Surface-associated fucoxanthin mediates settlement of bacterial epiphytes on the rockweed Fucus vesiculosus.
The chemical defence against microfouling in the brown seaweed Fucus vesiculosus was investigated and an inhibitor of bacterial settlement was isolated by bioassay-guided fractionation of non-polar surface extracts. UV-vis and mass spectrometry were used to identify the compound as the carotenoid fucoxanthin. The metabolite was tested at the natural concentration (in a surface volume based assay) against the settlement of four bacterial strains isolated from F. vesiculosus and 11 strains isolated from co-occurring algae and marine sediment. Surface concentrations between 1.4 and 6 μg cm(-2) resulted in 50% inhibition of four of these isolates, which were studied in more detail using a surface area-based assay, while a fifth isolate proved to be less sensitive. The presence of fucoxanthin on the surface of F. vesiculosus was demonstrated with two different surface extraction methods. Fucoxanthin was detected at concentrations between 0.7 and 9 μg cm(-2) on the algal surface. Fucoxanthin was still present at the algal surface after removal of associated diatoms through mechanical cleaning and germanium dioxide treatment and was thus mainly produced by F. vesiculosus rather than by diatoms. Thus, the photosynthetic pigment fucoxanthin appears to be ecologically relevant as a surface-associated antimicrobial agent, acting against the settlement of bacteria on the surface of the macroalga F. vesiculosus.


Expression and rapid experience-dependent regulation of type-A GABAergic receptors in the songbird auditory forebrain.
GABAergic transmission influences sensory processing and experience-dependent plasticity in the adult brain. Little is known about the functional organization of inhibitory circuits in the auditory forebrain of songbirds, a robust model extensively used in the study of central auditory processing of behaviorally relevant communication signals. In particular, no information is currently available on the expression and organization of GABAA receptor-expressing neurons. Here, we studied the distribution and regulation of GABAA receptors in the songbird auditory forebrain, with a specific focus on α5, a subunit implicated in tonic inhibition and sensory learning. We obtained a zebra finch cDNA that encodes the α5-subunit (GABRA5) and carried out a detailed analysis of its expression via in situ hybridization. GABRA5 was highly expressed in the caudomedial nidopallium (NCM), caudomedial mesopallium, and field L2. Using double fluorescence in situ hybridization, we demonstrate that a large fraction of GABRA5-expressing neurons is engaged by auditory experience, as revealed by the song-induced expression of the activity-dependent gene zenk. Remarkably, we also found that α5 expression is rapidly regulated by sensory stimulation: 30 min of conspecific song playbacks significantly increase the number of GABRA5-expressing neurons in NCM, but not in other auditory areas. This effect is selective for α5, but not γ2 transcripts. Our results suggest that α5-containing GABAA receptors likely play a key role in central auditory processing and may contribute to the experience-dependent plasticity underlying auditory learning.


Inhibition of glioma proliferation and migration by magnetic nanoparticle mediated JAM-2 silencing.
Brain invasion is a biological hallmark of glioma that leads to its aggressiveness and prognosis. Junctional adhesion molecule-2 (JAM-2) was found to be overexpressed in human glioma. In this study, the effects of JAM-2 silencing mediated by cell-penetrating magnetic nanoparticles were investigated on glioma cell proliferation and migration in vitro and in vivo. The results showed that the deregulation of JAM-2 in glioma cell lines could cause a dramatic decrease in cell proliferation and migration in vitro. The expression level of cytoskeleton remodeling and migration associated protein genes appeared to be a downstream factor of JAM-2. Furthermore, silencing of JAM-2 expression in implanted glioma cells was found to impair in vivo tumor growth significantly. These data provide new evidence for the role of JAM-2 in the progression of glioma and show its great potential in human glioma gene therapeutics.


Evaluation of acute fixation strength for mechanical tacking devices and fibrin sealant versus polypropylene suture for laparoscopic ventral hernia repair.
The purpose of this comparative study is to evaluate the acute fixation strength of mechanical tacking devices and fibrin sealant against polypropylene suture for laparoscopic ventral hernia repair. Three metallic mechanical tacking devices (ProTack, Salute, EndoANCHOR), 4 absorbable tacking devices (AbsorbaTack, PermaSorb, I-Clip, and SorbaFix), and 2 types of fibrin sealant (Tisseel, Artiss) were compared with 0-polypropylene suture. Three constructs from each device or an amount of sealant sufficient to cover a 3 × 3 cm(2) area were used to affix a 4 × 3 cm piece of absorbable barrier-coated mesh (Proceed, Ethicon, Inc) to the peritoneal surface of porcine abdominal wall. Ten samples were completed for each fixation modality. Acute fixation strength was measured via a lap shear test on an Instron tensiometer. Acute fixation strength was significantly greater for suture (59.7 7.2 N) compared with all laparoscopic tacking devices and to fibrin sealant (P < .001 for all comparisons). Protack (29.5 ± 2.8 N) was stronger than Absorbatack (13.2 ± 3.7 N; P = .029). Protack, Permasorb, SorbaFix, and I-clip were stronger than fibrin sealant (P < .05 for all comparisons). The acute fixation strengths of metallic or absorbable tacks as well as fibrin sealant are all significantly less than that achieved with polypropylene suture. These factors should be considered in selecting the type of mechanical fixation for patients undergoing laparoscopic ventral hernia repair.


Transcriptional response to hepatitis C virus infection and interferon-alpha treatment in the human liver.
Hepatitis C virus (HCV) is widely used to investigate host-virus interactions. Cellular responses to HCV infection have been extensively studied in vitro However, in human liver, interferon (IFN)-stimulated gene expression can mask direct transcriptional responses to infection. To better characterize the direct effects of HCV infection in vivo, we analyze the transcriptomes of HCV-infected patients lacking an activated endogenous IFN system. We show that expression changes observed in these patients predominantly reflect immune cell infiltrates rather than cell-intrinsic pathways. We also investigate the transcriptomes of patients with endogenous IFN activation, which paradoxically cannot eradicate viral infection. We find that most IFN-stimulated genes are induced by both recombinant IFN therapy and the endogenous IFN system, but with lower induction levels in the latter, indicating that the innate immune response in chronic hepatitis C is too weak to clear the virus. We show that coding and non-coding transcripts have different expression dynamics following IFN treatment. Several microRNA primary transcripts, including that of miR-122, are significantly down-regulated in response to IFN treatment, suggesting a new mechanism for IFN-induced expression fine-tuning.


Chronic heart failure management and remote haemodynamic monitoring.
Heart failure (HF) has a large societal and economic burden and is expected to increase in magnitude and complexity over the ensuing years. A number of telemonitoring strategies exploring remote monitoring and management of clinical signs and symptoms of congestion in HF have had equivocal results. Early studies of remote haemodynamic monitoring showed promise, but issues with device integrity and implantation-associated adverse events hindered progress. Nonetheless, these early studies established that haemodynamic congestion precedes clinical congestion by several weeks and that remote monitoring of intracardiac pressures may be a viable and practical management strategy. Recently, the safety and efficacy of remote pulmonary artery pressure-guided HF management was established in a prospective, single-blind trial where randomisation to active pressure-guided HF management reduced future HF hospitalisations. Subsequent commercial use studies reinforced the utility of this technology and post hoc analyses suggest that tight haemodynamic management of patients with HF may be an additional pillar of therapy alongside established guideline-directed medical and device therapy. Currently, there is active exploration into utilisation of this technology and management paradigm for the timing of implantation of durable left ventricular assist devices (LVAD) and even optimisation of LVAD therapy. Several ongoing clinical trials will help clarify the extent and utility of this strategy along the spectrum of patient with HF from individuals with chronic, stable HF to those with more advanced disease requiring heart replacement therapy.


Depressive symptoms screening in postmenopausal women with symptomatic pelvic organ prolapse.
This study aimed to investigate the prevalence of depressive symptoms in postmenopausal women with symptomatic pelvic organ prolapse (POP) and to identify the factors associated with depressive symptoms in this population. We conducted a cross-sectional study involving postmenopausal women with symptomatic POP who visited the Center of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, between July 2016 and March 2017. We collected data pertaining to participants' sociodemographic characteristics and medical histories. The participants enrolled in the study were evaluated by POP quantification (POP-Q), the Pelvic Floor Distress Inventory-20 (PFDI-20), and the Pelvic Floor Impact Questionnaire-7 (PFIQ-7), and the severity of their depressive symptoms was assessed by the Patient Health Questionnaire-9 (participants with scores ≥10 were considered "positive" for depressive symptoms, whereas participants with scores <10 were considered "negative" for depressive symptoms). We performed independent-sample t tests, Mann-Whitney U test, chi-square tests, Fisher's exact test, and logistic regression to analyze our data. In all, 177 participants completed the entire study and were thus included in the analysis. Overall, 32.8% of participants were found to have depressive symptoms. We noted no differences in sociodemographic characteristics or POP-Q stage between participants with and without depressive symptoms (P > 0.05). However, depressive symptoms were associated with higher PFIQ-7 and PFDI-20 subscale scores (P < 0.001). PFIQ-7 subscale Urinary Impact Questionnaire (UIQ)-7 (odds ratio [OR] 1.038, 95% confidence interval [CI] 1.010-1.066, P = 0.008), PFDI-20 subscale UDI-6 (OR 1.025, 95% CI 1.007-1.044, P = 0.008), and Colorectal-Anal Distress Inventory-8 (OR 1.025, 95% CI 1.005-1.046, P = 0.016), which represented the impact on quality of life from lower urinary tract symptoms, the distress caused by lower urinary tract symptom and bowel dysfunction, respectively, were the risk factors that were independently associated with depressive symptoms after multiple logistic regression analysis. Depressive symptoms were present in approximately one-third of postmenopausal women with symptomatic POP. Depressive symptoms are not associated with POP stage, but are associated with the lower urinary tract symptom and bowel dysfunction scores attributable to prolapse. Clinicians should be mindful of whether patients with symptomatic POP have depressive symptoms and should address POP and any concomitant depressive symptoms as early as possible.


Dynamics of CD4 and CD8 T cell responses to cytomegalovirus in healthy human donors.
To study the dynamics of cytomegalovirus (CMV) immunity in healthy immunocompetent hosts, interferon-gamma-producing CD4 and CD8 T cell responses in the presence or absence of CMV antigens were measured from 15 CMV-seropositive donors and 13 CMV-seronegative donors. Cytokine responses in the absence of antigen were significantly higher in CMV-seropositive donors. Also, a disproportionate number of CD69(+) cells isolated ex vivo from CMV-seropositive donors were specific for CMV, suggesting recent reactivation in vivo. To examine changes in cellular responses over time, 10 seropositive donors were tested over a 6-month period. About half of the donors showed significant variability over time, but staphylococcal enterotoxin B responses remained relatively constant. These findings suggest that CMV can present a considerable and recurrent burden to the human immune system. By understanding the normal dynamics of CMV responses over time, it may be possible to better identify aberrant responses to CMV in immunocompromised hosts.


Child malaria treatment decisions by mothers of children less than five years of age attending an outpatient clinic in south-west Nigeria: an application of the PEN-3 cultural model.
Using the PEN-3 cultural model, this study sought to understand mothers treatment decisions about their child febrile illness by examining positive health beliefs and practices held by mothers, examine existential (unique) practices that are indigenous to mothers and have no harmful health consequences, and explore negative beliefs and practices that limit recommended responses to febrile illness in children. This qualitative study was conducted in the paediatric section of an outpatient clinic in south-west Nigeria. A total of 123 mothers with children less than five years of age with febrile illness diagnosed as malaria by physicians were individually interviewed on their treatment-seeking practices prior to visiting the clinic and their reasons for attendance at the clinic. For some mothers interviewed, effective treatment from the clinic for their child's febrile illness, coupled with physician's approach with malaria diagnosis and treatment practices was important in generating positive maternal treatment-seeking responses to child febrile illness. In addition, beliefs related to a child teething highlighted existential decisions with treatment-seeking for child febrile illness in this setting. Finally, the belief that febrile illness is not all that severe despite noticeable signs and symptoms was a concerning negative perception shared by some mothers in this study. The findings highlight the need to consider not only the responses that may serve as barriers to effective treatment, but also an acknowledgment of the positive and existential responses that are equally critical in influencing mothers' management of malaria in their children.


Microcirculation in Cardiovascular Diseases.
Microcirculation is a system composed of interconnected microvessels, which is responsible for the distribution of oxygenated blood among and within organs according to regional metabolic demand. Critical medical conditions, e. g., sepsis, and heart failure are known triggers of microcirculatory disturbance, which usually develops early in such clinical pictures and represents an independent risk factor for mortality. Therefore, hemodynamic resuscitation aiming at restoring microcirculatory perfusion is of paramount importance. Until recently, however, resuscitation protocols were based on macrohemodynamic variables, which increases the risk of under or over resuscitation. The introduction of hand-held video-microscopy (HVM) into clinical practice has allowed real-time analysis of microcirculatory variables at the bedside and, hence, favored a more individualized approach. In the cardiac intensive care unit scenario, HVM provides essential information on patients' hemodynamic status, e. g., to classify the type of shock, to adequate the dosage of vasopressors or inotropes according to demand and define safer limits, to guide fluid therapy and red blood cell transfusion, to evaluate response to treatment, among others. Nevertheless, several drawbacks have to be addressed before HVM becomes a standard of care.


Interventions to Increase Moderate-to-Vigorous Physical Activity in Elementary School Physical Education Lessons: Systematic Review.
This systematic review aimed to synthesize recent evidence on interventions to increase moderate-to-vigorous physical activity (MVPA) content of physical education (PE) in children age 8 to 11. A search of 6 databases was conducted in December 2019. Controlled intervention studies were included so long as they used objective measures of MVPA. Methodological quality was assessed using the appropriate Joanna Briggs Institute (JBI) Checklist. Random effects meta-analysis was used where appropriate. Of the 5459 records, only 5 studies met all inclusion criteria, reporting on 1452 participants; 3 quasi-experimental studies and 2 RCTs. All 5 eligible studies reported favorable intervention effects. Meta-analysis was possible from 4/5 studies: the mean difference between intervention and control groups at follow-up was +14.3% of lesson time in MVPA (confidence interval [CI] 2.7 to 25.8). Efforts to increase the MVPA content of elementary school PE are achievable. Two studies employed PE specialist teachers and 1 study used an expert instructor as their intervention, 2 studies worked with the class teachers using self-determination theory. All studies focused on health (MVPA) outcomes and included either "fitness infusions" or physically active games to engage students' in physical activities and increase their activity level.


Trends of the World Input and Output Network of Global Trade.
The international trade naturally maps onto a complex networks. Theoretical analysis of this network gives valuable insights about the global economic system. Although different economic data sets have been investigated from the network perspective, little attention has been paid to its dynamical behaviour. Here we take the World Input Output Data set, which has values of the annual transactions between 40 different countries of 35 different sectors for the period of 15 years, and infer the time interdependence between countries and sectors. As a measure of interdependence we use correlations between various time series of the network characteristics. First we form 15 primary networks for each year of the data we have, where nodes are countries and links are annual exports from one country to the other. Then we calculate the strengths (weighted degree) and PageRank of each country in each of the 15 networks for 15 different years. This leads to sets of time series and by calculating the correlations between these we form a secondary network where the links are the positive correlations between different countries or sectors. Furthermore, we also form a secondary network where the links are negative correlations in order to study the competition between countries and sectors. By analysing this secondary network we obtain a clearer picture of the mutual influences between countries. As one might expect, we find that political and geographical circumstances play an important role. However, the derived correlation network reveals surprising aspects which are hidden in the primary network. Sometimes countries which belong to the same community in the original network are found to be competitors in the secondary networks. E.g. Spain and Portugal are always in the same trade flow community, nevertheless secondary network analysis reveal that they exhibit contrary time evolution.


3D reconstruction of coronary arteries using frequency domain optical coherence tomography images and biplane angiography.
The aim of this study is to describe a new method for three-dimensional (3D) reconstruction of coronary arteries using Frequency Domain Optical Coherence Tomography (FD-OCT) images. The rationale is to fuse the information about the curvature of the artery, derived from biplane angiographies, with the information regarding the lumen wall, which is produced from the FD-OCT examination. The method is based on a three step approach. In the first step the lumen borders in FD-OCT images are detected. In the second step a 3D curve is produced using the center line of the vessel from the two biplane projections. Finally in the third step the detected lumen borders are placed perpendicularly onto the path based on the centroid of each lumen border. The result is a 3D reconstructed artery produced by all the lumen borders of the FD-OCT pullback representing the 3D arterial geometry of the vessel.


Validation of Accelerometer Prediction Equations in Children with Chronic Disease.
The purpose of this study was to assess the criterion validity of existing accelerometer-based energy expenditure (EE) prediction equations among children with chronic conditions, and to develop new prediction equations. Children with congenital heart disease (CHD), cystic fibrosis (CF), dermatomyositis (JDM), juvenile arthritis (JA), inherited muscle disease (IMD), and hemophilia (HE) completed 7 tasks while EE was measured using indirect calorimetry with counts determined by accelerometer. Agreement between predicted EE and measured EE was assessed. Disease-specific equations and cut points were developed and cross-validated. In total, 196 subjects participated. One participant dropped out before testing due to time constraints, while 15 CHD, 32 CF, 31 JDM, 31 JA, 30 IMD, 28 HE, and 29 healthy controls completed the study. Agreement between predicted and measured EE varied across disease group and ranged from (ICC) .13-.46. Disease-specific prediction equations exhibited a range of results (ICC .62-.88) (SE 0.45-0.78). In conclusion, poor agreement was demonstrated using current prediction equations in children with chronic conditions. Disease-specific equations and cut points were developed.


Primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma: a clonal T-cell lymphoproliferative disorder with indolent behavior.
Primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma, a provisional entity in the 2005 WHO-EORTC classification for cutaneous lymphomas, is not well characterized. Fifteen cases meeting the definition of this entity were identified. Fourteen represented solitary lesions on the head/neck (n=9), upper extremity (n=4), or trunk (n=1). One patient presented with multiple lesions on the trunk and extremities. Histologically, the infiltrate showed a nodular pattern in the dermis and subcutis without epidermotropism, and had a polymorphous composition with a predominance of small to medium-sized CD4-positive T cells. Most cases showed normal T-cell antigen expression; diminished/absent expression of CD7 was seen in three cases and CD2 expression was absent in one case. All cases showed a notable reactive infiltrate including frequent B cells, plasma cells, and histiocytes. Clonal TCR gene rearrangements were detected in each case. No clonal Ig gene rearrangements were detected. Out of the 11 patients with follow-up, none showed systemic disease. The majority resolved without relapse, one without treatment, four with excision, and four with radiation therapy. One patient developed local recurrence. The patient with multiple lesions had disease progression despite chemotherapy and stem cell transplant. These cases highlight the polymorphous histology and prominent reactive B-cell component of this entity. Diagnosis requires molecular genetic analysis, as prominent cytologic atypia and immunophenotypic aberrancy are rare. The differential diagnosis includes reactive lymphoid hyperplasia, mycosis fungoides and cutaneous B-cell lymphomas. In patients with isolated cutaneous lesions, the indolent behavior of this rare T-cell neoplasm should be recognized to avoid unnecessary treatment.


Nocardia abscessus sp. nov.
Chemotaxonomic and 16S rRNA gene sequence analyses of four bacterial strains isolated from clinical material clearly demonstrated that these bacteria belong to the genus Nocardia. DNA-DNA hybridization data as well as the physiological characteristics of the isolates indicated that they are closely related and belong to a single species that differs from previously described members of the genus. The name Nocardia abscessus sp. nov. is proposed for these organisms represented by strain IMMIB D-1592T (= DSM 44432T). Strain IMMIB D-1592T exhibits 56.8 and 60.0% DNA-DNA relatedness to Nocardia asteroides ATCC 19247T and Nocardia paucivorans DSM 44386T, respectively.


Understanding the Perceptions of Omani Women Regarding Life After a Breast Cancer Diagnosis.
There is a rising burden of breast cancer (BC) in the Eastern Mediterranean Region (EMR), and its sociopsychological impact is a quickly growing health concern in this region. Because understanding cancer patients' perceptions of life is integral to their treatment, they are also a concern for healthcare providers. This qualitative study, therefore, explored changes in Omani women's perceptions of life after a BC diagnosis. Semi-structured interviews were conducted individually with 21 Omani women undergoing treatment for BC at the Oncology Ward of Muscat's Royal Hospital from March to May 2017. The collected data were subjected to qualitative content analysis. After their cancer diagnosis, the women appeared to pass through three main stages in their coping processes. First, they passed through a stage of severe psychosocial distress and diminishment in personal identity. Next, they evolved strategies for coping based on cultural, religious and family resources. Finally, the women experienced acceptance and submission to the reality of the cancer as God's will with changes in attitudes and perceptions of the meaning of life. A BC diagnosis impacts Omani women severely, affecting their lives dramatically. They adopt coping strategies based on cultural, religious and spiritual beliefs. Healthcare providers need to acknowledge and facilitate women's spiritual and cultural coping strategies as an integral part of their treatment which holds potential to improve their prognosis. Such strategies should be individualised to suit each woman's experiences, perceptions and needs.


Pure early zygotic genes in the Asian malaria mosquito Anopheles stephensi.
The Asian malaria mosquito, Anopheles stephensi, is a major urban malaria vector in the Middle East and on the Indian subcontinent. Early zygotic transcription, which marks the maternal-to-zygotic transition, has not been systematically studied in An. stephensi or any other Anopheles mosquitoes. Improved understanding of early embryonic gene expression in An. stephensi will facilitate genetic and evolutionary studies and help with the development of novel control strategies for this important disease vector. We obtained RNA-seq data in biological triplicates from four early An. stephensi embryonic time points. Using these data, we identified 70 and 153 pure early zygotic genes (pEZGs) under stringent and relaxed conditions, respectively. We show that these pEZGs are enriched in functional groups related to DNA-binding transcription regulators, cell cycle modulators, proteases, transport, and cellular metabolism. On average these pEZGs are shorter and have less introns than other An. stephensi genes. Some of the pEZGs may arise de novo while others have clear non-pEZG paralogs. There is no or very limited overlap between An. stephensi pEZGs and Drosophila melanogaster or Aedes aegypti pEZGs. Interestingly, the upstream region of An. stephensi pEZGs lack significant enrichment of a previously reported TAGteam/VBRGGTA motif found in the regulatory region of pEZGs in D. melanogaster and Ae. aegypti. However, a GT-rich motif was found in An. stephensi pEZGs instead. We have identified a number of pEZGs whose predicted functions and structures are consistent with their collective roles in the degradation of maternally deposited components, activation of the zygotic genome, cell division, and metabolism. The pEZGs appear to rapidly turn over within the Dipteran order and even within the Culicidae family. These pEZGs, and the shared regulatory motif, could provide the promoter or regulatory sequences to drive gene expression in the syncytial or early cellular blastoderm, a period when the developing embryo is accessible to genetic manipulation. In addition, these molecular resources may be used to achieve sex separation of mosquitoes for sterile insect technique.


Usefulness of 3-Tesla Cardiac Magnetic Resonance to Detect Mitral Annular Disjunction in Patients With Mitral Valve Prolapse.
Mitral annulus disjunction (MAD) is characterized by a separation between the atrial wall mitral junction and the left ventricular (LV) free wall. Little is known regarding cardiac magnetic resonance (CMR) performance to detect MAD and its prevalence in mitral valve prolapse (MVP). Based on 89 MVP patients (63 women; mean age 64 ± 13) referred for CMR assessment of MR, either from myxomatous mitral valve disease (MMVP) (n = 40; 45%) or fibroelastic disease (n = 49; 55%), we sought to assess the frequency of MAD and its consequences on LV morphology. Patients were classified in 2 groups according to MAD presence (MAD+) or absence (MAD-). MAD (measuring 8 ± 4 mm) was diagnosed in 35% (31 of 89) of MVP patients, more frequently in MMVP than fibroelastic disease (60% vs 14%). MAD+ was associated with MMVP; bileaflet MVP and nonsustain ventricular tachycardia but not with the severity of MR. Diagnostic accuracy of transthoracic echocardiography for the detection of MAD was fair (65% sensitivity, 96% specificity) with CMR as reference. MAD+ showed significantly enlarged basal and mid LV diameters and enlarged mitral-annulus diameter. In patients with late gadolinium enhancement, presence of LV fibrosis at level of papillary muscle was more frequent in MAD+. After adjustment on age and MR severity, MMVP, and enlarged end-systolic mitral annulus diameter were independently associated with MAD+. In conclusion, MAD was present in about 1/3 of MVP patients, mostly in MMVP and independent of MR severity. Enlarged mitral-annulus and basal LV diameters, nonsustain ventricular tachycardia and papillary muscle fibrosis were associated with MAD presence.


Comparison of direct versus concentrated smear microscopy in detection of pulmonary tuberculosis.
Sputum smear microscopy is fast and inexpensive technique for detecting tuberculosis (TB) in high incidence areas but has low sensitivity. Physical and chemical sputum processing along with centrifugation have been found to show promise in overcoming this limitation. Our objective was to compare the sensitivity of smear microscopy obtained with smears made directly from respiratory specimens to those from concentrated specimens. By active screening, 915 TB suspects were identified from Dhaka Central Jail and sputum specimens were aseptically collected. Direct smears were prepared by taking a small portion of the purulent part of the sputum with a sterile loop. The specimens were then processed by a standard N-acetyl-L-cysteine-NaOH digestion-decontamination method to prepare concentrated specimens. Both smears were then air dried, heat fixed, and stained by the Ziehl-Neelsen staining technique. The stained slides were examined under oil immersion and were graded following International Union Against Tuberculosis and Lung Diseases guidelines. All the specimens were inoculated into Lowenstein-Jensen (L-J) media and culture results were considered as gold standard to calculate sensitivity. Of 915 specimens, 73 (8%) specimens were positive both on direct and concentrated methods, one sample was positive on direct microscopy but was negative on concentrated method. An extra 14 (1.5%) samples were positive on concentrated method which were negative on direct smear. In L-J media 105 specimens were found positive for TB bacilli and of them, 74 (70.5%) and 87 (82.9%) were positive in direct and concentrated smear, respectively. The sensitivity of direct and concentrated smear microscopy was different when using positive culture as the gold standard (71% vs. 83%). The results showed that concentrated technique increases the sensitivity of microscopy up to 12%. Therefore, the national programs in high TB burden countries may consider incorporating the technique into their guidelines at least in the district and higher level laboratories to improve case finding strategy.


Association of parental investment of time and cost in food provisioning with adherence to dietary guidelines for the consumption of fruits, vegetables and non-core foods in pre-schoolers.
To assess whether parent-reported time and cost for provision of food is associated with consumption of fruits, vegetables and non-core foods in pre-schoolers. Cross-sectional analysis of baseline data from the Healthy Habits randomised controlled trial. Two subscales of the Children's Dietary Questionnaire (CDQ) were used to assess fruit and vegetable, and non-core food consumption. Thirty pre-schools in the Hunter Region of New South Wales, Australia. Parents (n 396) with a child aged 3-5 years attending a participating pre-school were recruited. Parents needed to reside with that child for at least four days per week and have primary responsibility for providing meals and snacks to their child. Sixty-three per cent of children had a parent-reported subscale score indicating adherence to dietary guidelines for fruit and vegetable intake, while 64% of children had a subscale score indicating they were exceeding dietary guidelines for non-core foods. Regression models revealed significant positive associations between higher CDQ scores for non-core foods (indicating higher consumption levels) and minutes that parents spent preparing food (P=0·032 and 0·025) and amount spent on purchasing food (P=0·043 and 0·020). The magnitude of the effects was small (estimate=0·003 and 0·001). Time and cost spent by parents on provision of food was not significantly associated with child fruit and vegetable consumption. Further explorations into time spent on food preparation and cost of food procurement are warranted to help address the increased consumption of non-core foods by pre-school children.


Tuberculous Spondylitis of the Craniovertebral Junction.
Craniovertebral junction tuberculosis is rare, accounting for 0.3 to 1% of all tuberculous spondylitis cases. MR imaging is the modality of choice to detect bone involvement, abscess formation and subligamentous spreading of the pus, to differentiate from other lesions affecting the craniovertebral junction, and to determine the efficacy of treatment. Given the fact that surgical treatment of patients with craniovertebral junction tuberculosis has been associated with a high mortality rate ranging up to 10% and recurrence rate ranging up to 20%, conservative is the standard of treatment for most patients. This article presents a patient with craniovertebral junction Mycobacterium tuberculosis infection diagnosed with CT-guided biopsy. A halo vest was applied and antituberculous treatment with rifampicin, isoniazid and ethambutol was initiated. At 6-month follow-up, the patient was asymptomatic; CT of the cervical spine showed healing of the bony lesions. The halo vest was removed and physical therapy was recommended. Antituberculous treatment was continued for a total of 18 months, without any evidence of infection recurrence.


The epidemiology of bacteremia with febrile neutropenia: experience from a single center, 1988-2004.
The epidemiology of bacteremic febrile neutropenia differs between locations and constitutes the basis for selection of empiric antibiotic therapy for febrile neutropenia. To describe the epidemiology of bacteremia among patients with neutropenia in a single center in Israel. We conducted a prospective data collection on all patients with neutropenia (< 500/mm3) and clinically significant bacteremia or fungemia during the period 1988-2004. Among adults (462 episodes) the most common bloodstream isolate was Escherichia coli. Gram-negative bacteria predominated throughout the study period and the ratio between Gram-negative and Gram-positive bacteremia increased from 1.7 to 2.3. Among children (752 episodes), the ratio between Gram-negative and Gram-positive bacteremia reversed from 1.2 to 0.7, due to increasing prevalence of coagulase-negative staphylcoccal bacteremia. Both among adults and children, the length of hospital stay prior to bacteremia had a major impact on the pathogens causing bacteremia and their antibiotic susceptibilities. The prevalence of E. coli decreased with time in hospital, while the rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp., Enterococcus spp. and Candida spp. increased. Resistance to broad-spectrum empiric monotherapy in our center was observed in > 40% of Gram-negative bacteria when bacteremia was acquired after 14 days in hospital. Improved infection-control measures for neutropenic cancer patients in our center are needed. Empiric antibiotic treatment should be tailored to patients' risk for multidrug-resistant organisms. Individual hospitals should monitor infection epidemiology among cancer patients to guide empiric antibiotic treatment.


Trimming of a migrated metal stent for malignant colonic stricture using argon plasma coagulation.
We report the first case of trimming of a migrated metal colonic stent for stent induced severe anorectal pain. We present a case of a 54-year-old female with history of metastatic colorectal carcinoma who had stent placement secondary to obstruction. Subsequent distal migration of the stent caused ulcerations into the rectal mucosa and excruciating anorectal pain. We used argon plasma coagulation (APC) to successfully trim the exposed distal portion of the metal stent and rat tooth forceps to retrieve the stent fragments. The use of APC for trimming metallic stents is an effective procedure that can be used to trim migrated rectal stents that result in significant rectal pain. To date, few studies have been published that use APC to trim metallic stents placed in the gastrointestinal tract. To the best of our knowledge, ours is the only known case in which the indication for stent trimming was severe stent induced rectal pain. The procedure resulted in complete relief of patient symptoms. Therefore, APC is a safe and effective way to trim colo-rectal stents to definitively relieve the symptom of stent induced rectal pain in patients who have experienced distal stent migration and mucosal ulceration.


Does retrograde warm blood cardioplegia provide equal protection to both ventricles? A magnetic resonance spectroscopy study in pigs.
The degree of protection provided to the right ventricle during retrograde continuous normothermic blood cardioplegia (RCNBC) remains controversial. The purpose of this study was to determine whether RCNBC is able to provide "adequate" nutritive flow to both ventricles to prevent ischemic metabolism in normal swine hearts. Localized 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in energy metabolism and intracellular pH (pHi) in each ventricle separately. Isolated normal swine hearts received 20 minutes of antegrade continuous normothermic blood cardioplegia (ACNBC) for collection of control (baseline) data, followed by 20 minutes of RCNBC. This protocol was repeated four times in five hearts and twice in two hearts. Perfusion pressure was maintained between 70 to 85 and 38 to 43 mm Hg during ACNBC and RCNBC, respectively. pHi, creatine phosphate (PCr), inorganic phosphate (Pi), and ATP were measured continuously in each ventricle during ACNBC and RCNBC, using localized 31P MRS with two surface coils. RCNBC resulted in a significant increase in Pi (LV 222% and RV 244% of the baseline levels, respectively) and a decrease in PCr (left ventricle [LV] to 68% and right ventricle [RV] to 31% of the baseline levels, respectively) in both ventricles relative to ACNBC. The PCr level was significantly lower in the RV than in the LV (31% versus 68%, P<.001) during RCNBC. In one series of experiments (n=5) where ACNBC and RCNBC were alternated every 20 minutes (ACNBC, RCNBC, ACNBC, RCNBC, ACNBC) for a total of 100 minutes, Pi and PCr recovered completely. A continuous and significant decrease in ATP was observed in the RV, and no recovery of ATP was found when switching from RCNBC to ACNBC. No significant decrease in ATP was observed in the LV. pHi remained unchanged in both ventricles during alternate ACNBC and RCNBC. Energy metabolism in the RV is less well preserved than in the LV during RCNBC. A combination of ACNBC and RCNBC seems to provide good cardiac protection as measured by the recovery of cardiac energetics and pHi.


Incomplete lineage sorting is common in extant gibbon genera.
We sequenced reduced representation libraries by means of Illumina technology to generate over 1.5 Mb of orthologous sequence from a representative of each of the four extant gibbon genera (Nomascus, Hylobates, Symphalangus, and Hoolock). We used these data to assess the evolutionary relationships between the genera by evaluating the likelihoods of all possible bifurcating trees involving the four taxa. Our analyses provide weak support for a tree with Nomascus and Hylobates as sister taxa and with Hoolock and Symphalangus as sister taxa, though bootstrap resampling suggests that other phylogenetic scenarios are also possible. This uncertainty is due to short internal branch lengths and extensive incomplete lineage sorting across taxa. The true phylogenetic relationships among gibbon genera will likely require a more extensive whole-genome sequence analysis.


Toward an understanding of the influence of cultural background and domain experience on the effects of risk-pricing formats on risk perception.
Risk-information framing can be a powerful tool for aiding the communication of risk and improving decision making. However, little work has investigated the extent that these framing effects depend on the characteristics of the perceiver. In our study, we examine whether the effects of different risk-pricing formats on risky choices are the same for all individuals, no matter their domain experience or cultural background, or whether there are interactions between these factors. Survey 1 revealed that three risk-pricing formats of the same choice problem resulted in the same individuals making different risky choices (preference reversal), suggesting that risk perception was distorted by the risk-pricing format manipulation. In Survey 2, the effects of the risk-pricing formats were shown to differ by the participants' cultural background (Asian vs. European) and the extent of their domain experience. The fact that there were no differences between the cultural or domain experience groups in their overall tendency to select riskier (cf. safer) choices indicates that risk behavior differences between groups are often closely linked to perceptual, rather than simply attitudinal, cognitive processes. The results demonstrate the complex, interactive cognitive processes that are used to encode risk information, involving the framing of the information and the cultural background and previous experiences of the individual. We conclude that it is important to consider the characteristics of the individual (e.g., culture, domain experience, etc.) when manipulating risk-information framing with the aim of improving risk communication.


Activation of acetylcholine receptors on clonal mammalian BC3H-1 cells by high concentrations of agonist.
1. Currents were recorded through acetylcholine (ACh) receptor channels on clonal BC3H-1 cells in the presence of high concentrations of ACh (20-1000 microM) and carbamylcholine (180-1000 microM). 2. Channel openings at high agonist concentrations occur in clusters separated by long silent periods (seconds). Clusters, in turn, show groups of closely spaced openings separated by relatively long (hundreds of milliseconds) closed periods. The closed periods between clusters and between groups within clusters are thought to reflect two desensitized states (Sakmann, Patlak & Neher, 1980). 3. Openings within groups consist largely of long-duration openings. An excess of brief-duration openings is seen at all high agonist concentrations; most brief openings occur as isolated, solitary openings. 4. The distribution of closed periods within groups shows four exponential components with time constants separated by several fold over the range of 50 microseconds to 50 ms. 5. The distribution of closed periods within groups is analysed as a function of agonist concentration, to estimate rate constants for transitions in a hypothetical reaction scheme for receptor activation. One or two of these components (depending on agonist and agonist concentration) appear to reflect agonist binding and channel gating. It is hypothesized that the other closed-period components within groups at high agonist concentrations result from additional states of doubly liganded receptors which have closed ion channels. 6. With ACh as agonist the data indicate that binding and activation saturate at concentrations above 130 microM. The data are quantitatively consistent with measurements made at low concentrations of ACh (Sine & Steinbach, 1986b), and indicate that a four-state linear scheme is able to describe major features of ACh-receptor activation on BC3H-1 cells. The channel opening rate is estimated to be about 450 s-1 and the closing rate about 35 s-1 (-70 mV, 11 degrees C). The concentration dependence of closed durations suggests that some positive co-operativity exists in agonist binding. The dissociation constant with one ACh molecule bound is about 50 microM, and that with two bound is about 10 microM (for an ACh receptor with a closed channel). 7. Saturation is not observed with carbamylcholine, even at 1 mM. The data are consistent with data obtained at low concentrations of carbamylcholine, and are in over-all agreement with the interpretation of data obtained with ACh. The affinity for carbamylcholine is estimated to be about 20-fold lower than with ACh.(ABSTRACT TRUNCATED AT 400 WORDS)


The fertility-inhibiting effect of mosquitoes: Socio-economic differences in response to the Zika crisis in Colombia.
We estimated the impact of the Zika virus outbreak on birth rates and demand for health care services in Colombia. Our analysis exploits the variation in the level of natural protection against mosquito-transmitted diseases across the country. This characteristic induced exogenous variation in Zika incidence, which allows us to construct a control group of municipalities with similar historical fertility trends but with differential exposure to the Zika crisis. We implemented a difference-in-differences model after matching, as well as synthetic control. We found a decrease in birth rates of approx. 10% in the last two quarters of 2019. The impact of the virus was similar irrespective of the women's education level, and we found no discernible impact on teenage pregnancy.


First isolation of Cryptococcus uzbekistanensis from an immunocompromised patient with Lymphoma.
Cryptococcus species are known agents of opportunistic infections in healthy and immunocompromised hosts. Here we describe the first case of Cryptococcus uzbekistanensis causing bone marrow infection in an elderly Asian man with undiagnosed T cell lymphoma presenting with fever of unknown origin, pancytopenia, and exposure to chicken manure.


11C-methionine-18F-FDG dual-PET-tracer-based target delineation of malignant glioma: evaluation of its geometrical and clinical features for planning radiation therapy.
It is important to correctly and precisely define the target volume for radiotherapy (RT) of malignant glioma. 11C-methionine (MET) positron emission tomography (PET) holds promise for detecting areas of glioma cell infiltration: the authors' previous research showed that the magnitude of disruption of MET and 18F-fluorodeoxyglucose (FDG) uptake correlation (decoupling score [DS]) precisely reflects glioma cell invasion. The purpose of the present study was to analyze volumetric and geometrical properties of RT target delineation based on DS and compare them with those based on MRI. Twenty-five patients with a diagnosis of malignant glioma were included in this study. Three target volumes were compared: 1) contrast-enhancing core lesions identified by contrast-enhanced T1-weighted images (T1Gd), 2) high-intensity lesions on T2-weighted images, and 3) lesions showing high DS (DS ≥ 3; hDS). The geometrical differences of these target volumes were assessed by calculating the probabilities of overlap and one encompassing the other. The correlation of geometrical features of RT planning and recurrence patterns was further analyzed. The analysis revealed that T1Gd with a 2.0-cm margin was able to cover the entire high DS area only in 6 (24%) patients, which indicates that microscopic invasion of glioma cells often extended more than 2.0 cm beyond a Gd-enhanced core lesion. Insufficient coverage of high DS regions with RT target volumes was suggested to be a risk for out-of-field recurrence. Higher coverage of hDS by T1Gd with a 2-cm margin (i.e., higher values of "[T1Gd + 2 cm]/hDS") had a trend to positively impact overall and progression-free survival. Cox regression analysis demonstrated that low coverage of hDS by T1Gd with a 2-cm margin was predictive of disease recurrence outside the Gd-enhanced core lesion, indicative of out-of-field reoccurrence. The findings of this study indicate that MRI is inadequate for target delineation for RT in malignant glioma treatment. Expanding the treated margins substantially beyond the MRI-based target volume may reduce the risk of undertreatment, but it may also result in unnecessary irradiation of uninvolved regions. As MET/FDG PET-DS seems to provide more accurate information for target delineation than MRI in malignant glioma treatment, this method should be further evaluated on a larger scale.


Parkinson's VPS35[D620N] mutation induces LRRK2-mediated lysosomal association of RILPL1 and TMEM55B.
We demonstrate that the Parkinson's VPS35[D620N] mutation alters the expression of ~220 lysosomal proteins and stimulates recruitment and phosphorylation of Rab proteins at the lysosome. This recruits the phospho-Rab effector protein RILPL1 to the lysosome where it binds to the lysosomal integral membrane protein TMEM55B. We identify highly conserved regions of RILPL1 and TMEM55B that interact and design mutations that block binding. In mouse fibroblasts, brain, and lung, we demonstrate that the VPS35[D620N] mutation reduces RILPL1 levels, in a manner reversed by LRRK2 inhibition and proteasome inhibitors. Knockout of RILPL1 enhances phosphorylation of Rab substrates, and knockout of TMEM55B increases RILPL1 levels. The lysosomotropic agent LLOMe also induced LRRK2 kinase-mediated association of RILPL1 to the lysosome, but to a lower extent than the D620N mutation. Our study uncovers a pathway through which dysfunctional lysosomes resulting from the VPS35[D620N] mutation recruit and activate LRRK2 on the lysosomal surface, driving assembly of the RILPL1-TMEM55B complex.


C/EBPalpha is a DNA damage-inducible p53-regulated mediator of the G1 checkpoint in keratinocytes.
The basic leucine zipper transcription factor, CCAAT/enhancer binding protein alpha (C/EBPalpha), is abundantly expressed in keratinocytes of the skin; however, its function in skin is poorly characterized. UVB radiation is responsible for the majority of human skin cancers. In response to UVB-induced DNA damage, keratinocytes activate cell cycle checkpoints that arrest cell cycle progression and prevent replication of damaged DNA, allowing time for DNA repair. We report here that UVB radiation is a potent inducer of C/EBPalpha in human and mouse keratinocytes, as well as in mouse skin in vivo. UVB irradiation of keratinocytes resulted in the transcriptional up-regulation of C/EBPalpha mRNA, producing a >70-fold increase in C/EBPalpha protein levels. N-Methyl-N'-nitro-N-nitrosoguanidine, etoposide, and bleomycin also induced C/EBPalpha. UVB-induced C/EBPalpha was accompanied by an increase in p53 protein and caffeine, an inhibitor of ataxia-telangiectasia-mutated kinase, and ataxia-telangiectasia-mutated and Rad3-related kinase inhibited UVB-induced increases in both C/EBPalpha and p53. UVB irradiation of p53-null or mutant p53-containing keratinocytes failed to induce C/EBPalpha. UVB irradiation of C/EBPalpha knockdown keratinocytes displayed a greatly diminished DNA damage G(1) checkpoint, and this was associated with increased sensitivity to UVB-induced apoptosis. Our results uncover a novel role for C/EBPalpha as a p53-regulated DNA damage-inducible gene that has a critical function in the DNA damage G(1) checkpoint response in keratinocytes.


Comparison of effectiveness of silicone gel sheeting with microporous paper tape in the prevention of hypertrophic scarring in a rabbit model.
To determine the effectiveness of treating scars with microporous paper tape or silicone gel sheeting (SGS) in preventing hypertrophic scarring. Forty hypertrophic scars were induced in a validated rabbit ear model. Wounds were randomized and bandaged for 30 days with either SGS (20 wounds), paper tape (20 wounds), or untreated controls (40 wounds). Two outcome measures of hypertrophic scarring included (1) histologic measurement of scar elevation index (SEI) and (2) blinded photograph analysis using a visual analog scale. In histologic comparison, no difference in mean (SE) SEI between treatment groups was seen (paper tape group, 1.32 [0.2]; SGS group, 1.41 [0.18]; control, 1.35 [0.23]; P = .51). In photographic analysis, both treatment groups were superior to the control group (P < .01), whereas no difference was seen between the SGS and paper tape groups (P = .88). Paper tape and SGS demonstrated equal effectiveness in the prevention of hypertrophic scarring on visual analysis, whereas histologic analysis demonstrated no difference in treatment groups from controls. The effectiveness of paper tape in preventing hypertrophic scarring in humans will require further laboratory and clinical investigation.


Leveraging Contextual Information in Extracting Long Distance Relations from Clinical Notes.
Relation extraction from biomedical text is important for clinical decision support applications. In post-marketing pharmacovigilance, for example, Adverse Drug Events (ADE) relate medical problems to the drugs that caused them and were the focus of two recent shared challenges. While good results were reported, there was a room for improvement. Here, we studied two new improved methods for relation extraction: (1) State-of-the-art deep learning contextual representation model called BERT, Bidirectional Encoder Representations from Transformers; (2) Selection of negative training samples based on the "near-miss" hypothesis (the Edge sampling). We used the datasets from MADE and N2C2 Task-2 for performance evaluation. BERT and Edge together improved performance of ADE and Reason (indication) relations extraction by 6.4-6.7 absolute percentage (and error rate reduction of 24%-28%). ADE and Reason relations contained longer text between the entities, which BERT and Edge were able to leverage to achieve the performance improvement. While the performance improvement for medication attribute relations was smaller in absolute percentages, error rate reduction was still considerable.


Multicentre randomised clinical trials in trauma care.
Multicentre clinical trials in trauma care are gaining prominence as a means of generating good-quality evidence to inform and influence clinical practice. We believe multicentre trials have an important role to play in supporting evidence-based practice, and further investment in such trials is justified.


Transition Icons for Time-Series Visualization and Exploratory Analysis.
The modern healthcare landscape has seen the rapid emergence of techniques and devices that temporally monitor and record physiological signals. The prevalence of time-series data within the healthcare field necessitates the development of methods that can analyze the data in order to draw meaningful conclusions. Time-series behavior is notoriously difficult to intuitively understand due to its intrinsic high-dimensionality, which is compounded in the case of analyzing groups of time series collected from different patients. Our framework, which we call transition icons, renders common patterns in a visual format useful for understanding the shared behavior within groups of time series. Transition icons are adept at detecting and displaying subtle differences and similarities, e.g., between measurements taken from patients receiving different treatment strategies or stratified by demographics. We introduce various methods that collectively allow for exploratory analysis of groups of time series, while being free of distribution assumptions and including simple heuristics for parameter determination. Our technique extracts discrete transition patterns from symbolic aggregate approXimation representations, and compiles transition frequencies into a bag of patterns constructed for each group. These transition frequencies are normalized and aligned in icon form to intuitively display the underlying patterns. We demonstrate the transition icon technique for two time-series datasets-postoperative pain scores, and hip-worn accelerometer activity counts. We believe transition icons can be an important tool for researchers approaching time-series data, as they give rich and intuitive information about collective time-series behaviors.


Athlete's hernia--a true, early direct inguinal hernia: diagnosis, pathophysiology, and surgical treatment.
Athlete's hernia (AH) is an activity limiting condition that presents as chronic inguinal pain in elite athletes. The diagnosis involves a thorough history and physical examination and can be aided by ultrasound interrogation of the groin. Operative treatment with a direct tissue repair of the inguinal floor successfully alleviates symptoms and allows for full return to activity. A retrospective analysis of patients with the diagnosis of AH from January 1998 to May 2010 who underwent operative repair was reviewed. Patients were evaluated based on age, gender, sport, time to presentation, subjective and objective physical findings, imaging findings, operative findings, length of follow-up, and return to activity. Ninety-six patients (6 females) with a median age of 22.6 years were evaluated. In the majority of these patients, operative exploration revealed a wide external ring with separation of the fibers of the external oblique aponeurosis and an unprotected and bulging transverses abdominis aponeurosis, very akin to an early direct inguinal hernia. The mean initial follow-up time was 6 weeks at which point all but two of the patients were able to resume their full level of activity without restrictions. The diagnosis of AH, although somewhat elusive, can be easily established with a high degree of suspicion after doing a thorough history and physical exam augmented with ultrasonography. AH is equivalent to an early direct inguinal hernia found in young athletes and can be surgically corrected allowing return to full activity.


[Non lymphoid cells of the peripheral lymphoid organs. Recent morphological progress and current understanding (author's transl)].
Peripheral lymphoid organs have two groups of non lymphoid cells : that of macrophages which belongs to R. van Furth's system of mononuclear phagocytes and the one made of elements for long labelled "reticular cells". The use of electron microscopy has permitted a good understanding of these elements and a recognition of ubiquitary cells (fibroblasts, endothelial cells) and specific cells to the lymph node which seem to play a very important role in the immune reactions (interdigitated cells, reticulum cells, dendritic cells). We describe their light and electron microscopical features and histoenzymatic characters, and present the actual concept of their origin and function. The latest discoveries on their classification are reviewed and have permitted to distinguish three categories of non lymphoid cells : first the group of reticulum cells (reticulum cells and dendritic cells), second that of mononuclear phagocytes (macrophages and interdigitated cells) and third that of endothelial cells. Other elements of questionable existence or insufficiently known do not appear in this classification : dark cells, Steinman and Cohn's dendritic cells and cells containing Birbeck's granules.


Design and dosimetric characteristics of a high dose rate remotely afterloaded endocavitary applicator system.
An applicator is described for endocavitary treatment of rectal cancers using a high dose rate (HDR) remote afterloading system with a single high-intensity 192Ir source as an alternative to the 50 kVp x-ray therapy contact unit most frequently used in this application. The applicator consists of a tungsten-alloy collimator with a 45 degree beveled end, placed in a protoscope with an elliptical cross-section. The resultant 3 cm diameter circular treatment aperture, located in the beveled face of the proctoscope, is irradiated by circular array of dwell positions located about 6.5 mm from the applicator surface. This beveled end allows patients with posterior wall tumors to be treated in the dorsal lithotomy position. The dose-rate distributions about the applicator were determined using a combination of thermoluminescent dosimetry (TLD-100 detectors) and radiochromic film dose measurement techniques along with Monte Carlo dosimetry calculations. TLD-100 (3 x 3 x 0.9 mm3 chips) measurements were used to measure the distribution of dose over the proctoscope surface as well as the central axis dose-rate distribution. Relative radiochromic film measurements were used to measure off-axis ratios (flatness and penumbra width) within the treatment aperture. These data were combined with Monte Carlo simulation results to obtain the final dose distribution. The tungsten collimator successfully limits the dose to the tissue in contact with the proctoscope walls to less than 12% of the prescribed dose. These results indicate that the HDR applicator system has slightly more penetrating depth-dose characteristics than the most widely used contact therapy x-ray machine. Flatness characteristics of the two treatment delivery systems are comparable, although the HDR endocavitary applicator has a significantly wider penumbra. Finally, the HDR applicator has a lower surface dose rate (1.5-4 Gy/min of dwell time) compared to 9-10 Gy/min for the x-ray unit. An applicator system has been developed for endocavitary treatment of early stage rectal carcinoma that uses a single-stepping source HDR remote afterloading system as a radiation source. The advantages of the HDR-based system over x-ray therapy contact units currently used in this clinical application are (a) enhanced flexibility in applicator design and (b) widespread availability of single-stepping source HDR remote afterloading systems.


Probability density of aperture-averaged irradiance fluctuations for long range free space optical communication links.
The probability density function (PDF) of aperture-averaged irradiance fluctuations is calculated from wave-optics simulations of a laser after propagating through atmospheric turbulence to investigate the evolution of the distribution as the aperture diameter is increased. The simulation data distribution is compared to theoretical gamma-gamma and lognormal PDF models under a variety of scintillation regimes from weak to strong. Results show that under weak scintillation conditions both the gamma-gamma and lognormal PDF models provide a good fit to the simulation data for all aperture sizes studied. Our results indicate that in moderate scintillation the gamma-gamma PDF provides a better fit to the simulation data than the lognormal PDF for all aperture sizes studied. In the strong scintillation regime, the simulation data distribution is gamma gamma for aperture sizes much smaller than the coherence radius rho0 and lognormal for aperture sizes on the order of rho0 and larger. Examples of how these results affect the bit-error rate of an on-off keyed free space optical communication link are presented.


Non-invasive monitoring of L-2-oxothiazolidine-4-carboxylate metabolism in the rat brain by in vivo 13C magnetic resonance spectroscopy.
The cysteine precursor L-2-oxothiazolidine-4-carboxylate (OTZ, procysteine) can raise cysteine concentration, and thus glutathione levels, in some tissues. OTZ has therefore been proposed as a prodrug for combating oxidative stress. We have synthesized stable isotope labeled OTZ (i.e. L-2-oxo-[5-(13)C]-thiazolidine-4-carboxylate, (13)C-OTZ) and tracked its uptake and metabolism in vivo in rat brain by (13)C magnetic resonance spectroscopy. Although uptake and clearance of (13)C-OTZ was detectable in rat brain following a bolus dose by in vivo spectroscopy, no incorporation of isotope label into brain glutathione was detectable. Continuous infusion of (13)C-OTZ over 20 h, however, resulted in (13)C-label incorporation into glutathione, taurine, hypotaurine and lactate at levels sufficient for detection by in vivo magnetic resonance spectroscopy. Examination of brain tissue extracts by mass spectrometry confirmed only low levels of isotope incorporation into glutathione in rats treated with a bolus dose and much higher levels after 20 h of continuous infusion. In contrast to some previous studies, bolus administration of OTZ did not alter brain glutathione levels. Even a continuous infusion of OTZ over 20 h failed to raise brain glutathione levels. These studies demonstrate the utility of in vivo magnetic resonance for non-invasive monitoring of antioxidant uptake and metabolism in intact brain. These types of experiments can be used to evaluate the efficacy of various interventions for maintenance of brain glutathione.


Structure of the rat alpha 1-acid glycoprotein gene.
The complete nucleotide sequence of the rat alpha 1-acid glycoprotein gene has been determined from an isolated lambda recombinant bacteriophage. Southern blot analysis and DNA sequencing indicate that there is only one gene per genome; it contains six exons and is located within a 3,200-base-pair fragment starting from a TATA box and extending to the polyadenylation signal AATAAA. Transcription starts 37 base pairs upstream from the beginning of the translation codon ATG. The TATA box (TATAAA) lies 26 base pairs upstream from this site. The gene contains several potential glucocorticoid receptor-binding sites, both inside and outside the structural gene.


Induction of actinorhodin production by rpsL (encoding ribosomal protein S12) mutations that confer streptomycin resistance in Streptomyces lividans and Streptomyces coelicolor A3(2).
A strain of Streptomyces lividans, TK24, was found to produce a pigmented antibiotic, actinorhodin, although S. lividans normally does not produce this antibiotic. Genetic analyses revealed that a streptomycin-resistant mutation str-6 in strain TK24 is responsible for induction of antibiotic synthesis. DNA sequencing showed that str-6 is a point mutation in the rpsL gene encoding ribosomal protein S12, changing Lys-88 to Glu. Gene replacement experiments with the Lys88-->Glu str allele demonstrated unambiguously that the str mutation is alone responsible for the activation of actinorhodin production observed. In contrast, the strA1 mutation, a genetic marker frequently used for crosses, did not restore actinorhodin production and was found to result in an amino acid alteration of Lys-43 to Asn. Induction of actinorhodin production was also detected in strain TK21, which does not harbor the str-6 mutation, when cells were incubated with sufficient streptomycin or tetracycline to reduce the cell's growth rate, and 40 and 3% of streptomycin- or tetracycline-resistant mutants, respectively, derived from strain TK21 produced actinorhodin. Streptomycin-resistant mutations also blocked the inhibitory effects of relA and brgA mutations on antibiotic production, aerial mycelium formation or both. These str mutations changed Lys-88 to Glu or Arg and Arg-86 to His in ribosomal protein S12. The decrease in streptomycin production in relC mutants in Streptomyces griseus could also be abolished completely by introducing streptomycin-resistant mutations, although the impairment in antibiotic production due to bldA (in Streptomyces coelicolor) or afs mutations (in S. griseus) was not eliminated. These results indicate that the onset and extent of secondary metabolism in Streptomyces spp. is significantly controlled by the translational machinery.


Identification of in vivo expressed vaccine candidate antigens from Staphylococcus aureus.
For the design of potent subunit vaccines, it is of paramount importance to identify all antigens immunologically recognized by a patient population infected with a pathogen. We have developed a rapid and efficient procedure to identify such commonly recognized antigens, and here we provide a comprehensive in vivo antigenic profile of Staphylococcus aureus, an important human pathogen. S. aureus peptides were displayed on the surface of Escherichia coli via fusion to one of two outer membrane proteins (LamB and FhuA) and probed with sera selected for high Ab titer and opsonic activity. A total of 60 antigenic proteins were identified, most of which are located or predicted to be located on the surface of the bacterium or secreted. The identification of these antigens and their reactivity with individual sera from patients and healthy individuals greatly facilitate the selection of promising vaccine candidates for further evaluation. This approach, which makes use of whole genome sequence information, has the potential to greatly accelerate and facilitate the formulation of novel vaccines and is applicable to any pathogen that induces Abs in humans and/or experimental animals.


Annual variability in seed production by woody plants and the masting concept: reassessment of principles and relationship to pollination and seed dispersal.
By analyzing 296 published and unpublished data sets describing annual variation in seed output by 144 species of woody plants, this article addresses the following questions. Do plant species naturally fall into distinct groups corresponding to masting and nonmasting habits? Do plant populations generally exhibit significant bimodality in annual seed output? Are there significant relationships between annual variability in seed production and pollination and seed dispersal modes, as predicted from economy of scale considerations? We failed to identify distinct groups of species with contrasting levels of annual variability in seed output but did find evidence that most polycarpic woody plants seem to adhere to alternating supra-annual schedules consisting of either high or low reproduction years. Seed production was weakly more variable among wind-pollinated taxa than animal-pollinated ones. Plants dispersed by mutualistic frugivores were less variable than those dispersed by either inanimate means or animals that predominantly behave as seed predators. We conclude that there are no objective reasons to perpetuate the concept of mast fruiting in the ecological literature as a shorthand to designate a distinct biological phenomenon. Associations between supra-annual variability in seed output and pollination and seed dispersal methods suggest the existence of important reproductive correlates that demand further investigation.


Update on the efficacy and tolerability of meropenem in the treatment of serious bacterial infections.
Meropenem is a carbapenem antibiotic approved by the US Food and Drug Administration for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and pediatric bacterial meningitis (in patients >or=3 months of age). In clinical trials, it also has shown efficacy as initial empirical therapy for the treatment of nosocomial pneumonia. Unlike other beta-lactam antibiotics, including third-generation cephalosporins, carbapenems have shown activity against extended-spectrum beta-lactamase-producing and AmpC chromosomal beta-lactamase-producing bacteria. Compared with imipenem, meropenem is more active against gram-negative pathogens and somewhat less active against gram-positive pathogens, and it does not require coadministration of a renal dehydropeptidase inhibitor. In most comparative trials, clinical and bacteriological response rates with imipenem and meropenem were similar. Compared with clindamycin/tobramycin, meropenem is associated with a reduced length of hospital stay and a shorter duration of therapy among patients with complicated intra-abdominal infections. Meropenem is well tolerated by children and adults and has an acceptable safety profile. Alternative meropenem dosing strategies for the optimization of outcomes are under investigation.


Craniofacial morphology in Turner syndrome.
The aim of the present investigation was to analyze craniofacial morphology in adults with Turner syndrome and to compare the morphology in patients with 45,X karyotypes to that found in subjects with other X-chromosome aberrations. A comparison between 41 Turner patients and a control group of 51 normal adult women revealed significant differences regarding craniofacial size and morphology. The calvarium, maxilla, and mandible were smaller in Turner syndrome patients and the cranial base was shorter and flattened. The maxilla and the mandible were retrognathic and posteriorly inclined in relation to the cranial base. Sagittal jaw relationship and overjet was greater in Turner syndrome. In the craniocervical area seven syndrome patients presented anomalies. Craniofacial morphology did not differ in 45,X cases and Turner patients with other X-chromosome aberrations. It was concluded that the posterior inclination and retrognathism of the maxilla and the mandible in Turner syndrome could be related to the altered shape of the cranial base.


Detection of Francisella tularensis by the polymerase chain reaction.
Francisella tularensis is the causative agent of tularaemia. Effective antibiotic treatment of tularaemia is now available, but the early diagnosis of tularaemia remains a problem. Four primers (three pairs) were designed to detect F. tularensis by the polymerase chain reaction (PCR), based on the previously published nucleotide sequence of T-cell epitopes of a F. tularensis membrane protein. Amplification of purified F. tularensis chromosomal DNA with the three pairs of primers resulted in three different products with sizes consistent with those predicted from sequence data (211 bp, 347 bp and 568 bp). The specificity of the PCR was confirmed as no amplification was detected with a range of other bacteria. The sensitivity of the PCR was determined with limiting dilution PCR and viable counts. The preliminary application of the PCR to the detection of F. tularensis in aerosols and experimentally infected mice was investigated. Comparison of the results with those from traditional culture indicated that PCR was more sensitive. The animal challenge test showed that, 24 h after inoculation with 15 cfu of F. tularensis, 38 (82.6%) of 46 blood samples were positive by PCR, whereas only 22 (47.8%) were positive by culture. The results showed that PCR is a helpful tool for the detection of F. tularensis in blood, liver and spleen which should enable the rapid confirmation of clinical diagnoses of tularaemia.


Blood count in new onset atrial fibrillation after acute myocardial infarction - a hypothesis generating study.
Atrial fibrillation (AF) is a common complication after acute myocardial infarction (AMI) and associated with increased morbidity and mortality. Previous studies identified high white and red blood cell count as potential risk factors for new onset AF. The objective of this retrospective, nested case-control study was to examine the association of different parameters of the blood count with the development of new onset of AF after AMI. A total of 66 consecutive patients with new onset AF after AMI and 132 sex and age matched controls were enrolled into the study and analyzed whether parameters of the blood count, including leukocytes, platelets, haemoglobin, haematocrit or erythrocyte count, are associated with the occurrence of AF after AMI. All AMI patients had undergone coronary angiography. Patients with post-AMI AF displayed significantly higher levels of haemoglobin (14.2 g/dl, IQR 12.4-15 vs. 12.9 g/dl, IQR 11.7-13.8; P< 0.001), haematocrit (41.7 %, IQR 36.6-44.3 vs. 38.7 %, IQR 34.7-41.5; P 0.0015), and erythrocyte count (4.6 T/l, IQR 4.1-5 vs. 4.2 T/l, IQR 3.9-4.65; P< 0.001). In the unadjusted and adjusted logistic regression analysis, the blood parameters most strongly associated with the outcome were serum haemoglobin (crude OR 2.20, 95% CI 1.40- 3.47, P 0.001; adjusted OR 3.82, 95% CI 1.71- 8.54, P 0.001) and erythrocyte count (crude OR 2.10, 95% CI 1.36-3.22, P 0.001; adjusted OR 3.79, 95% CI 1.73- 8.33, P 0.001), whereas haematocrit did not reach statistical significance. This study shows a significant independent association between serum haemoglobin, haematocrit, erythrocyte count and occurrence of AF after AMI. However, the pathophysiologic mechanism underlying these associations and its potential clinical applicability need to be further elucidated.


Inhaled tigecycline is effective against Mycobacterium abscessus in vitro and in vivo.
Mycobacterium abscessus causes chronic pulmonary infections. Owing to its resistance to most classes of antibiotics, treatment is complex and cure rates are only 45%. Tigecycline is active against M. abscessus, but severe toxicity and the need for IV administration limit its use. To assess the potential of inhaled tigecycline as a treatment for M. abscessus pulmonary disease, by measuring its efficacy in a mouse model of chronic M. abscessus pulmonary disease, establishing the intracellular activity of tigecycline against M. abscessus in human macrophages and measuring the activity of tigecycline in the sputum of cystic fibrosis patients. We infected GM-CSF knockout mice with M. abscessus by intrapulmonary aerosol. Infected mice were treated with tigecycline in 0.25, 1.25 and 2.5 mg doses, by inhalation, or untreated, for 28 days. Tigecycline was added to human peripheral blood-derived macrophages infected with M. abscessus to assess its intracellular activity. We performed a time-kill kinetics experiment of tigecycline against M. abscessus with and without sputum of cystic fibrosis patients. Inhaled tigecycline proved highly effective against M. abscessus in GM-CSF knockout mice. The effect was dose dependent. Tigecycline showed potent activity against M. abscessus in macrophages and retained most of its activity in the presence of sputum of cystic fibrosis patients. Inhaled tigecycline may represent a viable treatment option for M. abscessus pulmonary disease, where treatment outcomes are currently very poor. A stable and safe formulation is required to proceed to further pharmacodynamic studies and ultimately clinical trials.


Fibronectin matrix assembly is essential for cell condensation during chondrogenesis.
Mesenchymal cell condensation is the initiating event in endochondral bone formation. Cell condensation is followed by differentiation into chondrocytes, which is accompanied by induction of chondrogenic gene expression. Gene mutations involved in chondrogenesis cause chondrodysplasias and other skeletal defects. Using mesenchymal stem cells (MSCs) in an in vitro chondrogenesis assay, we found that knockdown of the diastrophic dysplasia (DTD) sulfate transporter (DTDST, also known as SLC26A2), which is required for normal cartilage development, blocked cell condensation and caused a significant reduction in fibronectin matrix. Knockdown of fibronectin with small interfering RNAs (siRNAs) also blocked condensation. Fibrillar fibronectin matrix was detected prior to cell condensation, and its levels increased during and after condensation. Inhibition of fibronectin matrix assembly by use of the functional upstream domain (FUD) of adhesin F1 from Streptococcus pyogenes prevented cell condensation by MSCs and also by the chondrogenic cell line ATDC5. Our data show that cell condensation and induction of chondrogenesis depend on fibronectin matrix assembly and DTDST, and indicate that this transporter is required earlier in chondrogenesis than previously appreciated. They also raise the possibility that certain of the skeletal defects in DTD patients might derive from the link between DTDST, fibronectin matrix and condensation.


Mst1/Mst2 regulate development and function of regulatory T cells through modulation of Foxo1/Foxo3 stability in autoimmune disease.
Foxp3 expression and regulatory T cell (Treg) development are critical for maintaining dominant tolerance and preventing autoimmune diseases. Human MST1 deficiency causes a novel primary immunodeficiency syndrome accompanied by autoimmune manifestations. However, the mechanism by which Mst1 controls immune regulation is unknown. In this article, we report that Mst1 regulates Foxp3 expression and Treg development/function and inhibits autoimmunity through modulating Foxo1 and Foxo3 (Foxo1/3) stability. We have found that Mst1 deficiency impairs Foxp3 expression and Treg development and function in mice. Mechanistic studies reveal that Mst1 enhances Foxo1/3 stability directly by phosphorylating Foxo1/3 and indirectly by attenuating TCR-induced Akt activation in peripheral T cells. Our studies have also shown that Mst1 deficiency does not affect Foxo1/3 cellular localization in CD4 T cells. In addition, we show that Mst1(-/-) mice are prone to autoimmune disease, and mutant phenotypes, such as overactivation of naive T cells, splenomegaly, and autoimmune pathological changes, are suppressed in Mst1(-/-) bone marrow chimera by cotransplanted wt Tregs. Finally, we demonstrate that Mst1 and Mst2 play a partially redundant role in Treg development and autoimmunity. Our findings not only identify Mst kinases as the long-searched-for factors that simultaneously activate Foxo1/3 and inhibit TCR-stimulated Akt downstream of TCR signaling to promote Foxp3 expression and Treg development, but also shed new light on understanding and designing better therapeutic strategies for MST1 deficiency-mediated human immunodeficiency syndrome.


Crisis, social support, and the family response: exploring the narratives of young breast cancer survivors.
This article explores how 70 younger women diagnosed with breast cancer draw on social support resources. The authors found that most respondents' core support networks were their families, and social support came in several forms including emotional, tangible, and informational. However, the authors also found that many respondents relied on a distinct form of social support, experiential support, which has not been identified in current research. Experiential support is defined as a relationship with someone who has gone through a similar illness and can help provide firsthand information, insight, and even hope. The authors conclude that experiential support is an important area for future research on social support and health outcomes.


The Effects of Non-Contingent Feedback on the Incidence of Plateau at V̇O2max.
The purpose of this study was to examine the effects of non-contingent feedback in the form of heart rate (HR) on the incidence of plateau at V̇O2max. Ten physically active males (age 24.8 yrs ± 4.2; mass 81.4 ± 9.0 kg; stature 1.80 ± 0.11 m, V̇O2max 53.2 ± 5.8 ml·kg-1.min-1) who were V̇O2max testing naïve but were cognisant as to the heart rate responses to exercise completed four incremental tests to volitional exhaustion, separated by ~72 h for the determination of V̇O2max and gas exchange threshold. The first trial served as a familiarisation with the remaining three being experimental conditions where HR was presented in a screen projection as either the actual response (HR-A) or 10 b·min-1 higher than recorded (HR-H) or 10 b·min-1 lower (HR-L). Throughout all trials V̇O2 was recorded on a breath-by-breath basis with plateau criteria of ≤ 50 ml·min-1. A significant difference was observed for Δ V̇O2 over the final two consecutive 30s sampling periods between HR-A, both HR-L and HR-H (p = 0.049) and for the incidence of plateau response between condition (p = 0.021). An additional significant difference was observed for sub-maximal Δ V̇O2 responses between HR-A and HR-H (p = 0.049) and HR-A and HR-L (p = 0.006). Non-significant differences were observed for all other criteria. These data indicate that when presented with non-contingent feedback in the form of HR, that the perceptually orientated pacing schema becomes disrupted promoting a sparing of the finite anaerobic capacity to compensate for the imbalance between the afferent signal and perception of effort.


Immobilized-enzyme reactors integrated with capillary electrophoresis for pharmaceutical research.
Enzymes play an essential role in many aspects of pharmaceutical research as drug targets, drug metabolizers, enzyme drugs and more. In this specific field, enzyme assays are required to meet a number of specific requirements, such as low cost, easy automation, and high reliability. The integration of an immobilized-enzyme reactor to capillary electrophoresis represents a unique approach to fulfilling these criteria by combining the benefits of enzyme immobilization, that is, increased stability and repeated use, as well as the minute sample consumption, short analysis time, and efficient analysis provided by capillary electrophoresis. In this review, we summarize, analyze, and discuss published works where pharmaceutically relevant enzymes were used to prepare capillary electrophoresis-integrated immobilized-enzyme reactors in an online manner. The presented assays are divided into three distinct groups based on the drug-enzyme relationship. The first, more extensively studied group employs enzymes that are considered to be therapeutic targets, the second group of assays present tools to assess drug metabolism and the third group assesses enzyme drugs. Furthermore, we examine various methods of enzyme immobilization and their implications for assay properties.


Benefits of modest weight or waist circumference loss in a remote North Queensland Indigenous population.
To quantify the potential benefit to individuals of differing magnitudes of weight or waist circumference loss in an Indigenous population. Data were from the Well Person's Health Check, a cohort study in 19 rural Indigenous communities in Far North Queensland. Baseline data were collected between 1998 and 2000 from 2,583 people aged 15 to 75, an estimated participation rate of 44.5%. Follow-up data were collected between 2004 and 2007 from 729 participants. Associations between change in weight and waist circumference for those who were overweight or obese (n=486) with changes in serum lipids, fasting glucose, blood pressure and Gamma-Glutamyltransferase (GGT) were estimated using linear regression. Weight or waist circumference loss was associated in a dose response fashion with blood pressure reduction (e.g. 10% or greater weight loss compared with no weight loss was associated with reduction of 11.3 mmHg systolic (95% confidence interval -17.8, -4.8). Those with greater waist circumference loss had a greater reduction in GGT (-8.3, 95% confidence interval -23.5, 6.8) but there was no apparent increase in GGT reduction with increasing weight loss, although these were measured with low precision. There was no apparent effect of either weight or waist circumference loss on serum lipids and fasting glucose in this population. This study shows potentially large beneficial effects of weight or waist circumference loss over several years in a remote living Indigenous cohort. The associations were large enough to be of clinical benefit, despite weight loss being modest for most.


MHC-genotype of progeny influenced by parental infection.
In a previous series of in vitro fertilization experiments with mice we found non-random combination of major histocompatibility complex (MHC) haplotypes in the very early embryos. Our results suggested that two selection mechanisms were operating: (i) the eggs selected specific sperm; and (ii) the second meiotic division in the eggs was influenced by the type of sperm that entered the egg. Furthermore, the proportion of MHC-heterozygous embryos varied over time, suggesting that non-random fertilization was dependent on an external factor that changed over time. As a higher frequency of heterozygous individuals correlated with an uncontrolled epidemic by MHV (mouse hepatitis virus), we suggested that MHV-infection might have influenced the outcome of fertilization. Here, we present an experiment that tests this hypothesis. We infected randomly chosen mice with MHV and sham-infected control mice five days before pairing. We recovered the two-cell embryos from the oviduct, cultured them until the blastocyst stage, and determined the genotype of each resulting blastocyst by polymerase chain reaction. We found the pattern that we expected from our previous experiments: virus-infected mice produced more MHC-heterozygous embryos than sham-infected ones. This suggests that parents are able to promote specific combinations of MHC-haplotypes during fertilization according to the presence or absence of a viral infection.


Crosstalk Between Aging, Circadian Rhythm, and Melatonin.
Circadian rhythms (CRs) are 24-hour periodic oscillations governed by an endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN), which organizes the physiology and behavior of organisms. Circadian rhythm disruption (CRD) is also indicative of the aging process. In mammals, melatonin is primarily synthesized in the pineal gland and participates in a variety of multifaceted intracellular signaling networks and has been shown to synchronize CRs. Endogenous melatonin synthesis and its release tend to decrease progressively with advancing age. Older individuals experience frequent CR disruption, which hastens the process of aging. A profound understanding of the relationship between CRs and aging has the potential to improve existing treatments and facilitate development of novel chronotherapies that target age-related disorders. This review article aims to examine the circadian regulatory mechanisms in which melatonin plays a key role in signaling. We describe the basic architecture of the molecular circadian clock and its functional decline with age in detail. Furthermore, we discuss the role of melatonin in regulation of the circadian pacemaker and redox homeostasis during aging. Moreover, we also discuss the protective effect of exogenous melatonin supplementation in age-dependent CR disruption, which sheds light on this pleiotropic molecule and how it can be used as an effective chronotherapeutic medicine.


A Preliminary Study: Antibiotic Resistance of Escherichia coli and Staphylococcus aureus from the Meat and Feces of Various South African Wildlife Species.
This study determined the antibiotic resistance patterns of Escherichia coli and Staphylococcus aureus from the raw meat and feces of three game species from three different farms across South Africa. The Kirby-Bauer disk diffusion method was used according to the Clinical and Laboratory Standards Institute 2018 guidelines. E. coli was tested against ampicillin, ceftazidime, chloramphenicol, streptomycin, sulphafurazole and tetracycline. S. aureus was tested against tetracycline, erthromycin, vancomycin, penicillin, oxacillin and cefoxitin. There were no significant differences in the E. coli antibiotic resistance profiles between the meat and fecal samples (except towards ceftazidime where 5% of the meat isolates were resistant and 0% of the fecal isolates). The S. aureus meat isolates showed high (75%) resistance towards penicillin and on average, 13% were resistant to oxacillin/ cefoxitin, indicating methicillin resistance. The results from this study indicate that there is incidence of antibiotic resistant bacteria from the feces and meat of wildlife species across South Africa, suggesting that cross contamination of the meat occurred during slaughter by antibiotic resistant bacteria from the abattoir personnel or equipment and or from carcass fecal matter. In addition, the results highlight the importance of food safety and hygiene procedures during slaughter to prevent cross-contamination of antibiotic resistant bacteria, as well as pathogens, onto raw meat.


[Method of isolating photochemically active pigmet-proteolipid complexes from chloroplasts].
The paper deals with the chromatography isolation method of pigment-lipoprotein complexes of photosystem I and II of pea chloroplasts on the DEAE-cellulose. The componenet composition and photochemical properties of isolated complexes are compared with the data available in literature concerning similar objects. The question about the use of pigment-lipoprotein complexes as the model systems for investigating structure organization and functional characteristics of different parts of the chloroplast photosynthetic apparatus is under discussion.


Putting order into the development of sensitivity to global motion.
We studied differences in the development of sensitivity to first-versus second-order global motion by comparing the motion coherence thresholds of 5-year-olds and adults tested at three speeds (1.5, 6, and 9 degrees s(-1)). We used Random Gabor Kinematograms (RGKs) formed with luminance-modulated (first-order) or contrast-modulated (second-order) concentric Gabor patterns with a sinusoidal spatial frequency of 3c deg(-1). To achieve equal visibility, modulation depth was set at 30% for first-order Gabors and at 100%, for second-order Gabors. Subjects were 24 adults and 24 5-year-olds. For both first- and second-order global motion, the motion coherence threshold of 5-year-olds was less mature for the slowest speed (1.5 degrees s(-1)) than for the two faster speeds (6 and 9 degrees s(-1)). In addition, at the slowest speed, the immaturity was greater for second-order than for first-order global motion. The findings suggest that the extrastriate mechanisms underlying the perception of global motion are different, at least in part, for first- versus second-order signals and for slower versus faster speeds. They also suggest that those separate mechanisms mature at different rates during middle childhood.


Mechanisms of sodium retention in heart failure: relation to the renin-angiotensin-aldosterone system.
Renal plasma flow (RPF), glomerular filtration rate (GFR), renal proximal tubular delivery of sodium and water evaluated by lithium clearance, and hormonal parameters were measured in 12 patients with congestive heart failure NYHA class II-IV before and after captopril treatment for 4 wk and in 13 healthy control subjects. RPF and GFR were significantly decreased in heart failure, whereas the filtration fraction (FF) was increased. Treatment with captopril increased RPF and decreased FF, whereas GFR was unchanged. Total and fractional urinary excretion of sodium were reduced in the patients compared with the controls, but increased after captopril. Fractional excretion of lithium was normal in heart failure and was increased by captopril. Atrial natriuretic peptide, guanosine 3',5'-cyclic monophosphate, and aldosterone in plasma were significantly elevated in heart failure and were reduced by treatment with captopril. Plasma renin activity was increased in patients, correlated inversely with RPF, and increased further after captopril treatment. It is concluded that the reduced sodium excretion in heart failure was caused by a combination of diminished glomerular filtration and enhanced tubular reabsorption beyond the proximal tubule and that treatment with captopril increased urinary sodium excretion partly due to an attenuated sodium reabsorption in the proximal tubule. The present data in patients with congestive heart failure are consistent with an increased intrarenal angiotensin II generation and an elevated plasma level of aldosterone being involved in the pathogenesis of the glomerular hemodynamic changes and the enhanced distal tubular reabsorption, respectively.


Osmotic stress activates phosphatidylinositol-3,5-bisphosphate synthesis.
Inositol phospholipids play multiple roles in cell signalling systems. Two widespread eukaryotic phosphoinositide-based signal transduction mechanisms, phosphoinositidase C-catalysed phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) hydrolysis and 3-OH kinase-catalysed PtdIns(4,5)P2 phosphorylation, make the second messengers inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) sn-1,2-diacylglycerol and PtdIns(3,4,5)P3. In addition, PtdIns(4,5)P2 and PtdIns3P have been implicated in exocytosis and membrane trafficking. We now show that when the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe are hyperosmotically stressed, they rapidly synthesize phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2) by a process that involves activation of a PtdIns3P 5-OH kinase. This PtdIns(3,5)P2 accumulation only occurs in yeasts that have an active vps34-encoded PtdIns 3-OH kinase, showing that this latter kinase makes the PtdIns3P needed for PtdIns(3,5)P2 synthesis and indicating that PtdIns(3,5)P2 may have a role in sorting vesicular proteins. PtdIns(3,5)P2 is also present in mammalian and plant cells: in monkey Cos-7 cells, its labelling is inversely related to the external osmotic pressure. The stimulation of a PtdIns3P 5-OH kinase-catalysed synthesis of PtdIns(3,5)P2, a molecule that might be a new type of phosphoinositide 'second messenger, thus appears to be central to a widespread and previously uncharacterized regulatory pathway.


The application of Compont gel in chronic obstructive jaundice rats model.
To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis. 90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology. Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group. Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.