National trends in augmentation cystoplasty in the 2000s and factors associated with patient outcomes.
Augmentation cystoplasty is a major surgery performed by pediatric urologists. We evaluated national estimates of children undergoing augmentation cystoplasty in the United States for trends during the 2000s, and analyzed patient and hospital factors associated with outcomes. Patients who underwent augmentation cystoplasty registered in the 2000 to 2009 Kids' Inpatient Database were included. Estimates of total number of augmentation cystoplasties performed and patient and hospital characteristics were evaluated for trends. Hierarchical models were created to evaluate patient and hospital factors associated with length of stay, total hospital charges and odds of having a postoperative complication. An estimated 792 augmentation cystoplasties were performed in 2000, which decreased to 595 in 2009 (p = 0.02). Length of stay decreased from 10.5 days in 2000 to 9.2 days in 2009 (p = 0.04). A total of 1,622 augmentation cystoplasties were included in the hierarchical models and 30% of patients had a complication identified. Patient factors associated with increased length of stay and increased odds of any complication included bladder exstrophy-epispadias complex diagnosis and older age. Pediatric hospitals had 31% greater total hospital charges (95% CI 7-55). The estimated number of augmentation cystoplasties performed in children in the United States decreased by 25% in the 2000s, and mean length of stay decreased by 1 day. The cause of the decrease is multifactorial but could represent changing practice patterns in the United States. Of the patients 30% had a potential complication during hospitalization after augmentation cystoplasty. Older age and bladder exstrophy-epispadias complex diagnosis were associated with greater length of stay and increased odds of having any complication.


Activities of daily living dependency and disease-specific mortality during 12-year follow-up in an 80-year-old population.
Although total mortality is likely to be higher in elderly individuals with frailty or impaired activities of daily living (ADL), little is known about the relationships between disease-specific mortality and ADL dependency in the elderly. Therefore, we examined whether 12-year disease-specific mortality may be associated with ADL dependency in an 80-year-old population. In 1998, of 1,282 community-dwelling residents of Japan's Fukuoka Prefecture, 824 (64.3 %) (309 males and 515 females) participated, the remaining 458 subjects did not participate, and their deaths and causes of death were followed up for 12 years after the baseline examination. ADL dependency was determined according to the guidelines for disabled elderly from the Health, Labor, and Welfare Ministry of Japan, and ADL dependency was measured only at baseline. During the 12-year follow-up, 506 died, 276 did not die, and 42 were lost. Of the 506 who died, 128 died due to cardiovascular disease, 96 to respiratory tract disease, 87 to cancer, and 51 to senility. The subjects were classified into three groups as follows: ADL-1 (independent group, n = 600), ADL-2 (almost-independent group, n = 113), and ADL-3 (dependent group, n = 93).Total-cause mortality was 2.8 times higher in ADL-3 subjects, respiratory disease mortality was 4.1 times higher in ADL-3 subjects, and senility mortality was 5.7 times higher in ADL-3 subjects than in ADL-1 subjects, after adjusting for various confounding factors. There was no association between mortality due to cancer or cardiovascular disease and ADL dependency. We found an independent association between ADL dependency and mortality due to all causes, respiratory disease or senility, but no association with mortality due to cancer or cardiovascular disease. These findings suggest that improving ADL dependency may reduce all mortality and mortality due to respiratory disease or senility.


Consumption of selenium-enriched broccoli increases cytokine production in human peripheral blood mononuclear cells stimulated ex vivo, a preliminary human intervention study.
Selenium (Se) is a micronutrient essential for human health, including immune function. Previous research indicates that Se supplementation may cause a shift from T helper (Th)1- to Th2-type immune responses. We aim to test the potential health promoting effects of Se-enriched broccoli. In a human trial, 18 participants consumed control broccoli daily for 3 days. After a 3-day wash-out period, the participants were provided with Se-enriched broccoli containing 200 μg of Se per serving for 3 days. Plasma and peripheral blood mononuclear cell (PBMC) samples were collected at the start and end of each broccoli feeding period for analysis of total Se and measurement of cytokine production from PBMC stimulated with antigens ex vivo. Plasma Se content remained consistent throughout the control broccoli feeding period and the baseline of the Se-enriched broccoli period (1.22 μmol/L) and then significantly increased following 3 days of Se-enriched broccoli feeding. Interleukin (IL-2, IL-4, IL-5, IL-13, and IL-22) production from PBMC significantly increased after 3 days of Se-enriched broccoli feeding compared with baseline. This study indicates that consumption of Se-enriched broccoli may increase immune responses toward a range of immune challenges.


Effects of positive end expiratory pressure (PEEP) on intracranial and cerebral perfusion pressure in pediatric neurosurgical patients.
Positive end expiratory pressure (PEEP) improves oxygenation by optimizing alveolar recruitment and reducing intrapulmonary shunt. Unfortunately, PEEP can interfere with intracranial pressure (ICP) by increasing intrathoracic pressure. We hypothesized that the use of different PEEP levels could have an effect on intracranial and cerebral perfusion pressure (CPP), gas exchange, respiratory system mechanics, and hemodynamics in pediatric patients undergoing major neurosurgical procedures. Twenty-one consecutive pediatric patients undergoing surgical procedure for intracranial tumors were enrolled in this study, conducted between April 2008 and August 2009. Invasive radial pressure, central venous pressure (CVP), arterial oxygen saturation, ICP, and CPP were monitored. The middle cerebral artery mean velocity (V(med)) was determined by transcranial Doppler. At 0 cm H2O (ZEEP), the following parameters were recorded: systolic, mean, and diastolic arterial pressure, CVP, ICP, CPP, V(med), and arterial blood gases. After assessment at 0 PEEP (ZEEP), PEEP 4 and PEEP 8 were applied: all parameters were recorded at each level. The application of PEEP (from ZEEP to PEEP 8) significantly increased compliance of the respiratory system indexed to the weight of the patients (CrsI) (P=0.0001) without ICP modifications. No significant variations were observed in values of arterial pressure (MAP), CPP, V(med), total resistance of the respiratory system indexed to the weight of the patients (RRS(maxI)), and ohmic resistance of the respiratory system indexed to the weight of the patients (RRS(minI)). CVP significantly increased between ZEEP and PEEP 8 (P=0.02), and between PEEP 4 and PEEP 8 (P<0.05). Partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), partial arterial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2), and pH were not significantly modified. We describe cerebral hemodynamic responses to PEEP application in pediatrics. PEEP values up to 8 cm H2O seem to be safe in pediatric patients with intracranial neoplasm, and, in our opinion, PEEP should be applied immediately after surgery to restore lung recruitment.


The development of a mind-body-spirit certification program in nursing.
Stress and anxiety experienced by patients particularly during hospitalization can be positively affected by an approach to care that emphasizes the uniqueness of the patient, the patient-provider relationship, and mind-body-spirit interventions. Although patients seek care that addresses stress and promotes relaxation within the hospital environment, there is evidence that there are lost opportunities aimed at addressing these concerns within the current health care environment. Nursing leadership at Massachusetts General Hospital and the Massachusetts General Hospital Institute of Health Professions recognized a need to address this gap in knowledge that exists in the practice setting. The purpose of this article is to describe and discuss the development and implementation of a program in mind-body-spirit nursing that was developed collaboratively between the Massachusetts General Hospital Institute of Health Professions and the Benson-Henry Institute of Mind Body Medicine at Massachusetts General Hospital.


Negative reflection of nanoscale-confined polaritons in a low-loss natural medium.
Negative reflection occurs when light is reflected toward the same side of the normal to the boundary from which it is incident. This exotic optical phenomenon is not only yet to be visualized in real space but also remains unexplored, both at the nanoscale and in natural media. Here, we directly visualize nanoscale-confined polaritons negatively reflecting on subwavelength mirrors fabricated in a low-loss van der Waals crystal. Our near-field nanoimaging results unveil an unconventional and broad tunability of both the polaritonic wavelength and direction of propagation upon negative reflection. On the basis of these findings, we introduce a device in nano-optics: a hyperbolic nanoresonator, in which hyperbolic polaritons with different momenta reflect back to a common point source, enhancing the intensity. These results pave way to realize nanophotonics in low-loss natural media, providing an efficient route to control nanolight, a key for future on-chip optical nanotechnologies.


Acetal-derivatized dextran: an acid-responsive biodegradable material for therapeutic applications.
Dextran, a biocompatible, water-soluble polysaccharide, was modified at its hydroxyls with acetal moieties such that it became insoluble in water but freely soluble in common organic solvents enabling its use in the facile preparation of acid-sensitive microparticles. These particles degrade in a pH-dependent manner: FITC-dextran was released with a half-life at 37 degrees C of 10 h at pH 5.0 compared to a half-life of approximately 15 days at pH 7.4. Both hydrophobic and hydrophilic cargoes were successfully loaded into these particles using single and double emulsion techniques, respectively. When used in a model vaccine application, particles loaded with the protein ovalbumin (OVA) increased the presentation of OVA-derived peptides to CD8+ T-cells 16-fold relative to OVA alone. Additionally, this dextran derivative was found to be nontoxic in preliminary in vitro cytotoxicity assays. Owing to its ease of preparation, processability, pH-sensitivity, and biocompatibility, this type of modified dextran should find use in numerous drug delivery applications.


Roux-en-Y gastric bypass: an effective antireflux procedure in the less than morbidly obese.
Since Roux-en-Y gastric bypass (RYGBP) is an excellent antireflux procedure, why is it necessary to do it only for those who are morbidly obese: why not anyone who has had a longstanding severe weight problem with chronic disabling reflux esophagitis? RYGBP was done primarily as an antireflux procedure in 332 patients late from 1987 through October 1996. Eighty-nine were less than 100 lb (45 kg) overweight. Forty-five were lost to follow-up. All but one had Visick ratings from 2 to 4 preoperatively. Thirty-one were primary RYGBP and 13 were conversions from previous gastroplasties. The diagnosis in each case was made by esophagogastroscopy with esophageal biopsy with or without the Bernstein test when indicated. Postoperatively, only one patient was symptomatic. The remaining had Visick ratings of 1. The average preoperative weight of 192 lb (87 kg) dropped to 145 lb (66 kg) postoperatively, or 67% of excess weight loss at a mean of 56 months. Compared to the morbidly obese group, there was no significant difference in 1-year postoperative laboratory values. This study supports the efficacy and safety of RYGBP for reflux esophagitis in the less than morbidly obese patient. Esophagitis is truly a comorbid condition of severe obesity, and it should be accepted as such. The arbitrary elimination from the consideration of candidacy for this procedure by those with a body mass index of less than 35 kg/m2 and unproven comorbidity appears unjustified.


Capillary endothelial cell cultures: phenotypic modulation by matrix components.
Capillary endothelial cells of rat epididymal fat pad were isolated and cultured in media conditioned by bovine aortic endothelial cells and substrata consisting of interstitial or basement membrane collagens. When these cells were grown on interstitial collagens they underwent proliferation, formed a continuous cell layer and, if cultured for long periods of time, formed occasional tubelike structures. In contrast, when these cells were grown on basement membrane collagens, they did not proliferate but did aggregate and form tubelike structures at early culture times. In addition, cells grown on basement membrane substrata expressed more basement membrane constituents as compared with cells grown on interstitial matrices when assayed by immunoperoxidase methods and quantitated by enzyme-linked immunosorbent inhibition assays. Furthermore, when cells were grown on either side of washed, acellular amnionic membranes their phenotypes were markedly different. On the basement membrane surface they adhered, spread, and formed tubelike structures but did not migrate through the basement membrane. In contrast, when seeded on the stromal surface, these cells were observed to proliferate and migrate into the stromal aspect of the amnion and ultimately formed tubelike structures at high cell densities at longer culture periods (21 d). Thus, connective tissue components play important roles in regulating the phenotypic expression of capillary endothelial cells in vitro, and similar roles of the collagenous components of the extracellular matrix may exist in vivo following injury and during angiogenesis. Furthermore, the culture systems outlined here may be of use in the further study of differentiated, organized capillary endothelial cells in culture.


COVID-19 Infection and Late Manifestation of Pulmonary Aspergillosis.
We present the case of a 56-year-old woman who was diagnosed with severe coronavirus disease 2019 (COVID-19) pneumonia complicated by severe acute respiratory distress syndrome who was intubated for 19 days. She recovered from COVID-19 after a month. A computed tomography (CT) scan of the chest, after a month, showed improved infiltrates with a small residual cavity within the lingula. A CT angiogram showed a more confluent density in the lingular portion on follow-up 2 months later. She developed intermittent hemoptysis after 3 months in December 2020, which persisted for almost 6 months, and CT of the chest showed the lingular nodular with resolution of the cavitation. She underwent bronchoscopy with bronchoalveolar lavage, confirming Aspergillus fumigatus by galactomannan assay and histology showing branching hyphae. Once she started treatment with itraconazole, her hemoptysis resolved. The follow-up CT of the chest after 2 months of treatment did not show a cavity or a nodule in the lingula. Our patient developed invasive pulmonary aspergillosis (IPA) as a sequela of severe COVID-19 infection. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is an underrecognized complication that needs to be investigated on whether prophylactic treatment is required. Our case also demonstrates that the diagnosis of IPA needs to be considered months after COVID-19 infection when a superimposed fungal infection can occur after a viral infection if the patient continues to have persistent symptoms.


A general design of caging-group-free photoactivatable fluorophores for live-cell nanoscopy.
The controlled switching of fluorophores between non-fluorescent and fluorescent states is central to every super-resolution fluorescence microscopy (nanoscopy) technique, and the exploration of radically new switching mechanisms remains critical to boosting the performance of established, as well as emerging super-resolution methods. Photoactivatable dyes offer substantial improvements to many of these techniques, but often rely on photolabile protecting groups that limit their applications. Here we describe a general method to transform 3,6-diaminoxanthones into caging-group-free photoactivatable fluorophores. These photoactivatable xanthones (PaX) assemble rapidly and cleanly into highly fluorescent, photo- and chemically stable pyronine dyes upon irradiation with light. The strategy is extendable to carbon- and silicon-bridged xanthone analogues, yielding a family of photoactivatable labels spanning much of the visible spectrum. Our results demonstrate the versatility and utility of PaX dyes in fixed and live-cell labelling for conventional microscopy, as well as the coordinate-stochastic and deterministic nanoscopies STED, PALM and MINFLUX.


Genetic analysis of nicotine-induced seizures and hippocampal nicotinic receptors in the mouse.
A classical F2 and backcross genetic design was used to examine the relationship between sensitivity to nicotine-induced seizures and hippocampal nicotinic receptors. Nicotine was administered by i.v. infusion through cannulas implanted in the right jugular veins of mice from the C3H and DBA mouse strains and their derived F1, F2 and backcross (F1 X C3H and F1 X DBA) generations. Nicotine-induced seizure sensitivity was assessed by infusing nicotine at a 2.0 mg/kg/min concentration until the onset of a clonic seizure. After seizure testing, mice were sacrificed and the binding of alpha-bungarotoxin (BTX) was determined in three brain regions: cortex, midbrain and hippocampus. The pattern of results for the six generations for seizure sensitivity was similar to that observed for hippocampal BTX binding. Genetic analyses indicate that receptor concentrations in the hippocampus and seizure sensitivity are both influenced by a relatively simple genetic system which involves one or more genes acting in an additive fashion. In addition, the genetic correlation which is indicative of the extent to which two characters are influenced by the same genes, supports the relationship between nicotine-induced seizure sensitivity and hippocampal BTX binding. The results suggest that those animals which are sensitive to nicotine-induced seizures have a greater concentration of nicotinic receptors as determined by the binding of BTX than animals which are less sensitive to the convulsant effects of nicotine.


Development and feasibility of need-based yoga program for family caregivers of in-patients with schizophrenia in India.
Yoga has been found to be effective in the management of stress. This paper describes the development of a yoga program aimed to reduce burden and improve coping of family caregivers of inpatients with schizophrenia in India. Based on the assessment of caregiver needs, literature review, and expert opinion, a ten-day group yoga program was initially developed using the qualitative inductive method of inquiry. Each day's program included warm-up exercises, yogic asanas, pranayama, and satsang. A structured questionnaire eliciting comments on each day's contents was given independently to ten experienced yoga professionals working in the field of health for validation. The final version of the program was pilot-tested on a group of six caregivers of in-patients with schizophrenia admitted at NIMHANS, Bangalore. On the question of whether the program would help reduce the burden of caregivers, six of the ten experts (60%) gave a rank of four of five (very much useful). Based on comments of the experts, several changes were made to the program. In the pilot-testing stage, more than 60% of the caregivers assigned a score of four and above (on a five-point Likert scale, five being extremely useful) for the overall program, handouts distributed, and performance of the trainer. Qualitative feedback of the caregivers further endorsed the feasibility and usefulness of the program. The developed yoga program was found to be acceptable to caregivers of in-patients with schizophrenia.


Sexual Dimorphism in Lipid Metabolism and Gut Microbiota in Mice Fed a High-Fat Diet.
The gut microbiome plays an essential role in regulating lipid metabolism. However, little is known about how gut microbiome modulates sex differences in lipid metabolism. The present study aims to determine whether gut microbiota modulates sexual dimorphism of lipid metabolism in mice fed a high-fat diet (HFD). Conventional and germ-free male and female mice were fed an HFD for four weeks, and lipid absorption, plasma lipid profiles, and apolipoprotein levels were then evaluated. The gut microbiota was analyzed by 16S rRNA gene sequencing. After 4-week HFD consumption, the females exhibited less body weight gain and body fat composition and significantly lower triglyceride levels in very-low-density lipoprotein (VLDL) and cholesterol levels in high-density lipoprotein (HDL) compared to male mice. The fecal microbiota analysis revealed that the male mice were associated with reduced gut microbial diversity. The female mice had considerably different microbiota composition compared to males, e.g., enriched growth of beneficial microbes (e.g., Akkermansia) and depleted growth of Adlercreutzia and Enterococcus. Correlation analyses suggested that the different compositions of the gut microbiota were associated with sexual dimorphism in body weight, fat mass, and lipid metabolism in mice fed an HFD. Our findings demonstrated significant sex differences in lipid metabolism and the microbiota composition at baseline (during LFD), along with sex-dependent responses to HFD. A comprehensive understanding of sexual dimorphism in lipid metabolism modulated by microbiota will help to develop more sex-specific effective treatment options for dyslipidemia and metabolic disorders in females.


Coconut as a medium for the experimental production of aflatoxin.
Fresh, grated coconut has been found to be an excellent medium for aflatoxin production by Aspergillus flavus. Under optimal conditions, yields of 8 mg of total aflatoxin per g of substrate were obtained. Continuous agitation of the growth medium under moist conditions at 24 C produced highest yields. Aflatoxin was assayed both biologically and chromatographically. The aflatoxin content of cultures varied biphasically with the duration of incubation. It is suggested that this pattern could result from the sequential operation of factors promoting aflatoxin formation on the one hand and a detoxifying mechanism on the other.


A systematic review of clinical practice guidelines for myopic macular degeneration.
Myopic macular degeneration (MMD) is a primary cause of blindness and visual impairment in many parts of the world. A review of clinical practice guidelines (CPGs) for intervention selection are required with the increasing demand for MMD management in clinical practice as well as in national health services. Therefore, we aim to systematically review CPGs for MMD and assist the recommendations development of the Package of Eye Care Interventions (PECI) program of the World Health Organization. A systematic review of CPGs published on MMD between 2010 and April 2020 was conducted. Guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Cochrane systematic reviews were also included when the evidence from included CPGs were inadequate or contradict. After applying exclusion criteria and conducting the quality appraisal, two CPGs were finally included. The average of the AGREE II ratings for the identified Guidelines were 56 and 63 respectively (7 for each item). To provide further information on interventions for MMD, one Cochrane review on MMD was additionally identified and included in the study. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs were recommended for patients with myopic choroidal neovascularization (mCNV) as first-line therapy to improve vision and reduce central macular thickness, and ranibizumab showed significant effectiveness compared to photodynamic therapy (PDT). PDT was recommended to be performed in those resistant to the treatment by one CPG but lacked of adequate description and support. Data extracted from the Cochrane systematic reviews indicated that anti-VEGF therapy for mCNV had significant effectiveness in improving visual acuity and reducing CMT compared to PDT with moderate to low certainty of evidence. Ranibizumab and bevacizumab were considered as equally effective with moderate certainty. The outcomes of this review suggest that high quality clinical practice guidelines for MMD management are limited. Intravitreal injection of anti-VEGF agents was recommended as an effective intervention to treat myopic CNV as the first-line treatment, while there was inadequate guidance for the application of PDT in myopic CNV management. The use of other interventions for MMD were not recommended at this time and additional evidence is called for.


Porcine model elucidates function of p53 isoform in carcinogenesis and reveals novel circTP53 RNA.
Recent years have seen an increasing number of genetically engineered pig models of human diseases including cancer. We previously generated pigs with a modified TP53 allele that carries a Cre-removable transcriptional stop signal in intron 1, and an oncogenic mutation TP53R167H (orthologous to human TP53R175H) in exon 5. Pigs with the unrecombined mutant allele (flTP53R167H) develop mainly osteosarcoma but also nephroblastomas and lymphomas. This observation suggested that TP53 gene dysfunction is itself the key initiator of bone tumorigenesis, but raises the question which aspects of the TP53 regulation lead to the development of such a narrow tumour spectrum. Molecular analysis of p53 revealed the presence of two internal TP53 promoters (Pint and P2) equivalent to those found in human. Consequently, both pig and human express TP53 isoforms. Data presented here strongly suggest that P2-driven expression of the mutant R167H-Δ152p53 isoform (equivalent to the human R175H-Δ160p53 isoform) and its circular counterpart circTP53 determine the tumour spectrum and play a critical role in the malignant transformation in flTP53R167H pigs. The detection of Δ152p53 isoform mRNA in serum is indicative of tumorigenesis. Furthermore, we showed a tissue-specific p53-dependent deregulation of the p63 and p73 isoforms in these tumours. This study highlights important species-specific differences in the transcriptional regulation of TP53. Considering the similarities of TP53 regulation between pig and human, these observations provide useful pointers for further investigation into isoform function including the novel circTP53 in both the pig model and human patients.


Do trans fatty acids impair linoleic acid metabolism in children?
Trans isomeric fatty acids disturb the metabolism of essential polyunsaturated fatty acids in animals and in premature infants. We assessed whether similar effects may also occur in healthy children. Plasma phospholipid fatty acid composition was analysed in 53 apparently healthy children aged 1-15 years (mean 7.5 years). Trans fatty acids were found in all samples and contributed 1.78 +/- 0.10% (w/w, mean +/- SEM). There was no relation of the major trans isomer octadecenoic acid and of total trans fatty acids to the precursor essential fatty acid linoleic acid. In contrast, we found significant inverse correlations of trans octadecenoic acid and total trans isomers to the principal n-6 metabolite arachidonic acid as well as to the sum of all n-6 metabolites. Furthermore, there was an inverse correlation of total trans fatty acids to the ratio of arachidonic to linoleic acid, an indirect indicator of linoleic acid conversion. These findings are compatible with inhibition of arachidonic acid biosynthesis by trans fatty acids. Since the availability of long-chain polyunsaturated fatty acids, including arachidonic acid, is of essential importance for tissue growth and development, these findings question the safety of high dietary trans fatty acid intakes in childhood.


Influenza surveillance in an urban area.
In Houston the yearly influenza epidemics have been defined virologically by community surveillance obtained by testing specimens submitted from patients with acute respiratory illnesses seen by sentinel physicians. Mortality attributed to influenza and pneumonia has increased regularly during the period of intense influenza virus activity, but the peak has lagged two weeks behind the peak of activity defined by the virological surveillance. Most of the deaths occurred in persons aged 65 years and older; the average annual rate has been 103.5 per 100,000 in that age group. Hospitalizations for pneumonia and other acute respiratory conditions also peaked during influenza epidemics; the highest rate occurred in the elderly, but children under five years of age also had high rates. Morbidity in the ambulatory setting was highest in children. The average visit rate for children under five years of age was 28%; the rate decreased to about 10% for persons aged 10 years and older. Improved coverage with more immunogenic vaccines is needed to protect the elderly. Young children would benefit from universal immunization with available live attenuated vaccines.


First-line disease-modifying therapies in paediatric multiple sclerosis: a comprehensive overview.
Paediatric multiple sclerosis (MS) is defined as the onset of MS before the age of 18 years. Immunomodulatory disease-modifying therapies (i.e. the interferons [IFNs] and glatiramer acetate) are considered first-line treatments in adult patients with MS, but they are largely understudied in the paediatric population. IFNβ is a type 1 IFN produced by fibroblasts. The therapeutic effect achieved by IFNβ in MS is believed to be the result of a variety of mechanisms, including the inhibition of T-cell proliferation and a shift in cytokine production. There are currently two forms of recombinant IFNβ used therapeutically for MS: IFNβ-1a and IFNβ-1b. Two formulations of IFNβ-1a exist, one administered as an intramuscular injection once weekly and the other by subcutaneous injection three times per week. Only one type of IFNβ-1b product is on the market, a subcutaneous injection administered every other day. Pharmacokinetic studies of these agents in children do not exist and available data are primarily from studies in healthy adults. It does not appear that the various formulations differ significantly in terms of bioavailability or efficacy in adults. The toxicity profiles of the interferon formulations are similar, with the most common adverse effects in children including flu-like symptoms, injection site reactions and transient elevations in liver enzymes. Glatiramer acetate is a mixture of synthetic polypeptide chains consisting of four different amino acids. Glatiramer acetate appears to mimic the antigenic properties of myelin basic protein (MBP), and by doing so, alters T-cell activation in the periphery. Glatiramer acetate is administered as a once-daily subcutaneous injection. Similar to the IFNβ formulations, there are no pharmacokinetic studies of this agent in children. The most common adverse effects include injection site reactions and transient chest tightness. Fingolimod, a sphingosine 1-phosphate receptor modulator, is a new disease-modifying therapy that was approved by the US FDA in 2010 for the first-line treatment of relapsing forms of MS in adults. However, due to a lack of information and clinical data on this agent in the paediatric population, it is not included in this discussion. Dose-finding studies of the IFNs and glatiramer acetate in the paediatric population are limited. Dosing recommendations are largely based on tolerability studies, with most children and adolescents tolerating the full adult doses. Clinical studies of IFNs in children have not been objectively designed to establish the efficacy of these therapies, and evidence is limited to that of observational trials and retrospective case reports. However, the largest cohort (130 cases) of paediatric MS patients studied to date reported a reduction in annual relapse rate with all three of the different IFNβ formulations and glatiramer acetate after a follow-up period of more than 4 years. Treatment with one of the first-line agents should be offered to any patient after the occurrence of a second demyelinating episode. The efficacy of the four first-line disease-modifying agents is considered to be relatively equivalent, and the choice of agent should be determined on an individual patient basis, taking into account potential adverse effects and patient preferences. Current data suggest that the IFNs and glatiramer acetate are safe and effective therapies in paediatric patients with MS. However, further studies evaluating the pharmacokinetics, appropriate dosing and comparisons of efficacy among these agents are needed to determine the most appropriate and evidence-based treatment decisions in this population.


Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold.
Cyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the biological and structural profile of these appealing biomolecules, with a particular emphasis on those with anticancer properties, since cancers are the main cause of death all over the world. Additionally, we provide a consideration on supramolecular structuring and synthons, based on the proline-based DKP privileged scaffold, for inspiration in the design of compound libraries in search of ideal ligands, innovative self-assembled nanomaterials, and bio-functional architectures.


A single-cell atlas of the myometrium in human parturition.
Parturition is a well-orchestrated process characterized by increased uterine contractility, cervical ripening, and activation of the chorioamniotic membranes; yet, the transition from a quiescent to a contractile myometrium heralds the onset of labor. However, the cellular underpinnings of human parturition in the uterine tissues are still poorly understood. Herein, we performed a comprehensive study of the human myometrium during spontaneous term labor using single-cell RNA sequencing (scRNA-Seq). First, we established a single-cell atlas of the human myometrium and unraveled the cell type-specific transcriptomic activity modulated during labor. Major cell types included distinct subsets of smooth muscle cells, monocytes/macrophages, stromal cells, and endothelial cells, all of which communicated and participated in immune (e.g., inflammation) and nonimmune (e.g., contraction) processes associated with labor. Furthermore, integrating scRNA-Seq and microarray data with deconvolution of bulk gene expression highlighted the contribution of smooth muscle cells to labor-associated contractility and inflammatory processes. Last, myometrium-derived single-cell signatures can be quantified in the maternal whole-blood transcriptome throughout pregnancy and are enriched in women in labor, providing a potential means of noninvasively monitoring pregnancy and its complications. Together, our findings provide insights into the contributions of specific myometrial cell types to the biological processes that take place during term parturition.


Initial characterization of a pea mutant with light-independent photomorphogenesis.
We have identified a mutant of pea cultivar Alaska that has many of the characteristics normally associated with light-grown seedlings even when grown in complete darkness. We have designated this mutant lip1, for light independent photomorphogenesis. Etiolated wild-type pea seedlings are white to slightly yellow in color and have a distinct morphology characterized by elongated epicotyls and buds containing unexpanded leaves with small, undifferentiated cells. In contrast, mutant seedlings grown under the same conditions are yellow in color and have short epicotyls and expanded leaves showing clear cellular differentiation. Transmission electron microscopy revealed partially developed, agranal plastids in the dark-grown mutant, unlike wild-type seedlings that contain etioplasts with prolamellar bodies. The mutant also exhibits a much shorter lag period for chlorophyll accumulation when etiolated seedlings are transferred from darkness to white light. The dark-grown mutant has 10-fold less spectrally detectable phytochrome, which can be attributed to a 10-fold reduction in the level of the PHYA polypeptide. Cab, Fed1, and RbcS transcripts are present in dark-grown mutant seedlings at levels comparable to those produced in light-grown material. The levels of these transcripts show a normal decrease when green plants grown for 15 days in a light/dark cycle are transferred to continuous darkness. However, transcript levels remain high during dark treatment of seedlings grown for 9 days in continuous light, indicating that the dark adaptation response in this mutant is developmentally plastic. The lip1 mutant has several features in common with the deetiolated Arabidopsis mutants det1, det2, and cop1. However, there are also several important differences, including varying effects on phytochrome levels, organ-specific gene expression, plastid development, and response to dark adaptation.


Prevalence of overweight and obesity in Maiduguri, North-Eastern Nigeria.
The prevalence of obesity is on the increase worldwide including in many developing countries. There is no report on the magnitude of obesity among adults in Maiduguri, a major city in northeastern Nigeria. We selected a sample of 1650 men and women aged 15 years and above resident in Gwange ward in Maiduguri metropolitan council using a multistage sampling technique. Height, weight, waist (WC) and hip circumferences w measured. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Data were analyzed using SPSS version13. The ethics committee of the University of Maiduguri Teaching Hospital approved the study and consent was sought individually from the participants before being enlisted. The mean (SD) age of the respondents was 36.2 (14.4) years, with a range of 15 to 70 years. The mean (SD) ages of the males and females were 34.9 4.3) and 38.9 (14.0) years, respectively, (p < 0.001). The overall crude prevalence rates of overweight and obesity were 27.1% and 17.1%, respectively. In men, 40.6% were either overweight or obese, while in women 51.9% were either overweight or obese. We observed the highest prevalence rates of overweight and obesity in the middle age group. There were more obese females than males (14.05 vs. 4.3%) among both young and elderly (12.1% vs. 10.5%) subjects. The prevalence of overweight and obesity is high in Maiduguri metropolis particularly among women. Concerted efforts should be made to curb the menace of increasing rate of obesity in the metropolis through public enlightenment on the risks associated with obesity and the benefits of adopting a healthy lifestyle.


Enhanced persistence and collective migration in cooperatively aligning cell clusters.
Most cells possess the capacity to locomote. Alone or collectively, this allows them to adapt, to rearrange, and to explore their surroundings. The biophysical characterization of such motile processes, in health and in disease, has so far focused mostly on two limiting cases: single-cell motility on the one hand and the dynamics of confluent tissues such as the epithelium on the other. The in-between regime of clusters, composed of relatively few cells moving as a coherent unit, has received less attention. Such small clusters are, however, deeply relevant in development but also in cancer metastasis. In this work, we use cellular Potts models and analytical active matter theory to understand how the motility of small cell clusters changes with N, the number of cells in the cluster. Modeling and theory reveal our two main findings: cluster persistence time increases with N, whereas the intrinsic diffusivity decreases with N. We discuss a number of settings in which the motile properties of more complex clusters can be analytically understood, revealing that the focusing effects of small-scale cooperation and cell-cell alignment can overcome the increased bulkiness and internal disorder of multicellular clusters to enhance overall migrational efficacy. We demonstrate this enhancement for small-cluster collective durotaxis, which is shown to proceed more effectively than for single cells. Our results may provide some novel, to our knowledge, insights into the connection between single-cell and large-scale collective motion and may point the way to the biophysical origins of the enhanced metastatic potential of small tumor cell clusters.


Entrapped ovarian cyst. An unusual case of persistent abdominal pain.
Recurrent abdominal pain in the left fossa often mimicking attacks of subileus is described in a woman aged 48 with extensive adhesions caused by multiple surgical procedures. Repeated examinations with conventional abdominal radiography and barium meals were negative with regard to mechanical intestinal obstruction. A cystic lesion varying in size from 2 to 8 cm in diameter was seen adjacent to the left ovary on repeat US examinations and also on CT. Pain episodes were sometimes correlated to increasing size of the lesion which was finally thought to be either a peritoneal inclusion cyst (fluid trapped between pelvic adhesions) or, as was finally confirmed at surgery, a true ovarian cyst (corpus luteum cyst) similarly trapped.


[Late paraparesis as a postoperative complication in a patient undergoing the repair of a double aortic aneurysm].
We report a case of a fifty-seven (57)-years old man undergoing elective surgery of a thoracoabdominal and aortoiliac aneurysm in a single surgical time. The patients is operated undergoing general anesthetic combined with thoracic epidural blockade, and it was done two aortic cross-clamping: one to five cm of the aortic arch and the other to the infrarenal level. The most important intraoperative complications were during the thoracic aortic cross-clamping and the most important postoperative complication was related 48 hours later, to paraparesis after a hypotension episode what improved with rehabilitation treatment.


Predictors of mental health care use among male and female veterans deployed in support of the wars in Afghanistan and Iraq.
What factors predict whether Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) veterans who need mental health care receive that care? The present research examined factors associated with a need for care, sociodemographic characteristics, deployment experiences, and perceptions of care as gender-specific predictors of overall mental health care use and Veterans Affairs (VA) mental health care use for male and female OEF/OIF veterans (N = 1,040). Only veterans with a probable need for mental health care, as determined by scores on self-report measures of mental health symptomatology, were included in the sample. Overall, predictors of service use were similar for women and men. A notable exception was the finding that lower income predicted use of both overall and VA mental health care for women, but not men. In addition, sexual harassment was a unique predictor of VA service use for women, whereas non-White race was predictive of VA service use for men only. Knowledge regarding the factors that are associated with use of mental health care (broadly and at VA) is critical to ensuring that veterans who need mental health care receive it.


[Diagnosing pulmonary embolism during pregnancy: how should we do?].
No diagnostic strategy for pulmonary embo- lism (PE) during pregnancy is based on strong evidence and unanimously accepted. Clinical scores are not validated. The diagnostic yield of the non radiating tests is low: D-dimer is rarely negative in pregnant women and lower limb venous compression ultrasonography is poorly sensitive. Nevertheless, they are still recommended as first line exams. The radia- ting exams (ventilation-perfusion scintigra- phy and thoracic angio-CT) have an equiva- lent diagnostic yield (more than 90%). But both raise the risk of cancer: any childhood cancer for the fetus (scintigraphy), and breast cancer for the mother (angio-CT). However, the diagnosis of PE in the pregnant woman has a major impact and must be established with certainty, even if this requires performing radiation imaging.


A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis.
Early treatment is key for optimizing the therapeutic success of drugs, and the current initiating treatment that blocks the progression of bone destruction during the pre-arthritic stages remains unsatisfactory. The microbial disorder in rheumatoid arthritis (RA) patients is significantly reversed with effective treatment. Modulating aberrant gut microbiomes into a healthy state is a potential therapeutic approach for preventing bone damage. By using metagenomic shotgun sequencing and a metagenome-wide association study, we assessed the effect of Lactobacillus casei (L. casei) on the induction of arthritis as well as on the associated gut microbiota and immune disorders in adjuvant-induced arthritis (AIA) rats. Treatment of AIA rats with L. casei inhibited joint swelling, lowered arthritis scores, and prevented bone destruction. Along with the relief of arthritis symptoms, dysbiosis in the microbiome of arthritic rats was significantly reduced after L. casei intervention. The relative abundance of AIA-decreased Lactobacillus strains, including Lactobacillus hominis, Lactobacillus reuteri, and Lactobacillus vaginalis, were restored to normal and Lactobacillus acidophilus was upregulated by the administration of L. casei to the AIA rats. Moreover, L. casei downregulated the expression of pro-inflammatory cytokines, which are closely linked to the effect of the L. casei treatment-associated microbes. Functionally, the maintenance of the redox balance of oxidative stress was involved in the improvement in the L. casei-treated AIA rats. A single bacterium, L. casei (ATCC334), was able to significantly suppress the induction of AIA and protect bones from destruction in AIA rats by restoring the microbiome dysbiosis in the gut, indicating that using probiotics may be a promising strategy for treating RA, especially in the early stage of the disease.


Linear lesions for treating the recurrence of persistent atrial tachyarrhythmia after cryoballoon ablation of atrial fibrillation.
There is no consensus on the most effective radiofrequency ablation strategy for the initial or repeated treatment of persistent atrial tachyarrhythmia (ATa). To describe success and complication rates after the creation of left atrial (LA) linear lesions for recurrent persistent ATa following an index cryoballoon pulmonary vein isolation (PVI), and to identify predictors of ATa recurrence. During March 2013 to March 2020, we prospectively included all consecutive patients undergoing repeat procedures for the treatment of persistent ATa. Radiofrequency ablation consisting of the creation of linear lesions: a roofline, a mitral isthmus and/or septal line, and a cavotricuspid isthmus line. All patients were prospectively followed up for ATa recurrence. Overall, 133 patients underwent 170 procedures after initial cryoballoon PVI (n=715). At least one pulmonary vein reconnection was observed in 60 patients (45.1%), all of whom underwent successful re-disconnection. After all the procedures, >90% of patients had a lesion pattern consisting of a roofline, a mitral isthmus and/or septal line, and a cavotricuspid isthmus line. ATa was terminated in 41 patients (35%). There were three cases of tamponade (3/170 procedures, 1.8%). Ninety-two patients (69.2%) were in sinus rhythm after a median (interquartile range) of 36 (21-53) months since the index cryoballoon PVI. Diagnosis-to-ablation time and LA area were predictors of recurrence in multivariable analysis. The creation of linear lesions is a safe and effective treatment strategy for the recurrence of persistent ATa after cryoballoon PVI. Longer diagnosis-to-ablation time and larger LA area were predictive of ATa recurrence.


Phloem Girdling of Norway Spruce Alters Quantity and Quality of Wood Formation in Roots Particularly Under Drought.
Carbon (C) availability plays an essential role in tree growth and wood formation. We evaluated the hypothesis that a decrease in C availability (i) triggers mobilization of C reserves in the coarse roots of Picea abies to maintain growth and (ii) causes modification of wood structure notably under drought. The 6-year-old saplings were subjected to two levels of soil moisture (watered versus drought conditions) and root C status was manipulated by physically blocking phloem transport in the stem at three girdling dates (GDs). Stem girdling was done before the onset of bud break [day of the year (doy) 77], during vigorous aboveground shoot and radial stem growth (GD doy 138), and after cessation of shoot growth (GD doy 190). The effect of blockage of C transport on root growth, root phenology, and wood anatomical traits [cell lumen diameter (CLD) and cell wall thickness (CWT)] in earlywood (EW) and latewood (LW) was determined. To evaluate changes in belowground C status caused by girdling, non-structural carbohydrates (soluble sugars and starch) in coarse roots were determined at the time of girdling and after the growing season. Although fine root mass significantly decreased in response to blockage of phloem C transport, the phenology of root elongation growth was not affected. Surprisingly, radial root growth and CLD of EW tracheids in coarse roots were strikingly increased in drought-stressed trees, when girdling occurred before bud break or during aboveground stem growth. In watered trees, the growth response to girdling was less distinct, but the CWT of EW significantly increased. Starch reserves in the roots of girdled trees significantly decreased in both soil moisture treatments and at all GDs. We conclude that (i) radial growth and wood development in coarse roots of P. abies saplings are not only dependent on current photosynthates, and (ii) blockage of phloem transport induces physiological changes that outweigh drought effects imposed on root cambial activity and cell differentiation.


Evaluation of Pasteurella multocida serotype B:2 resistance to immune serum and complement system.
Members of gram-negative bacteria family Pasteurellaceae, include a large number of important economically human and veterinary pathogens. Organisms belonging to the family can colonize in mucosal surfaces of the respiratory, alimentary, genital tracts and cause diseases in various mammals, birds, and reptiles. Hemorrhagic septicemia is an acute disease of cattle and buffaloes in tropical countries caused by Pasteurella multocida serotype B:2. In the present study, the possible bactericidal activity of immune calf sera in the presence and absence of complement system was investigated. The results showed that P. multocida B:2 is highly resistant to positive serum, containing high levels of IgG and IgM obtained from calves after vaccination, and complement activity in normal fresh calf serum. This organism also grew rapidly in the normal fresh calf serum and the mixture of positive serum as well as normal fresh calf serum. As a control test an E. coli strain was subjected to the same experiment and found completely sensitive to the bactericidal activity of complement in calf and guinea pig fresh sera. Results were indicative of the presence of inhibitory mechanism(s) in P. multocida B:2 against bactericidal activity of immune calf serum and complement system.


Production of tumor necrosis factor alpha in human leukocytes stimulated by Cryptococcus neoformans.
Tumor necrosis factor alpha (TNF-alpha) is a key mediator of inflammation and may promote human immunodeficiency virus replication in latently infected cells. Since cryptococcosis often is associated with aberrations in the host inflammatory response and occurs preferentially in persons with AIDS, we defined the conditions under which human leukocytes produce TNF-alpha when stimulated by Cryptococcus neoformans. Peripheral blood mononuclear cells (PBMC) produced comparable amounts of TNF-alpha following stimulation with C. neoformans and lipopolysaccharide. Detectable TNF-alpha release in response to C. neoformans occurred only when fungi with small-sized capsules were used and complement-sufficient serum was added. Fractionation of PBMC established that monocytes were the predominant source of TNF-alpha. TNF-alpha gene expression and release occurred significantly later in PBMC stimulated with C. neoformans than in PBMC stimulated with LPS. C. neoformans was also a potent inducer of TNF-alpha from freshly isolated bronchoalveolar macrophages (BAM). Upon in vitro culture, BAM and monocytes bound greater numbers of fungal cells, yet their capacity to produce TNF-alpha following cryptococcal stimulation declined by 74 to 100%. However, this decline was reversed if the BAM and monocytes were cultured with gamma interferon. These data establish that C. neoformans can potently stimulate TNF-alpha release from human leukocytes. However, several variables profoundly affected the amount of TNF-alpha released, including the type of leukocyte and its state of activation, the size of the cryptococcal capsule, and the availability of opsonins.


Abortion Safety and Use with Normally Prescribed Mifepristone in Canada.
In the United States, mifepristone is available for medical abortion (for use with misoprostol) only with Risk Evaluation and Mitigation Strategy (REMS) restrictions, despite an absence of evidence to support such restrictions. Mifepristone has been available in Canada with a normal prescription since November 2017. Using population-based administrative data from Ontario, Canada, we examined abortion use, safety, and effectiveness using an interrupted time-series analysis comparing trends in incidence before mifepristone was available (January 2012 through December 2016) with trends after its availability without restrictions (November 7, 2017, through March 15, 2020). A total of 195,183 abortions were performed before mifepristone was available and 84,032 after its availability without restrictions. After the availability of mifepristone with a normal prescription, the abortion rate continued to decline, although more slowly than was expected on the basis of trends before mifepristone had been available (adjusted risk difference in time-series analysis, 1.2 per 1000 female residents between 15 and 49 years of age; 95% confidence interval [CI], 1.1 to 1.4), whereas the percentage of abortions provided as medical procedures increased from 2.2% to 31.4% (adjusted risk difference, 28.8 percentage points; 95% CI, 28.0 to 29.7). There were no material changes between the period before mifepristone was available and the nonrestricted period in the incidence of severe adverse events (0.03% vs. 0.04%; adjusted risk difference, 0.01 percentage points; 95% CI, -0.06 to 0.03), complications (0.74% vs. 0.69%; adjusted risk difference, 0.06 percentage points; 95% CI, -0.07 to 0.18), or ectopic pregnancy detected after abortion (0.15% vs. 0.22%; adjusted risk difference, -0.03 percentage points; 95% CI, -0.19 to 0.09). There was a small increase in ongoing intrauterine pregnancy continuing to delivery (adjusted risk difference, 0.08 percentage points; 95% CI, 0.04 to 0.10). After mifepristone became available as a normal prescription, the abortion rate remained relatively stable, the proportion of abortions provided by medication increased rapidly, and adverse events and complications remained stable, as compared with the period when mifepristone was unavailable. (Funded by the Canadian Institutes of Health Research and the Women's Health Research Institute.).


Physical bioenergetics: Energy fluxes, budgets, and constraints in cells.
Cells are the basic units of all living matter which harness the flow of energy to drive the processes of life. While the biochemical networks involved in energy transduction are well-characterized, the energetic costs and constraints for specific cellular processes remain largely unknown. In particular, what are the energy budgets of cells? What are the constraints and limits energy flows impose on cellular processes? Do cells operate near these limits, and if so how do energetic constraints impact cellular functions? Physics has provided many tools to study nonequilibrium systems and to define physical limits, but applying these tools to cell biology remains a challenge. Physical bioenergetics, which resides at the interface of nonequilibrium physics, energy metabolism, and cell biology, seeks to understand how much energy cells are using, how they partition this energy between different cellular processes, and the associated energetic constraints. Here we review recent advances and discuss open questions and challenges in physical bioenergetics.


Behavior management for children and adolescents with acquired brain injury.
Behavioral problems such as disinhibition, irritability, restlessness, distractibility, and aggression are common after acquired brain injury (ABI). The persistence and severity of these problems impair the brain-injured individual's reintegration into family, school, and community life. Since the early 1980s, behavior analysis and therapy have been used to address the behavioral sequelae of ABI. These interventions are based on principles of learning and behavior that have been robustly successful when applied across a broad range of other clinical populations. Most of the research on behavioral treatment after ABI has involved clinical case studies or studies employing single-subject experimental designs across a series of cases. The literature supports the effectiveness of these interventions across ages, injury severities, and stages of recovery after ABI. Recommended guidelines for behavior management include: direct behavioral observations, systematic assessment of environmental and within-patient variables associated with aberrant behavior, antecedent management to minimize the probability of aberrant behavior, provision of functionally equivalent alternative means of controlling the environment, and differential reinforcement to shape positive behavior and coping strategies while not inadvertently shaping emergent, disruptive sequelae. This package of interventions requires direction by a highly skilled behavioral psychologist or therapist who systematically monitors target behavior to evaluate progress and guide treatment decisions. A coordinated multisite effort is needed to design intervention protocols that can be studied prospectively in randomized controlled trials. However, there will continue to be an important role for single subject experimental design for studying the results of individualized interventions and obtaining pilot data to guide subsequent randomized controlled trails.


Predictors of breast cancer screening uptake: a pre intervention community survey in Malaysia.
Despite health education efforts to educate women on breast cancer and breast cancer screening modalities, the incidence of breast cancer and presentation at an advanced stage are still a problem in Malaysia. To determine factors associated with the uptake of breast cancer screening among women in the general population. This pre-intervention survey was conducted in a suburban district. All households were approached and women aged 20 to 60 years old were interviewed with pre-tested guided questionnaires. Variables collected included socio-demographic characteristics, knowledge on breast cancer and screening practice of breast cancer. Univariate and multivariate analysis were performed. 41.5% of a total of 381 respondents scored above average; the mean knowledge score on causes and risks factors of breast cancer was 3.41 out of 5 (SD1.609). 58.5% had ever practiced BSE with 32.5% performing it at regular monthly intervals. Uptake of CBE by nurses and by doctors was 40.7% and 37.3%, respectively. Mammogram uptake was 14.6%. Significant predictors of BSE were good knowledge of breast cancer (OR=2.654, 95% CI: 1.033-6.816), being married (OR=2.213, 95% CI: 1.201-4.076) and attending CBE (OR=1.729, 95% CI: 1.122-2.665). Significant predictors for CBE included being married (OR=2.161, 95% CI: 1.174-3.979), good knowledge of breast cancer (OR=2.286, 95% CI: 1.012-5.161), and social support for breast cancer screening (OR=2.312, 95% CI: 1.245-4.293). Women who had CBE were more likely to undergo mammographic screening of the breast (OR=5.744, 95% CI: 2.112-15.623), p<0.005. CBE attendance is a strong factor in promoting BSE and mammography, educating women on the importance of breast cancer screening and on how to conduct BSE. The currently opportunistic conduct of CBE should be extended to active calling of women for CBE.


Binding of human renin to plasma proteins and comparison with plasma active and inactive renin.
Inactive renin was partially purified from normal male plasma. It showed no enzymatic activity at pH 7.4, and its molecular weight by gel filtration was 53 000 compared with 45 000 for partially purified plasma active renin and 41 000 for pure renal renin. After exposure to pH 3.0 the inactive renin became enzymatically active but its molecular weight did not change. The acid-activation could be reversed when the renin was re-adjusted to pH 7.4 and warmed. Pure renal renin labelled with I125 was added to normal male plasma. It had a molecular weight of 40 000 by gel filtration. When the mixture was acidified and neutralized, some I125 label appeared in a high-molecular-weight peak, as might occur if the renin was associated with a binding protein. If the mixture of plasma and labelled renin was treated with guanidine hydrochloride, most of the label appeared in the high-molecular-weight peak. However, after both acid treatment and treatment with guanidine hydrochloride the 'high-molecular-weight' peak appeared in the void volume of the column (Mr 108 000) rather than in the position of inactive renin (Mr 53 000). Also, the I125 label in the peak was neither immunologically nor electrophoretically similar to renin. It may represent denatured renin bound to plasma proteins, e.g. alpha-2 macroglobulins. We conclude that 'inactive renin' is a prorenin-like material rather than a protein-bound form of active renin.


Responses of a direct ion storage dosimeter (DIS-1) to heavy charged particles.
The responses of a direct ion storage dosimeter (DIS-1) to energetic heavy charged particles were examined using (4)He, (12)C, (40)Ar and (56)Fe ion beams at the HIMAC at the National Institute of Radiological Sciences. The efficiency of the DIS-1 on the basis of absorbed dose was almost unity for the helium and carbon ions and was slightly decreased for the argon and iron ions. The linearity in the dose response and the angular independence for these heavy ions were fairly good. Although further studies are necessary, these results suggest that the DIS-1 would be a suitable passive dosimeter for measurements of absorbed dose in a field dominated by heavy charged particles such as the space environment.


Behavioral change and its neural correlates in visual agnosia after expertise training.
Agnosia, the impairment in object and face recognition despite intact vision and intelligence, is one of the most intriguing and debilitating neuropsychological deficits. The goal of this study was to determine whether S.M., an individual with longstanding visual agnosia and concomitant prosopagnosia, can be retrained to perform visual object recognition and, if so, what neural substrates mediate this reacquisition. Additionally, of interest is the extent to which training on one type of visual stimulus generalizes to other visual stimuli, as this informs our understanding of the organization of ventral visual cortex. Greebles were chosen as the stimuli for retraining given that, in neurologically normal individuals, these stimuli can engage the fusiform face area. Posttraining, S.M. showed significant improvement in recognizing Greebles, although he did not attain normal levels of performance. He was also able to recognize untrained Greebles and showed improvement in recognizing common objects. Surprisingly, his performance on face recognition, albeit poor initially, was even more impaired following training. A comparison of pre- and postintervention functional neuroimaging data mirrored the behavioral findings: Face-selective voxels in the fusiform gyrus prior to training were no longer so and were, in fact, more Greeble-selective. The findings indicate potential for experience-dependent dynamic reorganization in agnosia with the possibility that residual neural tissue, with limited capacity, will compete for representations.


Microarray analysis of tomato plants exposed to the nonviruliferous or viruliferous whitefly vector harboring Pepper golden mosaic virus.
Plants are routinely exposed to biotic and abiotic stresses to which they have evolved by synthesizing constitutive and induced defense compounds. Induced defense compounds are usually made, initially, at low levels; however, following further stimulation by specific kinds of biotic and abiotic stresses, they can be synthesized in relatively large amounts to abate the particular stress. cDNA microarray hybridization was used to identify an array of genes that were differentially expressed in tomato plants 15 d after they were exposed to feeding by nonviruliferous whiteflies or by viruliferous whiteflies carrying Pepper golden mosaic virus (PepGMV) (Begomovirus, Geminiviridae). Tomato plants inoculated by viruliferous whiteflies developed symptoms characteristic of PepGMV, whereas plants exposed to nonviruliferous whitefly feeding or nonwounded (negative) control plants exhibited no disease symptoms. The microarray analysis yielded over 290 spotted probes, with significantly altered expression of 161 putative annotated gene targets, and 129 spotted probes of unknown identities. The majority of the differentially regulated "known" genes were associated with the plants exposed to viruliferous compared with nonviruliferous whitefly feeding. Overall, significant differences in gene expression were represented by major physiological functions including defense-, pathogen-, photosynthesis-, and signaling-related responses and were similar to genes identified for other insect-plant systems. Viruliferous whitefly-stimulated gene expression was validated by real-time quantitative polymerase chain reaction of selected, representative candidate genes (messenger RNA): arginase, dehydrin, pathogenesis-related proteins 1 and -4, polyphenol oxidase, and several protease inhibitors. This is the first comparative profiling of the expression of tomato plants portraying different responses to biotic stress induced by viruliferous whitefly feeding (with resultant virus infection) compared with whitefly feeding only and negative control nonwounded plants exposed to neither. These results may be applicable to many other plant-insect-pathogen system interactions.


[Adverse drug reaction surveillance in pediatric and adult patients in an emergency room].
Adverse drug reactions (ADR) in the pediatric emergency room of a tertiary care hospital in Spain are described and compared with the adult ward. Identification of cases was carried out through review of admission diagnoses and selection of those included in a previous list of diagnoses considered as possible ADR, that were thereafter verified. During 25 months, in 47.107 pediatric consultations were detected 451 cases as suspicious of ADR (0.96%). The ADR was moderate in 29 and serious in 1, being hospitalized 4. In adults, there were 68,431 consultations, and 704 cases detected (1.03%); moderate 218, serious 34 and mortal 1, being hospitalized 101. The most common reactions were dermatological (43.9% in children, 19.5% in adults) and of digestive nature (28.5 and 36.6%, respectively). The drugs most frequently involved in children were antimicrobials (49.5%), drugs used in respiratory illnesses (19.9%), non-steroid anti-inflammatory drugs (NSAID) (10.4%) and vaccines (9.2%); only two recently marketed products were involved. In adults, drugs involved were NSAID (28.2%), cardiovascular drugs (15.9%), antimicrobials (14.5%) and drugs active in digestive system (11.1%). There were 10 cases of hypoglycemia in diabetic adults, probably by interaction of hypoglycemic agents with angiotensin-converting enzyme inhibitors, and 7 cases of gastrointestinal hemorrhage associated with ketorolac, that generated an alert; 12 recently marketed products were involved. Intensive monitoring in emergency ward measures ADR problem, estimates underreporting, but it has a moderate value to generate alert or to survey new products.


Genome-wide identification and functional analysis of the splicing component SYF2/NTC31/p29 across different plant species.
This study systematically identifies plant SYF2/NTC31/p29 genes from 62 plant species by a combinatory bioinformatics approach, revealing the importance of this gene family in phylogenetics, duplication, transcriptional, and post-transcriptional regulation. Alternative splicing is a post-transcriptional regulatory mechanism, which is critical for plant development and stress responses. The entire process is strictly attenuated by a complex of splicing-related proteins, designated splicing factors. Human p29, also referred to as synthetic lethal with cdc forty 2 (SYF2) or the NineTeen complex 31 (NTC31), is a core protein found in the NTC complex of humans and yeast. This splicing factor participates in a variety of biological processes, including DNA damage repair, control of the cell cycle, splicing, and tumorigenesis. However, its function in plants has been seldom reported. Thus, we have systematically identified 89 putative plant SYF2s from 62 plant species among the deposited entries in the Phytozome database. The phylogenetic relationships and evolutionary history among these plant SYF2s were carefully examined. The results revealed that plant SYF2s exhibited distinct patterns regarding their gene structure, promoter sequences, and expression levels, suggesting their functional diversity in response to developmental cues or stress treatments. Although local duplication events, such as tandem duplication and retrotransposition, were found among several plant species, most of the plant species contained only one copy of SYF2, suggesting the existence of additional mechanisms to confer duplication resistance. Further investigation using the model dicot and monocot representatives Arabidopsis and rice SYF2s indicated that the splicing pattern and resulting protein isoforms might play an alternative role in the functional diversity.


Robust circadian rhythm in heart rate and its variability: influence of exogenous melatonin and photoperiod.
Heart rate (HR) and heart rate variability (HRV) undergo marked fluctuations over the 24-h day. Although controversial, this 24-h rhythm is thought to be driven by the sleep-wake/rest-activity cycle as well as by endogenous circadian rhythmicity. We quantified the endogenous circadian rhythm of HR and HRV and investigated whether this rhythm can be shifted by repeated melatonin administration while exposed to an altered photoperiod. Eight healthy males (age 24.4 +/- 4.4 years) participated in a double-blind cross-over design study. In both conditions, volunteers were scheduled to 16 h-8 h rest : wake and dark : light cycles for nine consecutive days preceded and followed by 29-h constant routines (CR) for assessment of endogenous circadian rhythmicity. Melatonin (1.5 mg) or placebo was administered at the beginning of the extended sleep opportunities. For all polysomnographically verified wakefulness periods of the CR, we calculated the high- (HF) and low- (LF) frequency bands of the power spectrum of the R-R interval, the standard deviation of the normal-to-normal (NN) intervals (SDNN) and the square root of the mean-squared difference of successive NN intervals (rMSSD). HR and HRV variables revealed robust endogenous circadian rhythms with fitted maxima, respectively, in the afternoon (16:36 hours) and in the early morning (between 05:00 and 06:59 hours). Melatonin treatment phase-advanced HR, HF, SDNN and rMSSD, and these shifts were significantly greater than after placebo treatment. We conclude that endogenous circadian rhythmicity influences autonomic control of HR and that the timing of these endogenous rhythms can be altered by extended sleep/rest episodes and associated changes in photoperiod as well as by melatonin treatment.


[Human sympathetic-adrenal system during water immersion].
The activity of the sympathoadrenal system (SAS) of 12 volunteers exposed to water immersion for 7 days was studied. Before and after water immersion six of the test subjects were exposed to acceleration of +3 Gz for 15 min. It was demonstrated that water immersion increased the hormonal activity and decreased the transmitter activity of the SAS. Exposure to acceleration stimulated the SAS, thus increasing immersion tolerance.


[Left ventricular hypertrophy in hypertension: functional aspects].
The purpose of this study was to detect the anatomical and functional response of the left ventricle in essential, uncomplicated hypertension. Fifty outpatients, whose hypertension (DBP greater than 95 mmHg on three separate visits) had been documented from few weeks to a maximum of 5 years, showing neither electrocardiographic abnormalities nor other signs referable to target organ damage, underwent an M-mode, computerised echocardiographic study. Twenty-seven patients has never been treated, and 23 patients were withdrawn from previous treatments for at least one month. Echocardiographic data of the left ventricle were compared with those of 38 normals, matched by sex, age and body surface area. Hypertensives showed a significant increase in both LV mass index (p less than 0.001) and relative wall thickness (p less than 0.001), a pattern of concentric hypertrophy, which prevented an inappropriate rise in wall tension. Twenty-four patients, whose LV mass was above the mean normal value plus two standard deviations, were considered to have left ventricular hypertrophy. The remaining 26 patients were classified as non hypertrophic, for their mass resulted lower than the mean value of controls plus 2 SD: left ventricular mass was 152 +/- 32 g/m2 and 97 +/- 19 g/m2, respectively (p less than 0.001). Systolic performance was enhanced in both subgroups of hypertensives, since their values of fractional shortening and those of mean-Vcf were both above the line which represents the normal relationship with end-systolic stress. Diastolic relaxation, evaluated by means of time to peak filling rate, was impaired only in the hypertensive subjects with increased LV mass (p less than 0.001 vs. normotensive), being retained in the non-hypertrophic patients. In the whole hypertensive group, LV mass index poorly correlated with casual systolic blood pressure (r = 0.31; p less than 0.05), while time to peak filling rate showed a good correlation with LV mass index (r = 0.76; p less than 0.001). We conclude that: 1) in essential hypertension without electrocardiographic abnormalities or target organ damage, echocardiographic left ventricular hypertrophy is a rather frequent finding; 2) the pattern of concentric hypertrophy, by reducing the increase in wall tension due to pressure load, contributes to the retained, or enhanced, systolic performance seen in our series; 3) on the other hand, left ventricular filling seems to be impaired in relation to the degree of myocardial hypertrophy.


Split-belt treadmill adaptation shows different functional networks for fast and slow human walking.
New walking patterns can be learned over short time scales (i.e., adapted in minutes) using a split-belt treadmill that controls the speed of each leg independently. This leads to storage of a modified motor pattern that is expressed as an aftereffect in regular walking conditions and must be de-adapted to return to normal. Here we asked whether the nervous system adapts a general walking pattern that is used across many speeds or a specific pattern affecting only the two speeds experienced during split-belt training. In experiment 1, we tested three groups of healthy adult subjects walking at different split-belt speed combinations and then assessed aftereffects at a range of speeds. We found that aftereffects were largest at the slower speed that was used in split-belt training in all three groups, and it decayed gradually for all other speeds. Thus adaptation appeared to be more strongly linked to the slow walking speed. This result suggests a separation in the functional networks used for fast and slow walking. We tested this in experiment 2 by adapting walking to split belts and then determining how much fast regular walking washed out the slow aftereffect and vice versa. We found that 23-38% of the aftereffect remained regardless of which speed was washed out first. This demonstrates that there is only partial overlap in the functional networks coordinating different walking speeds. Taken together, our results suggest that there are some neural networks for controlling locomotion that are recruited specifically for fast versus slow walking in humans, similar to recent findings in other vertebrates.


Avian flu pandemic: Can we prevent it?
Outbreaks of highly pathogenic H5N1 avian influenza in Southeast Asia, Europe and Africa have led to devastating consequences for poultry, and have resulted in numerous infections in humans. Although these infections from the animal reservoir continue to accumulate, the virus does not seem to spread extensively among humans. However, for example, a process of genetic reassortment could occur in a human who is co-infected with avian influenza A virus and a human strain of influenza A virus. The resulting new virus might then be able to easily infect humans and spread from human to human. Therefore, many experts expect the occurrence of a pandemic due to a mutant virus which can be easily transmitted among humans. Thus, currently, a major public health concern is the next influenza pandemic; yet it remains unclear how to control such a crisis. In this paper, we investigate relations between the evolution of virulence and an effectiveness of pandemic control measures after the emergence of mutant avian influenza; one is an elimination policy of infected birds with avian influenza and the other is a quarantine policy of infected humans with mutant avian influenza. We found that each of these prevention policies can be ineffective (i.e., increase human morbidity or mortality). Further, interestingly, the same intervention might, under the same conditions, increase human morbidity and decrease human mortality, or vice versa. Our practical findings are that the quarantine policy can effectively reduce both human morbidity and mortality but the elimination policy increases either human morbidity or mortality in a worst case situation.


Early Pleistocene faunivorous hominins were not kleptoparasitic, and this impacted the evolution of human anatomy and socio-ecology.
Humans are unique in their diet, physiology and socio-reproductive behavior compared to other primates. They are also unique in the ubiquitous adaptation to all biomes and habitats. From an evolutionary perspective, these trends seem to have started about two million years ago, coinciding with the emergence of encephalization, the reduction of the dental apparatus, the adoption of a fully terrestrial lifestyle, resulting in the emergence of the modern anatomical bauplan, the focalization of certain activities in the landscape, the use of stone tools, and the exit from Africa. It is in this period that clear taphonomic evidence of a switch in diet with respect to Pliocene hominins occurred, with the adoption of carnivory. Until now, the degree of carnivorism in early humans remained controversial. A persistent hypothesis is that hominins acquired meat irregularly (potentially as fallback food) and opportunistically through klepto-foraging. Here, we test this hypothesis and show, in contrast, that the butchery practices of early Pleistocene hominins (unveiled through systematic study of the patterning and intensity of cut marks on their prey) could not have resulted from having frequent secondary access to carcasses. We provide evidence of hominin primary access to animal resources and emphasize the role that meat played in their diets, their ecology and their anatomical evolution, ultimately resulting in the ecologically unrestricted terrestrial adaptation of our species. This has major implications to the evolution of human physiology and potentially for the evolution of the human brain.


Near-Infrared Self-Powered Linearly Polarized Photodetection and Digital Incoherent Holography Using WSe2/ReSe2 van der Waals Heterostructure.
Polarization-sensitive photodetection has attracted considerable attention as an emerging technology for future optoelectronic applications such as three-dimensional (3D) imaging, quantum optics, and encryption. However, traditional photodetectors based on Si or III-V InGaAs semiconductors cannot directly detect polarized light without additional optical components. Herein, we demonstrate a self-powered linear-polarization-sensitive near-infrared (NIR) photodetector using a two-dimensional WSe2/ReSe2 van der Waals heterostructure. The WSe2/ReSe2 heterojunction photodiode with semivertical geometry exhibits excellent performance: an ideality factor of 1.67, a broad spectral photoresponse of 405-980 nm with a significant photovoltaic effect, outstanding linearity with a linear dynamic range wider than 100 dB, and rapid photoswitching behavior with a cutoff frequency up to 100 kHz. Strongly polarized excitonic transitions around the band edge in ReSe2 lead to significant 980 nm NIR linear-polarization-dependent photocurrent. This linear polarization sensitivity remains stable even after exposure to air for longer than five months. Furthermore, by leveraging the NIR (980 nm)-selective linear polarization detection of this photodiode under photovoltaic operation, we demonstrate digital incoherent holographic 3D imaging.


Ten years of sedoanalgesia and how it has affected urological practice.
This article describes the use of midazolam in combination with local anaesthesia for the performance of endoscopic and open operations in urological practice. The technique is called sedoanalgesia. The sedation greatly facilitates the possibilities of local anaesthetic surgery and has transformed urological practice. Eighty percent of urological cases in our unit can be performed as a day case using this method. The procedure is not only safe but highly cost-effective.


Early events in herpes simplex virus lifecycle with implications for an infection of lifetime.
Affecting a large percentage of human population herpes simplex virus (HSV) types -1 and -2 mainly cause oral, ocular, and genital diseases. Infection begins with viral entry into a host cell, which may be preceded by viral "surfing" along filopodia. Viral glycoproteins then bind to one or more of several cell surface receptors, such as herpesvirus entry mediator (HVEM), nectin-1, 3-O sulfated heparan sulfate (3-OS HS), paired immunoglobulin-like receptor α, and non-muscle myosin-IIA. At least five viral envelope glycoproteins participate in entry and these include gB, gC, gD and gH-gL. Post-entry, these glycoproteins may also facilitate cell-to-cell spread of the virus, which helps in the evasion of physical barriers as well as several components of the innate and adaptive immune responses. The spread may be facilitated by membrane fusion, movement across tight junctions, transfer across neuronal synapses, or the recruitment of actin-containing structures. This review summarizes some of the recent advances in our understanding of HSV entry and cell-to-cell spread.


Persistence of the circadian variation and altered response to hepatectomy of hepatic ornithine decarboxylase activity with malignant tumor burden.
We measured the effect of MC-26 mouse colon cancers (of different sizes) on the circadian rhythm of hepatic ornithine decarboxylase (ODC) activity and hepatic ODC activity during the 24 hr after 60% hepatectomy. Tumor-free control mice showed a normal circadian rhythm of ODC activity with the highest levels at 1100 hr and the lowest levels at 2300 hr. The amplitude of the rhythm was diminished significantly in mice with a large tumor burden (3% of their body weight), and hepatic ODC activity was significantly less than in the tumor-free mice at every point during the 24 hr of the study. In mice with "early" tumors (0.3% of body weight), basal activity of ODC was normal and there was no reactive increase in activity following hepatectomy. In contrast, mice with "late" (3% of body weight) tumors had significantly lower basal ODC activities and the increase in ODC activity following hepatectomy was prolonged and exaggerated. We concluded that tumor burden is associated with abnormal ODC activity and that these differences are exaggerated after hepatectomy. Furthermore, although average ODC concentrations in tumor-bearing mice fell precipitously, the circadian rhythm in hepatic ODC persisted. This finding indicates early recognition by the host of tumor presence, which has a profound negative regulatory effect on hepatic ODC. Apparently, this effect does not impinge on circadian control mechanisms, indicating that these signals act independently.


Dynamic optical coherence tomography of chronic venous ulcers.
Chronic ulcers, especially venous leg ulcers, are a major burden on the healthcare system. To date there are only few non-invasive established procedures for evaluation of blood perfusion in wounds. Dynamic optical coherence tomography (D-OCT) provides images of the skin's superficial vascularisation. This study aims to investigate if and how the D-OCT measurement of chronic wounds can provide new information about the vascularisation during the healing process. We examined 16 venous ulcers over 16 weeks and evaluated the vessel morphology and density using D-OCT at the wound bed, borders, two centimetres adjacent to the wound und at non-ulcerated skin on the contralateral leg. In D-OCT scans clumps were unique and the most common vessel type in the wound area of venous ulcers, whereas lines and serpiginous vessels were the most common in non-ulcerated skin. At the wound border mottle and cluster patterns occurred more frequently. Healthy skin showed a significant increase of mesh pattern. Vessel density significantly increased at the wound area compared to non-ulcerated skin. During the healing process the wound border showed the most vascular changes while only an increase in curves was observed in the wound centre. Non-healing wounds had fewer dots and blobs at the borders, fewer dots, coils, clumps, lines and serpiginous vessels at the centre and fewer dots in adjacent skin. Temperature analysis showed higher temperatures in non-ulcerated skin, followed by the wound margin and centre. Non-healing wounds showed the lowest temperatures in the wound centre. These results highlight the non-invasive use of D-OCT for the examination and monitoring of wound healing in chronic venous ulcers. D-OCT imaging of blood vessels may offer the potential to detect disorders of wound healing at an early stage, differentiate ulcers of different genesis and to tailor more individualized, patient-oriented therapy.


Comparison of myeloma cell contamination of bone marrow and peripheral blood stem cell harvests.
lt could be speculated for patients with myeloma and other lymphoproliferative disorders that peripheral blood stem cells may be preferable to bone marrow for autologous transplantation because they may be less contaminated by neoplastic cells. To test this possibility, the immunoglobulin heavy chain gene rearrangement and limiting dilution polymerase chain reaction were used to sensitively quantify myeloma cells in bone marrow and peripheral blood stem cell collections, taken at a similar time, from eight patients with multiple myeloma. Levels of residual disease in the peripheral blood stem cell harvests were variable and did not reflect the tumour burden in the marrow. Peripheral blood stem cells contained 1.7 to 23700-fold fewer myeloma cells compared with the bone marrow and would have resulted in reinfusion of 0.08 to 59480-fold fewer myeloma cells based on total reinfused CFU-GM and 0.24 to 24700-fold fewer myeloma cells based on total reinfused nucleated cells. Assuming that the proportion of clonogenic myeloma cells is equivalent, peripheral blood stem cells may be better than bone marrow as a source of haemopoietic stem cells for transplantation in multiple myeloma. The clinical followup suggested that patients transplanted with peripheral blood stem cells containing a low number of myeloma cells had better disease control than those transplanted with peripheral blood stem cells containing a high number.


The limited scar mastopexy: current concepts and approaches to correct breast ptosis.
The literature on short scar mastopexy was reviewed, with a focus on the different techniques. Currently four techniques have been described: the periareolar, the vertical, the inverted-T, and the L-shaped scar. The different techniques were evaluated with regard to patient selection, operative techniques, scar length, and complications. A large number of techniques have been published for minimal ptosis, whereas for significant ptosis, the number of surgical options is limited. It is evident that limited scar techniques can be applied to all grades of ptosis, but there is no one technique that can satisfactorily correct all degrees of ptosis. Plastic surgeons should weigh the advantages and limitations of each technique to correctly address breast ptosis. This article reviews an algorithmic approach to correct all degrees of ptosis with mastopexy.


The diagnostic utility of HASTE MRI in the evaluation of acute cholecystitis. Half-Fourier acquisition single-shot turbo SE.
The purpose of this study was twofold: (a) to determine the significance of high signal intensity surrounding the gallbladder as seen on T2-weighted HASTE (half-Fourier acquisition single shot turbo SE) MR images in patients with acute cholecystitis and (b) to determine the sensitivity of T2-weighted HASTE MR images in detecting gallbladder and common bile duct (CBD) calculi in patients with acute cholecystitis. Seventy-two patients with a suspicion of acute cholecystitis were referred for HASTE MRI over a 2 year period. Forty-one patients underwent MRI after sonography and the remaining 31 patients before sonography. MR images were independently evaluated for the presence of MR pericholecystic high signal and gallbladder and CBD calculi. Findings were correlated with results obtained at sonography and at surgery. Of the 72 patients imaged with HASTE MRI, 55 had cholecystitis based on clinical, sonographic, and/or surgical findings. Of these, 45 had acute and 10 had chronic cholecystitis. HASTE MRI demonstrated MR pericholecystic high signal in 41 of 45 (91%) of the patients with acute cholecystitis. The sensitivity of HASTE MRI in diagnosing acute cholecystitis was 91%. The specificity was 79%. The positive predictive value was 87%, the negative predictive value was 85%, and the overall accuracy of the test was 89%. Gallbladder stones were seen by HASTE MRI in 38 of 41 (93%) of patients with acute calculus cholecystitis demonstrated at sonography. CBD stones were demonstrated by HASTE MRI in seven of nine (78%) patients and by sonography in five of nine (56%) patients with documented choledocholithiasis on conventional cholangiography. HASTE MRI has a high degree of accuracy in diagnosing acute cholecystitis based on the single finding of pericholecystic MR high signal. A similar level of accuracy is demonstrated in detecting gallbladder stones. Biliary duct calculi are detected with even greater accuracy than with sonography in patients with acute cholecystitis. Invasive preoperative endoscopic retrograde cholangiography may therefore be limited to only those patients with acute cholecystitis and CBD stones demonstrated on HASTE MRI. These features make HASTE MRI and ideal imaging modality in the initial evaluation of acute biliary pain and may ultimately replace sonography in the preoperative evaluation of acute cholecystitis.


Clinical features of bacterial vaginosis in a murine model of vaginal infection with Gardnerella vaginalis.
Bacterial vaginosis (BV) is a dysbiosis of the vaginal flora characterized by a shift from a Lactobacillus-dominant environment to a polymicrobial mixture including Actinobacteria and gram-negative bacilli. BV is a common vaginal condition in women and is associated with increased risk of sexually transmitted infection and adverse pregnancy outcomes such as preterm birth. Gardnerella vaginalis is one of the most frequently isolated bacterial species in BV. However, there has been much debate in the literature concerning the contribution of G. vaginalis to the etiology of BV, since it is also present in a significant proportion of healthy women. Here we present a new murine vaginal infection model with a clinical isolate of G. vaginalis. Our data demonstrate that this model displays key features used clinically to diagnose BV, including the presence of sialidase activity and exfoliated epithelial cells with adherent bacteria (reminiscent of clue cells). G. vaginalis was capable of ascending uterine infection, which correlated with the degree of vaginal infection and level of vaginal sialidase activity. The host response to G. vaginalis infection was characterized by robust vaginal epithelial cell exfoliation in the absence of histological inflammation. Our analyses of clinical specimens from women with BV revealed a measureable epithelial exfoliation response compared to women with normal flora, a phenotype that, to our knowledge, is measured here for the first time. The results of this study demonstrate that G. vaginalis is sufficient to cause BV phenotypes and suggest that this organism may contribute to BV etiology and associated complications. This is the first time vaginal infection by a BV associated bacterium in an animal has been shown to parallel the human disease with regard to clinical diagnostic features. Future studies with this model should facilitate investigation of important questions regarding BV etiology, pathogenesis and associated complications.


Kinetics of the monomer-dimer reaction of yeast hexokinase PI.
Kinetic studies of the glucose-dependent monomer-dimer reaction of yeast hexokinase PI at pH 8.0 in the presence of 0.1 M-KCl have been carried out using the fluorescence temperature-jump technique. A slow-relaxation effect was observed which was attributed from its dependence on enzyme concentration to the monomer-dimer reaction; the reciprocal relaxation times tau-1 varied from 3 s-1 at low concentrations of glucose to 42 s-1 at saturating concentrations. Rate constants for association (kass.) and dissociation (kdiss.) were determined as a function of glucose concentration using values of the equilibrium association constant of the monomer-dimer reaction derived from sedimentation ultracentrifugation studies under similar conditions, and also from the dependence of tau-2 on enzyme concentration. kass. was almost independent of glucose concentration and its value (2 x 10(5) M-1.s-1) was close to that expected for a diffusion-controlled process. The influence of glucose on the monomer-dimer reaction is entirely due to effects on kdiss., which increases from 0.21 s-1 in the absence of glucose to 25 s-1 at saturating concentrations. The monomer and dimer forms of hexokinase have different affinities and Km values for glucose, and the results reported here imply that there may be a significant lag in the response of the monomer-dimer reaction to changes in glucose concentrations in vivo with consequent hysteretic effects on the hexokinase activity.