Criticality in the duration of quasistationary state.
The duration of the quasistationary states (QSSs) emerging in the d-dimensional classical inertial α-XY model, i.e., N planar rotators whose interactions decay with the distance r_{ij} as 1/r_{ij}^{α} (α≥0), is studied through first-principles molecular dynamics. These QSSs appear along the whole long-range interaction regime (0≤α/d≤1), for an average energy per rotator U<U_{c} (U_{c}=3/4), and they do not exist for U>U_{c}. They are characterized by a kinetic temperature T_{QSS}, before a crossover to a second plateau occurring at the Boltzmann-Gibbs temperature T_{BG}>T_{QSS}. We investigate here the behavior of their duration t_{QSS} when U approaches U_{c} from below, for large values of N. Contrary to the usual belief that the QSS merely disappears as U→U_{c}, we show that its duration goes through a critical phenomenon, namely t_{QSS}∝(U_{c}-U)^{-ξ}. Universality is found for the critical exponent ξ≃5/3 throughout the whole long-range interaction regime.


Technical and audiological factors in the implementation and use of digital signal processing hearing aids.
Fully digital hearing aids, to be worn behind or within the ear, are coming on to the market. The new possibilities and challenges of such aids are both technological and audiological in character. This paper describes some of the challenges, and one manufacturer's approach to them. The signal processing structure in one current digital hearing aid is presented, and justified in audiological terms, as a background to discussions of (i) the relative urgency of further advances in technology and audiological knowledge, and (ii) the challenges to the practice of hearing aid dispensing. It is concluded that further advances in rehabilitative audiology are more pressing than further major technological progress, and that the potential client benefits of the new generation of digital hearing aids will only be realized if the challenges they present to software design and dispensing practice are recognized and met.


Predicting the duration of symptoms in lower respiratory tract infection.
Acute lower respiratory tract infection (LRTI) presenting in primary care has a long natural history. Antibiotic treatment makes little or no difference to the duration of cough. Limited information is currently available regarding predictors of illness duration. To determine predictors of illness duration in acute LRTI in primary care. Secondary analysis of trial data to identify independent predictors of illness severity and duration. Primary care. Eight-hundred and seven patients aged 3 years and over with acute illness (21 days or less) presenting with cough as the main symptom plus at least one symptom or sign from sputum, chest pain, dyspnoea, or wheeze were recruited to the study. Main outcomes were duration of symptoms (rated at least a slight problem) and more severe symptoms (rated at least moderately bad). The average duration of cough (rated at least a slight problem) was 11.7 days and was shorter among children (duration -1.72 days; 95% confidence interval [CI] = -3.02 to -0.41) or in individuals with a history of fever (-1.22 days; 95% CI = -0.18 to 2.27). The duration of cough was longer among those with restricted activities on the day they saw the doctor (+0.69 days for each point of a 7-point scale). The duration of more severe symptoms was longer in those with a longer duration of symptoms prior to consultation, with a more severe cough on the day of seeing the doctor, and restriction of activities on the day of seeing the doctor. Illness duration may be predicted from a limited number of clinical symptoms and from prior history. These findings should be subjected to validation in a separate population. To minimise expectation about rapid resolution of illness, adults who have restricted activities could be advised that they are likely to experience symptoms for longer.


Spatiotemporal compression for efficient storage and transmission of high-resolution electrocorticography data.
High-resolution Electrocorticography (HR-ECoG) has emerged as a key strategic technology for recording localized neural activity with high temporal and spatial resolution with potential applications in brain-computer interfaces (BCI), and seizure detection for epilepsy. However, HR-ECoG has 400 times the resolution of conventional ECoG, making it a challenge to process, transmit and store the HR-ECoG data. Therefore, simple and efficient compression algorithms are vital for the feasibility of implantable wireless medical devices for HR-ECoG recordings. In this paper, following the observation that HR-ECoG signals have both high spatial and temporal correlations similar to video/image signals, various compression methods suitable for video/image- compression based on motion estimation, discrete cosine transform (DCT) and discrete wavelet transform (DWT)- are investigated for compressing HR-ECoG data. We first simplify these methods to satisfy the low-power requirements for implantable devices. Then, we demonstrate that spatiotemporal compression methods produce up to 46% more data reduction on HR-ECoG data than compression methods using only spatial compression do. We further show that this data reduction can be achieved with low hardware complexity. In particular, among the methods investigated, spatiotemporal compression using DCT-based methods provide the best trade-off between hardware complexity and compression performance, and thus we conclude that DCT-based compression is a promising solution for ultralow-power implantable devices for HR-ECoG.


Links between environment, diet, and the hunter-gatherer microbiome.
The study of traditional populations provides a view of human-associated microbes unperturbed by industrialization, as well as a window into the microbiota that co-evolved with humans. Here we discuss our recent work characterizing the microbiota from the Hadza hunter-gatherers of Tanzania. We found seasonal shifts in bacterial taxa, diversity, and carbohydrate utilization by the microbiota. When compared to the microbiota composition from other populations around the world, the Hadza microbiota shares bacterial families with other traditional societies that are rare or absent from microbiotas of industrialized nations. We present additional observations from the Hadza microbiota and their lifestyle and environment, including microbes detected on hands, water, and animal sources, how the microbiota varies with sex and age, and the short-term effects of introducing agricultural products into the diet. In the context of our previously published findings and of these additional observations, we discuss a path forward for future work.


Development of a method for measuring femoral torsion using real-time ultrasound.
Excessive femoral torsion has been associated with various musculoskeletal and neurological problems. To explore this relationship, it is essential to be able to measure femoral torsion in the clinic accurately. Computerized tomography (CT) and magnetic resonance imaging (MRI) are thought to provide the most accurate measurements but CT involves significant radiation exposure and MRI is expensive. The aim of this study was to design a method for measuring femoral torsion in the clinic, and to determine the reliability of this method. Details of design process, including construction of a jig, the protocol developed and the reliability of the method are presented. The protocol developed used ultrasound to image a ridge on the greater trochanter, and a customized jig placed on the femoral condyles as reference points. An inclinometer attached to the customized jig allowed quantification of the degree of femoral torsion. Measurements taken with this protocol had excellent intra- and inter-rater reliability (ICC2,1 = 0.98 and 0.97, respectively). This method of measuring femoral torsion also permitted measurement of femoral torsion with a high degree of accuracy. This method is applicable to the research setting and, with minor adjustments, will be applicable to the clinical setting.


Use of yohimbine and 4-aminopyridine to antagonize xylazine-induced immobilization in North American Cervidae.
Four captive moose (Alces alces), 4 mule deer (Odocoileus hemionus), and 5 white-tailed deer (Odocoileus virginianus) were immobilized with xylazine (0.63 to 1.29 mg/kg of body weight, IM). Mean induction times for the moose were 17 minutes and for the deer, 14 and 10 minutes, respectively. According to published data and past experience, the dosage of xylazine used would be expected to provide 115, 120, and 100 minutes of immobilization in captive moose, mule deer, and white-tailed deer, respectively. In the present study, maximal sedation of the moose and deer was reversed with successive injections (given IV) of yohimbine (0.15 mg/kg) and 4-aminopyridine (0.26 to 0.29 mg/kg). These produced sternal recumbency-to-arousal intervals of 1 to 15 minutes and recumbency-to-standing or walking intervals of 1 to 24 minutes. Relapses to recumbency were not observed. The injections of the reversal drugs produced marked increases in respiratory rate and heart in the moose and deer, without occurrence of muscle tremors or convulsions. The administrations of yohimbine and 4-aminopyridine markedly enhanced the speed of recovery from xylazine-induced immobilization in moose and deer.


Metrics on RNA secondary structures.
Many different programs have been developed for the prediction of the secondary structure of an RNA sequence. Some of these programs generate an ensemble of structures, all of which have free energy close to that of the optimal structure, making it important to be able to quantify how similar these different structures are. To deal with this problem, we define a new class of metrics, the mountain metrics, on the set of RNA secondary structures of a fixed length. We compare properties of these metrics with other well known metrics on RNA secondary structures. We also study some global and local properties of these metrics.


Infection with Influenzavirus A in a murine model induces epithelial bronchial lesions and distinct waves of innate immune-cell recruitment.
Inflammatory lesions after Influenza A viruses (IAV) are potential therapeutic target for which better understanding of post-infection immune mechanisms is required. Most studies to evaluate innate immune reactions induced by IAV are based on quantitative/functional methods and anatomical exploration is most often non-existent. We aimed to study pulmonary damage and macrophage recruitment using two-photon excitation microscopy (TPEM) after IAV infection. We infected C57BL/6 CD11c+YFP mice with A/Puerto Ricco/8/34 H1N1. We performed immune cell analysis, including flow cytometry, cytokine concentration assays, and TPEM observations after staining with anti-F4/80 antibody coupled to BV421. We adapted live lung slice (LLS) method for ex-vivo intravital microscopy to analyze cell motility. TPEM provided complementary data to flow cytometry and cytokine assays by allowing observation of bronchial epithelium lesions and spreading of local infection. Addition of F4/80-BV421 staining allowed us to precisely determine timing of recruitment and pulmonary migration of macrophages. Ex-vivo LLS preserved cellular viability, allowing us to observe acceleration of macrophage motility. After IAV infection, we were able to explore structural consequences and successive waves of innate immune cell recruitment. By combining microscopy, flow cytometry and chemokine measurements, we describe novel and precise scenario of innate immune response against IAV.


An Overview of Conventional Drugs and Nanotherapeutic Options for the Treatment and Management of Pediatric Acute Lymphoblastic Leukemia.
Acute lymphoblastic leukemia (ALL) is a common form of pediatric cancer affecting the lymphoblast, a type of white blood cell found in the bone marrow. In this disease, the normal lymphoblast cells transform into leukemic cells and subsequently enter the bloodstream. Leukemic cells found in patients with ALL have shown differences in cholesterol uptake and utilization. Current treatment consists of chemotherapy, chimeric antigen receptor (CAR) therapy, and hematopoietic stem cell transplantation (HSCT). In addition, minimal residual disease (MRD) has become an effective tool for measuring treatment efficacy and the potential for relapse. Chemotherapy resistance remains a significant barrier in the treatment of ALL. Biomarkers such as an upregulated Akt signaling pathway and an overexpressed VLA-4 integrin-protein have been associated with drug resistance. Nanoparticles have been used to favorably alter the pharmacokinetic profile of conventional drug agents. These drug-delivery systems are designed to selectively deliver their drug payloads to desired targets. Therefore, nanoparticles offer advantages such as improved efficacy and reduced toxicity. This review highlights conventional treatment options, distinctive characteristics of pediatric ALL, therapeutic challenges encountered during therapy, and the key role that nanotherapeutics play in the treatment of ALL.


A Phytochrome Sensory Domain Permits Receptor Activation by Red Light.
Optogenetics and photopharmacology enable the spatio-temporal control of cell and animal behavior by light. Although red light offers deep-tissue penetration and minimal phototoxicity, very few red-light-sensitive optogenetic methods are currently available. We have now developed a red-light-induced homodimerization domain. We first showed that an optimized sensory domain of the cyanobacterial phytochrome 1 can be expressed robustly and without cytotoxicity in human cells. We then applied this domain to induce the dimerization of two receptor tyrosine kinases-the fibroblast growth factor receptor 1 and the neurotrophin receptor trkB. This new optogenetic method was then used to activate the MAPK/ERK pathway non-invasively in mammalian tissue and in multicolor cell-signaling experiments. The light-controlled dimerizer and red-light-activated receptor tyrosine kinases will prove useful to regulate a variety of cellular processes with light.


Identification and characterization of a Babesia bigemina thrombospondin-related superfamily member, TRAP-1: a novel antigen containing neutralizing epitopes involved in merozoite invasion.
Thrombospondin-related anonymous protein (TRAP) has been described as a potential vaccine candidate for several diseases caused by apicomplexan parasites. However, this protein and members of this family have not yet been characterized in Babesia bigemina, one of the most prevalent species causing bovine babesiosis. The 3186-bp Babesia bigemina TRAP-1 (BbiTRAP-1) gene was identified by a bioinformatics search using the B. bovis TRAP-1 sequence. Members of the TRAP and TRAP-related protein families (TRP) were identified in Babesia and Theileria through a search of the TSP-1 adhesive domain, which is the hallmark motif in both proteins. Structural modeling and phylogenetic analysis were performed with the identified TRAP proteins. A truncated recombinant BbiTRAP-1 that migrates at approximately 107 kDa and specific antisera were produced and used in Western blot analysis and indirect fluorescent antibody tests (IFAT). B-cell epitopes with neutralizing activity in BbiTRAP-1 were defined by enzyme-linked immunosorbent assays (ELISA) and invasion assays. Three members of the TRAP family of proteins were identified in B. bigemina (BbiTRAP-1 to -3). All are type 1 transmembrane proteins containing the von Willebrand factor A (vWFA), thrombospondin type 1 (TSP-1), and cytoplasmic C-terminus domains, as well as transmembrane regions. The BbiTRAP-1 predicted structure also contains a metal ion-dependent adhesion site for interaction with the host cell. The TRP family in Babesia and Theileria species contains the canonical TSP-1 domain but lacks the vWFA domain and together with TRAP define a novel gene superfamily. A variable number of tandem repeat units are present in BbiTRAP-1 and could be used for strain genotyping. Western blot and IFAT analysis confirmed the expression of BbiTRAP-1 by blood-stage parasites. Partial recognition by a panel of sera from B. bigemina-infected cattle in ELISAs using truncated BbiTRAP-1 suggests that this protein is not an immunodominant antigen. Additionally, bovine anti-recombinant BbiTRAP-1 antibodies were found to be capable of neutralizing merozoite invasion in vitro. We have identified the TRAP and TRP gene families in several Babesia and Theileria species and characterized BbiTRAP-1 as a novel antigen of B. bigemina. The functional relevance and presence of neutralization-sensitive B-cell epitopes suggest that BbiTRAP-1 could be included in tests for future vaccine candidates against B. bigemina.


How dental patients determine their care.
Identifying the factors patients use to arrive at dental treatment decisions is useful in the marketing and planning of clinical treatment. Dentists perceive these factors in a certain way. This article discusses the factors used by patients in making treatment decisions and compares those factors with the perceptions of experienced dental practitioners.


Oral reduced L-glutathione improves growth in pediatric cystic fibrosis patients.
Consensus nutritional guidelines for patients with cystic fibrosis (CF) recommend aggressive treatment of growth failure. Oral reduced glutathione (GSH) has been shown to improve cachexia and case reports have demonstrated improved growth in pediatric patients with CF. No controlled studies using oral GSH in CF have, however, been reported. The aim of the study was to determine whether oral GSH could improve growth in CF. Secondarily, to determine whether oral GSH could improve other systemic clinical markers. We performed a placebo-controlled, randomized, double-blind, repeated-measures clinical trial in 44 pediatric patients with CF ages 18 months to 10 years. Primary outcomes were change in weight percentile, body mass index (BMI) percentile, height percentile, and fecal calprotectin. Secondary outcomes included liver function tests and measures of systemic inflammation. Each participant was studied for 6 months, with data obtained at baseline, 3 months, and 6 months. Blood samples were obtained on the baseline and 6-month visits. Subjects were treated with oral GSH or placebo (calcium citrate), each 65 mg · kg(-1) · day(-1) divided into 3 doses per day at mealtimes, and administered daily for 6 months. The GSH treatment group gained an average of 0.67 standard deviation (SD) in weight-for-age-and sex z score (wfaszs), (19.1 weight percentile points) during the course of 6 months, with no adverse effects (vs placebo with an increase of 0.1 SD in wfaszs [2.1 weight percentile points], P < 0.0001). Fecal calprotectin improved, GSH -52.0 vs placebo 0.5), also BMI for GSH improved 0.69 SD BMI-adjusted-for-age-and-sex z score versus placebo 0.22 SD (BMI percentile 21.7 GSH vs 5.2 placebo), and height 0.2 SD in height-for-age-and-sex z score (hfaszs) GSH versus -0.06 SD hfaszs placebo [height percentile 7.0 GSH vs -2.6 placebo], all P < 0.0001). Secondary outcomes improved significantly, as well. Oral reduced L-GSH significantly improves measures of growth status and gut inflammation in CF.


Future requirements for and supply of ophthalmologists. What do the forecasts show?
Forecasts of the requirements for and supply of ophthalmologists in 1990 have produced conflicting results because of varying assumptions about the future utilization of eye care services, incidence and prevalence of ophthalmic disease, physician productivity, and availability of residency training positions. A typical "utilization-based" models, founded on present consumer behavior, predicts a substantial 1990 surplus of ophthalmologists at current rates of residency training. Two "need-based" models, founded on ideal rather than actual use, reach different conclusions because of varying use of a fragile data base and the need to rely heavily on the subjective judgment of experts with regard to norms of care. The 1980 Graduate Medical Educational National Advisory Committee forecasted a surplus, while the 1978 American Academy of Ophthalmology predicted a deficit. Utilization-based models may slightly underestimate future ophthalmologist requirements. However, analysis of the factors that will influence future use suggests that need-based models are likely to overestimate the requirements. It is risky to accept the need-based model projections because of the high cost of a surplus, which include not only the expenses of training unneeded ophthalmologists but also the cost of their decreased exposure to disease and of declining physician morale, acumen, and thresholds for surgical procedures. Because free market mechanisms are ineffective in governing the supply of health providers, it will be necessary for the profession itself to review the current and projected supply and to set limits on the number of persons in training.


Suppression of interferon-induced oligo-2',5'-adenylate synthetase induction in persistent infection.
Persistent infections with several strains of mumps virus (strains Torii and Miyahara), measles virus (strains Edmonston, CAM-70, AIK-C and Schwarz) and subacute sclerosing panencephalitis (SSPE) virus (Hälle and Mantooth) were established in various cell lines (FL, KB, A549, SK-AS, 293, K562, Ramos and NC-37). Oligo-2',5'-adenylate synthetase activity was demonstrated to be only slightly induced by interferon in cytoplasmic and nuclear fractions of cell lines persistently infected with mumps virus. In these cells, resistance to vesicular stomatitis virus infection was not induced by interferon treatment. Treatment of the persistently infected cells with interferon for 10 and 24 h did not stimulate an increase in the amount of synthetase mRNA. In cells persistently infected with measles and SSPE viruses, reduced induction of the enzyme varied with host cell types. Induction of the enzyme was not found in K562, SK-AS and KB cells, but was recognized in NC-37 and FL cells.


Rab35 GTPase Triggers Switch-like Recruitment of the Lowe Syndrome Lipid Phosphatase OCRL on Newborn Endosomes.
Phosphoinositide (PtdIns) homeostasis requires a tight spatial and temporal regulation during the endocytic process [1]. Indeed, PtdIns(4,5)P2 plays a crucial role in endocytosis by controlling clathrin-coated pit formation, whereas its conversion into PtdIns4P right after scission of clathrin-coated vesicles (CCVs) is essential for successful uncoating and cargo sorting [1-6]. In non-neuronal cells, endosomal PtdIns(4,5)P2 hydrolysis critically relies on the lipid phosphatase OCRL [7-9], the inactivation of which causes the Oculo-Cerebro-Renal syndrome of Lowe [10, 11]. To understand the coupling between PtdIns(4,5)P2 hydrolysis and endosome formation, a key issue is thus to unravel the mechanism by which OCRL is recruited on CCVs precisely after their scission from the plasma membrane. Here we found that the Rab35 GTPase, which plays a fundamental but poorly understood role in endosomal trafficking after cargo internalization [12-21], directly recruits the OCRL phosphatase immediately after scission of the CCVs. Consistent with Rab35 and OCRL acting together, depletion of either Rab35 or OCRL leads to retention of internalized receptors such as the endogenous cation-independent mannose-6-phosphate receptor (CI-MPR) in peripheral clathrin-positive endosomes that display abnormal association with PtdIns(4,5)P2- and actin-binding proteins. Remarkably, Rab35 loading on CCVs rapidly follows the recruitment of the AP2-binding Rab35 GEF/activator DENND1A (connecdenn 1) and the disappearance of the Rab35 GAP/inhibitor EPI64B. We propose that the precise spatial and temporal activation of Rab35 acts as a major switch for OCRL recruitment on newborn endosomes, post-scission PtdIns(4,5)P2 hydrolysis, and subsequent endosomal trafficking.


The effect of phospholipase C on human blood platelets.
The effect of phospholipase C (EC 184.108.40.206) on human blood platelets has been studied. Phospholipase C from Bacillus cereus was purified to homogeneity as judged by analytical and sodium dodecyl sulphate disc gel electrophoresis and by immunoelectrophoresis. Human platelets isolated from platelet-rich plasma by gel filtration or by centrifugation and washing were incubated with phospholipase C. A loss of 20-45% of the total platelet phospholipid was observed, whereas 88% was hydrolyzed when platelet homogenates were submitted to identical enzyme treatment. Intact platelets lost 50-75% phosphatidylethanolamine, 20-50% phosphatidylcholine, and 20-25% phosphatidylserine. Sphingomyelin was not a substrate for the enzyme under the conditions used. The platelets contained no detectable endogenous phospholipase C activity. The loss of phospholipid was not accompanied by aggregation of the platelets, nor did the platelets lose their ability to aggregate with ADP or thrombin. Total platelet factor 3 releasable by freezing and thawing was reduced. Measurements of releasable platelet factor 4 and the efflux of serotonin showed that no release reaction was triggered even when up to 45% of the total phospholipid in the platelets was hydrolyzed. When sphingomyelinase was added together with, before, or after phospholipase C, aggregation occurred. Sphingomyelinase alone gave no aggregation. The gel-filtered platelets also aggregated upon addition of purified phospholipase C from Clostridium perfringens. The distribution of phospholipids in the platelet membrane is discussed.


Understanding the Correlation Between DSA, Complement Activation, and Antibody-Mediated Rejection in Heart Transplant Recipients.
Donor-specific HLA antibodies (DSA) are associated with increased rates of rejection and of graft failure in cardiac transplantation. The goal of this study was to determine the association of preformed and posttransplant development of newly detected DSA (ndDSA) with antibody-mediated rejection (AMR) and characterize the clinical relevance of complement-activating DSA in heart allograft recipients. The study included 128 adult and 48 pediatric heart transplant patients transplanted between 2010 and 2013. Routine posttransplant HLA antibody testing was performed by IgG single-antigen bead test. The C3d single-antigen bead assay was used to identify complement-activating antibodies. Rejection was diagnosed using International Society for Heart and Lung Transplantation criteria. In this study, 22 patients were transplanted with preexisting DSA, and 43 patients developed ndDSA posttransplant. Pretransplant (P < 0.05) and posttransplant (P < 0.001) ndDSA were associated with higher incidence of AMR. Patients with C3d + DSA had significantly higher incidence of AMR compared with patients with no DSA (P < 0.001) or patients with C3d-DSA (P = 0.02). Nine (36%) of 25 patients with AMR developed transplant coronary artery disease compared with 17 (15.9%) of 107 patients without AMR (P < 0.05). Among the 47 patients who received ventricular assistant device (VAD), 7 of 9 VAD+ patients with preformed DSA experienced AMR compared with 7 of 38 VAD+ patients without preformed DSA, indicating presensitization to donor HLA significantly increased the risk of AMR (P < 0.01). Preformed and posttransplant ndDSA were associated with AMR. C3d + DSA correlates with complement deposition on the graft and higher risk of AMR which may permit the application of personalized immunotherapy targeting the complement pathway.


Involvement of autophagy in melatonin-induced cytotoxicity in glioma-initiating cells.
Glioblastoma-initiating cells (GICs) represent a stem cell-like subpopulation within malignant glioblastomas responsible for tumor development, progression, therapeutic resistance, and tumor relapse. Thus, eradication of this subpopulation is essential to achieve stable, long-lasting remission. We have previously reported that melatonin decreases cell proliferation of glioblastoma cells both in vitro and in vivo and synergistically increases effectiveness of drugs in glioblastoma cells and also in GICs. In this study, we evaluated the effect of the indolamine alone in GICs and found that melatonin treatment reduces GICs proliferation and induces a decrease in self-renewal and clonogenic ability accompanied by a reduction in the expression of stem cell markers. Moreover, our results also indicate that melatonin treatment, by modulating stem cell properties, induces cell death with ultrastructural features of autophagy. Thus, data reported here reinforce the therapeutic potential of melatonin as a treatment of malignant glioblastoma both by inhibiting tumor bulk proliferation or killing GICs, and simultaneously enhancing the effect of chemotherapy.


Radical Copolymerization of Vinyl Ethers and Cyclic Ketene Acetals as a Versatile Platform to Design Functional Polyesters.
Free-radical copolymerization of cyclic ketene acetals (CKAs) and vinyl ethers (VEs) was investigated as an efficient yet simple approach for the preparation of functional aliphatic polyesters. The copolymerization of CKA and VE was first predicted to be quasi-ideal by DFT calculations. The theoretical prediction was experimentally confirmed by the copolymerization of 2-methylene-1,3-dioxepane (MDO) and butyl vinyl ether (BVE), leading to rMDO =0.73 and rBVE =1.61. We then illustrated the versatility of this approach by preparing different functional polyesters: 1) copolymers functionalized by fluorescent probes; 2) amphiphilic copolymers grafted with poly(ethylene glycol) (PEG) side chains able to self-assemble into PEGylated nanoparticles; 3) antibacterial films active against Gram-positive and Gram-negative bacteria (including a multiresistant strain); and 4) cross-linked bioelastomers with suitable properties for tissue engineering applications.


Familiarity of teaching skills among general practitioners transfer training trainers in China: a cross-sectional survey.
The insufficient number of general practitioners (GPs) is a major challenge facing China's healthcare system. The purpose of the GP transfer training programme was to provide training for experienced doctors to transition to general practice. However, research on the competencies of GP transfer training trainers in teaching skills in China is limited. This cross-sectional study aimed to examine the baseline familiarity with teaching skills among Chinese GP transfer training trainers. An online survey was conducted among trainers who participated in the 2021 Sichuan Province General Practice Training Trainer Program. The survey collected data on participants' characteristics and familiarity with 20 skills in three essential teaching knowledge areas: the core functions of primary care (five questions), preparation for lesson plan (four questions), and teaching methods (11 questions). In total, 305 participants completed the survey. Familiarity rates were generally low across all three essential teaching knowledge areas. No significant differences were observed in familiarity rates between the tertiary and secondary hospitals. This study revealed gaps in the teaching skills of GP transfer training trainers in China. These results suggest the necessity for targeted training programs to enhance the teaching skills and competencies of trainers.


Challenges and Successes Using Nanomedicines for Aerosol Delivery to the Airways.
Numerous diseases affect the respiratory tract and the aerosol administration has been widely considered as an adapted and non-invasive method for local delivery. This pathway induces a lung concentration and thus also limits, systemic side effects. However, aerosol delivery of active pharmaceutical ingredients represents a real challenge, due to numerous obstacles such as the specific respiratory movement, the presence of mucus or surfactant, and the mucociliary clearance. Nanomedicines, such as liposomes, micelles or nanoparticles, offer the possibility to increase bioavailability and favor intracellular penetration of specific drugs into lung tissue. This review focuses on the description of aerosol formulations and cellular barriers including design, characteristics and progressive adaptation to airways anatomy. Then, aerosolized formulations currently clinically approved, or in clinical trial are summarized according to the encapsulated drug. In a final section, promising aerosol formulations in pre-clinical studies are detailed.


[Physical diagnosis--ascites].
The diagnosis of ascites can be made very likely by a good clinical history and a well-directed physical examination, if the patient suffers from a disease which can cause ascites. The physician should ask about recent weight gain, change in abdominal girth and ankle oedema. With a positive history, the likelihood of the presence of ascites may increase 3 to 4-fold. When the findings at physical examination are also positive, the likelihood may increase 10 to 20-fold. A fluid wave is the most specific but less sensitive symptom. Shifting dullness, bulging flanks and flank dullness are less specific but much more sensitive parameters. The presence of ascites is very unlikely if the prior probability is low and both the patient's answers and the findings at physical examination are negative. Abdominal ultrasound, the gold standard, is not strictly indicated for diagnosing ascites: if based on the trial tried: pretest probability, clinical history and physical examination, the diagnosis is very likely or very unlikely. Ultrasonography is always indicated, however, when ascites is suspected and a positive finding is of clinical relevance.


Diurnal Variation in Accommodation, Binocular Vergence, and Pupil Size.
Our results show significant diurnal variations in accommodative function and the magnitude of the phoria. Therefore, when comparing visual measures in clinical or laboratory settings, performing the visual examination at the same time of day (±1 h) is encouraged. The aim of this study was to evaluate the accommodation, binocular vergence, and pupil behavior on three different times during the day. Twenty collegiate students (22.8 ± 2.1 years) participated in this study. Participants visited the laboratory on three different days at two-hourly intervals (morning: 9:00-11:00 AM; afternoon: 2:00- 4.00 PM; evening: 7.00-9.00 PM). The binocular vergence and accommodative function was measured using clinical optometric procedures, and the accommodative response and pupil function were evaluated in binocular conditions using the WAM-5500 auto refractometer. The accommodative amplitude for the right and left eyes showed statistically significant differences for the time interval (P = .001; P = .02, respectively), revealing higher accommodative amplitude in the morning and afternoon in comparison to the evening. Participants were more esophoric when assessed in the morning in comparison with the evening at far and near (P = .02, P = .01, respectively), and when assessed in the afternoon in comparison with the evening at far distance (P = .02). The magnitude of accommodative response was higher in the morning, and it decreased throughout the day at 500 cm (P < .001), 40 cm (P = .05) and 20 cm (P < .001). No statistically significant differences were obtained for any other variable. This study shows small diurnal variations in some accommodative and binocular vergence parameters, but no effects were observed for the pupil response. These outcomes are of special relevance for eye care specialists when performing repeated accommodative or binocular vergence measures. However, the diurnal variations were modest and may not influence a routine orthoptic examination.


Breast cancer in a male-to-female transsexual patient with a BRCA2 mutation.
Breast cancer is rare in male patients. Certain predisposing factors, be they genetic (e.g., BRCA2 gene mutations) or hormonal (imbalance between estrogen and androgen levels), have been implicated in male breast cancer pathophysiology. Male-to-female (MtF) transsexualism is a condition that generally involves cross-sex hormone therapy. Anti-androgens and estrogens are used to mimic the female hormonal environment and induce the cross-sex secondary characteristics. In certain situations, the change in the hormonal milieu can be disadvantageous and favor the development of hormone-dependent pathologies, such as cancer. We report a case of a MtF transgender patient who developed breast cancer after 7 years of cross-sex hormonal therapy. The patient was found to be BRCA2 positive, and suffered recurrent disease. The patient was unaware of being a member of an established BRCA2 mutation-positive kindred. This represents the first case of a BRCA2 mutation predisposing to breast cancer in a MtF transgender patient.


Associations of Electric Shock and Extremely Low-Frequency Magnetic Field Exposure With the Risk of Amyotrophic Lateral Sclerosis.
We explored the associations of occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and electric shocks with the risk of amyotrophic lateral sclerosis (ALS) in a pooled case-control study (European Multidisciplinary ALS Network Identification to Cure Motor Neurone Degeneration (Euro-MOTOR)) of data from 3 European countries. ALS patients and population-based controls were recruited in Ireland, Italy, and the Netherlands between 2010 and 2015. Lifetime occupational and lifestyle histories were obtained using structured questionnaires. We applied previously developed job exposure matrices assigning exposure levels to ELF-MF and potential for electric shocks. Odds ratios and 95% confidence intervals were estimated by means of logistic regression for exposure to either ELF-MF or electric shocks, adjusted for age, sex, study center, education, smoking, and alcohol consumption and for the respective other exposure. Complete occupational histories and information on confounding variables were available for 1,323 clinically confirmed ALS cases and 2,704 controls. Both ever having had exposure to ELF-MF above the background level (odds ratio = 1.16, 95% confidence interval: 1.01, 1.33) and ever having had potential exposure above background for electric shocks (odds ratio = 1.23, 95% confidence interval: 1.05, 1.43) were associated with ALS. Adjustment for the respective other exposure resulted in similar risk estimates. Heterogeneity in risks across study centers was significant for both exposures. Our findings support possible independent associations of occupational exposure to ELF-MF and electric shocks with the risk of ALS.


Liquid morphologies on structured surfaces: from microchannels to microchips
Liquid microchannels on structured surfaces are built up using a wettability pattern consisting of hydrophilic stripes on a hydrophobic substrate. These channels undergo a shape instability at a certain amount of adsorbed volume, from a homogeneous state with a spatially constant cross section to a state with a single bulge. This instability is quite different from the classical Rayleigh Plateau instability and represents a bifurcation between two different morphologies of constant mean curvature. The bulge state can be used to construct channel networks that could be used as fluid microchips or microreactors.


Tissue specific and variable collagen proliferation in Swiss albino mice treated with clenbuterol.
Chronic administration of clenbuterol, a beta-adrenoceptor agonist (2 mg/kg body weight/day for 30 days) to mice resulted in an increased body mass. Measurement of dry tissue mass suggested a protein anabolic effect in the gastrocnemius and heart. Quantitative estimation of collagen content, a non-contractile element as calculated from hydroxyproline assay revealed its proliferation in the gastrocnemius, cardiac ventricle, intestine and to some extent also in the kidney. Clenbuterol did not induce collagen proliferation in non-muscle tissues such as the lungs and liver. Histopathological examination of sections from treated ventricles showed an extensive collagen infiltration in the subendocardium and at myonecrosis sites.


Sex-hormone-induced inflammation and fibromuscular proliferation in the rat lateral prostate.
The subacute administration of estradiol-17 beta was shown to be a potent inducer of an inflammatory response specific to the lateral prostate of the castrated Wistar rat. The subsequent administration of dihydrotestosterone restored the wet weight of the gland while maintaining the inflammation established with estrogen treatment. These changes are histologically similar to a spontaneously arising nonbacterial prostatitis previously reported by others in the aging rat lateral prostate. When the same hormones were administered on a chronic basis, the intensity of the inflammation increased with time and was accompanied by a fibromuscular proliferation that consisted of fibroblasts, smooth muscle cells, and collagen. These chronic changes correlated well with studies by other investigators on human benign prostatic hyperplasia (BPH) where certain forms of BPH were associated with a significant degree of inflammation and fibromuscular growth. The present studies therefore establish a model system for the hormonal induction of an inflammatory reaction in the rat lateral prostate that precedes and could be causally related to proliferative responses in the fibromuscular stroma. The potentially important similarities that exist between these experimental findings and the human problems of nonbacterial prostatitis and benign prostatic hyperplasia warrant additional study.


Binary halftone image resolution increasing by decision tree learning.
This paper presents a new, accurate, and efficient technique to increase the spatial resolution of binary halftone images. It makes use of a machine learning process to automatically design a zoom operator starting from pairs of input-output sample images. To accurately zoom a halftone image, a large window and large sample images are required. Unfortunately, in this case, the execution time required by most of the previous techniques may be prohibitive. The new solution overcomes this difficulty by using decision tree (DT) learning. Original DT learning is modified to obtain a more efficient technique (WZDT learning). It is useful to know, a priori, sample complexity (the number of training samples needed to obtain, with probability 1 - delta, an operator with accuracy epsilon): we use the probably approximately correct (PAC) learning theory to compute the sample complexity. Since the PAC theory usually yields an overestimated sample complexity, statistical estimation is used to evaluate, a posteriori, a tight error bound. Statistical estimation is also used to choose an appropriate window and to show that DT learning has good inductive bias. The new technique is more accurate than a zooming method based on simple inverse halftoning techniques. The quality of the proposed solution is very close to the theoretical optimal obtainable quality for a neighborhood-based zooming process using the Hamming distance to quantify the error.


Shifting hierarchies of interleukin-10-producing T cell populations in the central nervous system during acute and persistent viral encephalomyelitis.
Interleukin-10 (IL-10) mRNA is rapidly upregulated in the central nervous system (CNS) following infection with neurotropic coronavirus and remains elevated during persistent infection. Infection of transgenic IL-10/green fluorescent protein (GFP) reporter mice revealed that CNS-infiltrating T cells were the major source of IL-10, with minimal IL-10 production by macrophages and resident microglia. The proportions of IL-10-producing cells were initially similar in CD8(+) and CD4(+) T cells but diminished rapidly in CD8(+) T cells as the virus was controlled. Overall, the majority of IL-10-producing CD8(+) T cells were specific for the immunodominant major histocompatibility complex (MHC) class I epitope. Unlike CD8(+) T cells, a large proportion of CD4(+) T cells within the CNS retained IL-10 production throughout persistence. Furthermore, elevated frequencies of IL-10-producing CD4(+) T cells in the spinal cord supported preferential maintenance of IL-10 production at the site of viral persistence and tissue damage. IL-10 was produced primarily by the CD25(+) CD4(+) T cell subset during acute infection but prevailed in CD25(-) CD4(+) T cells during the transition to persistent infection and thereafter. Overall, these data demonstrate significant fluidity in the T-cell-mediated IL-10 response during viral encephalitis and persistence. While IL-10 production by CD8(+) T cells was limited primarily to the time of acute effector function, CD4(+) T cells continued to produce IL-10 throughout infection. Moreover, a shift from predominant IL-10 production by CD25(+) CD4(+) T cells to CD25(-) CD4(+) T cells suggests that a transition to nonclassical regulatory T cells precedes and is retained during CNS viral persistence.


Monoclonal antibody technique for detection of estrogen receptors in human breast cancer: greater sensitivity and more accurate classification of receptor status than the dextran-coated charcoal method.
Estrogen receptor (ER) concentrations have been determined in 191 freshly prepared cytosols from breast cancer biopsies using both the monoclonal enzyme immunoassay (ER-EIA) and the dextran-coated charcoal (ER-DCC) methods in a single laboratory. The concentrations of the ER detected using the two methods are highly and significantly correlated (linear regression curve: ER-EIA = 15.5 + 0.82 ER-DCC; r = 0.97). Nevertheless, it may be most correct to interpret the data by resolving the correlation into two lines, one describing the fit for cytosols with low and intermediate concentrations (the first 75% of the distribution of ER values for all primary breast cancers; less than 217 fmol ER/mg cytosol protein) and one describing the fit for cytosols with the highest ER concentrations (i.e., greater than or equal to 217 fmol ER/mg cytosol protein). Using a cutoff limit of 10 fmol/mg cytosol protein to distinguish between ER positive and ER negative biopsies, discrepancies in the classification of ER status were found in only 6% (12 of 191) of the cases using the two different methods. In all 12 cases, the ER concentrations as determined by both methods were in the lower range of receptor concentrations (0-53 fmol/mg cytosol protein). Of the 12 discrepancies, 10 biopsies were classified as ER negative using the ER-DCC method but ER positive using the ER-EIA method. Additional available data for these 10 patients indicate that the ER-EIA assay yielded the more biologically "correct" result. All 10 of these biopsies were either progesterone receptor positive or had nuclear ER. By identifying the outliers of the linear regression curves (points exceeding the 80% confidence interval) of the logarithmically transformed ER concentrations, 9 of the 12 biopsies were identified. Thus, it is unlikely that the observed discrepancies are due to random events in most cases here. Since most of the few deviations observed appear to represent true differences in the sensitivities of the two methods, the ER-EIA method appears to be superior to the ER-DCC method in our hands. The concentration of ER in 47 cytosols stored at -70 degrees C for 3-6 yr was analyzed using the ER-EIA method, and results were compared to the concentration of ER found using the ER-DCC method on freshly prepared cytosols when the biopsies had been received at the laboratory. The linear regression curve of the correlation between ER concentrations determined using the two methods did not differ significantly from that found for the 191 freshly prepared cytosols.


Differential expression of a novel C-terminally truncated splice form of SMAD5 in hematopoietic stem cells and leukemia.
SMADs are evolutionarily conserved transducers of the differentiation and growth arrest signals from the transforming growth factor/BMP (TGF/BMP) family of ligands. Upon receptor activation, the ligand-restricted SMADs(1-35) are phosphorylated in the C-terminal MH2 domain and recruit the common subunit SMAD4/DPC-4 gene to the nucleus to mediate target gene expression. Frequent inactivating mutations of SMAD4, or less common somatic mutations of SMAD2 seen in solid tumors, suggest that these genes have a suppressor function. However, there have been no identified mutations of SMAD5, although the gene localizes to the critical region of loss in chromosome 5q31.1 (chromosome 5, long arm, region 3, band 1, subband 1) in myelodysplasia (MDS) and acute myelogenous leukemia (AML). A ubiquitously expressed novel isoform, SMAD5beta, encodes a 351 amino acid protein with a truncated MH2 domain and a unique C-terminal tail of 18 amino acids, which may be the functional equivalent of inactivating mutations. The levels of SMAD5beta transcripts are higher in the undifferentiated CD34(+) hematopoietic stem cells than in the terminally differentiated peripheral blood leukocytes, thereby implicating the beta form in stem cell homeostasis. Yeast 2-hybrid interaction assays reveal the lack of physical interactions between SMAD5beta and SMAD5 or SMAD4. The expression of SMAD5beta may represent a novel mechanism to protect pluripotent stem cells and malignant cells from the growth inhibitory and differentiation signals of BMPs. (Blood. 2000;95:3945-3950)


Incorporation of the carbocyclic analog of 2'-deoxyguanosine into the DNA of herpes simplex virus and of HEp-2 cells infected with herpes simplex virus.
The carbocyclic analog of 2'-deoxyguanosine (CdG) is active against herpes simplex virus (HSV), human cytomegalovirus, and human hepatitis-B virus. In order to understand the mechanism of action of this compound against HSV, we have evaluated (a) the incorporation of [3H]CdG into viral and host DNA in HEp-2 cells infected with HSV and (b) the interaction of the 5'-triphosphate of CdG (CdG-TP) with the HSV DNA polymerase and human DNA polymerases alpha, beta, and gamma (EC 184.108.40.206). Incubation of HSV-1-infected HEp-2 cells with [3H]CdG resulted in the incorporation of CdG into both the HSV and the host cell DNA. These results indicated that CdG-TP was used as a substrate for HSV DNA polymerase and for at least one of the cellular DNA polymerases. Degradation of both viral and host DNA with micrococcal nuclease and spleen phosphodiesterase indicated that CdG was incorporated primarily into internal positions in both DNAs. The viral DNA containing CdG sedimented in neutral and alkaline sucrose gradients in the same way as did viral DNA labeled with [3H]thymidine, indicating that the HSV DNA containing CdG was similar in size to untreated HSV DNA. CdG-TP was a competitive inhibitor of the incorporation of dGTP into DNA by the HSV DNA polymerase (Ki of 0.35 microM) and the human DNA polymerase alpha (Ki of 1 microM). CdG-TP was not a potent inhibitor of either DNA polymerase beta or gamma. Using DNA-sequencing technology, CdG-TP was found to be an efficient substrate for HSV DNA polymerase. Incorporation of CdG monophosphate (CdG-MP) into the DNA by HSV DNA polymerase did not interfere with subsequent chain extension. These results suggested that the antiviral activity of CdG was due to its incorporation into the DNA and subsequent disruption of viral functions. In contrast, CdG-TP was not as good as dGTP as a substrate for DNA synthesis by DNA polymerase alpha, and incorporation of CdG-MP by DNA polymerase alpha inhibited further DNA chain elongation.


[Mechanism of action of alpha-neurotoxins from snake venom on nicotinic cholinoreceptors of sympathetic ganglion neurons in the rabbit].
Effect of alpha-neurotoxins from snake venoms (alpha-bungarotoxin and alpha-cobratoxin, 10(-6)M) on the ACh-induced current and on the fast excitatory postsynaptic current (EPSC) were studied in voltage-clamped neurons of the isolated rabbit superior cervical ganglion treated with atropine (10(-6)M) alpha-Neurotoxins produced potentiating or inhibitory effects on ACh-induced current and only inhibitory effect on EPSC. alpha-Neurotoxins did not change single channel current and lifetime for short-living nicotinic channels and prolonged the lifetime for long-living channels as well as EPSC decay. It is suggested that the inhibitor effect of alpha-neurotoxins on ACh-induced current and on EPSP is due to partial blockade of nicotinic Ach receptors and that their potentiating effect on ACh-induced current results from the prolonged lifetime for long-living channels.


Differences in characteristics and outcomes between community- and hospital-acquired acute kidney injury: A systematic review and meta-analysis .
No comprehensive review has examined the difference between community-acquired (CA) and hospital-acquired (HA) acute kidney injury (AKI) in terms of patient characteristics, in-hospital mortality, and hospital stay length. We conducted a systematic review and meta-analysis of observational studies, using MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Library from their inceptions to April 10, 2016. Observational studies that (1) were published in peer-reviewed journals; (2) compared CA-AKI with HA-AKI, irrespective of the AKI definition during the same period; and (3) investigated in-hospital mortality and length of hospital stay were studied. Differences in the patients' baseline characteristics were analyzed, and a meta-analysis was conducted to compare the in-hospital mortality and length of hospital stay. Eight eligible observational studies with 17,939 patients were included. The systematic review showed that patients with CA-AKI had a significantly higher rate of AKI stage 3 compared with those with HA-AKI. The meta-analysis revealed that patients with CA-AKI showed significantly lower in-hospital mortality (odds ratio (OR) = 2.79; Z = 8.22; 95% confidence interval (CI), 2.18 - 3.56; p < 0.001) and shorter length of hospital stay (OR = 2.55; Z = 5.81; 95% CI, 1.86 - 3.50; p < 0.001). Subanalyses of studies conducted in developing and developed countries showed that patients with CA-AKI had lower in-hospital mortality and shorter length of hospital stay. Jackknife sensitivity analyses confirmed the replicability of these findings (p < 0.001). The results indicate that significant differences exist in clinical phenotypes between CA- and HA-AKI, even when standardized diagnosis criteria are used. .


The effectiveness of emergency obstetric referral interventions in developing country settings: a systematic review.
Pregnancy complications can be unpredictable and many women in developing countries cannot access health facilities where life-saving care is available. This study assesses the effects of referral interventions that enable pregnant women to reach health facilities during an emergency, after the decision to seek care is made. Selected bibliographic databases were searched with no date or language restrictions. Randomised controlled trials and quasi experimental study designs with a comparison group were included. Outcomes of interest included maternal and neonatal mortality and other intermediate measures such as service utilisation. Two reviewers independently selected, appraised, and extracted articles using predefined fields. Forest plots, tables, and qualitative summaries of study quality, size, and direction of effect were used for analysis. Nineteen studies were included. In South Asian settings, four studies of organisational interventions in communities that generated funds for transport reduced neonatal deaths, with the largest effect seen in India (odds ratio 0·48 95% CI 0·34-0·68). Three quasi experimental studies from sub-Saharan Africa reported reductions in stillbirths with maternity waiting home interventions, with one statistically significant result (OR 0.56 95% CI 0.32-0.96). Effects of interventions on maternal mortality were unclear. Referral interventions usually improved utilisation of health services but the opposite effect was also documented. The effects of multiple interventions in the studies could not be disentangled. Explanatory mechanisms through which the interventions worked could not be ascertained. Community mobilisation interventions may reduce neonatal mortality but the contribution of referral components cannot be ascertained. The reduction in stillbirth rates resulting from maternity waiting homes needs further study. Referral interventions can have unexpected adverse effects. To inform the implementation of effective referral interventions, improved monitoring and evaluation practices are necessary, along with studies that develop better understanding of how interventions work.


The Role of Medication in Supporting Emotional Wellbeing in Young People with Long-Term Needs.
Young people frequently use and access prescribed medications for a range of health problems. Medications aimed at treating both common health problems and long-term physical and mental health needs in adolescence can have a significant effect on a young person's emotional well-being. We use a series of case studies to illustrate the challenges for healthcare professionals supporting young people with medication use. The studies illustrate the efficacy and limitations of medication on improving emotional well-being by alleviating illness and distress, and how this efficacy must be balanced against both the adverse effects and the burden of treatment. There are specific challenges for medication management during adolescence including issues of adherence/concordance, facilitating autonomy and participation in decision making, and promoting independence.


Social determinants of loneliness among older Americans.
To further understand loneliness among older persons, a conceptual model, predicated on a social-support perspective, was examined. Results were based on 1,071 participants in the congregate and home-delivered meal programs of the Senior Citizens Nutrition and Activities Program in Hillsborough County, Florida. A series of stepwise multiple regression analyses showed that loneliness was greater among men, those with no children, those with no friends, those more physically disabled, those who subjectively felt that their health was poorer, and those who subjectively felt that their economic condition was inadequate. Not related directly to loneliness but with indirect influence were age, race, education, marital status, and poverty status. Those variables with no direct or indirect effect included rural or urban location, identification of emotional closeness with existing children or friends, and living alone. Theoretically, the results do not fully support the social-support perspective but point to the impact of a broad spectrum of demographic, health, economic, and social factors.


[Detection of viremia in children with manifestations of an oral herpes infection].
Immunofluorescent examination of blood smears from 155 children aged from 1 to 11 years with manifestations of herpetic infection in the oral cavity (primary acute stomatitis diagnosed in 108, recurrent in 47) was carried out. Antigens of herpes virus in blood leukocytes from sick children were detected in 50.9 +/- 4.8% of cases of acute stomatitis and in 51.0 +/- 7.3% of cases in the period of exacerbation of chronic stomatitis. Herpes virus antigens were detected significantly more frequently in the specimens obtained in the febrile period and in those collected during the first 3 days of the disease or relapse. Examinations of 30 children of the control group yielded herpes virus antigen in 1 case only.


[Clinostatic variations of the lumbosacral spine and obstetrical mechanics].
An X-ray study of the lumbar spine after childbirth in 2 groups of patients (one control group and one group with engagement dystocia) picked up one difference between the groups. The patients who gave birth spontaneously, presented with hyperlordosis which was relieved when lying down. In contrast, the patients who had presented engagement dystocia, presented with hyperlordosis which was aggravated when lying down.


House Dust Mites in Erzincan Province.
We aimed to determine the species of the house dust mites seen in Erzincan, the number of mites per gram of dust in the houses, and the relationship between temperature and the number of mite specimens. For this purpose, 54 dust samples collected from 18 houses located in different districts of Erzincan province between November 2013 and January 2014. These samples were examined by a lactic acid precipitation method. Of the houses in which the dust samples were collected, 94.44% were found to be positive in terms of mites. A total of 844 mite specimens were isolated from the dust samples, and the mean number of mites per gram of dust was found to be 18.34. The most common species was found to be Acarus siro (55.55%) and was followed by Dermatophagoides pteronyssinus (50.00%), Tyrophagus putrescentiae (22.22%), Histiostoma sp. (22.22%), Lepidoglyphus destructor (16.66%), T. perniciosus(11.11%), Euroglyphus maynei (11.11%), Glycyphagus privatus (11.11%), Cheyletus sp. (11.11%), Tarsonemus sp. (11.11%), and Tetranychus sp. (11.11%). Mite-holding rate of the houses in Erzincan province was found to be 94.44%. The mean number of mites per gram of dust was found to be 18.34. The most common mite species was A. siro, which was followed by D. pteronyssinus.


Fentanyl nasal spray for the treatment of cancer pain.
Breakthrough pain, a transitory flare of pain in patients with otherwise controlled chronic pain, has been well characterized in cancer patients but despite medical awareness, sometimes remains underdiagnosed and therefore undertreated. Oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablets are the first medications developed specifically for the treatment of breakthrough pain in opioid-tolerant patients. Since oral administration of fentanyl is not an option for many cancer patients, the development of intranasal fentanyl spray (INFS) emerged as a more effective method of administration. Intranasal administration of fentanyl has several advantages over the oral/gastrointestinal route and clinical trials have shown that it is superior to OTFC while being well tolerated and more acceptable by the majority of patients. The aim of this review is to summarize the pharmacological characteristics and data obtained from clinical studies of INFS in the past few years, and present Fentanyl Pectin Nasal Spray (PecFent), which uses an innovative delivery system and is now approved in the EU. Finally, we discuss the impact that it may have in the future management of breakthrough pain in cancer patients, because an accurate diagnosis followed by the best treatment is crucial for effective pain alleviation.


Control of plasminogen activator activity in the thecal layer of the largest preovulatory follicle in the hen ovary.
Although the existence of plasminogen activator (PA) activity and the factors that regulate it in ovarian granulosa cells of both mammalian and avian species have been extensively documented, very little information has been generated concerning the control of PA activity in the adjacent thecal layer. This study was conducted to evaluate the effects of several physiological and pharmacological agents on PA activity in dispersed cells from the thecal layer of the largest preovulatory follicle in the hen ovary 17-16 h before ovulation. LH (50 and 100 ng) in the presence of 3-isobutyl-1-methylxanthine (0.01 mM) stimulated an approximate 25% increase in cell-associated PA activity, possibly via elevated levels of cAMP. Prostaglandin E1 and E2 (PGE1 and PGE2; 0.1 and 1 microM), but not PGI2 or PGF2 alpha (1 microM), enhanced PA activity and cAMP formation, effects that were potentiated by 0.01 mM 3-isobutyl-1-methylxanthine. Activation of Gs with cholera toxin (0.01-10 ng/tube) or adenylyl cyclase with forskolin (0.01-10 microM) stimulated cAMP formation and PA activity in a dose-dependent manner. Exposure of cells to the cAMP analog 8-bromo-cAMP (0.1-5 mM) caused similar increases in thecal cell PA activity. Incubation of cells with phorbol 12-myristate 13-acetate (PMA; 3.2-162 nM), an agonist known to activate protein kinase-C, resulted in a dose-dependent increase in PA activity. However, an equimolar concentration of phorbol 13-monoacetate (162 nM), an inactive analog of PMA that does not activate protein kinase-C, was without effect. Coincubation of cells with forskolin (1 microM) and PMA (32 nM) resulted in a synergistic stimulation of secreted PA activity, apparently via an enhancement of adenylyl cyclase activity. Treatment of cells with the calcium ionophore A23187 (0.01-1 microM) suppressed basal PA activity. However, PA activity stimulated by PMA (32 nM) was synergistically increased after coincubation with a 0.05-microM concentration of A23187, but was inhibited at doses of 0.5 and 1 microM. Taken collectively, the data indicate that PA activity is present in the thecal layer of the largest preovulatory follicle in the ovary of the domestic hen. Furthermore, several endocrine factors (i.e. LH and PGs) were found to stimulate PA activity, possibly via both the adenylyl cyclase-cAMP-protein kinase-A and phosphoinositide-protein kinase-C pathways. In light of these findings, we propose that the preovulatory increase in PGs and LH activates PA in the thecal layer of the largest preovulatory follicle, resulting in proteolytic degradation of the follicular connective tissue and, ultimately, ovulation.


Two-colour fluorescent imaging in organisms using self-assembled nano-systems of upconverting nanoparticles and molecular switches.
The water-insolubility of a potentially versatile photoresponsive 'turn-on' fluorescence probe was overcome by incorporating it into a nano-assembly containing an upconverting nanoparticle wrapped in an amphiphilic polymer. The appeal of the nano-system is not only in the ability to turn "on" and "off" the fluorescence from the organic chromophore using UV and visible light, it is in the fact that the nanoparticle acts as a static probe because it emits red and green light when excited by near infrared light, which is not effected by UV and visible light. This dual-functioning emission behaviour was demonstrated in live organisms.


New species of kathlaniid (Nematoda: Cosmocercoidea) collected from hynobiid salamanders in Japan.
Falcaustra odaiensis n. sp. (Nematoda: Cosmocercoidea: Kathlaniidae) is described from the Japanese clawed salamander, Onychodactylus japonicus (Houttuyn, 1782), and Ishizuchi salamander, Hynobius hirosei Lantz, 1931 (Caudata: Hynobiidae), in Japan. This nematode is characterized by having multiple pseudosuckers in the male. It resembles Falcaustra araxiana, Falcaustra duyagi, Falcaustra lambdiensis, Falcaustra pillaii, Falcaustra siamensis, and Falcaustra washingtonensis, but is readily distinguished by the spicule length and/or egg size. This is the first Falcaustra species described from Japanese salamanders.


Natural killer cells in asthma.
The worldwide prevalence, morbidity, and mortality of asthma have dramatically increased over the last few decades and there is a clear need to identify new effective therapeutic and prophylactic strategies. Despite high numbers of NK cells in the lung and their ability to generate a variety of immunomodulatory mediators, the potential of NK cells as therapeutic targets in allergic airway disease has been largely overlooked. The fact that IgE, acting through FcγRIII, can activate NK cells resulting in cytokine/chemokine production implies that NK cells may contribute to IgE-mediated allergic responses. Indeed, current evidence suggests that NK cells can promote allergic airway responses during sensitization and ongoing inflammation. In animal models, increased NK cells are observed in the lung following antigen challenge and depletion of the cells before immunization inhibits allergic airway inflammation. Moreover, in asthmatics, NK cell phenotype is altered and may contribute to the promotion of a pro-inflammatory Th2-type environment. Conversely, driving NK cells toward an IFN-γ-secreting phenotype can reduce features of the allergic airway response in animal models. However, we have limited knowledge of the signals that drive the development of distinct subsets and functional phenotypes of NK cells in the lung and thus the role and therapeutic potential of NK cells in the allergic airway remains unclear. Here we review the potentially diverse role of NK cells in allergic airway disease, identify gaps in current knowledge, and discuss the potential of modulating NK cell function as a treatment strategy in asthma.


[Neurohistologic and histochemical characteristics of Loeschke's zone of the medulla in the cat].
Neuronal organization and transmitter characteristics of chemosensitive area on the ventral medulla surface (zone L) of the cat were studied using neurohistological and histochemical methods. Neurons of different shape and size are heterogeneously distributed in zone L. They are concentrated mostly at the level of the hypoglossal nerve root, their number decreasing in the rostral and caudal directions. Negligible part of zone L neurons is choline- and monoaminergic, whereas the majority of neurons appears to release other transmitters. Cholinergic and noncholinergic cholinoceptive neurons as well as neurons sensitive to catecholamines and serotonin, are found in zone L. The conclusion is made that catecholamine-, serotonin- and cholinergic fibres found in zone L may be of local origin or run from other structures.


A resident-created hospitalist curriculum for internal medicine housestaff.
The growth of hospital medicine has led to new challenges, and recent graduates may feel unprepared to meet the expanding clinical duties expected of hospitalists. At our institution, we created a resident-inspired hospitalist curriculum to address the training needs for the next generation of hospitalists. Our program provided 3 tiers of training: (1) clinical excellence through improved training in underemphasized areas of hospital medicine, (2) academic development through required research, quality improvement, and medical student teaching, and (3) career mentorship. In this article, we describe the genesis of our program, our final product, and the challenges of creating a curriculum while being internal medicine residents. Journal of Hospital Medicine 2016;11:646-649. © 2016 Society of Hospital Medicine.


The Therapeutic Effects of Singing in Neurological Disorders.
Music making (playing an instrument or singing) is a multimodal activity that involves the integration of auditory and sensorimotor processes. The ability to sing in humans is evident from infancy, and does not depend on formal vocal training but can be enhanced by training. Given the behavioral similarities between singing and speaking, as well as the shared and distinct neural correlates of both, researchers have begun to examine whether singing can be used to treat some of the speech-motor abnormalities associated with various neurological conditions. This paper reviews recent evidence on the therapeutic effects of singing, and how it can potentially ameliorate some of the speech deficits associated with conditions such as stuttering, Parkinson's disease, acquired brain lesions, and autism. By reviewing the status quo, it is hoped that future research can help to disentangle the relative contribution of factors to why singing works. This may ultimately lead to the development of specialized or "gold-standard" treatments for these disorders, and to an improvement in the quality of life for patients.


Identification of a key role of widespread epigenetic drift in Barrett's esophagus and esophageal adenocarcinoma.
Recent studies have identified age-related changes in DNA methylation patterns in normal and cancer tissues in a process that is called epigenetic drift. However, the evolving patterns, functional consequences, and dynamics of epigenetic drift during carcinogenesis remain largely unexplored. Here we analyze the evolution of epigenetic drift patterns during progression from normal squamous esophagus tissue to Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) using 173 tissue samples from 100 (nonfamilial) BE patients, along with publically available datasets including The Cancer Genome Atlas (TCGA). Our analysis reveals extensive methylomic drift between normal squamous esophagus and BE tissues in nonprogressed BE patients, with differential drift affecting 4024 (24%) of 16,984 normally hypomethylated cytosine-guanine dinucleotides (CpGs) occurring in CpG islands. The majority (63%) of islands that include drift CpGs are associated with gene promoter regions. Island CpGs that drift have stronger pairwise correlations than static islands, reflecting collective drift consistent with processive DNA methylation maintenance. Individual BE tissues are extremely heterogeneous in their distribution of methylomic drift and encompass unimodal low-drift to bimodal high-drift patterns, reflective of differences in BE tissue age. Further analysis of longitudinally collected biopsy samples from 20 BE patients confirm the time-dependent evolution of these drift patterns. Drift patterns in EAC are similar to those in BE, but frequently exhibit enhanced bimodality and advanced mode drift. To better understand the observed drift patterns, we developed a multicellular stochastic model at the CpG island level. Importantly, we find that nonlinear feedback in the model between mean island methylation and CpG methylation rates is able to explain the widely heterogeneous collective drift patterns. Using matched gene expression and DNA methylation data in EAC from TCGA and other publically available data, we also find that advanced methylomic drift is correlated with significant transcriptional repression of ~ 200 genes in important regulatory and developmental pathways, including several checkpoint and tumor suppressor-like genes. Taken together, our findings suggest that epigenetic drift evolution acts to significantly reduce the expression of developmental genes that may alter tissue characteristics and improve functional adaptation during BE to EAC progression.


QTc prolongation in children following congenital cardiac disease surgery.
IntroductionQTc prolongation has been reported in adults following cardiopulmonary bypass; however, this phenomenon has not been studied in children with congenital cardiac disease. This study's aim was to formally assess QTc in children undergoing cardiac surgery. Pre-operative and post-operative electrocardiograms during hospital stays were prospectively analysed on 107 consecutive patients under 18 years of age undergoing cardiac surgery. QTc was measured manually in leads II, V4, and V5. Measurements of 440 and 480 milliseconds were used to categorise patients. Peri-procedural data included bypass and cross-clamp time, medications, and electrolyte measurements. Outcome data included arrhythmias, length of mechanical ventilation, and hospital stay. Patients with post-operative new bundle branch block or ventricularly paced rhythm were excluded. In all, 59 children were included, out of which 26 had new QTc over 440 milliseconds and 6 of 59 had new QTc over 480 milliseconds post-operatively. The mean increase in post-operative QTc was 25 milliseconds, p=0.0001. QTc over 480 was associated with longer cross-clamp time, p=0.003. Other risk factors were not associated with post-operative QTc prolongation. This phenomenon was transient with normalisation occurring in 67% of patients over 60 hours on average. One patient with post-operative QTc over 440 milliseconds developed ventricular tachycardia. There was no correlation between prolonged QTc and duration of mechanical ventilation, or hospital stay.ConclusionA significant number of children undergoing cardiac surgery showed transient QTc prolongation. The precise aetiology of QT prolongation was not discerned, though new QTc over 480 milliseconds was associated with longer cross-clamp time. In this cohort, transient QTc prolongation was not associated with adverse sequela.


Separation and Identification of Glycan Anomers Using Ultrahigh-Resolution Ion-Mobility Spectrometry and Cryogenic Ion Spectroscopy.
The analysis of carbohydrates, or glycans, is challenging for established structure-sensitive gas-phase methods. The multitude of possible stereo-, regio-, and structural isomers makes them substantially more complex to analyze than DNA or proteins, and no one method is currently able to fully resolve them. While the combination of tandem mass spectrometry (MS) and ion-mobility spectrometry (IMS) have made important inroads in glycan analysis, in many cases, this approach is still not able to identify the precise isomeric form. To advance the techniques available for glycan analysis, we employ two important innovations. First, we perform ultrahigh-resolution mobility separation using structures for lossless ion manipulations (SLIM) for isomer separation and pre-selection. We then complement this IMS-MS stage with a cryogenic IR spectroscopic dimension since a glycan's vibrational spectrum provides a fingerprint that is extremely sensitive to the precise isomeric form. Using this unique approach in conjunction with oxygen-18 isotopic labeling, we show on a range of disaccharides how the two α and β anomers that every reducing glycan adopts in solution can be readily separated by mobility and identified based on their IR spectra. In addition to highlighting the power of our technique to detect minute differences in the structure of isomeric carbohydrates, these results provide the means to determine if and when anomericity is retained during collision-induced dissociation (CID) of larger glycans.


Effect of collection time and exercise restriction on the prediction of urine protein excretion, using urine protein/creatinine ratio in dogs.
Nonproteinuric and proteinuric dogs were studied to determine whether the urine protein/creatinine ratio from a 24-hour urine sample could be used to predict urine protein excretion. Urine protein/creatinine ratios estimated from urine produced during daylight hours and from that produced during nighttime hours were compared to determine whether time of sample collection influenced the prediction of the urine protein excretion value. Urine protein/creatinine ratios in urine from male dogs were compared with those from female dogs to determine whether sex had an influence on the value. Hospitalized and nonhospitalized dogs were used to determine the effect of exercise restriction. The urine protein/creatinine ratio varied significantly between healthy and proteinuric dogs (P = 0.0001). It was not influenced by collection period or sex. Animals not confined to hospital cages had a significantly lower urine protein/creatinine ratio than did hospitalized animals confined to a cage (P = 0.003).


Mullerian adenosarcoma of the female genital tract.
Mullerian adenosarcoma is an uncommon, but not rare, mixed tumor containing a neoplastic but benign or mildly atypical epithelial element and a sarcomatous, usually low-grade, stromal component. The most common site is the uterine corpus but adenosarcoma also occurs in the cervix and ovary and more rarely in the vagina, fallopian tube, arising from peritoneal surfaces, or outside the female genital tract, for example in the intestine. Most uterine cases have a polypoid gross appearance, sometimes resulting in the formation of multiple polyps. Characteristic histologic features include a low power "phyllodes-like" architecture with leaf-like projections lined by a variety of benign Mullerian type epithelia, sometimes with squamous metaplasia. Intraglandular stromal protrusions are a characteristic feature. The stroma may be uniformly cellular but there is typically increased cellularity around the epithelial elements, resulting in the formation of a cambium layer. Using the World Health Organization definition, stromal mitotic activity of 2 or more per 10 high-power fields is required for a diagnosis of adenosarcoma but in practice the diagnosis is made with stromal mitotic activity less than this if the characteristic architecture and cambium layer is present. The stromal component is usually morphologically "low-grade" and of endometrial stromal or fibroblastic type (hormone receptor and CD10 positive). Sometimes it is high grade, resembling undifferentiated sarcoma. Additional features sometimes present include heterologous stromal elements or sex cord-like differentiation. Uterine adenosarcomas are, in general, low-grade neoplasms capable of local recurrence after polypectomy or hysterectomy and much less commonly distant metastasis. The 2 most important adverse prognostic factors, which sometimes coexist, are deep myometrial invasion and sarcomatous overgrowth; the latter is usually associated with morphologically "high-grade" stromal elements with loss of expression of hormone receptors and CD10. Adenosarcoma may be confused with a variety of lesions and one of the main differential diagnoses is adenofibroma in which the stromal component is, by definition, morphologically benign. However, occasional adenofibromas recur or even metastasize. As such, it has been suggested that all adenofibromas should be classified as adenosarcomas, albeit with low-malignant potential. Ovarian adenosarcomas are much more likely to exhibit malignant behavior than their uterine counterparts, probably due to the lack of an anatomic barrier to peritoneal dissemination.


Somatomedin-C in human fetal pancreas. Cellular localization and release during organ culture.
The presence of somatomedin-C/insulin-like growth factor I (SM-C/IGF-I) was investigated in human fetal pancreatic glands obtained after prostaglandin-induced abortion at 14-17 wk of gestation. Pancreatic explants were cultured in medium containing 11.1 or 22.2 mM glucose and 20% fetal calf serum for 8-10 days. During this period they were exposed, on two separate occasions, to serum-free culture medium for 24 h. SM-C/IGF-I and insulin were measured radioimmunologically in the serum-free media and in acid-ethanol-extracted homogenates of the cultured explants. SM-C/IGF-I was measurable in the conditioned media only after extraction by reverse-phase chromatography to remove somatomedin-binding proteins. On gel filtration at neutral pH of extracted medium samples, the immunoreactive SM-C/IGF-I was recovered in the region of the homogeneous peptide with an apparent molecular weight of 7000-8000. Explants cultured in 22.2 mM glucose contained more SM-C/IGF-I and had a tendency to release more of the peptide into the culture medium than explants cultured in 11.1 mM. There was no difference in insulin content or release between the two groups. By immunocytochemistry, SM-C/IGF-I was localized to the beta-cells of the endocrine pancreas in both freshly fixed tissue and cultured explants. We conclude that the human fetal pancreas contains SM-C/IGF-I and secretes the peptide during tissue culture. The presence of SM-C/IGF-I in the islets of Langerhans may contribute to the growth and development of the insulin-producing beta-cell.


Guanine nucleotide-dependent translocation of RhoA from cytosol to high affinity membrane binding sites in human erythrocytes.
The translocation of the small GTP-binding protein Rho from the cytosolic to membrane-bound form is an early step in many cellular signal-transduction events, but little is known regarding the mechanism of Rho association with the plasma membrane. We have used membranes from human erythrocytes to uncover a novel class of integral membrane components involved in the Rho-membrane association. Membranes of human erythrocytes contain several proteins of the Ras superfamily. Using specific antibodies and C3 exoenzyme of Clostridium botulinum we have identified one of them as RhoA. This protein was detected in both cytosol and membrane fractions of hypotonically lysed erythrocytes. We found that cytosolic Rho bound specifically to the cytoplasmic surface of the erythrocyte membrane and that the translocation of Rho to the membrane was absolutely dependent on the prior incubation of the cytosol with guanosine 5'--gamma-thio-triphosphate (1-50 microM) at low Mg2+ concentration. Rho binding sites could not be extracted from the membrane using conditions that extracted all other peripheral proteins and were unaffected by heat treatment and protease digestion. Rho binding was saturable, with a Kd in the range 1-5.0 nM, and the number of binding sites was estimated to be approx. (1-2) x 10(3) sites per cell. This is the first report of Rho binding to integral membrane components. The identity of these components may reveal novel aspects of the mechanism by which Rho exerts its multiple biochemical effects.


Comparative esterase electrophoretic polymorphism of Escherichia coli isolates obtained from animal and human sources.
To determine whether enzyme electrophoretic polymorphism in Escherichia coli populations was influenced by environmental background, the mobilities of four electrophoretically variable esterases (A, B, C and I) were examined. The distinction between isolates was established by significant differences in the electrophoretic distribution and the genetic diversity coefficient of individual esterases. Principal components analysis on each population and on all strains revealed three groups of allozymes. The first, characterized by slow electrophoretic mobilities of esterase B, was frequently observed in strains obtained from human extra-intestinal infections and rarely in commensal organisms. The second, characterized by fast mobilities of esterases A and B, was frequently found in animal isolates. The third, characterized by prominence of the most common mobilities of esterases B and A, was recovered in all populations. These results were confirmed by discriminant analysis. Among the 610 strains investigated, 316 electrophoretic types (distinctive combinations of allozymes of the four varieties of esterases) were distinguished, illustrating high esterase polymorphism.


Clinical evaluation of occupational asthma.
In this paper, the procedures in the assessment of occupational asthma (OA) are discussed. Only the most common subtype of OA is considered here, i.e. that in which symptoms appear after a latency period from the beginning of exposure. OA is characterized by variable bronchial obstruction, and variable bronchial hyperresponsiveness caused by specific agents inhaled at work. The clinical investigation of OA is a stepwise approach which includes a comprehensive history together with physiological and immunological studies. The first step is to identify symptoms and relate exposure at work to the presence in the workplace of substances known to provoke OA. The presence of bronchial asthma must then be confirmed; this is achieved by assessing the reversibility of bronchial obstruction and/or the presence of nonspecific bronchial hyperreactivity and/or the presence of significant peak expiratory flow (PEF) variability. The relationship between work and symptoms may first be assessed by means of serial measurements of PEF and of nonspecific bronchial hyperreactivity during periods at work and away from work. When the suspected agent is a high-molecular-weight (HMW) or a low-molecular-weight (LMW) agent known to act through an immunoglobulin E (IgE)-mediated mechanism, skin tests and/or research for specific IgE should be performed. In case of sensitization, where a relationship between asthma and work has been demonstrated by means of serial monitoring of PEF, a diagnosis can be made. If the suspected agent is a LMW agent, a specific inhalation challenge test in the laboratory or at the workplace is necessary.


Rapid diagnostic tests for malaria at sites of varying transmission intensity in Uganda.
In Africa, fever is often treated presumptively as malaria, resulting in misdiagnosis and the overuse of antimalarial drugs. Rapid diagnostic tests (RDTs) for malaria may allow improved fever management. We compared RDTs based on histidine-rich protein 2 (HRP2) and RDTs based on Plasmodium lactate dehydrogenase (pLDH) with expert microscopy and PCR-corrected microscopy for 7000 patients at sites of varying malaria transmission intensity across Uganda. When all sites were considered, the sensitivity of the HRP2-based test was 97% when compared with microscopy and 98% when corrected by PCR; the sensitivity of the pLDH-based test was 88% when compared with microscopy and 77% when corrected by PCR. The specificity of the HRP2-based test was 71% when compared with microscopy and 88% when corrected by PCR; the specificity of the pLDH-based test was 92% when compared with microscopy and >98% when corrected by PCR. Based on Plasmodium falciparum PCR-corrected microscopy, the positive predictive value (PPV) of the HRP2-based test was high (93%) at all but the site with the lowest transmission rate; the pLDH-based test and expert microscopy offered excellent PPVs (98%) for all sites. The negative predictive value (NPV) of the HRP2-based test was consistently high (>97%); in contrast, the NPV for the pLDH-based test dropped significantly (from 98% to 66%) as transmission intensity increased, and the NPV for expert microscopy decreased significantly (99% to 54%) because of increasing failure to detect subpatent parasitemia. Based on the high PPV and NPV, HRP2-based RDTs are likely to be the best diagnostic choice for areas with medium-to-high malaria transmission rates in Africa.


Application of enzyme-linked immunosorbent assay (ELISA) based on two E. granulosus antigens in the diagnosis of human hydatidosis.
A total of 180 sera consisting of 50 sera from Kenyans with surgically confirmed hydatidosis and 130 sera from individuals without hydatid disease were examined. "Antigen 880" (which is suspected to be similar to Antigen B) showed a sensitivity of 88%. No false reactions were obtained with sera from individuals with non-hydatid infections, hence a specificity of 100% was recorded with this antigen. "Antigen 346" (which is similar to Capron's "Arc 5") showed a sensitivity of 52% and a specificity of 100%. It is concluded that "Antigen 880" may be more useful than "Arc 5" in the diagnosis of human hydatidosis in Kenya due to the high sensitivity obtained with the antigen.


Single-Cell Transcriptomics of Glioblastoma Reveals a Unique Tumor Microenvironment and Potential Immunotherapeutic Target Against Tumor-Associated Macrophage.
The main immune cells in GBM are tumor-associated macrophages (TAMs). Thus far, the studies investigating the activation status of TAM in GBM are mainly limited to bulk RNA analyses of individual tumor biopsies. The activation states and transcriptional signatures of TAMs in GBM remain poorly characterized. We comprehensively analyzed single-cell RNA-sequencing data, covering a total of 16,201 cells, to clarify the relative proportions of the immune cells infiltrating GBMs. The origin and TAM states in GBM were characterized using the expression profiles of differential marker genes. The vital transcription factors were examined by SCENIC analysis. By comparing the variable gene expression patterns in different clusters and cell types, we identified components and characteristics of TAMs unique to each GBM subtype. Meanwhile, we interrogated the correlation between SPI1 expression and macrophage infiltration in the TCGA-GBM dataset. The expression patterns of TMEM119 and MHC-II can be utilized to distinguish the origin and activation states of TAMs. In TCGA-Mixed tumors, almost all TAMs were bone marrow-derived macrophages. The TAMs in TCGA-proneural tumors were characterized by primed microglia. A different composition was observed in TCGA-classical tumors, which were infiltrated by repressed microglia. Our results further identified SPI1 as a crucial regulon and potential immunotherapeutic target important for TAM maturation and polarization in GBM. We describe the immune landscape of human GBM at a single-cell level and define a novel categorization scheme for TAMs in GBM. The immunotherapy against SPI1 would reprogram the immune environment of GBM and enhance the treatment effect of conventional chemotherapy drugs.


Anogenital warts in children.
Evaluation and treatment of pediatric condylomata acuminata are challenging problems. Careful and thorough evaluation for the possibility of sexual abuse is mandatory in all cases. New molecular techniques of HPV DNA detection and typing have not proved helpful in determining the source of the infection but may assist in identifying children who are at risk for the development of carcinoma. Ideal therapy does not exist; non-intervention may be the most appropriate choice for the majority of patients who carry low-risk viral types. Many unanswered questions remain regarding the biology and epidemiology of HPV in children and adults. Clinical and basic science research specifically designed to address the concerns of the pediatric age group is urgently needed.


Acupuncture for blunt chest trauma: A protocol for a double-blind randomized control trial.
Blunt chest trauma (BCT) accounts for up to 65% of polytrauma patients. In patients with 0 to 2 rib fractures, treatment interventions are typically limited to oral analgesics and breathing exercises. Patients suffering from BCT experience symptoms of severe pain, poor sleep, and inability to perform simple daily life activities for an extended period of time thereafter. In this trial, we aim to investigate the efficacy of acupuncture as a functional and reliable treatment option for blunt chest trauma patients. The study is designed as a double-blind randomized control trial. We will include 72 patients divided into 2 groups; the acupuncture group (Acu) and placebo group (Con). The acupuncture group will receive true acupuncture using a uniquely designed press tack needle. The control group will receive placebo acupuncture treatment through the use of a similarly designed press tack needle without the needle element. The acupoints selected for both groups are GB 34, GB 36, LI 4, LU 7, ST 36, and TH 5. Both groups will receive 1 treatment only following the initial visit to the medical facility and upon diagnosis of BCT. Patient outcome measurements include: Numerical Rating Scale, Face Rating Scale, respiratory function flowmeter, Verran Snyder-Halpern sleep scale, and the total amount of allopathic medication used. Follow-up time will be scheduled at 4 days, 2 weeks, and lastly 3 months. The results of this study can potentially provide a simple and cost-effective analgesic solution to blunt chest trauma patients. This novel study design can serve as supporting evidence for future double-blind studies within the field of acupuncture. The study will be conducted in the thoracic surgical department and acupuncture department in China Medical University Hospital, Taichung, Taiwan. The study will be conducted on blunt chest trauma patients and is anticipated to have minimum risk of adverse events. Enrollment of the patients and data collection will start from March 2020. Study completion time is expected in March 2022. (CMUH109-REC1-002), (NCT04318496).


[Prevalence of multiple sclerosis in Colombia].
Multiple sclerosis (MS) is the commonest demyelinating condition of the nervous system. It is characterized by numerous demyelinating areas or plaques of demyelination which are found dispersed throughout the nervous system. It has been shown that MS is less frequent in tropical regions than in subtropical regions. In Latin America particularly, there are some studies which show this phenomenon. However, in Colombia no studies of prevalence of MS have been done. To determine the prevalence of multiple sclerosis in five provinces of Colombia (Antioquia, Caldas, Santander, Risaralda and Bolivar). The capture-recapture method was used for two sources to determine the number of cases defined on the criteria of Poser et al seen between July 1995 and June 2000. The prevalence (cases of MS per 100,000 inhabitants) varied between 1.48 in Antioquia (95% CI 1.12; 1.78) and 4.98 in Risaralda (95% CI 3.52; 6.43). Seventy two percent were women. The regions included in this study represented 25% of the population of Colombia. There is a low prevalence of MS which is as expected in tropical areas. Persons with MS in these regions may be very useful in the study of other factors involved in the aetiology of MS (genetic). The capture-recapture method is an excellent tool for carrying out prevalence studies since it is cheap and requires little time.


Acidosis Activates Endoplasmic Reticulum Stress Pathways through GPR4 in Human Vascular Endothelial Cells.
Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined. GPR4 (G protein-coupled receptor 4) is a member of the proton-sensing G protein-coupled receptors and it has high expression in endothelial cells (ECs). We have previously reported that acidosis induces a broad inflammatory response in ECs. Acidosis also increases the expression of several endoplasmic reticulum (ER) stress response genes such as CHOP (C/EBP homologous protein) and ATF3 (activating transcription factor 3). In the current study, we have examined acidosis/GPR4- induced ER stress pathways in human umbilical vein endothelial cells (HUVEC) and other types of ECs. All three arms of the ER stress/unfolded protein response (UPR) pathways were activated by acidosis in ECs as an increased expression of phosphorylated eIF2α (eukaryotic initiation factor 2α), phosphorylated IRE1α (inositol-requiring enzyme 1α), and cleaved ATF6 upon acidic pH treatment was observed. The expression of other downstream mediators of the UPR, such as ATF4, ATF3, and spliced XBP-1 (X box-binding protein 1), was also induced by acidosis. Through genetic and pharmacological approaches to modulate the expression level or activity of GPR4 in HUVEC, we found that GPR4 plays an important role in mediating the ER stress response induced by acidosis. As ER stress/UPR can cause inflammation and cell apoptosis, acidosis/GPR4-induced ER stress pathways in ECs may regulate vascular growth and inflammatory response in the acidic microenvironment.