Production and Administration of Therapeutic Mesenchymal Stem/Stromal Cell (MSC) Spheroids Primed in 3-D Cultures Under Xeno-free Conditions.
Mesenchymal stem/stromal cells (MSCs) hold great promise in bioengineering and regenerative medicine. MSCs can be isolated from multiple adult tissues via their strong adherence to tissue culture plastic and then further expanded in vitro, most commonly using fetal bovine serum (FBS). Since FBS can cause MSCs to become immunogenic, its presence in MSC cultures limits both clinical and experimental applications of the cells. Therefore, studies employing chemically defined xeno-free (XF) media for MSC cultures are extremely valuable. Many beneficial effects of MSCs have been attributed to their ability to regulate inflammation and immunity, mainly through secretion of immunomodulatory factors such as tumor necrosis factor-stimulated gene 6 (TSG6) and prostaglandin E2 (PGE2). However, MSCs require activation to produce these factors and since the effect of MSCs is often transient, great interest has emerged to discover ways of pre-activating the cells prior to their use, thus eliminating the lag time for activation in vivo. Here we present protocols to efficiently activate or prime MSCs in three-dimensional (3D) cultures under chemically defined XF conditions and to administer these pre-activated MSCs in vivo. Specifically, we first describe methods to generate spherical MSC micro-tissues or 'spheroids' in hanging drops using XF medium and demonstrate how the spheres and conditioned medium (CM) can be harvested for various applications. Second, we describe gene expression screens and in vitro functional assays to rapidly assess the level of MSC activation in spheroids, emphasizing the anti-inflammatory and anti-cancer potential of the cells. Third, we describe a novel method to inject intact MSC spheroids into the mouse peritoneal cavity for in vivo efficacy testing. Overall, the protocols herein overcome major challenges of obtaining pre-activated MSCs under chemically defined XF conditions and provide a flexible system to administer MSC spheroids for therapies.


Multidetector computed tomography and blunt thoracoabdominal trauma.
Computed tomography has had an increasing role in the evaluation of patients after blunt trauma. Important findings in thoracic trauma include acute traumatic aortic injury, pneumothorax, hemothorax, pulmonary contusions and lacerations, mediastinal hematoma, and diaphragmatic rupture. The solid abdominal viscera may lacerate; infarct; or suffer vascular, ductal, or pyelocalyceal disruption. The bladder and intestines may rupture. In abdominal pelvic trauma, the direction of applied force often results in an identifiable constellation of injuries. This article reviews how multidetector computed tomography (MDCT) is used in the trauma patient. Technical advances of increased cephalocaudad coverage speed and improved z-axis resolution intrinsic to MDCT, together with effective contrast utilization, make MDCT invaluable in the setting of trauma.


[Treatment principles for the metabolic syndrome].
GENERAL PRINCIPLES: The general progression throughout the world in type 2 diabetes has lead medical Authorities to develop mass screening but also prevention measures, notably for "high-risk" subjects such as those exhibiting a metabolic syndrome. Studies on the topic have shown that preventing type 2 diabetes was possible via lifestyle changes, possibly in association with pharmacological therapy (metformine, acarbose, thiazolidinediones, orlistat). The other therapeutic stakes in the context of the metabolic syndrome also concern the management of all identified cardiovascular risk factors. REGARDING HYPERTENSION: there are currently no specific recommendations available in the framework of metabolic syndrome, with regard to lowering blood pressure and how to obtain it. However there is evidence that patients may benefit from the strict control of blood pressure (< or =130/85 mm Hg). REGARDING DYSLIPIDEMIA: LDL cholesterol remains the main target, with a goal depending on individual cardiovascular risk (<1 or 1.30 g/l in the case of metabolic syndrome). Statins are of major interest in this context. However, it is also established that normalisation of triglycerides and HDL cholesterol contributes to the improvement of cardiovascular Issues. The respective indications for fibrates or fibrate/statin associations still need to be defined in primary as in secondary prevention.


Atypical primary malignant melanoma originating in the spinal canal: A case report and literature review.
Central nervous system (CNS) malignant melanomas are rare tumors of the CNS that are thought to arise from aberrant changes in melanocytes of the neural crest or melanocytic elements of the pia mater during early embryonic development. As a rare type of CNS malignant melanoma, only a few cases of primary malignant melanoma in the spinal canal have been reported thus far. The majority of these studies have reported on the diagnosis, radiographic features and gross total resection of primary spinal canal malignant melanoma; however, the prognosis and ideal treatment of patients with residual tumors remain elusive. The current study presented the rare case of a patient with primary malignant melanoma originating from the thoracic spinal canal, without any history of irradiation exposure and with an incompletely resected tumor. Disease-free survival of >2.5 years was observed in this patient who was treated with concurrent chemoradiotherapy followed by adjuvant chemotherapy with temozolomide and bevacizumab.


Advanced Imaging of Brain Metastases: From Augmenting Visualization and Improving Diagnosis to Evaluating Treatment Response.
Early detection of brain metastases and differentiation from other neuropathologies is crucial. Although biopsy is often required for definitive diagnosis, imaging can provide useful information. After treatment commences, imaging is also performed to assess the efficacy of treatment. Contrast-enhanced magnetic resonance imaging (MRI) is the traditional imaging method for the evaluation of brain metastases, as it provides information about lesion size, morphology, and macroscopic properties. Newer MRI sequences have been developed to increase the conspicuity of detecting enhancing metastases. Other advanced MRI techniques, that have the capability to probe beyond the anatomic structure, are available to characterize micro-structures, cellularity, physiology, perfusion, and metabolism. Artificial intelligence provides powerful computational tools for detection, segmentation, classification, prediction, and prognosis. We highlight and review a few advanced MRI techniques for the assessment of brain metastases-specifically for (1) diagnosis, including differentiating between malignancy types and (2) evaluation of treatment response, including the differentiation between radiation necrosis and disease progression.


Analysis of an anxiolytic technique applied in 1179 patients undergoing oral surgery.
The aim of this study was to evaluate the effects of sedation with benzodiazepines in a large population of patients undergoing oral surgery and age-related implications. A group of 1 179 consecutive patients undergoing oral surgery in the Dental Clinic of the University of Padua between 2001 and 2003 was evaluated by analysing their anaesthesiological records. The patients were divided into 5 age groups. All were pre-sedated with chlordemethyldiazepam per os, while induction of maximum subjective tranquillity was obtained with fractionated doses of intravenous diazepam. Arterial pressure (AP), heart rate (HR), anxiety level, pathologies, drugs taken, types of intervention, techniques of loco-regional anaesthesia, immediately preoperative AP and HR and tranquillity, intraoperative AP and HR, data regarding postoperative psychomotor recovery, complications and drugs used for the treatment of perioperative pain, were evaluated in each group. Most of the patients (679) were in the 45-64 year-old group. Cardiovascular, respiratory and digestive pathologies proved to be age-dependent. Control AP and HR respectively increased and decreased with age. The doses of chlordemethyldiazepam used induced age-dependent preoperative tranquillity levels. The doses of i.v. diazepam necessary to obtain maximal preoperative subjective tranquillity fell as a function of age. The AP and HR values respectively increased during intervention and decreased in the first hour of intervention. Normal psychomotor recovery was less evident in older patients. The most significant corrective intraoperative interventions consisted of the administration of sublingual hypotensive drugs and in the immediate treatment of some cases of orthostatic hypotension and vaso-vagal syncope. The sedation technique and the antistress procedures employed proved safe and the intra- or postoperative complications almost non-existent. The variations observed in the parameters considered are compatible with the greater age of the treated subjects.


Distribution of Iron Uptake Systems Encoding Genes Among the Clinical Isolates of Escherichia coli Compared to Foodstuffs Isolates.
Bacteria require iron ions to grow and infect the host, which, by using iron uptake systems, acquire free iron from their host cell. Escherichia coli is one of the most important pathogens to cause food poisoning and clinical infections. The aim of this study was to assess the distribution of iron uptake systems encoding genes in clinical isolates of E.coli compared to food samples isolates. This investigation was conducted to determine the prevalence of E. coli isolated from various sources of food and clinical specimens. The E. coli isolates confirmed by the standard microbiological methods. The isolates were examined for the presence of iut A and iuc A genes by specific primers using the polymerase chain reaction technique. A total of 100 and 50 isolates of E. coli were collected from clinical samples and foodstuffs, respectively. The prevalence of E. coli in the food and clinical samples was 33.33% and 64.10%, respectively. The frequency of iut A and iuc A genes in the food and clinical isolates were 76%-84% and 86% - 83%, respectively. Our results showed that the prevalence of E. coli isolates with iut A and iuc A genes was relatively higher compared to many previous studies. The existence of these genes in E. coli strains is likely to be related to pathogenicity in those strains, which requires further studies in the future.


Epidemiological Characteristics of Human Anthrax - China, 2018-2021.
The epidemic of human anthrax is at a low level in China in recent years, but the reported incidence increased in 2021. In order to understand the current landscape of research and knowledge about anthrax in China, the epidemiological characteristics of anthrax in humans from 2018 to 2021 were analyzed and the prevention and control suggestions were proposed. Surveillance data of anthrax in humans and livestock, together with human outbreaks data during 2018-2021, were collected and analyzed by descriptive statistics methods. The number and proportion of outbreaks, cases and deaths by provincial-level administrative divisions (PLADs), clinical types, and contributing factors were calculated. A total of 1,244 cases of human anthrax and 53 outbreaks were reported from 2018 to 2021 in China. While the incidence of anthrax declined from 2018 to 2020, it increased in 2021. The regions of anthrax were mainly located in the west and the northeast PLADs of China, though cases were reported in some central and eastern PLADs in 2021. Young and middle-aged men involved in animal husbandry were found to be at a higher risk of anthrax. All the reported outbreaks were associated with the exposure of infected livestock. A total of 296 livestock anthrax cases were reported. The increased incidence and wider geographical distribution of human anthrax in 2021 were found to be the result of inadequate supervision of diseased animals as well as updated diagnostic criteria. As such, the monitoring of risk factors and emergency preparation procedures should be strengthened at the national level. In addition, it is also critical to strengthen health education for high-risk occupational groups and strengthen professional training for local clinicians. Finally, more measures should be carried out to strengthen anthrax surveillance in livestock husbandry.


A 75-year-old woman with primary antiphospholipid syndrome presenting with livedoid vasculopathy.
The clinical presentation of primary antiphospholipid syndrome (PAPS) can vary, often mimicking many other medical conditions. Therefore, it is difficult to diagnose at the first presentation because of the absence of classical symptoms. We described an unusual presentation of PAPS mimicking livedoid vasculopathy (LV), where the only diagnostic clue at the initial presentation was skin lesions in both lower legs. A 75-year-old Han Chinese woman presented with features mimicking LV, without clinically significant antiphospholipid syndrome (APS). After many relevant laboratory examinations and histopathological examination, the patient was finally diagnosed as having PAPS. LV should not be treated as an independent disease, but as a skin manifestation. A high degree of suspicion of APS is needed in patients presenting or diagnosed with LV. Early interventions are necessary to prevent and reduce the risk of thrombosis. This case presents a rare clinical manifestation and provides significant information on PAPS.


A case of shigellosis with intractable septic shock and convulsions.
Although shigellosis is a potentially fatal disease that may cause a number of extra-intestinal manifestations, intractable septic shock is an unusual complication. Here we describe a 6-month-old infant who developed severe septic shock and convulsions during an episode of dysentery caused by multidrug-resistant Shigella dysenteriae. The case presentation demonstrates how shigellosis can lead to rare and potentially misleading complications such as septic shock when not treated adequately and promptly.


[Molecular epidemiology of infectious diseases].
Data on molecular epidemiology of bacterial infections is summarized. The term definitions of "molecular epidemiology", "taxonomic species" are given, the limits and species structure of prokaryotes are described. The basic mechanisms of the prokaryotes variability in the epidemic process, as well as the possibilities and limitations of microbiological, molecular-biological and population--genetic typing methods, are characterized. The tactics of molecular-biological studies in analyzing the population structure on the global, regional and local levels is presented. The economic effectiveness of measures taken with due consideration of information on the clonal structure of causative agents of hospital infections is shown.


Vascular endoscopic and macroscopic observations after crush stenting of coronary artery bifurcations in pigs.
The crush stent technique has recently been proposed to limit the development of restenosis between drug-eluting stents implanted at coronary artery bifurcations. We studied the stent expansion, apposition to the vessel, and aspect of the overlapping stents after in vivo crush stent implantation. Crush stent implantation was performed at coronary bifurcations in anesthetized swines. The treated sites were examined using intravascular ultrasound and a vascular endoscope. The stents removed from the vessel were analyzed macroscopically. After final kissing balloon inflation, an adequate apposition of the stent to the vessel wall was confirmed by vascular endoscopy and visual inspection. However, the side-branch stent was narrowed at the site of stent overlap, and the overlapping stents in the main branch created a metal mass, which could promote the development of thrombosis. The technique of crush stent implantation with additional kissing balloon inflation is feasible and promising. However, it may be limited by thrombosis and restenosis at the carina because of stent overlapping and potential incomplete apposition. Additional studies are needed to confirm the safety and long-term clinical results of this technique.


Na+-Ca2+ exchange activity in rat skeletal myotubes: effect of lithium ions.
The whole-cell patch-clamp technique coupled with intracellular [Ca2+] measurements was used to investigate the sodium-calcium exchange mechanism in rat skeletal muscle cells in primary culture. Replacing external Na+ ions with Li+ or N-methyl-D-glucamine (NMDG+) ions generated outward currents which were correlated with significant increases of free cytosolic-calcium concentration. These results strongly argue for a functional Na+-Ca2+ exchange mechanism working in its reverse mode. Moreover, the outward currents were sensitive to the new compound KB-R7943 (10 microM), which has been shown to be a potent inhibitor of the sodium-calcium exchanger. Outward Na+-Ca2+ exchange current densities were reduced in the presence of external Li+ as compared to those measured in the presence of NMDG+. After replacing internal sodium by lithium ions, rapid changes of external lithium concentrations generated sarcolemmal currents which were accompanied by subsequent variations of intracellular calcium activity. The currents were dependent on extracellular Li+ with a half-maximal activation at 67 mM and a Hill coefficient of 2.9. This work shows that the Na+-Ca2+ exchanger is able to significantly influence the myoplasmic calcium concentration of cultured rat myotubes. On the other hand, our results suggest that Li+ ions may substitute Na+ ions to catalyse an electrogenic Li+/Ca2+ counter transport.


Visiting multiple sites for immunization and vaccine coverage levels of preschool children in 3 urban clinics: potential indicator of record scatter?
Record scatter is a clinic-level impediment to accurately reporting immunization coverage levels but may be attributed to certain patient characteristics. We determine the association between visiting multiple sites for immunization and underimmunization among urban clinic patients. After collecting immunization histories for patients aged 3-35 months, caregivers were surveyed by telephone. 159/483 caregivers (32.9%) were interviewed. Visiting > 2 sites for immunizations was associated with underimmunization, adjusted Odds Ratio (95% Confidence Interval)=2.7 (1.2-6.5). An interruption in health insurance showed a trend toward association with visiting > or = 2 sites. Our results support the need for working registries, clinic outreach, and continued evaluation of both.


Measuring the economic burden for TB patients in the End TB Strategy and Universal Health Coverage frameworks.
Tuberculosis (TB) is a disease of poverty. Ensuring access to health care without the risk of financial hardship due to out-of-pocket health care expenditures (Universal Health Coverage [UHC]) is essential for providing accessible care to underprivileged populations, but this is not enough. The End TB Strategy promotes both patient-centred TB services and social protection measures, which aim to mitigate the economic hardship faced by TB patients and their households due to direct medical and non-medical expenditures, as well as to lost income. The strategy includes a target that no families should face catastrophic total costs due to TB. The indicator linked to this target aims to capture the total economic burden linked to TB care, and thus differs from the 'catastrophic expenditure on health' indicator, a key component of the UHC monitoring framework aligned with the Sustainable Development Goals. Countries, and particularly high TB burden countries, are expected to conduct nationally representative TB patient cost surveys to establish baseline measurements for the catastrophic costs indicator. Findings from these surveys should also help identify entry points for developing policies to ensure better financial and social protection for TB patients. In this paper, we define the key measurable concepts for TB patient cost surveys, notably the types of costs that are captured, and related affordability measures. We discuss methods for measuring these notions in the UHC framework and contrast them with how they are measured in TB patient cost surveys.


Mobilization of Haemophilus influenzae chromosomal markers by an Escherichia coli F' factor.
Filter matings between E. coli K-12 strains carrying an F'::Tn5,Tn9 factor with H. influenzae Rd strains gave rise to kanamycin-chloramphenicol-resistant H. influenzae strains at a frequency of approximately 10(-6). Transfer of the F' factor to H. influenzae was verified by expression of unselected markers in H. influenzae (lac+ or cotransfer of the nonselected antibiotic resistance), physical presence of a high-molecular-weight plasmid in recipient H. influenzae cells, and detection by Southern hybridization analysis of DNA sequences specific for the F' factor replication and partition functions in recipient H. influenzae cells. H. influenzae (F' Tn5,Tn9) strains were capable of transferring kanamycin and chloramphenicol resistances to other H. influenzae strains and were capable of mobilizing H. influenzae chromosomal markers at a low frequency. Insertion of a Tn5 element in the H. influenzae genome near the novobiocin resistance gene increased the frequency of transfer of novobiocin resistance about 30-fold. Transfer of other chromosomal markers also increased, although to a lesser extent, and ordered transfer of chromosomal markers could be demonstrated. Gene transfer was insensitive to DNase I, and transfer of chromosomal (but not F' factor) markers was dependent on the H. influenzae rec-1 and rec-2 gene functions.


CYP17 inhibitors in prostate cancer: latest evidence and clinical potential.
Since androgen signaling plays a pivotal role in the proliferation and metastasis of prostate cancer, androgen deprivation therapy (ADT) or castration therapy is considered the backbone of treatment for newly diagnosed metastatic prostate cancer. However, almost all men experience disease progression on ADT to a state known as metastatic castration-resistant prostate cancer (mCRPC), which continues to be driven by intratumoral androgen synthesis or androgen receptor signaling. Hence, the extragonadal ablation of androgen synthesis from pregnane precursors holds much promise. An inhibitor of cytochrome P450 17α-hydroxy/17,20-lyase (CYP17) enzymes, abiraterone acetate, has already been approved for men with mCRPC. Newer CYP17 inhibitors continue to be developed which are either more selective or have concomitant inhibitory actions on AR signaling. These include VT-464, orteronel, and galeterone. Herein, we focus on the molecular mechanism of action, efficacy, latest evidence, and clinical potential of CYP17 inhibitors in prostate cancer.


Evaluation of Validity, Reliability, and Feasibility of 3 Patient-Reported Foot and Ankle Outcome Measures.
A wide range of patient-reported outcome measures have been developed to assess the impact of foot and ankle pathology on patients' function. In this study, Manchester-Oxford Foot Questionnaire (MOXFQ), Foot and Ankle Ability Measure (FAAM), and Revised-Foot Function Index (R-FFI) scores were assessed independently of their developers for validity, reliability, item bias, acceptability, and feasibility. We prospectively recruited 100 consecutive patients with a range of foot and ankle disorders over a 6-month period. Patients completed a set of 3 questionnaires at initial consultation. Patients were subsequently sent questionnaires in a random order with a prepaid envelope and asked to complete them with 2 to 14 days. To assess feasibility in routine clinical practice, the time taken to complete questionnaires was evaluated in a cohort of 65 patients. The mean age of patients was 51.7 years (range 20 to 85). The majority were females (64 of 96). The internal consistency of all 3 questionnaires was high, suggesting good intercorrelation among the items of each questionnaire. The questionnaires were reproducible and valid. There was strong correlation between the total scores of all 3 questionnaires. There was no item bias on the overall scores by the assumed independent variables such as age, sex, site, and pathology. Form completion rates were 98% for MOXFQ, 89% for FAAM, and 75% for FFI. MOXFQ was the easiest to understand and complete. No significant difference was found in the time taken to complete each questionnaire. All 3 scores correlate with the level of function and have very good reproducibility. For routine use, the MOXFQ has good practical properties of patient acceptability, high item response rate, and ease of completion.


[ANEMIA OF CHRONIC DISEASES AS A SYSTEMIC MANIFESTATION OF CHRONIC PULMONARY OBSTRUCTIVE DISEASE].
Anemia of chronic disease (ACD) is one of the most frequent forms of anemia is often observed in patients with infections, cancer and chronic inflammatory or autoimmune diseases. The underlying mechanisms are complex and include dysregulation of iron homeostasis and erythropoietin production, impaired proliferation of erythroid progenitor cells and reduced life span of red blood cells. Moreover, ACD is often superimposed by malnutrition, bleeding and renal failure. ACD is mediated through inflammatory cytokines and characterized by low serum iron (hypoferremia) and often increased reticuloendothelial stores of iron. ACD is usually normocytic, normochromic anemia, but it can become microcytic and hypochromic as the disease progresses. Hepcidin, the main regulator of iron homeostasis and its synthesis, is inhibited by iron deficiency and stimulated by inflammation. In many patients the disease is associated with several extrapulmonary manifestations regarded as the expression of the systemic inflammatory state of chronic obstructive pulmonary disease (COPD). Recent studies showed that anemia in patients with COPD is more frequent than expected, with its prevalence ranging from 8 to 33%. Systemic inflammation may be an important pathogenic factor, but anemia in COPD can also be the result of a number of factors, such as the treatment with certain drugs (angiotensin-converting enzyme inhibitors or theophylline), endocrine disorders, acute exacerbations and oxygen therapy. Anemia in COPD patients is strongly associated with increased functional dyspnea, decreased exercise capacity and is an independent predictor of mortality. Treatment options to correct anemia used in other chronic diseases, such as congestive heart failure, cancer or chronic kidney disease have not been explored in COPD (i.e. erythropoietic agents, iron supplements or combined therapy). It is not known whether treating the underlying inflammation could improve hematological characteristics. It is important to develop basic diagnostic modalities for this group of patients and formulate methods of anemia correction.


The Transactivating Function 2 (AF-2) of Estrogen Receptor (ER) α is Indispensable for ERα-mediated Physiological Responses and AF-1 Activity.
Estrogen has various physiological functions and the estrogen receptor (ER) is a key regulator of those functions. ERα is a ligand-dependent transcription factor and that activity is mediated by the transactivating function-1 (AF-1) in the N-terminal domain and transactivating function-2 (AF-2) in the C-terminal ligand-binding domain. The functions of ERα AF-1 and AF-2 have been characterized by various in vitro experiments, however, there is still less information about the in vivo physiological functions of ERα AF-1 and AF-2. Recently, we established a genetically mutated ERα AF-2 knock-in mouse (AF2ERKI) that possesses L543A, L544A mutated-ERα. This AF-2 core mutation disrupted AF-2 function and resulted in ERα null phenotypes. This mouse model revealed that proper AF-2 core structure and function are indispensable for ERα-mediated physiological responses and AF-1 functionality. AF2ER mutation reverses the ERα antagonists to agonists and that activity is mediated by AF-1 solely. The pure antagonist, ICI182780/fulvestrant, activated several estrogen-mediated physiological responses in the AF2ERKI mouse. The AF2ERKI mouse model will be able to discern estrogen physiological functions which involve AF-1.


SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling.
Recurrent point mutations in SPOP define a distinct molecular subclass of prostate cancer. Here, we describe a mouse model showing that mutant SPOP drives prostate tumorigenesis in vivo. Conditional expression of mutant SPOP in the prostate dramatically altered phenotypes in the setting of Pten loss, with early neoplastic lesions (high-grade prostatic intraepithelial neoplasia) with striking nuclear atypia and invasive, poorly differentiated carcinoma. In mouse prostate organoids, mutant SPOP drove increased proliferation and a transcriptional signature consistent with human prostate cancer. Using these models and human prostate cancer samples, we show that SPOP mutation activates both PI3K/mTOR and androgen receptor signaling, effectively uncoupling the normal negative feedback between these two pathways.


Theoretical analyses of cellular transmembrane voltage in suspensions induced by high-frequency fields.
A change of the transmembrane voltage is considered to cause biophysical and biochemical responses in cells. The present study focuses on the cellular transmembrane voltage (Δφ) induced by external fields. We detail analytical equations for the transmembrane voltage induced by external high-frequency (above the relaxation frequency of the cell membrane) fields on cells of a spherical shape in suspensions and layers. At direct current (DC) and low frequencies, the cell membrane was assumed to be non-conductive under physiologic conditions. However, with increasing frequency, the permittivity of the cytoplasm/extracellular medium and conductivity of the membrane must be accounted for. Our main work is to extend application of the analytical solution of Δφ to the high-frequency range. We first introduce the transmembrane voltage generated by DC and low-frequency exposures on a single cell. Then, we focus on cell suspensions exposed to high-frequency fields. Using the effective medium theory and the reasonable assumption, the approximate analytical solution of Δφ on cells in suspensions and layers can be derived. Phenomenological effective medium theory equations cannot be used to calculate the local electric field of cell suspensions, so we raised a possible solution based on the Bergman theory.


[Therapy of continuously bleeding oesophageal varices by self expanding metal stents].
We report that haemostasis was obtained by the use of SEMS in two patients with bleeding oesophageal varices which failed conventional therapy (vasoactive drugs, antibiotics, endoscopy, and Sengstaken balloon tamponade). One patient subsequently died of sepsis; the other was treated with TIPS and was discharged.


Main Therapeutic Uses of Some Moroccan Hot Springs' Waters.
Morocco has an important groundwater reserve, especially in the Atlas domain, corresponding to its largest water reservoir. This reserve comes from rainwater infiltrated into rocks and sediments to give rise to mineralized waters feeding many springs and having curative properties, which confer each spa-specific therapeutic indications, based on the medicinal properties of its waters. All over the world, mineral waters of thermal springs have interesting therapeutic uses to cure some diseases; unfortunately, such potential is underexploited in Morocco. This narrative review deals with the distribution of thermal springs in Morocco, the classification of their thermal waters, and their health effects, with the aim to enhance them. For this purpose, previous studies' results on different aspects of thermal waters were searched in the most famous scientific databases, by using targeted specific keywords. Literature has shown that Morocco contains several thermal springs, scattered throughout the Middle Atlas, in the South, and in the Rif, which are regarded as waters of high therapeutic quality, whose thermal cures are often recommended to people suffering from rheumatism and locomotor system's diseases, skin diseases such as eczema and psoriasis, cardiovascular diseases, overweight, or respiratory troubles. However, apart from the unique and real thermal station of Moulay Yacoub, the other thermal springs are exploited in an empirical and artisanal way, mainly by a local population. So, as hydrotherapy constitutes a good choice of natural therapy using water components as a complement or alternative to conventional treatments, a better understanding of the thermal springs' distribution in Morocco, their thermal waters' classification, and their potential health effects may enable their valorization through a better use of their waters.


Using 19F NMR to Investigate Cationic Carbon Dot Association with Per- and Polyfluoroalkyl Substances (PFAS).
There is much concern about per- and polyfluoroalkyl substances (PFAS) based on their environmental persistence and toxicity, resulting in an urgent need for remediation technologies. This study focused on determining if nanoscale polymeric carbon dots are a viable sorbent material for PFAS and developing fluorine nuclear magnetic resonance spectroscopy (19F NMR) methods to probe interactions between carbon dots and PFAS at the molecular scale. Positively charged carbon dots (PEI-CDs) were synthesized using branched polyethyleneimine to target anionic PFAS by promoting electrostatic interactions. PEI-CDs were exposed to perfluorooctanoic acid (PFOA) to assess their potential as a PFAS sorbent material. After exposure to PFOA, the average size of the PEI-CDs increased (1.6 ± 0.5 to 7.8 ± 1.8 nm) and the surface charge decreased (+38.6 ± 1.1 to +26.4 ± 0.8 mV), both of which are consistent with contaminant sorption. 19F NMR methods were developed to gain further insight into PEI-CD affinity toward PFAS without any complex sample preparation. Changes in PFOA peak intensity and chemical shift were monitored at various PEI-CD concentrations to establish binding curves and determine the chemical exchange regime. 19F NMR spectral analysis indicates slow-intermediate chemical exchange between PFOA and CDs, demonstrating a high-affinity interaction. The α-fluorine had the greatest change in chemical shift and highest affinity, suggesting electrostatic interactions are the dominant sorption mechanism. PEI-CDs demonstrated affinity for a wide range of analytes when exposed to a mixture of 24-PFAS, with a slight preference toward perfluoroalkyl sulfonates. Overall, this study shows that PEI-CDs are an effective PFAS sorbent material and establishes 19F NMR as a suitable method to screen for novel sorbent materials and elucidate interaction mechanisms.


Ideal glass transition in a simple two-dimensional lattice model.
We present a simple lattice model showing a glassy behavior. R matrix analysis predicts critical termination of the supercooled fluid branch at density rho(g)=0.1717. This prediction is confirmed by dynamical numerical simulations, showing power-law divergences of relaxation time tau1/2, as well as the four-susceptibility chi4 peak's location and height exactly at the predicted density. The power-law divergence of chi4 continues up to chi4 as high as 10(4). Finite-size scaling study reveals the divergence of the correlation length accompanying the transition.


Gastric motor and sensory function.
Abnormalities of gastric sensory and motor function are considered key players in the pathogenesis of upper gastrointestinal symptoms in functional dyspepsia and in gastroparesis. This review summarizes recent progress in our understanding of normal and pathologic gastric sensory and motor function. Several novel tests have been developed to study gastric sensitivity and meal-induced accommodation, including scintigraphic analysis of meal distribution within the stomach, single photon emission computed tomography of gastric volumes, and nutrient or water challenge tests. Several studies have reported on the occurrence of delayed gastric emptying in functional dyspepsia and in gastroparesis, but the correlation with symptoms was generally poor. The pathways and neurotransmitter involved in gastric hypersensitivity are progressively being unraveled. Several studies have confirmed and focused on increased symptom occurrence after nutrient challenge in functional dyspepsia. The role of the proximal stomach in the control of food intake and the stomach as a target in the treatment of obesity are areas of intense research. Studies have reported on pharmacologic approaches as well as electric stimulation in the treatment of gastric sensorimotor dysfunction. Progress in our understanding of normal and abnormal gastric sensory and motor function may lead to new or improved treatment modalities. Areas of major advances are the study of meal-induced symptoms in functional dyspepsia, unraveling of the role of the stomach in the control of food intake, and the use of gastric electric stimulation in gastroparesis and in obesity.


Semi-automatic forensic approach using mandibular midline lingual structures as fingerprint: a pilot study.
Previous research proposed the use of the mandibular midline neurovascular canal structures as a forensic finger print. In their observer study, an average correct identification of 95% was reached which triggered this study. To present a semi-automatic computer recognition approach to replace the observers and to validate the accuracy of this newly proposed method. Imaging data from Computer Tomography (CT) and Cone Beam Computer Tomography (CBCT) of mandibles scanned at two different moments were collected to simulate an AM and PM situation where the first scan presented AM and the second scan was used to simulate PM. Ten cases with 20 scans were used to build a classifier which relies on voxel based matching and results with classification into one of two groups: "Unmatched" and "Matched". This protocol was then tested using five other scans out of the database. Unpaired t-testing was applied and accuracy of the computerized approach was determined. A significant difference was found between the "Unmatched" and "Matched" classes with means of 0.41 and 0.86 respectively. Furthermore, the testing phase showed an accuracy of 100%. The validation of this method pushes this protocol further to a fully automatic identification procedure for victim identification based on the mandibular midline canals structures only in cases with available AM and PM CBCT/CT data.


A novel role for C3 in antibody-induced red blood cell clearance and antigen modulation.
Hemolytic transfusion reactions (HTRs) due to incompatible red blood cell (RBC) transfusions are a leading cause of transfusion associated death. Although many transfused incompatible RBCs are cleared, some remain in circulation despite the presence of RBC-specific antibodies, potentially due to "antigen modulation." With a goal of better understanding incompatible RBC clearance, we generated a murine model with RBC-specific expression of a clinically significant human antigen (KEL2) known to be involved in antigen modulation as well as in HTRs. Wild-type (WT) recipients transfused with transgenic KEL2 RBCs generated anti-KEL glycoprotein alloantibodies, which fixed complement, led to intravascular hemolysis, and resulted in decreased levels of KEL2 antigen detectable on cells remaining in circulation. Antigen modulation did not appear to solely reflect removal of RBCs with higher antigen expression, because cells continued to display antigen modulation in the absence of significant clearance. Recipients genetically lacking complement exhibited lesser degrees of incompatible RBC clearance and antigen modulation in comparison with WT or FcγR knock-out (KO) animals, suggesting a role for complement in RBC clearance. In summary, this HTR model may serve as a platform to test strategies to downmodulate antigen and inhibit incompatible RBC clearance, thus potentially mitigating transfusion dangers.


Role of bifidobacteria in the hydrolysis of chlorogenic acid.
This study aimed to explore the capability of potentially probiotic bifidobacteria to hydrolyze chlorogenic acid into caffeic acid (CA), and to recognize the enzymes involved in this reaction. Bifidobacterium strains belonging to eight species occurring in the human gut were screened. The hydrolysis seemed peculiar of Bifidobacterium animalis, whereas the other species failed to release CA. Intracellular feruloyl esterase activity capable of hydrolyzing chlorogenic acid was detected only in B. animalis. In silico research among bifidobacteria esterases identified Balat_0669 as the cytosolic enzyme likely responsible of CA release in B. animalis. Comparative modeling of Balat_0669 and molecular docking studies support its role in chlorogenic acid hydrolysis. Expression, purification, and functional characterization of Balat_0669 in Escherichia coli were obtained as further validation. A possible role of B. animalis in the activation of hydroxycinnamic acids was demonstrated and new perspectives were opened in the development of new probiotics, specifically selected for the enhanced bioconversion of phytochemicals into bioactive compounds.


Tuberculous Lymphadenitis Is Associated with Enhanced Baseline and Antigen-Specific Induction of Type 1 and Type 17 Cytokines and Reduced Interleukin-1β (IL-1β) and IL-18 at the Site of Infection.
Tuberculous lymphadenitis (TBL) is characterized by an expansion of Th1 and Th17 cells with altered serum levels of proinflammatory cytokines. However, the cytokine profile at the site of infection, i.e., the affected lymph nodes, has not been examined in detail. To estimate the baseline and mycobacterial antigen-stimulated concentrations of type 1, type 17, and other proinflammatory cytokines in patients with TBL (n = 14), we examined both the baseline and the antigen-specific concentrations of these cytokines before and after chemotherapy and compared them with those in individuals with pulmonary tuberculosis (PTB) (n = 14). In addition, we also compared the cytokine responses in whole blood and those in the lymph nodes of TBL individuals. We observed significantly enhanced baseline and antigen-specific levels of type 1 cytokines (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]) and a type 17 cytokine (interleukin-17 [IL-17]) and significantly diminished baseline and antigen-specific levels of proinflammatory cytokines (IL-1β and IL-18) in the whole blood of TBL individuals compared to those in the whole blood of PTB individuals. Moreover, we also observed a pattern of baseline and antigen-specific cytokine production at the site of infection (lymph node) similar to that in the whole blood of TBL individuals. Following standard antituberculosis (anti-TB) treatment, we observed alterations in the baseline and/or antigen-specific levels of IFN-γ, TNF-α, IL-1β, and IL-18. TBL is therefore characterized by enhanced baseline and antigen-specific production of type 1 and type 17 cytokines and reduced baseline and antigen-specific production of IL-1β and IL-18 at the site of infection.


Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats.
In metabolic syndrome (MetS), previous studies have suggested that cognitive decline is worsened. Among the factors associated with cognition, decreased brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. We previously reported that exercise training with calorie restriction yielded protection against cognitive decline via BDNF in the hippocampus of hypertensive rats. The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). After treatment for 28 days, body weight, insulin, fasting blood glucose, adiponectin, systolic blood pressure, and oxidative stress in the hippocampus were significantly lower, and BDNF expression in the hippocampus was significantly higher in CR and CR+A than in HF. Cognitive performance determined by the Morris water maze test was significantly higher in CR than in HF, whereas the benefit was attenuated in CR+A. In conclusion, calorie restriction protects against cognitive decline via up-regulation of BDNF/TrkB through an antioxidant effect in the hippocampus of dietary-induced obesity rats.


Enzymatic recognition of DNA modifications induced by singlet oxygen and photosensitizers.
DNA modifications induced either by photosensitization (illumination in the presence of methylene blue) or by chemically generated singlet oxygen (thermal decomposition of an 1,4-etheno-2,3-benzodioxin) are recognized and incised by repair endonucleases present in crude bacterial cell extracts. Only a small fraction of the incised modifications are sites of base loss (AP-sites) sensitive to exonuclease III, endonuclease IV from E. coli or to the UV-endonuclease from M. luteus. Cell extracts from E. coli strains overproducing or defective in endonuclease III recognize the modifications induced by illumination in the presence of methylene blue just as well as do those from wild-type E. coli strains. This indicates that dihydropyrimidine derivatives, which are characteristic of hydroxyl radical-induced DNA modifications, are absent. In contrast, most of the modifications induced are not recognized by a cell extract from a fpg strain defective in formamidopyrimidine-DNA glycosylase FPG protein). Furthermore, incision by a cell extract from an E. coli strain overproducing FPG protein takes place at much lower protein concentration than with the wild-type strain. Experiments with purified FPG protein confirm that this enzyme is responsible for the recognition of singlet oxygen-induced DNA base modifications.


[miR-129 in the diagnosis, treatment and prediction of clinical prognosis of prostate cancer].
To explore the value of miR-129 in the diagnosis, treatment and prediction of the clinical prognosis of PCa by observing the correlation between miR-129 and the progression of the malignancy. This retrospective analysis included 310 male patients who visited the Department of Urology of the General Hospital of Eastern Theater Command from January 2014 to January 2022, 80 as normal healthy men, 80 with BPH, and the other 150 with PCa treated by radical prostatectomy without chemotherapy, radiotherapy or androgen-deprivation therapy. We determined the miR-129 expression in the serum and prostatic tissue of all the subjects by real-time quantitative PCR (RT-qPCR), performed pathological grading of the primary cancerous and pericancerous (≥ 3 cm from the focus) prostate tissues from the 150 PCa patients, collected the demographic and clinical data on all the subjects, and analyzed the correlation of their demographic data with the clinical parameters. We selected and transfected PC-3 and DU-145 cell lines with miR-129 precursor or miR-129 scramble, assessed the proliferation ability of each cell line and detected the expression levels of related proteins by cell proliferation assay and Western blot. The expression of miR-129 was significantly decreased in the serum of the PCa patients compared with that in the normal healthy men and BPH patients (P < 0.01), so was it in the PCa tissue in comparison with that in the pericancerous prostatic tissue (P < 0.01), and it was negatively correlated with the preoperative serum PSA level (P < 0.001), histological grade (P < 0.001), pathological stage (P < 0.001), Gleason score (P < 0.001), lymph node metastasis (P = 0.02), angiolymphatic invasion (P = 0.021) and biochemical recurrence (BCR) (P=0.001). Kaplan-Meier analysis showed a strong correlation of down-regulated miR-129 expression with a lower BCR-free survival rate, while multivariate survival analysis indicated that the expression of miR-129 was an independent prognostic indicator of BCR-free survival of the PCa patients (P < 0.001). Highly expressed miR-129 significantly inhibited the proliferation of PCa cells by regulating the expressions of cell cycle-regulatory proteins. The expression of miR-129 is significantly down-regulated in PCa tissues, which plays an important role in inhibiting the proliferation of PCa cells and tumor progression and improving BCR-free survival. Therefore, miR-129 can be considered as a new independent biomarker for the diagnosis, treatment and prediction of the clinical prognosis of PCa.


Bladder cancer in renal allograft recipients: risk factors and outcomes.
Solid organ transplant recipients have an increased cancer risk owing to immunosuppression and oncogenic viral infections. We report on the incidence and types of bladder cancer in kidney transplant recipients in Ireland, describing possible additional risk factors and outcomes in these patients. We identified kidney transplant recipients diagnosed with de novo bladder cancer between January 1, 1994, and July 31, 2012, by integrating data from the Irish National Cancer Registry and National Renal Transplant Registry. We calculated the standardized incidence ratio (SIR) and examined patient and tumor characteristics and 1-year survival rate. Fifteen patients were diagnosed with de novo bladder cancer during the study period, representing 0.48% of kidney transplant recipients. The SIR was 2.5 (95% CI, 1.4-4.2; P < .001). The mean interval between transplantation and diagnosis of bladder tumor was 8.6 years and mean age at time of diagnosis was 55.7 years. Sixty percent of patients were male. The tumor types were transitional cell carcinoma (9 patients), squamous cell carcinoma (3 patients), adenocarcinoma (1 patient), carcinoma in situ (1 patient), and diffuse large B-cell lymphoma (1 patient). Beside immunosuppression, risk factors associated with bladder cancer were urogenital disease (6 patients), cyclophosphamide exposure (2 patients), BK nephropathy (1 patient), analgesic nephropathy (1 patient), and extensive smoking (1 patient). Eight patients underwent radical cystectomy for invasive tumors, with resection of other pelvic organs in 7 patients. Mortality rate within the first year was 40%. Bladder cancer occurred more commonly in kidney transplant recipients with a predominance of aggressive tumors and a high mortality. In patients with preexisting risk factors such as urologic abnormalities and cyclophosphamide exposure careful assessment before transplantation and vigilant monitoring posttransplantation with a low threshold for cystoscopy may improve outcomes.


Pilot study of a novel mandibular advancement device for the control of snoring.
Mandibular advancement devices (MADs) have been introduced as a conservative, non-invasive treatment for socially disturbing snoring and mild obstructive sleep apnea (OSA). A prospective, non-randomized pilot study was conducted to investigate the efficacy, feasibility, side-effects and compliance of Somnoguard, an immediately intraorally adaptable MAD made from thermoplastic material. Twenty consecutive heavy snorers with a respiratory disturbance index of <20 events/h were prospectively selected. Prior to the adaptation of the appliance, ambulatory polygraphy was carried out without a MAD. After a 1-month habituation period, a polygraphic evaluation was carried out with the device. Treatment success was defined as a reduction in the apnea-hypopnea index (AHI) of at least 50%. The results indicated a success rate of 65%. The AHI decreased from 8.4 +/- 2.9 events/h at baseline to 3.9 +/- 1.8 events/h with the device (p = 0.001). At 1-month follow-up, significant reductions in the snoring index (p < 0.001) and the Epworth Sleepiness Scale (ESS) score (p = 0.036) were noted. At 6-month follow-up, similar results were achieved, with significant drops in the snoring index (p = 0.025) and ESS score (p = 0.033). We conclude that immediate intraoral adaptation of a low-cost fabricated "one-size-only" MAD is a feasible and well-tolerated treatment for snoring and mild OSA. Further research is needed to evaluate this thermoplastic appliance as a strategy to "screen" the efficacy of MAD treatment in the individual patient with a less expensive appliance before constructing a more expensive custom-made MAD.


Traumatic bilateral dissection of cervical internal carotid artery in the wake of a car accident: A case report.
Bilateral carotid artery dissection secondary to severe trauma is rare and can be potentially life -threatening if not diagnosed and treated properly. We report a 29-year-old female who was admitted to the emergency department after a car accident. The patient was conscious at the time of admission and presented with an initial Glasgow Coma Scale (GCS) of 15 presenting normal vital signs. The patient developed motor dysphasia with right upper limb paresis a few hours after the admission. Magnetic resonance imaging (MRI) revealed a bilateral cervical internal carotid artery (ICA) occlusion in addition to left frontal lobe infarct in a subacute phase. Medical management was successful and the patient was discharged from the hospital two weeks after the admission. Noninvasive vascular imagining modalities are merging as the gold standard in the early detection of carotid artery dissection (CAD). Typical pathognomonic findings on MRI include double lumen and intimal flap. The management with systemic anticoagulation or antiplatelet therapy is aimed to prevent the development of ischemic stroke. In case of medical therapy being ineffective or in case of complication or any disorders suffered by a patient, endovascular treatment is performed. With early detection and proper management, traumatic dissection of cervical carotid artery can have a benign outcome. As for the current patient, medical treatment with anticoagulation was sufficient and surgical management was therefore not required. Improvement in the patients' speech was observed; nevertheless the continuation of speech therapy was indicated.


Non-invasive therapy to reduce the body burden of aluminium in Alzheimer's disease.
There are unexplained links between human exposure to aluminium and the incidence, progression and aetiology of Alzheimer's disease. The null hypothesis which underlies any link is that there would be no Alzheimer's disease in the effective absence of a body burden of aluminium. To test this the latter would have to be reduced to and retained at a level that was commensurate with an Alzheimer's disease-free population. In the absence of recent human interference in the biogeochemical cycle of aluminium the reaction of silicic acid with aluminium has acted as a geochemical control of the biological availability of aluminium. This same mechanism might now be applied to both the removal of aluminium from the body and the reduced entry of aluminium into the body while ensuring that essential metals, such as iron, are unaffected. Based upon the premise that urinary aluminium is the best non-invasive estimate of body burden of aluminium patients with Alzheimer's disease were asked to drink 1.5 L of a silicic acid-rich mineral water each day for five days and, by comparison of their urinary excretion of aluminium pre-and post this simple procedure, the influence upon their body burden of aluminium was determined. Drinking the mineral water increased significantly (P<0.001) their urinary excretion of silicic acid (34.3 +/- 15.2 to 55.7 +/- 14.2 micromol/mmol creatinine) and concomitantly reduced significantly P=0.037) their urinary excretion of aluminium (86.0 +/- 24.3 to 62.2 +/- 23.2 nmol/mmol creatinine). The latter was achieved without any significant (P>0.05) influence upon the urinary excretion of iron (20.7 +/- 9.5 to 21.7 +/- 13.8 nmol/mmol creatinine). The reduction in urinary aluminium supported the future longer-term use of silicic acid as non-invasive therapy for reducing the body burden of aluminium in Alzheimer's disease.


[Bio-based pharmaceutical polymers, possibility of their chemical modification and the applicability of modified polymers].
Different types of polymers are widely used in biomedical, pharmaceutical and cosmetic purposes. Their applications are curbed, if the polymers can not break down by the body or if the polymer itself is harmful or decompose to harmful material. Authors provide an overview of different types of pharmaceutical polymers of various sources, of the structural characterization and possibilities of their chemical modification and of the classical and instrumental analytical examination methods. The paper deals with the limitations of the use of biopolymers, as well.


Thoughts on early intervention.
The concept of early psychological intervention in response to traumatic events has been a compelling notion since World War I. Recently, its wisdom applied to mass disasters such as September 11th, has been called into question. A review of relevant research reveals support for its continued utilization, but not without caution. Crisis intervention, in response to mass disasters, should consist of an integrated multi-component intervention system.


Bringing managed care home: strategies for success.
Managed care continues to increase in market share and greatly influence the provision of home care services. Written from a home care nurse's experience and perspective, this article gives an overview of the current managed-care climate and suggests strategies agencies and nurses can use to be successful in working with this market.


Fabrication of a Novel Au Star@AgAu Yolk-Shell Nanostructure for Ovarian Cancer Early Diagnosis and Targeted Therapy.
A novel CYPA-targeted, SiO2 encapsulated Au star@AgAu yolk-shell nanostructure (YSNS) was synthesized and used for ovarian cancer early diagnosis and therapy. Diverse spectroscopic and microscopic methods were utilized to investigate the pattern of the yolk-shell nanostructure. In addition, in vitro and in vivo experiments were carried out. It can be found that the ratio of HAuCl4 and AgNO3 played a critical role in the constitution of the yolk-shell nanostructure. The as-prepared yolk-shell nanostructure showed excellent SERS performance, which could be utilized as SERS substrate for specific sensitivity analysis of ovarian cancer markers cyclophilin A (CYPA) with detectable limit of 7.76*10-10 μg/mL. In addition, the as-prepared yolk-shell nanostructure possessed outstanding photothermal performance, which could be used as photothermal agent for ovarian cancer therapy. Experiments in vitro and in vivo proved that the as-prepared yolk-shell nanostructures are ideal candidate for early diagnosis and therapy for ovarian cancer in one platform. This work holds promise to offer a new method for the detection and therapy of ovarian cancer in the early stage.


Effect of family responsibilities and job strain on ambulatory blood pressure among white-collar women.
This study was conducted to determine whether large family responsibilities and their combination with high job strain were associated with an increase in ambulatory blood pressure (BP) among white-collar women. A cross-sectional study was conducted in a stratified random sample of 199 white-collar women with or without children who were employed full time in jobs involving high or low strain. These women were selected from a population of 3183 women of all ages, employed in eight organizations in Quebec City, Canada. Subjects wore an ambulatory BP monitor for 24 hours during a working day. Mean BPs were calculated. Different measures of family responsibilities were used, based on the number of children and their ages, and domestic work. Job strain was measured using the Job Content Questionnaire recommended by Karasek. Family responsibility measures were significantly related to diurnal BP among women holding a university degree (N=69). Indeed, women having large family responsibilities had increases in systolic and diastolic BPs of 2.7 to 5.7/1.8 to 4.0 mm Hg (p< or =.05). Among women holding a university degree, increases in diurnal systolic and diastolic BPs reached 8.1 to 10.9/5.5 to 7.1 mm Hg (p< or =.01) among women having both large family responsibilities and high job strain. These results were independent of confounders. There was no significant association among women without a university degree (N=130). Large family responsibilities were associated with significant increases in diurnal systolic and diastolic BPs among white-collar women holding a university degree. In these women, the combined exposure of large family responsibilities and high job strain tended to have a greater effect on BP than the exposure to only one of these factors.


Depression in Australian women: the varied roles of spirituality and social support.
This study investigated the influence of spirituality on depression in Western Australian women. Two hundred and seventy-eight women (aged 18-78) completed an online survey about factors relating to daily spiritual experience, depression, anxiety and social support. Significant correlations were found between spiritual experience and depression, whereby individuals who reported higher spirituality also reported higher rates of social support and lower levels of depression. A major finding from this study was that spirituality accounted for a significant proportion of variance in depressive symptoms beyond the mediating effect of social support.


Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study.
Variation in the clinical manifestation of dementia has been associated with differences in cognitive reserve, although less is known about the cumulative effects of exposure to cognitive reserve factors over the life course. We examined the association of cognitive reserve-related factors over the lifespan with the risk of dementia in a community-based cohort of older adults. Information on early-life education, socioeconomic status, work complexity at age 20, midlife occupation attainment, and late-life leisure activities was collected in a cohort of dementia-free community dwellers aged 75+ y residing in the Kungsholmen district of Stockholm, Sweden, in 1987-1989. The cohort was followed up to 9 y (until 1996) to detect incident dementia cases. To exclude preclinical phases of disease, participants who developed dementia at the first follow-up examination 3 y after the baseline were excluded (n = 602 after exclusions). Structural equation modelling was used to generate latent factors of cognitive reserve from three periods over the life course: early (before 20 y), adulthood (around 30-55 y), and late life (75 y and older). The correlation between early- and adult-life latent factors was strong (γ = 0.9), whereas early-late (γ = 0.27) and adult-late (γ = 0.16) latent factor correlations were weak. One hundred forty-eight participants developed dementia during follow-up, and 454 remained dementia-free. The relative risk (RR) of dementia was estimated using Cox models with life-course cognitive reserve-enhancing factors modelled separately and simultaneously to assess direct and indirect effects. The analysis was repeated among carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele. A reduced risk of dementia was associated with early- (RR 0.57; 95% CI 0.36-0.90), adult- (RR 0.60; 95% CI 0.42-0.87), and late-life (RR 0.52; 95% CI 0.37-0.73) reserve-enhancing latent factors in separate multivariable Cox models. In a mutually adjusted model, which may have been imprecisely estimated because of strong correlation between early- and adult-life factors, the late-life factor preserved its association (RR 0.65; 95% CI 0.45-0.94), whereas the effect of midlife (RR 0.73; 95% CI 0.50-1.06) and early-life factors (RR 0.76; 95% CI 0.47-1.23) on the risk of dementia was attenuated. The risk declined progressively with cumulative exposure to reserve-enhancing latent factors, and having high scores on cognitive reserve-enhancing composite factors in all three periods over the life course was associated with the lowest risk of dementia (RR 0.40; 95% CI 0.20-0.81). Similar associations were detected among APOE ε4 allele carriers and noncarriers. Limitations include measurement error and nonresponse, with both biases likely favouring the null. Strong correlation between early- and adult-life latent factors may have led to a loss in precision when estimating mutually adjusted effects of all periods. In this study, cumulative exposure to reserve-enhancing factors over the lifespan was associated with reduced risk of dementia in late life, even among individuals with genetic predisposition.


[Expression of 5 muscarinic receptor subtypes in the scleral tissue of immature guinea pigs].
To investigate the expression of 5 muscarinic receptor subtypes in the scleral tissue of immature guinea pigs. The scleral tissue was collected from six 2-week-old pigmented guinea pigs to determine mRNA expressions of the muscarinic receptors with RT-PCR. Immunofluorescence was used to observe the protein expressions of the 5 muscarinic receptor subtypes. The mRNAs of the 5 muscarinic receptor subtypes were all detected in the scleral tissue, and the mRNA expression was the highest for M1 subtype. Green fluorescence of M1 to M5 subtypes surrounding the fibroblast nuclei were found in the scleral matrix using laser confocal microscopy. Five muscarinic receptor subtypes are present in the scleral tissues of immature guinea pigs, indicating the involvement of the muscarinic receptors in eye growth regulation.


Genome-wide identification and characterization of circular RNAs by high throughput sequencing in soybean.
Circular RNAs (circRNAs) arise during pre-mRNA splicing, in which the 3' and 5' ends are linked to each other by a covalent bond. Soybean is an ancient tetraploid, which underwent two whole genome duplications. Most of soybean genes are paralogous genes with multiple copies. Although many circRNAs have been identified in animals and plants, little is known about soybean circRNAs, especially about circRNAs derived from paralogous genes. Here, we used deep sequencing technology coupled with RNase R enrichment strategy and bioinformatic approach to uncover circRNAs in soybean. A total of 5,372 circRNAs were identified, approximately 80% of which were paralogous circRNAs generated from paralogous genes. Despite high sequence homology, the paralogous genes could produce different paralogous circRNAs with different expression patterns. Two thousand and one hundred thirty four circRNAs were predicted to be 92 miRNAs target mimicry. CircRNAs and circRNA isoforms exhibited tissue-specific expression patterns in soybean. Based on the function of circRNA-host genes, the soybean circRNAs may participate in many biological processes such as developmental process, multi-organism process, and metabolic process. Our study not only provided a basis for research into the function of circRNAs in soybean but also new insights into the plant circRNA kingdom.


Effect of different elastase inhibitors on leukocyte elastase pre-adsorbed to elastin.
The effect of three elastase inhibitors (MeO-Suc-Ala-Ala-Pro-Val-CH2Cl, eglin c and alpha 1-proteinase inhibitor) on the hydrolysis of [3H]elastin was determined. The low-molecular mass inhibitors inactivated elastase nearly completely, regardless of whether or not the enzyme was adsorbed to its substrate elastin prior to the addition of the inhibitors. In contrast, elastase preadsorbed to elastin was much less sensitive to the inhibitory effect of alpha 1-proteinase inhibitor than the free elastase.


RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation.
Embryonic stem cells (ESCs) maintain high genomic plasticity, which is essential for their capacity to enter diverse differentiation pathways. Posttranscriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2Bub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of relatively long genes during ESC differentiation. Furthermore, we identify the deubiquitinase USP44 as a negative regulator of H2B ubiquitylation, whose downregulation during ESC differentiation contributes to the increase in H2Bub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner.


Structure based virtual screening to identify inhibitors against MurE Enzyme of Mycobacterium tuberculosis using AutoDock Vina.
The Mur E enzyme of Mur pathway of Mycobacterium tuberculosis is an attractive drug target as it is unique to bacteria and is absent in mammalian cells. The virtual screening of large libraries of drug like molecules against a protein target is a common strategy used to identify novel inhibitors. However, the method has a large number of pitfalls, with large variations in accuracy caused in part by inaccurate protocols, use of improper standards and libraries, and system dependencies such as the potential for nonspecific docking from large active-site cavities. The screening of drug-like small molecules from diversity sets can, however, be used to short-list potential fragments as building blocks to generate leads with improved specificity. We describe a protocol to implement this strategy, which involves an analysis of the active site and known inhibitors to identify orthospecific determinants, virtual screening of a drug-like diversity library to identify potential drug primitives, and inspection of the potential docked fragments for both binding potential and toxicity. The protocol is implemented on the M.tb Mur E protein which has a large active site with poor enrichment of known positives and a set of drug-like molecules that meets this criteria is presented for further analysis. MTB - Mycobacterium tuberculosis, NCI - National Cancer Institute, PDB - Protein Databank.


Morphometric analysis of pars plana development in humans.
Quantitative features of pars plana development in humans are not well characterized. Knowledge of the dimensions of this region is important for our understanding of the anatomy of infant eyes for the purposes of surgery. The purpose of this study was to provide a morphometric description of pars plana growth in relation to 1) postconceptional age and 2) axial length. We reviewed histologic specimens from 204 human eyes of postconceptional ages ranging from 10 weeks to 5 years. Axial length and temporal pars plana width were measured directly with a reticule system. The relationships among pars plana width, axial length, and postconceptional age were examined. The most rapid phase of pars plana growth occurred between 26 weeks and 35 weeks gestation. A linear relationship between pars plana width and axial length existed once the axial length reached 12 mm (correlation coefficient = 0.918; P = 0.0001). In infants of 38-42 weeks postconceptional age, mean pars plana width was 1.87 mm (range, 0.9-2.8 mm; standard direction = 0.48 mm), and mean axial length was 17.7 mm (range, 15-23 mm; standard direction = 1.9 mm). After the age of 62 weeks postconception, all eyes had a temporal pars plana width > or = 3 mm and an axial length > or = 19 mm. The estimated age at which there was a 95% chance of the pars plana width being > or = 3 mm was 64.4 weeks (95% fiducial confidence limits, 60.8-86.2 weeks). The pars plana first develops during the second trimester of gestation. A rapid growth phase occurs between 26 weeks and 35 weeks postconception. The dimensions of the pars plana are correlated closely with axial length and postconceptional age. Assuming that a pars plana width of 3 mm is required for surgery to be performed via a pars plana approach, we estimate that pars plana vitreous surgery can be performed when the patient is at least 62 weeks old (postconception), which is a 6-month-old full-term infant.


Salt consumption by Australian adults: a systematic review and meta-analysis.
Salt reduction is a public health priority because it is a leading contributor to the global burden of disease. As in Australia there is uncertainty about the current level of salt intake, we sought to estimate current levels. Random effects meta-analysis of data from 31 published studies and one unpublished dataset that reported salt or sodium consumption by Australian adults on the basis of 24-hour urine collections or dietary questionnaires. MEDLINE (via Ovid) and EMBASE (to August 2016). Thirty-one published studies and one unpublished dataset (1989-2015; 16 836 individuals) were identified. The mean weighted salt consumption estimated from 24-hour urine collections was 8.70 g/day (95% CI, 8.39-9.02 g/day); after adjusting for non-urinary salt excretion, the best estimate of salt intake in Australia is 9.6 g/day. The mean weighted intake was 10.1 g/day (95% CI, 9.68-10.5 g/day) for men and 7.34 g/day (95% CI, 6.98-7.70 g/day) for women. Mean weighted consumption was 6.49 g/day (95% CI, 5.94-7.03 g/day) when measured with diet diaries, 6.76 g/day (95% CI, 5.48-8.05 g/day) when assessed with food frequency questionnaires, and 6.73 g/day (95% CI, 6.34-7.11) when assessed by dietary recall. Salt intake had not decreased between 1989 and 2015 (R2 = -0.02; P = 0.36). Salt intake in Australian adults exceeds the WHO-recommended maximum of 5 g/day and does not appear to be declining. Measuring salt intake with methods based on self-reporting can substantially underestimate consumption. The data highlight the need for ongoing action to reduce salt consumption in Australia and robust monitoring of population salt intake.


Cellular phenotype of androgen receptor-immunoreactive nuclei in the developing and adult rat brain.
Androgen exposure during development and adulthood promotes cell-to-cell communication, modulates the size of specific brain nuclei, and influences hormone-dependent behavioral and neuroendocrine functions. Androgen action involves the activation of androgen receptors (AR). To elucidate the mechanisms involved in AR-mediated effects on forebrain development, double-label fluorescent immunohistochemistry and confocal microscopy were employed to identify the cellular phenotype of AR-immunoreactive (AR(+)) cells in the developing (embryonic day 20, postnatal days 0, 4, 10) and adult male rat forebrain. Sections were doubly labeled with antibodies directed against AR and one of the following: neurons (immature, nestin; mature, NeuN) or astrocytes [immature, vimentin; mature, glial fibrillary acidic protein (GFAP)] or mature oligodendrocytes (mGalC). In all brain regions examined, by far the majority of AR(+) cells were neurons. In addition, small subsets of AR(+) cells were identified as mature astrocytes (GFAP(+)) but only in specific brain regions at specific ages. AR(+)/GFAP(+) cells were observed in the cerebral cortex but only in postnatal day 10 rats and in the arcuate nucleus of the hypothalamus but only in adult rats. Immature neurons, immature astrocytes, and oligodendrocytes were not AR(+) at any age, in any region. Thus, both neurons and astrocytes in the male rat forebrain contain ARs, suggesting that androgens, via ARs, may exert effects on both cell types in an age- and region-dependent manner.


Isolation of special antibodies which react only with homologous enterotoxins from Vibrio cholerae and Enterotoxigenic Escherichia coli.
Cholera enterotoxin (CT) and heat-labile enterotoxin (LT) produced by enterotoxigenic Escherichia coli share a common antigenic determinant. In addition, CT and LT each have a unique antigenic determinant. Antisera were prepared by immunoaffinity chromatography against these unique antigenic determinants, that is, antiserum that reacted with CT but not with LT and antiserum that reacted with LT but not with CT. Antiserum against the common antigenic determinant to CT and LT was also prepared by immunoaffinity chromatography. The specificities of these antisera were demonstrated by Ouchterlony double-gel diffusion tests and by neutralization of the activities of CT and LT to cause morphological changes in Chinese hamster ovary cells.


Flagellar assembly mutants in Escherichia coli.
Genetic and biochemical analysis of mutants defective in the synthesis of flagella in Escherichia coli revealed an unusual class of mutants. These mutants were found to produce short, curly, flagella-like filaments with low amplitude ( approximately 0.06 mum). The filaments were connected to characteristic flagellar basal caps and extended for 1 to 2 mum from the bacterial surface. The mutations in these strains were all members of one complementation group, group E, which is located between his and uvrC. The structural, serological, and chemical properties of the filament derived from the mutants closely resemble those of the flagellar hook structure. On the basis of these properties, it is suggested that these filaments are "polyhooks", i.e., repeated end-to-end polymers of the hook portion of the flagellum. Polyhooks are presumed to be the result of a defective cistron which normally functions to control the length of the hook region of the flagellum.


Investigated geometrical characteristics and image density of left ventricle of multi-detector computed tomography in early coronary artery disease patients.
Coronary artery disease (CAD) remains the leading cause of death worldwide. Currently, cardiac multi-detector computed tomography (MDCT) is widely used to diagnose CAD. The purpose in this study is to identify informative and useful predictors from left ventricular (LV) in the early CAD patients using cardiac MDCT images. Study groups comprised 42 subjects who underwent a screening health examination, including laboratory testing and cardiac angiography by 64-slice MDCT angiography. Two geometrical characteristics and one image density were defined as shape, size and stiffness on MDCT image. The t-test, logistic regression, and receiver operating characteristic curve were applied to assess and identify the significant predictors. The Kappa statistics was used to exam the agreements with physician's judgments (i.e., Golden of True, GOT). The proposed three characteristics of LV MDCT images are important predictors and risk factors for the early CAD patients. These predictors present over 80% of AUC and higher odds ratio. The Kappa statistics was 0.68 for the combinations of shape and stiffness into logistic regression. The shape, size and stiffness of the left ventricular on MDCT can be used to be the effective indicators in the early CAD patients. Besides, the combinations of shape and stiffness into logistic regression could provide substantial agreement with physician's judgments.


Study of the Effect of Grafting Method on Surface Polarity of Tempo-Oxidized Nanocellulose Using Polycaprolactone as the Modifying Compound: Esterification versus Click-Chemistry.
Esterification and click-chemistry were evaluated as surface modification treatments for TEMPO-oxidized nanocelluloses (TONC) using Polycaprolactone-diol (PCL) as modifying compound in order to improve the dispersion of nanofibers in organic media. These two grafting strategies were analyzed and compared. The first consists of grafting directly the PCL onto TONC, and was carried out by esterification between hydroxyl groups of PCL and carboxyl groups of TONC. The second strategy known as click-chemistry is based on the 1,3-dipolar cycloaddition reaction between azides and alkyne terminated moieties to form the triazole ring between PCL and TONC. The grafted samples were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and Thermogravimetry analysis (TGA). Further, the effects of the two treatments on the surface hydrophobization of TONC were investigated by contact angle measurements. The results show that both methods confirm the success of such a modification and the click reaction was significantly more effective than esterification.


Sertraline can reduce uremic pruritus in hemodialysis patient: A double blind randomized clinical trial from Southern Iran.
Uremic pruritus is an undesirable complication of end stage renal disease (ESRD). In spite of introduction of many treatments for this complication, it has no certain cure. The aim of this study was to assess sertraline effect on uremic pruritus. In the present clinical trial study, we randomly divided our patients into two groups; trial group that received sertraline and control group that consumed placebo. We measured the severity of pruritus by two scoring systems (visual analogue scale and DUO) at the beginning and during the study with a-2-week interval. Data were analyzed by SPSS 18.0 and a P value < 0.050 considered as significant. The mean age of our patients was 44.1 ± 16.1 years. Pruritus intensity significantly decreased in both groups (P < 0.001) and both scoring systems. Although the amount of decrease in trial group was significantly more than control group (P < 0.001). We found a direct relation between blood urea nitrogen and phosphorus and the degree of itching in VAS system (P < 0.009). There was a reverse significant relation between itching and calcium in both scoring systems (P < 0.012). Also pruritus intensity was directly correlated with C-reactive protein in both scoring systems (P < 0.05). Depends on present study and previous ones, inflammation appears to play a significant role in uremic itching. Sertraline is an effective drug in reducing this complaint possibly due to its effect on reducing inflammatory cytokines. In addition there is no need to adjust sertraline dosage in patients with ESRD. Sertraline might be a treatment for patients with ESRD who do not respond to other routine drugs.


Genomic instability and bystander effects induced by high-LET radiation.
An understanding of the radiobiological effects of high-linear energy transfer (LET) radiation is essential for radiation protection and human risk assessment. Ever since the discovery of X-rays was made by Röntgen more than a century ago, it has always been accepted that the deleterious effects of ionizing radiation, such as mutation and carcinogenesis, are due mainly to direct damage to DNA. With the availability of a precision single-particle microbeam, it is possible to demonstrate, unequivocally, the presence of a bystander effect with many biological end points. These studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha-particles, and that cell-cell communication processes play a critical role in mediating the bystander phenomenon. Following exposure to high-LET radiation, immortalized human bronchial (BEP2D) and breast (MCF-10F) cells have been shown to undergo malignant transformation through a series of successive steps, before becoming tumorigenic in nude mice. There is a progressive increase in genomic instability, determined either by gene amplification or allelic imbalance, with the highest incidence observed among established tumor cell lines, relative to transformed, nontumorigenic and control cell lines.


Health and developmental outcomes at 18 months in very preterm infants with bronchopulmonary dysplasia.
To determine whether very preterm infants who are oxygen-dependent at 28 days of life but not at 36 weeks' gestational age are at high risk of morbidities at 18 months. A total of 217 infants born in a tertiary care center at 24 to 28 weeks' gestation in 1987 to 1992, classified into three groups: neonatal comparison group, O2 <28 days of life (n = 76); bronchopulmonary dysplasia (BPD)-1, O2 >/=28 days but not at 36 weeks' gestational age (n = 48); and BPD-2, O2 >/=36 weeks (n = 93). Growth, persistent respiratory problems (asthma, tracheostomy, home oxygen therapy), surgery, hospitalizations, and neurodevelopmental impairments. Among the three groups, no differences were found in weight, height, head circumference, or total number of days of rehospitalizations for any causes, or in rate of rehospitalizations to the intensive care unit, persistent respiratory problems, cerebral palsy, or sensory impairment. Children with BPD-2 needed more hernia repairs compared with the other two groups (comparison group: 12% vs BPD-1: 10% vs BPD-2: 30%), had more days of readmissions for respiratory problems (comparison group: 2.0 vs BPD-1: 2.0 vs BPD-2 6.3 [BPD-1 vs BPD-2]), had a lower mean developmental quotient (comparison group: 97.4 +/- 15.0 vs BPD-1: 97.9 +/- 11.6 vs BPD-2: 90.7 +/- 19.3). Intraparenchymal cerebral lesions, high family adversity, and prolonged ventilation were the most important factors influencing the developmental outcome. Children with BPD-1 are similar in all respect at 18 months to children in the comparison group. Children with BPD-2 are similar to the other groups at 18 months in growth, general health, and neurologic outcome but differ in having a higher number of days of rehospitalizations for respiratory causes, more hernia repairs, and more developmental delays.


Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion.
Basophils orchestrate protection against reinfections with gastrointestinal helminths and ticks, but the underlying mechanisms remain elusive. We investigated the role of Fc receptors on basophils, the antibody isotypes IgG1 and IgE, and basophil-derived IL-4/IL-13 during challenge infections with Heligmosomoides polygyrus and Nippostrongylus brasiliensis. Using mixed bone marrow chimeras, we found that activating Fc receptors on basophils were required for protective immunity but not for regulation of basophil homeostasis. Furthermore, rapid worm expulsion was impaired in IgE-deficient but not in IgG1-deficient mice. Basophils promoted the recruitment of other effector cells into the small intestine and induced expression of the antihelminthic proteins resistin-like molecule β and mucin 5ac. Selective deletion of IL-4/IL-13 in basophils resulted in impaired worm expulsion. Collectively, our results indicate that IgE-mediated activation of basophils and the release of basophil-derived IL-4/IL-13 are critical steps in protective immunity against helminths. Therefore, development of effective vaccines against helminths should consider boosting the IL-4/IgE/basophil axis of the immune system.


Melatonin targets MoIcl1 and works synergistically with fungicide isoprothiolane in rice blast control.
Melatonina natural harmless molecule-displays versatile roles in human health and crop disease control such as for rice blast. Rice blast, caused by the filamentous fungus Magnaporthe oryzae, is one devastating disease of rice. Application of fungicides is one of the major measures in the control of various crop diseases. However, fungicide resistance in the pathogen and relevant environmental pollution are becoming serious problems. By screening for possible synergistic combinations, here, we discovered an eco-friendly combination for rice blast control, melatonin, and the fungicide isoprothiolane. These compounds together exhibited significant synergistic inhibitory effects on vegetative growth, conidial germination, appressorium formation, penetration, and plant infection by M. oryzae. The combination of melatonin and isoprothiolane reduced the effective concentration of isoprothiolane by over 10-fold as well as residual levels of isoprothiolane. Transcriptomics and lipidomics revealed that melatonin and isoprothiolane synergistically interfered with lipid metabolism by regulating many common targets, including the predicted isocitrate lyase-encoding gene MoICL1. Furthermore, using different techniques, we show that melatonin and isoprothiolane interact with MoIcl1. This study demonstrates that melatonin and isoprothiolane function synergistically and can be used to reduce the dosage and residual level of isoprothiolane, potentially contributing to the environment-friendly and sustainable control of crop diseases.


Ship in bottle synthesis of yolk-shell MnS@hollow carbon spheres for sodium storage.
Yolk-shell structure can effectively alleviate the volume change of electrodes during electrochemical charge/discharge. In this paper, we provide a new ship in bottle strategy to synthesize MnS@C sodium ion battery anode with yolk-shell nanostructure. The obtained yolk-shell structures were uniform spheres. The space between the carbon shell and MnS core allows the volume change of MnS without deforming the carbon shell or damaging the solid electrolyte interface film formed on the outer surface. The MnS@C yolk-shell structure showed stable cycle stability (336 mAh g-1capacity after 200 cycles at 0.5 A g-1current density).


Tolerance to dietary phenolics and diet breadth in three seed-eating birds: implications for Graminivory.
The ability to cope with plant secondary compounds (PSCs) has profound implications for an animal's behavior. In the present study, we assessed the tolerance to dietary phenolics in three seed-eating birds: Zonotrichia capensis, Saltatricula multicolor, and Diuca diuca, which differ in their diet breadth. Seeds in their habitat have distinct chemical composition: grass seeds have less PSCs, specifically, less total phenolics than forb seeds. Based on the detoxification limitation hypothesis and using published data of the natural history of these birds in the central Monte desert, we postulate that predominantly and exclusively graminivorous birds such as D. diuca and S. multicolor, respectively, are less tolerant due, in part, to a lower detoxification capacity than those with greater diet breadth, Z. capensis. To achieve this goal, we measured the food intake of diets varying in their concentration of tannic acid (TA). Indicators of tolerance were body mass change, food, TA and water intake, and glucuronic acid output throughout the experiment. Zonotrichia capensis performed better along the tolerance experiment: it maintained body mass from 0 to 4% TA diet, food and TA intake were higher than the other two species at the end of the experiment, and glucuronic acid output by Z. capensis was greater than D. diuca and S. multicolor from 2% TA diet until the end of the experiment. Our results suggest that Z. capensis is the most tolerant species and this physiological trait may explain their greater diet breadth.


The Efficacy of Nasal Steroids in Treatment of Otitis Media with Effusion: A Comparative Study.
Introduction Otitis media with effusion (OME) continues to be an important pediatric clinical problem, and more studies are needed to decide the proper treatment for it. Objective To assess the efficacy of nasal steroids in the management of OME by comparing its results with that of oral steroid and that of nasal saline spray as placebo. Methods This study was carried on 60 patients with OME who were divided into three groups: in group 1, 20 patients received mometasone furoate spray, one puff in each nostril daily, for 3 months; in group 2, 20 patients received oral prednisolone, 5 mg three times per day for the first 3 weeks; in group 3, 20 patients received nasal saline spray, one puff in each nostril daily for 3 months. Results A highly significant difference between systemic or topical (nasal spray) steroid therapy and saline nasal spray was detected (p < 0.001), and the difference between systemic and topical steroid was nonsignificant (p > 0.05). Conclusion Nasal steroid spray can be used as an effective treatment for OME, giving a significant result similar to systemic steroid. Further studies are needed to investigate its use for longer duration and in recurrent cases.


Apparent functional role for a cysteine-rich polydnavirus protein in suppression of the insect cellular immune response.
Polydnaviruses suppress the cellular immune response and inhibit growth and development in their lepidopteran host, allowing survival of their endoparasitic hymenopteran host. Characterization of genes disrupting insect physiological systems is a major objective in the study of polydnaviruses. Recently, a cysteine-rich gene family encoding a motif composed of invariable cysteine residues flanking hypervariable intercysteine amino acids was described (S.D. Dib-Hajj, B.A. Webb, and M.D. Summers, Proc. Natl. Acad. Sci. USA 90:3765-3769, 1993). They noted similarities to the positive selection pressure for mutations within the vertebrate major histocompatibility complex (MHC) class II genes and speculated that this class of polydnavirus genes may target and disrupt the insect immune system. To study the functional activity of this family of predicted cysteine-rich proteins, the VHv1.1 gene product was produced from bacterial and baculovirus expression systems. Polyclonal antiserum produced from the bacterial fusion protein reacted with a 30-kDa protein from hemocytes, cell-free plasma, and fat body of parasitized larvae. Immunofluorescence analysis of hemocytes from parasitized insects detected the 30-kDa protein bound to granulocytes and plasmacytes. To assay the functional activity of the 30-kDa VHv1.1 protein, a recombinant baculovirus was constructed allowing in vivo expression of the 30-kDa polydnavirus protein from infected insects. Expression of the VHv1.1 protein from the baculovirus system reduced the encapsulation response to washed wasp eggs relative to controls. The experimental evidence demonstrates that Campoletis sonorensis polydnavirus-infected cells secrete VHv1.1 into the hemolymph, where it binds to hemocytes and is associated with the inhibition of the cellular immune response.


Raman spectroscopic investigations on conformational changes induced by some phenol derivatives on phospholipid membranes.
Some phenol derivatives which uncouple oxidative phosphorylation in mitochondria alter the dipalmitoylphosphatidylcholine membrane structure in the same way that elevating the temperature does. Below the transition temperature, they disorder the membrane gel-phase by inducing the pretransition situation at concentrations within significant biological limits. When the temperature is higher than Tm, their effect on the membrane structure is negligible. The comparison of these phenol derivatives having uncoupling activity with a phenol derivative which does not have such activity demonstrates that the latter does not induce a similar physical effect.


A composite likelihood method for bivariate meta-analysis in diagnostic systematic reviews.
Diagnostic systematic review is a vital step in the evaluation of diagnostic technologies. In many applications, it involves pooling pairs of sensitivity and specificity of a dichotomized diagnostic test from multiple studies. We propose a composite likelihood (CL) method for bivariate meta-analysis in diagnostic systematic reviews. This method provides an alternative way to make inference on diagnostic measures such as sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. Its main advantages over the standard likelihood method are the avoidance of the nonconvergence problem, which is nontrivial when the number of studies is relatively small, the computational simplicity, and some robustness to model misspecifications. Simulation studies show that the CL method maintains high relative efficiency compared to that of the standard likelihood method. We illustrate our method in a diagnostic review of the performance of contemporary diagnostic imaging technologies for detecting metastases in patients with melanoma.


Reviewing lymnaeid vectors of fascioliasis by ribosomal DNA sequence analyses.
Snails of the family Lymnaeidae are of great parasitological importance due to the numerous helminth species they transmit, mainly trematodiases (such as fascioliasis) of considerable medical and veterinary impact. The present knowledge of the genetics and host-parasite relationships of this gastropod group is far from adequate. Fascioliasis is caused by two species, Fasciola hepatica and F. gigantica, which, as in the case of other trematodes, show a marked snail host specificity. Many lymnaeid species involved in fascioliasis transmission still show a confused systematic-taxonomic status. The need for tools to distinguish and characterize species and populations of lymnaeids is evident and the present review concerns new molecular tools developed in recent years using nuclear ribosomal DNA sequences. The small subunit or 18S gene and the internal transcribed spacers ITS-2 and ITS-1 are analysed and evaluated as markers for taxon differentiation and relationships within the Lymnaeidae from genus and species levels to subspecies and population levels. rDNA sequence differences and genetic distances, and their value for reconstructing phylogenetic trees using different methods are considered. Nuclear rDNA sequences are appropriate tools on which to base a review of the systematics and taxonomy of the family Lymnaeidae, without excluding other valuable snail characteristics already available. A reconstruction of the lymnaeid system towards a more natural classification will undoubtedly be helpful in understanding parasite transmission and epidemiological features as well the dispersion of an emerging-reemerging disease such as fascioliasis. Nomenclature for nuclear rDNA genotyping in lymnaeids includes the main rDNA sequence regions able to furnish important information on interspecific differentiation and grouping as well as intraspecific variability of lymnaeid species. The composite haplotype code includes the rDNA markers arranged in order according to their well-known usefulness, in its turn related to their respective, more or less rapid evolutionary ratios, to distinguish between different taxonomic levels, from supraspecific taxa to the species level and up to the population level.