White (WPW) syndrome were studied. For all of them the site of the accessory pathway was known from invasive catheter mapping. A 37-SQUID (superconducting quantum interference device) sensor multichannel system (KRENIKON) was used, allowing synchronous registration with all channels. The site of the electrophysiological activity at the beginning of the delta wave was determined. Magnetic resonance images of the heart were obtained to correlate the biomagnetically localized activity with the anatomy. Magnetocardiographic localization of the bypass tract corresponded with catheter mapping with a spatial difference of 0-5 cm, 1.8 cm on the average, compared to the results obtained by catheter mapping. Thus, magnetocardiography is a promising new method for noninvasive localization of accessory pathways in WPW patients. This may streamline further invasive procedures.


Light-Emitting Chiral Nematic Dimers with Anomalous Odd-Even Effect.
In this report, based on the results derived from the extensive study into the thermal and photophysical properties, an anomalous mesomorphic behavior of photoluminescent, chiral nematic (N*) liquid crystalline dimers, belonging to two different series has been revealed. They comprise cholesterol and fluorescent three-ring Schiff base or salicylaldimine core interlinked via an ω-oxyalkanoyloxy spacer of varying length and parity. The effect of molecular structure on the liquid crystal (LC) behavior and photophysical properties of both the series has been probed by varying the length of the terminal n-alkoxy tails for a fixed (odd or even) parity of the spacer. The detailed investigations using complementary techniques not only evidenced the existence of the N* phase in all the dimers synthesized but also the occurrence of an intriguing odd-even effect; blue phases (BPs) exist in all the dimers comprising even-membered spacer, which surprisingly remains totally absent in their odd-membered counterparts. While the results reported hitherto are exactly opposite to the aforesaid findings, this atypical behavior has been interpreted in terms of the over-all shape of the dimers rendered by the orientation of terminal tails. Photophysical studies carried out clearly revealed the intrinsic light emitting feature of the dimers not only in their dilute solutions but also in their three condensed states viz., solid, N* phase, and isotropic liquid state; the emission intensities of the N* phase varies with the change in temperature, as expected. CD spectra of the N* phase recorded as a function of temperature show bisignate CD band characteristically, signifying large chiral correlations in the molecular self-assembly, while the origin of bands from positive to negative region suggests a right-handed twist of the N* helix.


[Q-fever--occurrence and significance of this disease in the Czech Republic and Slovak Republic].
The paper summarizes the most important knowledge of Q fever and its causative agent Coxiella burnetti since the first descriptions of nosologic unit and causative agent until now. With respect to disease occurrence, distribution and importance the attention is focused on the territory of the former Czechoslovakia, i.e. currently on the territories of the Czech Republic and Slovak Republic. Taking into account normal occurrence of C. burnetii in cows which is however shown in latent form only, taking into account that no cases of human clinical infections related to these latent infections in cattle have been reported at present either in the territory of the Czch Republic or of the Slovak Republic, and considering that the results of experimental infections in sheep by the autochthonous strain of C. burnetii did not reveal its virulence, it can be stated that the strains of C. burnetti currently circulating on cattle farms are little virulent or even avirulent. This decrease in virulence can be ascribed to repeated subcultures of C. burnetti strains in cattle populations excluding ticks from this circulation. Q fever prevention should currently include measures to avoid in the territories of the Czech and Slovak Republics uncontrolled imports of infected animals and/or contaminated raw materials from animal or plant sources to introduce foreign fully virulent strains that can cause clinical infections both in humans and in domestic animals.