Advances in research on echinococcoses epidemiology in China.
Echinococcoses are serious zoonotic diseases in China's vast, western and north-western pastoral areas that has one of the highest prevalence in the world. The two most common forms, cystic echinococcosis (CE) and alveolar echinococcosis (AE), are co-epidemic in some areas causing a grave threat to people's health and economic development. Echinococcus spp. are transmitted through domestic, sylvatic and mixed cycles involving many kinds of host. Successful transmission requires a favourable environment for the growth of the parasites and survival of their eggs, while the unique customs and religious beliefs in the endemic areas pose a challenge to the prevention and control of these parasites. Based on previous epidemiological studies, this paper reviews the particular factors affecting the transmission of Echinococcus parasites in China, with a focus on biological (parasite genotype and the species, age, sex and density of hosts), environmental (landscape and climate) and social (age, gender, ethnicity, education, occupation, life style, cultural customs, living conditions and hygiene practices of humans in the endemic areas). These three factors interact with each other and jointly determine the parasites' transmission intensity, the study of which supports the formulation of the strategies and measures that are significant for control of these infections.


Trends in cataract surgery and postoperative endophthalmitis in Western Australia (1980-1998): the Endophthalmitis Population Study of Western Australia.
Postoperative endophthalmitis results from an intraocular infection and usually occurs following cataract surgery. It has significant morbidity and causes severe visual impairment or blindness of the eye. The aim of this study was to assess the trends in the incidence rates of cataract surgery and postoperative endophthalmitis in Western Australia for the period 1980-1998. The Western Australian Record Linkage Project was used to link the morbidity records for all patients treated for cataract surgery in Western Australia in 1980-1998. Patient records were selected using the international classification for diagnosis and procedure codes pertaining to cataract surgery and postoperative endophthalmitis. All cases of postoperative endophthalmitis were validated by case-note review. The separate databases of the Royal Perth Hospital microbiology and anaesthetic departments as well as the vitreo-retinal surgeon logbooks were used to cross-validate the hospital morbidity database. Trends in the incidence rates of cataract surgery and postoperative endophthalmitis were assessed by Poisson regression. There were 94,653 cataract procedures performed for 63,007 patients in Western Australia during the 19-year period. The majority (88%) of cataract procedures performed were in patients aged 60 years or older. Postoperative endophthalmitis developed in 188 patients, with serious visual impairment occurring in 70.6% of patients for whom visual acuity data was available at presentation. The incidence rate of cataract surgery increased more than three-fold from 1981 (102 per 100,000 person years) to 1998 (345 per 100,000 person years), mainly due to the increase in extracapsular cataract extraction during the 1980s and phacoemulsification extraction from 1990 onwards. In contrast, the average annual incidence rate of postoperative endophthalmitis remained relatively unchanged at around 2 per 1000 cataract procedures over the same period. Cataract surgery is becoming more prevalent in the elderly as the life expectancy of the population increases. There has been a dramatic shift in surgical practice during the last 30 years with small-incision phacoemulsification being the predominant method of intervention used since 1990. Despite changes in surgical practice the incidence rate of postoperative endophthalmitis has remained the same.


The transcriptional response of Saccharomyces cerevisiae to proapoptotic concentrations of Pichia membranifaciens killer toxin.
PMKT (Pichia membranifaciens killer toxin) reportedly has antimicrobial activity against yeasts and filamentous fungi. In previous research we posited that high PMKT concentrations pose a serious challenge for cell survival by disrupting plasma membrane electrochemical gradients, inducing a transcriptional response similar to that of certain stimuli such as hyperosmotic shock. This response was related to the HOG-pathway with Hog1p phosphorylation and a transitional increase in intracellular glycerol accumulation. Such a response was consistent with the notion that the effect induced by high PMKT concentrations lies in an alteration to the ionic homeostasis of the sensitive cell. By contrast, the evidence presented here shows that low PMKT doses lead to a cell death process in Saccharomyces cerevisiae accompanied by cytological and biochemical indicators of apoptotic programmed cell death, namely, the production of reactive oxygen species, DNA strand breaks, metacaspase activation and cytochrome c release. Furthermore, dying cells progressed from an apoptotic state to a secondary necrotic state, and the rate at which this change occurred was proportional to the intensity of the stimulus. We have explored the global gene expression response of S. cerevisiae during that stimulus. The results obtained from DNA microarrays indicate that genes related with an oxidative stress response were induced in response to proapoptotic concentrations of PMKT, showing that the coordinated transcriptional response is not coincident with that obtained when ionophoric concentrations of PMKT are used. By contrast, cwp2Δ mutants showed no signs of apoptosis, indicating that the initial steps of the killer mechanism coincide when proapoptotic (low) or ionophoric (high) PMKT concentrations are used. Additionally, low dosages of PMKT promoted Hog1p phosphorylation and glycerol accumulation.


Analysis of trichothecene mycotoxins in human blood by capillary column gas chromatography-ammonia chemical ionization mass spectrometry.
Capillary column gas chromatography-ammonia chemical ionization mass spectrometry was found to be an excellent technique for the trace detection and identification of underivatized trichothecene mycotoxins. Abundant (M + H)+ and/or (M + NH4)+ pseudo-molecular ions were observed for T-2 toxin, HT-2 toxin, T-2 triol, diacetoxyscirpenol, deoxynivalenol and verrucarol under the conditions developed. This method was successfully applied to the analysis of human blood samples spiked with mycotoxins in the 0-500 ng/g range during a recent interlaboratory exercise. T-2 toxin and diacetoxyscirpenol were detected in these samples in the 2-180 ng/g range. Detection limits of 0.7 and 3.6 ng/g for T-2 toxin and diacetoxyscirpenol, respectively, were possible owing to the specificity of the method.


Endothelial cell loss in four types of intraocular lens implant procedures.
Corneal endothelial cell loss is compared in four types of cataract procedures with intraocular lens implants performed by the authors. A total of 110 intracapsular cataract extractions, 182 extracapsular cataract extractions and 107 phacoemulsifications, divided into 47 anterior chamber emulsifications and 60 posterior chamber emulsifications (all with intraocular lens implants) are compared. A significant feature of these procedures is the incidence of endothelial cell loss greater than 1,200 cells/mm2. This occurred in 1% of the intracapsular cataract extractions, 4% of the planned extracapsular cataract extractions, 13% of the posterior chamber phacoemulsifications, and 17% of the anterior chamber phacoemulsifications. Pachymetry is a poor method for judging operative corneal endothelial trauma. Based upon the results of this study, it remains to be seen whether the advantages of phacoemulsification mitigate against the increased incidence of significant endothelial cell loss.


How a sticky fluid facilitates prey retention in a carnivorous pitcher plant (Nepenthes rafflesiana).
Nepenthes pitcher plants grow in nutrient-poor soils and produce large pitfall traps to obtain additional nutrients from animal prey. Previous research has shown that the digestive secretion in N. rafflesiana is a sticky viscoelastic fluid that retains insects much more effectively than water, even after significant dilution. Although the retention of prey is known to depend on the fluid's physical properties, the details of how the fluid interacts with insect cuticle and how its sticky nature affects struggling insects are unclear. In this study, we investigated the mechanisms behind the efficient prey retention in N. rafflesiana pitcher fluid. By measuring the attractive forces on insect body parts moved in and out of test fluids, we show that it costs insects more energy to free themselves from pitcher fluid than from water. Moreover, both the maximum force and the energy required for retraction increased after the first contact with the pitcher fluid. We found that insects sink more easily into pitcher fluid than water and, accordingly, the surface tension of N. rafflesiana pitcher fluid was lower than that of water (60.2 vs. 72.3 mN/m). By analysing the pitcher fluid's wetting behaviour, we demonstrate that it strongly resists dewetting from all surfaces tested, leaving behind residual films and filaments that can facilitate re-wetting. This inhibition of dewetting may be a further consequence of the fluid's viscoelastic nature and likely represents a key mechanism underlying prey retention in Nepenthes pitcher plants. STATEMENT OF SIGNIFICANCE: Carnivorous Nepenthes pitcher plants secrete sticky viscoelastic fluids that prevent insects from escaping after falling into the pitcher. What physical mechanisms are responsible for the fluid's retentive function? First, insects sink and drown more readily in N. rafflesiana pitcher fluid due to its reduced surface tension. Second, once within the fluid, our force measurements show that it costs more energy to separate insects from pitcher fluid than from water. Third, the fluid strongly resists dewetting, making it harder for insects to extract themselves and covering their cuticle with residues that facilitate re-wetting. Such striking inhibition of dewetting may represent a previously unrecognised mechanism of prey retention by Nepenthes. Pitcher fluid fulfils a well-defined biological function and may serve as a model for studying the mechanics of complex fluids.


Fibrous histiocytoma of bladder.
A case of benign fibrous histiocytoma of the bladder is presented. The occurrence is rare, and criteria for defining malignant potential are unreliable. Careful follow-up evaluations are important.


Progresses on three pattern recognition receptor families (TLRs, RLRs and NLRs) in teleost.
Pattern recognition receptors (PRRs) are a class of immune sensors that play crucial roles in detecting and responding to the conserved patterns of microorganisms. To date, many PRRs, such as TLRs, RLRs and NLRs, as well as their downstream molecules have been identified and characterized in teleost, while their ligands and immunoregulatory mechanisms remain largely unknown. In the present review, we described and discussed the main members of TLR/RLR/NLR families, including their expression profiles, signaling transductions and functions in teleost. And some splicing isoforms from TLR/RLR/NLR families were also addressed, which play synergistic and/or antagonistic roles in response to pathogen infections in teleost. TLRs sense different pathogens by forming homodimer and/or heterodimer. Beyond, functions of TLRs can also be affected by migrating. And some endolysosomal TLRs undergo proteolytic cleavage and in a pH-dependent mechanism to attain a mature functional form that mediate ligand recognition and downstream signaling. Until now, more than 80 members in TLR/RLR/NLR families have been identified in teleost, while only TLR5, TLR9, TLR19, TLR21, TLR22, MDA5, LGP2, NOD1 and NOD2 have direct evidence of ligand recognition in teleost. Meanwhile, new ligands as well as signaling pathways do occur during evolution of teleost. This review summarizes progresses on the TLRs/RLRs/NLRs in teleost. We attempt to insight into the ligands recognition and signaling transmission of TLRs/RLRs/NLRs in teleost.


Small atypical cervical nodes detected on sonography in patients with squamous cell carcinoma of the head and neck: probability of metastasis.
The purpose of this study was to assess the probability of metastasis of small atypical cervical lymph nodes detected on sonography in patients with squamous cell carcinoma (SCC) of the head and neck. We reviewed, retrospectively and blindly, sonographic findings of 148 patients (118 men and 30 women; mean age, 58.2 years) who underwent curative neck dissection. Each lymph node was classified by using a 4-point scale: 1, definitely benign; 2, indeterminate (small [short-axis diameter <10 mm for levels I and II and <7 mm for levels III-VI] atypical node); 3, definitely metastatic; and 4, large (>3-cm) metastatic. Lymph nodes were considered atypical if they met at least 1 of the following criteria: a long- to short-axis diameter ratio of less than 2.0, absence of a normal echogenic hilum, and heterogeneous echogenicity of the cortex. These results were verified, on a level-by-level basis, with histopathologic findings. Small atypical nodes were found on sonography in 63 cervical levels of 48 patients, of which 18 (28.6%) were proved to have metastatic nodes. The probability of metastasis was significantly higher with than without a large (>3-cm) ipsilateral metastatic node (0.50 versus 0.20; P = .038) and marginally higher with than without an ipsilateral metastatic node (0.41 versus 0.16; P = .061) but not significantly associated with the T stage of the primary tumor (P = .238) or the presence of an ipsilateral tumor (P = .904). Metastasis was encountered in about 30% of small atypical cervical nodes on sonography in patients with SCC of the head and neck. Our results indicate that small atypical nodes must be interpreted with consideration of metastatic nodes in the ipsilateral neck.


Toll-interacting protein polymorphisms in viral bronchiolitis outcomes.
Toll-interacting protein is a key factor in regulating innate immunity responses via gatekeeping Toll-like receptors. Genetic variance in innate immunity has been linked with susceptibility to infections. Children with viral bronchiolitis in infancy are at increased risk of later asthma. The aim was to evaluate the role of toll-interacting protein gene point mutations in severity of bronchiolitis and subsequent risk of asthma. Infants less than 6 months old were recruited during hospitalization due to bronchiolitis. In all, 166 children were prospectively followed up to age of 1.5, 6, and 11 years. Clinical data on viral etiology and severity markers, and further post-bronchiolitis asthma and lung function outcomes were compared with genetic differences in two single-nucleotide point mutations rs116938768 and rs5743854 in the toll-interacting protein gene. Toll-interacting protein rs116938768 or rs5743854 did not show significant associations with severity markers or viral etiology of bronchiolitis. Follow-up data on current asthma or lung function at 6 or 11 years of age after bronchiolitis were not associated with the investigated mutations. Toll-interacting protein gene point mutations in rs116938768 or rs5743854 were not involved with the clinical course of viral bronchiolitis in early infancy, and did not predict post-bronchiolitis asthma or lung function reduction by the age of 11 years.


Hormonal monitoring of the first trimester of pregnancy.
The hormonal changes and maternal adaptations of human pregnancy are among the most remarkable phenomena in nature. Endocrinologic parameters in the early gestation period have been used to predict abnormal pregnancies and to identify fetuses that have chromosomal aberrations. This article focuses on the changes in hormones that are secreted by the maternal-fetal-placental unit that are unique for the first trimester of pregnancy and their impact on clinical outcome.


Interaction of a putative BH3 domain of clusterin with anti-apoptotic Bcl-2 family proteins as revealed by NMR spectroscopy.
Clusterin (CLU) is a multifunctional glycoprotein that is overexpressed in prostate and breast cancers. Although CLU is known to be involved in the regulation of apoptosis and cell survival, the precise molecular mechanism underlying the pro-apoptotic function of nuclear CLU (nCLU) remains unclear. In this study, we identified a conserved BH3 motif in C-terminal coiled coil (CC2) region of nCLU by sequence analysis and characterized the molecular interaction of the putative nCLU BH3 domain with anti-apoptotic Bcl-2 family proteins by nuclear magnetic resonance (NMR) spectroscopy. The chemical shift perturbation data demonstrated that the nCLU BH3 domain binds to pro-apoptotic BH3 peptide-binding grooves in both Bcl-X(L) and Bcl-2. A structural model of the Bcl-X(L)/nCLU BH3 peptide complex reveals that the binding mode is remarkably similar to those of other Bcl-X(L)/BH3 peptide complexes. In addition, mutational analysis confirmed that Leu323 and Asp328 of nCLU BH3 domain, absolutely conserved in the BH3 motifs of BH3-only protein family, are critical for binding to Bcl-X(L). Taken altogether, our results suggest a molecular basis for the pro-apoptotic function of nCLU by elucidating the residue specific interactions of the BH3 motif in nCLU with anti-apoptotic Bcl-2 family proteins.


Infant inhibited temperament in primates predicts adult behavior, is heritable, and is associated with anxiety-relevant genetic variation.
An anxious or inhibited temperament (IT) early in life is a major risk factor for the later development of stress-related psychopathology. Starting in infancy, nonhuman primates, like humans, begin to reveal their temperament when exposed to novel situations. Here, in Study 1 we demonstrate this infant IT predicts adult behavior. Specifically, in over 600 monkeys, we found that individuals scored as inhibited during infancy were more likely to refuse treats offered by potentially-threatening human experimenters as adults. In Study 2, using a sample of over 4000 monkeys from a large multi-generational family pedigree, we demonstrate that infant IT is partially heritable. The data revealed infant IT to reflect a co-inherited substrate that manifests across multiple latent variables. Finally, in Study 3 we performed whole-genome sequencing in 106 monkeys to identify IT-associated single-nucleotide variations (SNVs). Results demonstrated a genome-wide significant SNV near CTNNA2, suggesting a molecular target worthy of additional investigation. Moreover, we observed lower p values in genes implicated in human association studies of neuroticism and depression. Together, these data demonstrate the utility of our model of infant inhibited temperament in the rhesus monkey to facilitate discovery of genes that are relevant to the long-term inherited risk to develop anxiety and depressive disorders.


The importance of the local environment in the transmission of respiratory syncytial virus.
The role of the environment in the spread of respiratory infections is poorly understood, and consequently probably underappreciated. To improve our understanding of the environmental drivers of respiratory syncytial virus (RSV) transmission, we examined RSV seasonality in two settings with unusual seasonal patterns: The Gambia (where RSV epidemics occur at different times of the year) and Southeast Florida (where RSV seasonality differs from the rest of mainland USA). We used published data to correlate the seasonality of RSV with rainfall and child nutrition in the Gambia, and with rainfall and temperature in Florida. In the Gambia, RSV incidence was more strongly and more consistently correlated with child nutrition (r = -0.73 [95%CI -0.90 to -0.38]) than with rainfall (r = 0.37 [95%CI 0.20 to 0.52]). In Southeast Florida RSV incidence was strongly correlated with rainfall two months previously (r = 0.65 [95%CI 0.40 to 0.81]) compared to North Florida where RSV incidence was strongly correlated with temperature (r = -0.75 [95%CI -0.87 to -0.56]). We propose that nutrition is the dominant environmental driver of RSV seasonality in the Gambia, while rainfall is the dominant driver of RSV seasonality in Southeast Florida. This reinforces the importance of an ecological scale understanding of disease transmission: only with such an evidence base can setting-specific recommendations be made for public health interventions that are targeted for maximum efficacy.


The low dose dexamethasone suppression test: effect of time of administration and dose.
The dexamethasone suppression test (DST) is used to determine the sensitivity of the hypothalamic-pituitary-adrenal axis (HPA-axis) to negative feedback. Dexamethasone is usually administered at 23:00 h or at midnight but this is often not convenient. The aim of this study was to determine whether the administration of dexamethasone at 21:00 h as compared to 23:00 h would alter the degree to which 08:00 h plasma cortisol was suppressed the following morning. Three healthy males (mean+/-SE: 32+/-7 yr) and 3 healthy females (mean+/-SE: 35+/-7 yr) took part in the study. Each subject was orally administered 1 of 3 doses of dexamethasone (0.25 mg, 0.5 mg, or 1.0 mg) on 3 separate occasions in random order at least a week apart. Each dose of dexamethasone was taken at either 21:00 h or 23:00 h so that each subject underwent 6 tests. The differences in cortisol suppression between times and doses of dexamethasone were assessed using Analysis of Variance. Plasma cortisol was suppressed less in response to 0.25 mg dexamethasone at both 21:00 h and 23:00 h as compared with doses of dexamethasone of 0.5 mg or 1.0 mg (p=0.004). Suppression of plasma cortisol in response to each dose of dexamethasone was similar regardless of the timing of dexamethasone administration (p=0.5). We conclude that in healthy subjects 0.25 mg dexamethasone suppresses plasma cortisol less than either 0.5 mg or 1.0 mg and that 0.5 mg dexamethasone suppresses plasma cortisol to a similar extent as 1.0 mg dexamethasone. Moreover, changing the administration time of dexamethasone from 23:00 h to 21:00 h does not effect the degree to which cortisol is suppressed in healthy subjects.


On the in vivo function of the mitral heart valve leaflet: insights into tissue-interstitial cell biomechanical coupling.
There continues to be a critical need for developing data-informed computational modeling techniques that enable systematic evaluations of mitral valve (MV) function. This is important for a better understanding of MV organ-level biomechanical performance, in vivo functional tissue stresses, and the biosynthetic responses of MV interstitial cells (MVICs) in the normal, pathophysiological, and surgically repaired states. In the present study, we utilized extant ovine MV population-averaged 3D fiducial marker data to quantify the MV anterior leaflet (MVAL) deformations in various kinematic states. This approach allowed us to make the critical connection between the in vivo functional and the in vitro experimental configurations. Moreover, we incorporated the in vivo MVAL deformations and pre-strains into an enhanced inverse finite element modeling framework (Path 1) to estimate the resulting in vivo tissue prestresses [Formula: see text] and the in vivo peak functional tissue stresses [Formula: see text]. These in vivo stress estimates were then cross-verified with the results obtained from an alternative forward modeling method (Path 2), by taking account of the changes in the in vitro and in vivo reference configurations. Moreover, by integrating the tissue-level kinematic results into a downscale MVIC microenvironment FE model, we were able to estimate, for the first time, the in vivo layer-specific MVIC deformations and deformation rates of the normal and surgically repaired MVALs. From these simulations, we determined that the placement of annuloplasty ring greatly reduces the peak MVIC deformation levels in a layer-specific manner. This suggests that the associated reductions in MVIC deformation may down-regulate MV extracellular matrix maintenance, ultimately leading to reduction in tissue mechanical integrity. These simulations provide valuable insight into MV cellular mechanobiology in response to organ- and tissue-level alternations induced by MV disease or surgical repair. They will also assist in the future development of computer simulation tools for guiding MV surgery procedure with enhanced durability and improved long-term surgical outcomes.


Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis.
The role of Ras oncogenes in promoting cellular transformation is well established. However, the contribution of Ras signaling to interactions between tumor cells and their host environment remains poorly characterized. Here, we demonstrate that the inflammatory mediator interleukin-8 (CXCL-8/IL-8) is a transcriptional target of Ras signaling. Using a tumor xenograft model, we show that Ras-dependent CXCL-8 secretion is required for the initiation of tumor-associated inflammation and neovascularization. Collectively, our data identify a novel mechanism by which the Ras oncogene can elicit a stromal response that fosters cancer progression.


Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis.
With the recent advances in the understanding of the interaction of the immune system with developing tumor, it has become imperative to consider the immunological parameters for both cancer diagnosis and disease prognosis. Additionally, in the era of emerging immunotherapeutic strategies in cancer, it is very important to follow the treatment outcome and also to predict the correct immunotherapeutic strategy in individual patients. There being enormous heterogeneity among tumors at different sites or between primary and metastatic tumors in the same individual, or interpatient heterogeneity, it is very important to study the tumor-immune interaction in the tumor microenvironment and beyond. Importantly, molecular tools and markers identified for such studies must be suitable for monitoring in a noninvasive manner. Recent studies have shown that the immune checkpoint molecules play a key role in the development and progression of tumors. In-depth studies of these molecules have led to the development of most of the cancer immunotherapeutic reagents that are currently either in clinical use or under different phases of clinical trials. Interestingly, many of these cell surface molecules undergo alternative splicing to produce soluble isoforms, which can be tracked in the serum of patients. Several studies demonstrate that the serum levels of these soluble isoforms could be used as noninvasive markers for cancer diagnosis and disease prognosis or to predict patient response to specific therapeutic strategies.


Experiences of Pregnant Women With Obesity.
To explore how pregnant women with obesity feel about their bodies before and during pregnancy. Qualitative descriptive design. Obstetric and gynecologic offices in a rural setting in Maryland that employed physicians and midwives as prenatal care providers. A purposive sampling technique was used to recruit a sample of 20 women. Inclusion criteria were pregnant women ages 18 to 35 years with a prepregnancy body mass index of greater than 30 kg/m2, in the third trimester of the pregnancy (28-40 weeks gestation), and receiving regular prenatal care from a licensed provider. A typology analysis chart was used to group participants' responses from their interviews in the areas of positive or negative feelings regarding their prepregnancy body and weight, and positive or negative feelings regarding their pregnant body. Data were analyzed using a four-square matrix by identifying those participants who felt positive regarding their prepregnancy body/weight and pregnant body (n = 6), felt negative regarding their prepregnancy body/weight and pregnant body (n = 3), felt negative regarding their prepregnant body but positive regarding their pregnant body (n = 8), and felt positive regarding their prepregnant body but negative about their pregnant body (n = 3). Pregnancy had allowed many of the women to gain a sense of achievement, where the growth of the fetus and subsequent weight gain were seen as positive attributes, and they embraced the functionality of their bodies.


Incidental coronary calcifications on routine chest CT: Clinical implications.
Coronary artery calcification (CAC) is a marker of atherosclerosis and an independent risk factor for cardiac-related mortality, with much of the 50% decline in mortality over the past 30 years being attributed to early detection of coronary disease and intervention of modifiable risk factors. With over 10 million computed tomography (CT) examinations of the chest performed in the United States yearly, CAC can be identified in a very large number of patients. In this review, we discuss the clinical evidence underlying the relationship between radiologic identification of CAC, atherosclerosis, and cardiac outcomes and the implications of its assessment on standard chest CT. We conclude that reporting of incidental coronary calcification found on non-gated chest CT would have a great impact on both management and mortality and thus, in the appropriate setting, should be noted in the impression of the radiologic report when identified.


Location of chlorhexidine in DMPC model membranes: a neutron diffraction study.
Chlorhexidine (CHX) is an effective anti-bacterial agent whose mode of action is thought to be the disruption of the cell membrane. It is known to partition into phospholipid bilayers of aqueous model-membrane preparations. Neutron diffraction data taken at 36 degrees C on the location of CHX in phosphatidylcholine (PC) bilayers is presented. The center of mass of the deuterated hydrocarbon chain of CHX is found to reside 16A from the center of the bilayer in 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (14:0-14:0PC). This places the drug near the glycerol backbone of the lipid, and suggests a mode of action whereby the molecule is bent in half and inserts wedge-like into the lipid matrix. This mechanism is distinct from detergent-like mechanisms of membrane disruption and more similar to some anti-microbial peptide action, where peptides insert obliquely into the bilayer headgroup region to disrupt its structure.


Antioxidant Properties of a Nanostructured Clathrate Complex Selenopyran with β-Cyclodextrin in Model Systems of Oxidative Stress.
We studied the effect of nanostructured clathrate complex 9-phenyl-symm-octahydoselenoxanthene (selenopyran) with β-cyclodextrin on the generation of ОН· radicals in the Fenton system and parameters of oxidative stress in rat liver cells incubated at 37°С for 1 h. The complex inhibits the development of free-radical oxidative processes induced by ROS and the most toxic ОН· radicals, reduces the increased level of ROS induced by prooxidants, and exhibits antioxidant activity.


Enzyme coupling method on calibrated nylon spheres: application to the selective trypsinization of histones in chromatin.
A new method consisting of a two-step activation was developed in order to covalently immobilize enzymes on calibrate nylon 66 spheres. This efficient method associates for the first time peptide bond cleavage and O-alkylation of the support. Optimal conditions for activation and protein coupling were defined, and immobilized trypsin was used to investigate the histone accessibility on chromatin. This approach, which allows us to degrade first progressively H1, indicates that H4 seems inaccessible both in relaxed and condensed chromatin.


Effect of 3-amino-1-propanol on the phosphatidylinositol (PI) and glycosyl phosphatidylinositol (GPI) systems of Tetrahymena.
3-Amino-1-propanol (AP), a substance replacing ethanolamine in phosphatidylethanolamine (PE) significantly reduced 32P incorporation to phosphatidylinositol (PI) and glycosyl-phosphatidylinositol (GPI) in the unicellular organism Tetrahymena pyriformis. At 10 mM, AP completely inhibited the incorporation of 32P into PI. 3H-arachidonate incorporation into PI was also inhibited, while that into diacylglycerol (DAG) was high. The experiments indicate the presence and metabolism of inositol phospholipids and GPI in T. pyriformis.


Cellular, molecular, and carcinogenic effects of radiation.
(1) The biologic effects of ionizing radiation at the cellular and molecular levels differ from those of many chemical agents. Radiation is a classic genotoxic agent. The important DNA lesion with respect to its cytotoxic and mutagenic effects appears to be the DNA double strand break, whereas chemotherapeutic alkylating agents induce primarily base damage from adduct formation and cross-linking. Radiation-induced mutations result primarily from large-scale structural changes in DNA as a result of mechanisms such as chromosomal deletions, rearrangements, and homologous recombination, rather than point mutation as generally observed with alkylating agents. Finally, radiation is highly cytotoxic; a significantly increased frequency of specific gene mutations is usually observed only following doses that produce significant cell killing. (2) Radiation may not be a very potent inducer of second malignant tumors, at least in most cases. This prediction is derived from the localized nature of the exposure during clinical radiotherapy, in which the dose to normal tissues is minimized, and from the fact that radiation tends to be cytotoxic rather than mutagenic. The very high doses employed in curative radiotherapy may thus kill potentially transformed cells in the field. An exception to this general prediction may be Hodgkin's disease, in which a relatively large volume of tissue is treated with lower total radiation doses. (3) We have a firm scientific basis on which to predict the carcinogenic effects of radiation at many tissue sites, owing to extensive quantitative epidemiologic data in human populations. Unlike for chemical agents, radiation can be easily detected, and the absorbed dose to critical tissues is precisely measured. Thus, we know about the sensitivity of many target tissues to radiation-induced cancer. (4) A number of factors can modify the carcinogenic effects of radiation. It is likely that important interactive effects will occur between radiation and chemotherapeutic alkylating agents, which may depend upon the timing and order of the treatments as well as the particular agent(s) employed. (5) Genetic predisposition to radiation-induced cancer may be a confounding factor in the prediction of its effects in any given individual.


The anorexia of ageing.
Ageing is associated with a reduction in appetite and food intake, which has been termed the 'anorexia of ageing'. After age 70-75 years average body weight decreases, even in healthy people, disproportionately due to loss of lean tissue. The 'physiological' anorexia and weight loss of ageing predispose to pathological weight loss and malnutrition. Marked weight loss is common in the elderly and a major cause of morbidity and increased mortality. The cause(s) of the anorexia of ageing are largely unknown. We have identified several possibilities. Animal and preliminary human studies indicate that ageing is associated with increased satiety factors and a reduced feeding drive. Endogenous opioids stimulate eating. We administered i.v. infusions of the opioid antagonist naloxone to young and older adults. Overall, the suppression of food intake was not different in the two age groups, but was increased in older women, suggesting reduced stimulation of feeding by endogenous opioids in this group. Plasma concentrations of the satiety hormone cholecystokinin (CCK) increase with ageing. Intravenous CCK-8 infusion produced greater suppression of food intake in older than young subjects (33.5 vs 15.5% P = 0.026), indicating that sensitivity to the satiating effects of CCK is at least maintained and may increase with age. This raises the possibility of using CCK antagonists as stimulants of appetite and food intake in malnourished older people.


Moving thermal gradients in gas chromatography.
This paper examines the separation effects of a moving thermal gradient on a chromatographic column in gas chromatography. This movement of the gradient has a focusing effect on the analyte bands, limiting band broadening in the column. Here we examine the relationship between the slope of this gradient, the velocity of the gradient and the resulting band width. Additionally we examine how transport of analytes along the column at their analyte specific constant temperatures, determined by the gradient slope and velocity, affects resolution. This examination is based primarily on a theoretical model of partitioning and transport of analyte under low concentration conditions. Preliminary predictions indicate that analytes reach near constant temperatures, relative positions and resolutions in less than 100cm of column transport. Use of longer columns produces very little improvement in resolution for any fixed slope. Properties of the thermal gradient determine a fixed solute band width for each analyte. These widths are nearly reached within the first 40-70cm, after which little broadening or narrowing of the bands occur. The focusing effect of the thermal gradient corrects for broad injections, reduces effects of irregular stationary phase coatings and can be used with short columns for fast analysis. Thermal gradient gas chromatographic instrumentation was constructed and used to illustrate some characteristics predicted from the theoretical results.


Key regulators of mitochondrial biogenesis are increased in kidneys of growth hormone receptor knockout (GHRKO) mice.
The growth hormone receptor knockout (GHRKO) mice are remarkably long-lived and highly insulin sensitive. Alterations in mitochondrial biogenesis are associated with aging and various metabolic derangements. We have previously demonstrated increased gene expression of key regulators of mitochondriogenesis in kidneys, hearts and skeletal muscles of GHRKO mice. The aim of the present study was to quantify the protein levels of the following regulators of mitochondriogenesis: peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), AMP-activated protein kinase α (AMPKα), phospho-AMPKα (p-AMPKα), sirtuin-3 (SIRT-3), endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), nuclear respiratory factor-1 (NRF-1) and mitofusin-2 (MFN-2) in skeletal muscles and kidneys of GHRKOs in comparison to normal mice. We also were interested in the effects of calorie restriction (CR) and visceral fat removal (VFR) on these parameters. Both CR and VFR improve insulin sensitivity and can extend life span. The renal levels of PGC-1α, AMPKα, p-AMPKα, SIRT-3, eNOS, p-eNOS and MFN-2 were increased in GHRKOs. In the GHRKO skeletal muscles, only MFN-2 was increased. Levels of the examined proteins were not affected by CR (except for PGC-1α and p-eNOS in skeletal muscles) or VFR. GHRKO mice have increased renal protein levels of key regulators of mitochondriogenesis, and this may contribute to increased longevity of these knockouts.


Association between ferritin and hepcidin levels and inflammatory status in patients with type 2 diabetes mellitus and obesity.
The aim of this study was to determine the association between iron parameters and inflammation in obese individuals with and without type 2 diabetes mellitus (T2DM). We studied 132 obese individuals (OB), 60 individuals with T2DM, 106 obese individuals with T2DM (T2DOB), and 146 controls (C). All of were men aged >30 y. Biochemical, iron nutrition, and oxidative stress parameters were determined. Peripheral mononuclear cells were isolated and total RNA was extracted to quantify tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, interleukin (IL)-6, toll-like receptor (TLR)-2/4 and hepcidin by quantitative reverse transcription polymerase chain reaction. OB, T2DM, and T2DOB individuals had higher ferritin, retinol-binding protein 4, and thiobarbituric acid reactive substance (TBAR) levels than controls. T2DOB and T2DM individuals showed high high-sensitivity C-reactive protein (hsCRP) levels and OB with and without T2DM had elevated levels of serum hepcidin. Heme oxygenase activity was high in OB and T2DM and there were no differences observed in superoxide dismutase and glutathione parameters. A correlation between TBARS and ferritin in T2DOB was observed (r = 0.31; P < 0.006). Multiple linear regression analysis showed an association between diabetes and obesity with ferritin, TBARS, and hsCRP levels. The upper quartiles of ferritin, TBARS and hepcidin showed an adjusted odd ratio for T2DM of 1.782, 2.250, and 4.370, respectively. TNF-α, IL-6, hepcidin, NF-κB, TLR-2/4 mRNA abundances were increased in T2DM and T2DOB. Elevated hsCRP and hepcidin levels, and increased gene expression of TNF-α, IL-6, NF-κB, and TLR-2/4 in patients with diabetes, obesity, or both exacerbate and perpetuate the insulin resistance and inflammatory state.


Efficacy of Bladder Ultrasound in Prediction of Resolution of Vesicoureteral Reflux After Endoscopic Subureteral Hyaluronic Acid/Dextranomer (Deflux) Injection.
To evaluate the efficacy of bladder ultrasound (US) in predicting the resolution of vesicoureteral reflux (VUR) after subureteral endoscopic Deflux injection in low-grade vs high-grade VUR patients. Between 2014 and 2020, 160 children (220 ureters) were administered subureteral Deflux injection for treatment of primary VUR. The mean age at surgery was 72 months. Low-grade reflux (grades II-III) was observed in 190 ureters and high-grade reflux (grades IV-V) was observed in 30 ureters. Bilateral surgery was performed in 60 patients. All patients had follow-up using bladder US and voiding cystourethrography (VCUG) at 3 months and 12 months. Outcome included identification of Deflux mounds by bladder US and correlation of Deflux mounds identified with radiographic success rates of VUR on VCUG. Single Deflux injection showed radiographic success rates in 98% of low grade reflux patients and 26.7% of high grade reflux patients at last follow-up. Bladder US was able to detect Deflux mounds in 89% of low grade reflux and 43.3% of high grade reflux patients at last follow up. Our study demonstrated higher sensitivity, Positive predictive value and accuracy in Deflux detection by bladder US in low grade reflux vs high grade reflux patients. Bladder-US was highly sensitive for detection of Deflux implants. Bladder-US could be adjusted in follow-up of patients with low-grade reflux treated by Deflux injection, while VCUG could be preserved for follow-up of high-grade reflux, this will lead to reduction of unnecessary radiation exposure during VCUG for children with low grade reflux.


Failure of internal fixation of the anterior ring for unstable pelvic fractures, the experience of a single institute.
This study aimed to share our experience of anterior ring fixation failure for unstable pelvic fractures and propose corresponding treatment strategies. From January 2009 to December 2018, 93 charts of patients with pelvic fractures were retrospectively reviewed. Patients with failure of the anterior ring internal fixation within 3 months after initial surgery were analyzed. Quality of reduction was evaluated using the Majeed scoring system. Patients aging ≥ 18 years, with unstable pelvic fractures, Tile classification type B and type C pelvic fractures, combined injury of other organs that did not affect the operation and without important neurovascular damage were included. The exclusion criteria included: (1) pathological fracture, or combined with pelvic bone tumor or severe osteoporosis; (2) femoral fracture and thoracolumbar fracture; (3) open pelvic fracture; (4) Morel-Lavallée injury; (5) complicated acetabular fracture. The quality of the reduction of the anterior pelvic ring injury was evaluated on the x-ray film using the Majeed scoring system. According to the Tile classification of fracture, there were 23 cases of type B1, 17 cases of type B2, 11 cases of type B3, 28 cases of type C1, 6 cases of type C2, and 8 cases of type C3. The duration from injury to pelvic internal fixation ranged from 5 to 28 days. Seven out of 93 patients experienced failure of internal fixation of the anterior pelvic ring within 3 months, including 2 patients fixed with an external fixator and 5 patients fixed with a plate. Five patients undergoing revision surgery were followed up for 6-36 months with an average of 18 months. According to Majeed's score at the last follow-up in the 5 patients undergoing revision surgery, there were 2 cases of excellent, 2 cases of good, 1 case of fair. The excellent and good rate reached 80%. The treatment of complicated unstable pelvic fractures requires performing internal fixation surgery within 2 weeks. It is necessary to make a preoperative plan and stabilize the posterior ring first, avoiding a single steel plate crossing the pubic symphysis.


Association between changes in body composition and risk of developing Type 2 diabetes in Koreans.
To examine the effects of longitudinal changes in fat mass or lean body mass on risk of Type 2 diabetes in Korean adults. Participants included 18 687 Korean adults (aged 20-79 years) who underwent routine medical check-ups in 2007-2008 and again in 2011-2012 with a mean (range) of 4.3 (3.0-5.7) years interval. Total fat, fat-free, and soft fat-free masses were determined using bioelectrical impedance. A total of 692 subjects (3.7%) developed Type 2 diabetes during follow-up. Those who developed diabetes had a greater increase in percent body fat (2.9 ± 3.0 vs 2.6 ± 3.2 percentage points, P = 0.043), as well as greater decreases in percent fat-free mass (-3.0 ± 3.3 vs -2.7 ± 3.3 percentage points, P = 0.008) and percent soft fat-free mass (-2.8 ± 3.1 vs -2.4 ± 3.1 percentage points, P = 0.003) compared with those who did not develop diabetes. In multiple logistic regression analysis, an increase in total fat mass of > 10% was associated with an increased odds ratio for diabetes (1.29, 1.05-1.60), and a decreased total fat mass was associated with lower odds ratio (0.75, 0.58-0.96). A loss of total fat-free mass of > 5% (odds ratio 1.08, 0.90-1.30) or an increase in total fat-free mass (odds ratio 0.96, 0.71-1.28) was not significantly associated with the risk of diabetes after adjustments for baseline waist circumference and glucose levels. These results show that changes in total body fat mass, but not lean body mass, are associated with development of Type 2 diabetes, independently of baseline measures of general or central obesity.


The aging of lympho-hematopoietic stem cells.
The extensive self-renewal capacity of hematopoietic stem cells (HSCs) implies that this cell population may not age and thus may provide undiminished replenishment of blood cells throughout the lifespan of an organism. In contrast, accumulating experimental evidence supports the premise that HSCs show signs of aging and may have a limited functional lifespan. We summarize here the evidence for HSC aging, discuss the possible molecular mechanisms that may be involved and show evidence of a genetic connection between the effects of age on blood-forming cells and the longevity of mice. We speculate that age-related functional decline in adult tissue HSCs limits longevity in mammals.


ANP gene expression in rat hearts during hypoxia.
It is unclear whether the increase in plasma atrial natriuretic peptide (ANP) concentration during hypoxia is due to direct, hypoxia-induced upregulation of ANP secretion in the heart, or to pressure overload of the right ventricle (RV) following hypoxia-induced pulmonary hypertension. To test the hypothesis that hypoxia leads to an early upregulation of the ANP gene, we examined the influence of acute and prolonged inspiratory hypoxia (6 h, 1 or 3 weeks) on the expression of ANP messenger ribonucleic acid (mRNA) in rat heart and compared the results with the expression of the ANP gene after acute pressure overload induced by experimental coarctation of the main pulmonary artery. As a molecular marker for hypertrophy we determined the ratio of alpha- and beta-myosin gene expression. Hypoxia increased systolic RV pressure from 20.0 +/- 1.6 mmHg to 27.8 +/- 1.6 mmHg (P < 0.01) and 41.6 +/- 2.1 mmHg (P < 0. 05) after 1 and 3 weeks hypoxia respectively. The ANP plasma concentration did not change significantly after 6 h or 1 week: 232 +/- 21 pg/ml (control), 246 +/- 25 pg/ml (6 h), 268 +/- 25 pg/ml (1 week), but increased significantly after 3 weeks hypoxia (446.8 +/- 99.56 pg/ml; P < 0.05). ANP mRNA levels in different regions of the heart did not change after 6 h or 1 week hypoxia. After 3 weeks hypoxia ANP mRNA had increased 2.7-fold in the RV (P < 0.05), 4. 2-fold in the left ventricle (LV, P < 0.05), 3.5-fold in the septum (S, P < 0.05) and about 1.4-fold in the right (n.s.) and left atrium (n.s.). Relative ventricular masses increased significantly only for the RV (190%, P < 0.05) during hypoxia. The beta/alpha-myosin mRNA ratio did not change after 6 h hypoxia but, contrary to ANP gene expression, increased after just 1 week (6.1-fold in RV, 7.8-fold in LV, 6-fold in S; P < 0.05) and was more pronounced in the RV after 3 weeks (9.4-fold in RV, 7.6-fold in LV, 9.1-fold in S; P < 0.05). The increase in the beta/alpha-myosin mRNA ratio in the LV contrasts with a lack of increase in relative ventricular mass. Acute pressure overload in the RV after pulmonary arterial banding significantly increased ANP-mRNA and the beta/alpha-myosin mRNA ratio after 1 day in the RV. In the LV ANP mRNA was unchanged. The delayed upregulation of the ANP gene suggests that hypoxia per se is not a significant stimulus for ANP gene expression in the heart and that hypoxia-induced ANP-gene expression in the heart is regulated predominantly by the increase in RV afterload due to hypoxia-induced increased pulmonary pressure. The upregulation of ANP and beta-myosin mRNA in the LV during chronic hypoxia has yet to be elucidated.


Deep metric learning for otitis media classification.
In this study, we propose an automatic diagnostic algorithm for detecting otitis media based on otoscopy images of the tympanic membrane. A total of 1336 images were assessed by a medical specialist into three diagnostic groups: acute otitis media, otitis media with effusion, and no effusion. To provide proper treatment and care and limit the use of unnecessary antibiotics, it is crucial to correctly detect tympanic membrane abnormalities, and to distinguish between acute otitis media and otitis media with effusion. The proposed approach for this classification task is based on deep metric learning, and this study compares the performance of different distance-based metric loss functions. Contrastive loss, triplet loss and multi-class N-pair loss are employed, and compared with the performance of standard cross-entropy and class-weighted cross-entropy classification networks. Triplet loss achieves high precision on a highly imbalanced data set, and the deep metric methods provide useful insight into the decision making of a neural network. The results are comparable to the best clinical experts and paves the way for more accurate and operator-independent diagnosis of otitis media.


[Evaluation of the assembling and retention forces of constraint liners for total hip replacement].
Dislocation is a severe complication after total hip replacement which may cause revision surgery in some cases. The use of constraint inserts that are coupled to the femoral head by a snapping mechanism provides an opportunity for treatment of recurrent dislocations. This study was aimed to investigate the assembling and retention forces of a specific constraint liner. Using a universal testing machine the assembling forces were determined for head sizes of 28 and 32 mm and the clinically mostly used as well as the maximum cup size. Subsequently, under variation of load direction and pull-out velocity the retention forces were investigated. For primary assembly of the head the required compressive forces were in a range from 197 N and 283 N depending on head and cup size (each size n = 3). Repeated assembly led to a decrease of these forces up to 29%. The retention forces always were slightly below the assembling forces, i. e. forces to remove the heads from the inserts were between 183 N and 230 N (each size n = 3). Repeated disconnection caused a decrease of the retention forces up to 16%. An increase of load velocity as well as an oblique load direction resulted in an enhancement of the retention forces. For all investigated implant sizes the retention force for the femoral head was approximately ten-times less than the interface strength between the insert and the metal-back. In case of correct implant handling the risk of disconnection between the tested constraint insert and the corresponding metal-back has not to be considered in clinical practice.


Transcervical intralesional vasopressin injection compared with placebo in hysteroscopic myomectomy: a randomized controlled trial.
To evaluate the efficacy of transcervical intralesional vasopressin injection to submucous myoma in hysteroscopic myomectomy from 2011 to 2014. This was a prospective, randomized, double-blind study in a single center. Forty premenopausal women with symptomatic submucous myoma requiring hysteroscopic myomectomy were randomized to transcervical intralesional vasopressin injection or placebo in a 4:4 ratio. The primary outcome was operative time. Secondary outcomes including fluid volumes, blood loss, and visual clarity were compared between the two groups. The median duration for myomectomy was 19.9 minutes (range 3.1-54.2 minutes) in the vasopressin group compared with 29.0 minutes (range 8.0-60.9 minutes) in the placebo group, a nonsignificant difference (P=.14). There were significant reductions in the median volume of fluid used (4,200 mL [range 1,300-21,000 mL] compared with 9,800 mL (range 1,500-23,000 mL; P=.004) and fluid intravasation (0 mL [range 0-3,100] compared with 300 mL [range -150-3,150 mL; P=.029) in the vasopressin group. The median intraoperative blood loss was reduced (5 mL [range 1-50 mL] compared with 20 mL [range 1-150 mL; P=.002). The operative surgeon rated that 95% of the vasopressin group had "minimal" bleeding compared with 36.8% in the placebo group. The surgical field (visual analog scale [VAS] 9 [range 2-10] compared with 6 [range 2-10; P<.001]; 0=worst visual clarity, 10=best visual clarity) and the effluent fluid (VAS 1 [range 0-7] compared with 4 [range 0-8; P<.001]; 0=clear, 10=unclear) were statistically significantly clearer in the vasopressin group. Transcervical intralesional vasopressin injection in hysteroscopic myomectomy did not reduce operative time but did reduce volume of inflow fluid, fluid intravasation, intraoperative blood loss, and improving visual clarity. Centre for Clinical Research and Biostatistics, http://www.cct.cuhk.edu.hk/Registry/publictriallist.aspx, CUHK_CCT00291.


RTK SLAP down: the emerging role of Src-like adaptor protein as a key player in receptor tyrosine kinase signaling.
SLAP (Src like adaptor protein) contains adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains closely related in sequence to that of cytoplasmic Src family tyrosine kinases. Expressed most abundantly in the immune system, SLAP function has been predominantly studied in the context of lymphocyte signaling, where it functions in the Cbl dependent downregulation of antigen receptor signaling. However, accumulating evidence suggests that SLAP plays a role in the regulation of a broad range of membrane receptors including members of the receptor tyrosine kinase (RTK) family. In this review we highlight the role of SLAP in the ubiquitin dependent regulation of type III RTKs PDGFR, CSF-1R, KIT and Flt3, as well as Eph family RTKs. SLAP appears to bind activated type III and Eph RTKs via a conserved autophosphorylated juxtamembrane tyrosine motif in an SH2-dependent manner, suggesting that SLAP is important in regulating RTK signaling.


Fast and high precision algorithms for optimization in large-scale genomic problems.
There are several very difficult problems related to genetic or genomic analysis that belong to the field of discrete optimization in a set of all possible orders. With n elements (points, markers, clones, sequences, etc.), the number of all possible orders is n!/2 and only one of these is considered to be the true order. A classical formulation of a similar mathematical problem is the well-known traveling salesperson problem model (TSP). Genetic analogues of this problem include: ordering in multilocus genetic mapping, evolutionary tree reconstruction, building physical maps (contig assembling for overlapping clones and radiation hybrid mapping), and others. A novel, fast and reliable hybrid algorithm based on evolution strategy and guided local search discrete optimization was developed for TSP formulation of the multilocus mapping problems. High performance and high precision of the employed algorithm named guided evolution strategy (GES) allows verification of the obtained multilocus orders based on different computing-intensive approaches (e.g., bootstrap or jackknife) for detection and removing unreliable marker loci, hence, stabilizing the resulting paths. The efficiency of the proposed algorithm is demonstrated on standard TSP problems and on simulated data of multilocus genetic maps up to 1000 points per linkage group.


Synthesis of mono- and bis-spirooxindole derivatives "on water" using double salt of aluminum sulfate-sulfuric acid as a reusable catalyst.
The preparation of double salt of aluminum sulfate-sulfuric acid (Al4(SO4)6·(H2SO4)·24H2O) by the reaction of aluminum sulfate and sulfuric acid in water is described. Aluminum sulfate-sulfuric acid is characterized via some spectroscopic and microscopic techniques such as infrared spectroscopy (IR), X-ray diffraction spectroscopy (XRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) which corroborated the structure of the double salt. This double salt is soluble in water and insoluble in organic solvents. It was employed as a new catalyst for the synthesis of spirooxindole compounds on water with good to excellent yields. The double salt could be recycled and reused without appreciable loss of activity.


Comparison of fluoroscopic cardiovascular measurements from healthy dogs obtained at end-diastole and end-systole.
Quantitative measurements are commonly implemented to objectively evaluate heart size in dogs. However, recent studies suggest that the phase of cardiac cycle can impact vertebral heart score, thereby potentially influencing clinical management. This study used fluoroscopy to assess the impact of the cardiac cycle on quantitative cardiovascular measurements in healthy dogs of various breeds. This was a prospective study. Multiple cardiac and respiratory cycles were recorded fluoroscopically. Peak inspiratory end-systole and end-diastole frames were captured from 49 dogs in right lateral recumbency. Vertebral heart score (VHS), cardiothoracic ratio (CTR), vertebral left atrial size (VLAS), and caudal vena cava diameter ratio (CVCDR) measurements were performed. Mean cardiac measurements were compared between cardiac cycle phases, and the impact of body condition score (BCS), weight, thoracic conformation, sex, and age was evaluated. Cardiac cycle had a significant impact on VHS (mean difference: 0.36 ± 0.14 vertebral units between systole and diastole; p < 0.001) and CTR (mean difference: 2.2 ± 1.2% between systole and diastole; p < 0.001). Cardiac cycle had no significant impact on VLAS or CVCDR. Increasing BCS significantly increased variation between systole and diastole in CTR measurements (p = 0.024). The cardiac cycle has a significant effect on VHS and CTR but does not impact VLAS or CVCDR. These findings should be taken into consideration during clinical use of these measurements, especially if a patient is being monitored for cardiac changes over time via serial radiographs.


Parvovirus infection in a family with wheeze in an adult.
In a family outbreak of human parvovirus infection, a 59-year-old doctor had a prodromal illness with wheeze. This was followed by a distinct acute episode with itch and arthropathy and a two-month phase characterized by intermittent cough and wheeze.


Transvestism in a person with learning disabilities presenting with behavioural problems.
A case of transvestism is reported in a 47-year-old man with learning disabilities. He had developed encephalitis in childhood, which had resulted in moderate learning disabilities and epilepsy, and had been living in institutions from the age of six. He did not have any chance to express his sexual desire and this frustration manifested as aggressive behaviour. Recently, he moved to a community home and his deviant sexual behaviour became apparent. Management of his problems involves organizing a behavioural programme linking his cross dressing with aggressive behaviour.


Population response of the estuarine copepod Eurytemora affinis to its bioaccumulation of trace metals.
We evaluated the acute toxicities of metals cadmium (Cd), copper (Cu) and nickel (Ni) to a widely-distributed copepod Eurytemora affinis isolated from the Seine estuary. Both sexes of adult E. affinis were exposed separately to the three metals at concentration gradients to determine its 50% lethal concentration (LC50). After 4 days of exposure, both males and females showed a higher sensitivity to Cu (male LC50: 25.0 μg.L-1 and female LC50: 38.0 μg.L-1) than to Ni (male LC50: 90.0 μg.L-1 and female 161.0 μg.L-1) and Cd (male LC50: 127.8 μg.L-1 and female LC50: 90.0 μg.L-1). To assess for the first time, the extend of metal bioaccumulation and its effect at population scale, late stages (>200 μm) were collected and exposed to each metal at the concentration of 1/3 LC50, and to their mixture during 144 h without feeding. The Cd concentration consistently increased with time until the end of the experiment, whereas the Ni and Cu concentrations reached a plateau after 24 h and 72 h exposure, respectively. The results revealed that the copepods could accumulate Cu faster than Ni and Cd either in the treatment alone (0.58 L g-1.d-1) or in the three-metal mixture (0.72 L g-1.d-1) after 50% of exposure time (72 h). The number of individuals decreased in copepod populations except for the Cd treatment, where the number of nauplii increased. In addition, all treatments of metal exposure negatively affected bacterial densities in the copepod cultures, where the Cu treatment showed a negative remarkable effect compared with Cd and Ni treatment did.


High Weight-Specific Power Density of Thin-Film Amorphous Silicon Solar Cells on Graphene Papers.
Flexible thin-film solar cells with high weight-specific power density are highly desired in the emerging portable/wearable electronic devices, solar-powered vehicles, etc. The conventional flexible metallic or plastic substrates are encountered either overweight or thermal and mechanical mismatch with deposited films. In this work, we proposed a novel substrate for flexible solar cells based on graphene paper, which possesses the advantages of being lightweight and having a high-temperature tolerance and high mechanical flexibility. Thin-film amorphous silicon (a-Si:H) solar cells were constructed on such graphene paper, whose power density is 4.5 times higher than that on plastic polyimide substrates. In addition, the a-Si:H solar cells present notable flexibility whose power conversion efficiencies show little degradation when the solar cells are bent to a radius as small as 14 mm for more than 100 times. The application of this unique flexible substrate can be extended to CuInGaSe and CdTe solar cells and other thin-film devices requiring high-temperature processing.


In situ memory T cells and patterns of invasion predict outcome in patients with early-stage oral squamous cell carcinoma.
The objective of this study was to explore the prognostic value of in situ memory T cells and patterns of invasion (POI) in early stage oral squamous cell carcinoma (OSCC). One hundred fifty-seven patients with early stage (cT1T2N0) OSCC were identified from a pre-existing database of patients with oral cancer and were classified by POI according to hematoxylin-eosin staining. We examined the impact of the immunohistochemical expression of CD45RO in OSCC. Overall survival (OS) curves were calculated using the Kaplan-Meier method. Margin status was significantly associated with local recurrence in early stage OSCC (p= 0.000), and depth of invasion was also associated with regional recurrence (2 mm: p= 0.034; 4 mm: p= 0.015). The expression of CD45RO (p= 0.021) and POI (p= 0.027) individually was associated with OS, and patients in the group with combination score tended to have worse OS (p= 0.012). Combined evaluation of POI and CD45RO might prove to be a useful indicator for high-risk patients with occult metastases from early stage OSCC.


The exposures and health effects of benzene, toluene and naphthalene for Chinese chefs in multiple cooking styles of kitchens.
Commercial cooking has higher intensity and more severe instantaneous cooking pollution from volatile organic chemicals compared to home cooking, making health risk assessment of occupational exposure for chefs a priority. In this study, chefs from three cooking styles of kitchens, including steaming, frying, and grilling, were selected to investigate the external and internal exposures, health risks and effects of several typical aromatic hydrocarbons (benzene, toluene and naphthalene). Naphthalene was found to be the most concentrated contaminant in air samples among the different kitchens, while benzene had the lowest concentration. The concentration of toluene in frying kitchens was significantly higher than that in steaming kitchens. Air concentrations of toluene in frying kitchens, as well as benzene concentrations in grilling kitchens exceeded the standard level according to indoor air quality standard (GB/T18883-2002). Regarding the metabolites of pollutants in urine, the content of S-benzylmercapturic acids (S-BMA) for frying chefs was significantly higher than that for other cooking styles of chefs, which was consistent with the relatively higher air concentrations of toluene. There was a good correlation between internal and external exposure of the pollutants. The level of oxidative stress was influenced by 2-hydroxynaphthalene (2-OHN) and S-BMA, indicating the potential health risks of these occupational exposed chefs. This study indicates the need to improve the monitoring of typical aromatic hydrocarbons, as well as to investigate their potential health effects in large-scale groups, and improve the ventilation in kitchens.


Implementing an emergency medical services system in Kathmandu, Nepal: a model for "white coat diplomacy".
Wilderness medicine providers often visit foreign lands, where they come in contact with medical situations that are representative of the prevailing healthcare issues in the host countries. The standards of care for matters of acute and chronic care, public health, and crisis intervention are often below those we consider to be modern and essential. Emergency medical services (EMS) is an essential public medical service that is often found to be underdeveloped. We describe our efforts to support development of an EMS system in the Kathmandu Valley of Nepal, including training the first-ever class of emergency medical technicians in that country. The purpose of this description is to assist others who might attempt similar efforts in other countries and to support the notion that an effective approach to improving foreign relations is assistance such as this, which may be considered a form of "white coat diplomacy."


Cellulose extraction of Alstonia scholaris: A comparative study on efficiency of different bleaching reagents for its isolation and characterization.
The incredible benefits of Alstonia scholaris are piquing researchers' attention in extracting its cellulose and utilizing it in further therapeutic applications. This study is based on cellulose extraction from its stalks and processed through chemical pre-treatments to manifest its cellulose content by using different bleaching reagents. A comparison was made on efficiencies of three reagents and it is found that the hydrogen peroxide exposed maximum cellulose than sodium hypochlorite and sodium chlorite. The experimental results revealed that A. scholaris possess 68-70% cellulose content. FTIR spectrum shows that OH- and CH- vibrations of cellulose appeared at 3320 cm-1 & 2892 cm-1 respectively whereas SEM images show fibrillation, rough surface, and lumens in bleached fiber that attributes to the removal of lignin and hemicelluloses and confirms cellulose extraction. The XRD pattern certifies the crystalline nature and compactness of cellulose whereas tensile properties and TGA help in understanding its flexibility, mechanical strength, and thermal stability at 370 °C respectively.


Super-Resolution Ultrasound Localization Microscopy on a Rabbit Liver VX2 Tumor Model: An Initial Feasibility Study.
Ultrasound localization microscopy can image microvasculature in vivo without sacrificing imaging penetration depth. However, the reliance on super-resolution inference limits the applicability of the technique because subpixel tissue motion can corrupt microvascular reconstruction. Consequently, the majority of previous pre-clinical research on this super-resolution procedure has been restricted to low-motion experimental models with ample motion correction or data rejection, which precludes the imaging of organ sites that exhibit a high degree of respiratory and other motion. In this article, we present a novel anesthesia protocol in rabbits that induces safe, controllable periods of apnea to enable the long image-acquisition times required for ultrasound localization microscopy. We apply this protocol to a VX2 liver tumor model undergoing sorafenib therapy and compare the results to super-resolution images from conventional high-dose isoflurane anesthesia. We find that the apneic protocol was necessary to correctly identify the poorly vascularized tumor cores, as verified by immunohistochemistry, and to reveal the tumoral microvascular architecture.


Individual exposure to particulate matter and heart rate variability (HRV) in patients with previous myocardial infarction.
The exposures to particulate matter (PM) from urban air correlates with a variety of cardiovascular diseases, including myocardial infraction. Protection from the effects of particles on HRV by beta-blockers was observed.


First record of Hiroshiinoueana Kawabe, 1978 from China (Lepidoptera: Tortricidae: Olethreutinae), with descriptions of two new species.
The genus Hiroshiinoueana Kawabe, 1978 is recorded from China for the first time. Two new species, H. wuzhishanica sp. nov. and H. inequivalva sp. nov., are described and illustrated. A key to the species of Hiroshiinoueana is provided. Cytochrome oxidase subunit I (COI) sequences of the new species are deposited in GenBank.


Preparation technology and preservation mechanism of γ-CD-MOFs biaological packaging film loaded with curcumin.
To prevent food spoilage caused by microbial infection, the development of an environmentally friendly antimicrobial preservation material is crucial. Here, the microporous γ-CD-MOFs was utilized to encapsulate the hydrophobic active substance curcumin, resulting in the preparation of a non-toxic antimicrobial material (Cur-CD-MOFs). The results revealed that curcumin encapsulation in Cur-CD-MOFs occurred primarily in the carbonyl group, benzene ring, and enolic side ring of curcumin. The Cur-CD-MOFs had a 100% bactericidal effect on Escherichia coli and Staphylococcus aureus at 4 h and 8 h, and a strong inhibitory effect on aerial mycelium of Penicillium expansum and Botrytis cinerea. Furthermore, the incorporation of Cur-CD-MOFs improved the Pul/Tre film barrier and mechanical properties. The effectiveness of Cur-CD-MOFs-Pul/Tre in retaining fruit freshness was validated using Centennial Seedless grapes. This study confirmed that Cur-CD-MOFs is a promising antibacterial material, and Cur-CD-MOFs-Pul/Tre will be a potent candidate for food preservation.


Assessing the Impact of Atrazine on the Availability of Arsenic in Soils Using DGT Technique.
Arsenic (As) has been observed to co-exist with atrazine (ATR) in soils worldwide. ATR, as an organic chemical, may affect the availability of As and further influence its uptake by organisms. Here we used a novel passive sampling technique, DGT (diffusive gradients in thin-films), to compare with other two conventional sampling approaches (soil solution extraction and 'Olsen As' measurement) to investigate the influence of ATR addition (normal recommended level and contaminated level) on the availability of As in soils, to further interpret the potential risk of As in soil environment. The effect of adding ATR on the behaviour of As in soils was limited. When the concentration of ATR was much higher, the availability of As in soils was supressed, the labile pool size was also affected, but the R value did not change much. The properties of the soils also played an important role by affecting the states of the compounds.


Secretion of plasminogen activator in response to follicle-stimulating hormone in culture medium of human testicular cells from biopsy specimens.
Testicular cells from human biopsy specimens were cultured and plasminogen activator secreted into the medium was investigated. Follicle stimulating hormone stimulated plasminogen activator secretion. SDS-polyacrylamide gel electrophoresis followed by zymography showed that the molecular weight of plasminogen activator produced by human testicular cells is the same as that of human urokinase. Antigenicity was also found to be of the urokinase type but not of the tissue type.


The Impact of COVID-19 on Interventional Radiology Training Programs: What You Need to Know.
The COVID-19 pandemic has affected medical education in unprecedented ways. Herein, we briefly describe the affects of COVID-19 on Interventional Radiology residency training and summarize up to date guidance by governing bodies and key stakeholders.


The Influence of Heparan Sulfate on Breast Amyloidosis and the Toxicity of the Pre-fibrils Formed by β-casein.
Heparan sulfate (HS) as a mediator is usually involved in both inflammation and fibrosis. Besides, pre-fibrils are the intermediates of amyloid fibrils that usually cause cell death and tissue damage, like the amyloid-β in Alzheimer's disease, α-synuclein in Parkinson disease and islet amyloid polypeptide in type II diabetes mellitus. However, the related study was involved rarely in breast. Therefore, the combing technologies including hematoxylin-eosin staining and thioflavin S staining were used to investigate the influence of HS on breast amyloidosis. To further study the toxicity of the pre-fibrils formed by β-casein on the HC11 cells and the breast mammary gland, the combing technologies including pentamer formyl thiophene acetic acid fluorescence analysis, MTT assay, Annexin V/PI staining and hematoxylin-eosin staining were performed. The results demonstrated that HS, acted as an endogenous molecule, induced the inflammation and amyloid fibril formation at the same time, and there was a close relationship between inflammation and fibrosis of breast. In addition, the pre-fibrils formed by β-casein were toxic because they induced the death and apoptosis of HC11 cells, as well as the inflammation of mammary gland of rats. Therefore, the early examination and identify of the pre-fibrils in the breast were worth considering to prevent the disease development, and it was interesting to explore the HS mimetics to impair the breast amyloidosis and attenuate the inflammatory response in the future.


Anticonvulsant effects of ivermectin in genetically-epileptic chickens.
In genetically-photosensitive epileptic chickens, the anti-parasitic agent ivermectin, at 1.0 and 5.0 mg/kg, decreased or prevented seizures induced by intermittent photic stimulation without any side-effects on the central nervous system. The latency and duration of this anti-convulsant effect was dose-dependent. When combined with diazepam, ivermectin prolonged the anti-convulsant action of diazepam.


Chronic fatigue syndrome and cognitive deficit are associated with acute-phase neuropsychiatric manifestations of COVID-19: A 9-month follow-up study.
The preva lence of long-COVID symptoms is rising but it is not still possible to predict which patients will present them, and which types of symptoms they will present. We followed up 95 patients with confirmed COVID-19 for 9 months to identify and characterize long-COVID symptoms. Easy fatigability was the most common symptom (51.04%), followed by anxiety (38.54%), dyspnea (38.54%), and new-onset headache (38.54%). There was no association between COVID-19 severity in the acute phase and the number of long-COVID symptoms (F(1,93) = 0.75, p = 0.45), and cognitive function (MoCA) scores (F(1,90) = 0.073, p = 0.787) at follow-up. Being female (F(1,92) = - 2.27, p = 0.02), having a higher number of symptoms (F(1,93) = 2.76, p = 0.0068), and experiencing constitutional neuropsychiatric symptoms (F(1,93) = 2.529, p = 0.01) in the acute phase were associated with having chronic fatigue syndrome at follow-up. Moreover, constitutional neuropsychiatric symptoms in the acute phase were associated with a lower MoCA score (F(1,93) = 10.84, p = 0.001) at follow-up. Specific clinical presentations such as constitutional neuropsychiatric symptoms in the acute phase might be predictors of debilitating long-COVID symptoms such as chronic fatigue syndrome and cognitive deficits.


Tribological behaviors of laser textured surface under different lubrication conditions for rotary compressor.
Tribological behaviors of laser textured surface with elliptical dimples were experimentally compared with that of the smooth one under different lubrication conditions, including the poor-oil, rich-oil and dry lubrication. The lubrication regime was analyzed with the increasing operating load by ring-on-ring tribological tests. Finally, the performance impact of rolling piston rotary compressor with textures fabricated on the thrust surfaces was investigated. Results show that the tribological improvement strongly depends on lubrication condition. With the increase of applied loads under rich-oil and poor-oil lubrication, the effect of micro dimple promotes the critical load transforming lubrication regime, and expands the range of hydrodynamic lubrication, meanwhile maintains a similar minimum of friction coefficient as the smooth surface but enhances wear resistance. However, it is reverse to increase the friction coefficient and surface wear for the textured surfaces under dry lubrication. The compressor performance can be improved significantly by laser surface texturing with a 2% reduction of friction power consumption and a 2.5% enhancement of energy efficiency ratio.


The effect of low-dose pre-operative X-irradiation of implanted mouse mammary carcinomas on local recurrence and metastasis.
Pre-operative X-irradiation of s.c. implanted first-generation mammary tumours in C3H mice, using either 500 rad or two fractions of 350 rad, produced no improvement in the success of surgery in causing local control or in reduction of distant metastases. The metastasis rate was just significantly higher after the two-fraction treatment of the implanted tumour than after surgical removal alone. The results are in agreement with previously published results on carcinomas and a sarcoma but contrast with those for murine lymphomas.


Covalent bonding of riboflavin homologs by hepatic mitochondrial membrane enzymes.
Radioactive riboflavin and homologs of riboflavin possessing an ethyl group in positions 7- or 8-, or both were used to investigate the covalent bonding of the flavins. No strict correlation could be found between the location of the ethyl group and the activities of the enzymes known to be covalently-bound flavoproteins. It is proposed that the widely varying activities of these enzymes when utilizing certain homologs is the result of a combination of the abnormal flavin coenzyme and the differences in the specificity of the apoenzymes in the various tissues.


The prevalence of sexual dysfunction and associated risk factors in women with chronic pelvic pain: a cross-sectional study.
The aims of the study were to determine the prevalence of sexual dysfunction, its subtypes and associated risk factors in women with chronic pelvic pain (CPP) as compared to a general female population. We evaluated 112 women (mean age 34.73 +/- 8.07; age range 18-50) complaining of CPP with a comprehensive history including female sexual function index (FSFI) and several general assessment questions (GAQs), a complete physical examination and routine laboratory tests. A group of 108 healthy women (mean age 33.28 +/- 7.95; age range 19-52) without CPP were enrolled as cross-sectional controls. According to the general population, the incidence of female sexual dysfunction (FSD) was 67.8% in women with CPP and 32.2% in women without CPP (P < 0.0001). Among 112 CPP patients, 78 (69.6%) of them had FSD and 34 (30.4%) patients did not have FSD in the study (P < 0.0001). In that 78 patients, 42 patients (53.8%) had hypoactive sexual desire disorder, 26 patients (33.3%) had sexual arousal disorder, 17 patients (21.7%) had orgasmic disorder and finally 58 patients (74.3%) had sexual pain disorder. The FSFI scores in both groups were as follows: (patients vs. controls; median value; P value, respectively): desire: 3.31 versus 3.98 (P < 0.0001); arousal: 3.58 versus 4.35 (P < 0.0001); lubrication: 4.20 versus 4.88 (P < 0.0001); orgasm: 3.70 versus 4.48 (P < 0.0001); sexual satisfaction: 3.80 versus 4.64 (P < 0.0001); sexual pain: 2.75 versus 4.98 (P < 0.0001) and total FSFI score: 21.35 versus 27.29 (P < 0.0001). The prevalence of FSD was higher in women with CPP than in a general healthy population not complaining of CPP. Investigation of female sexuality was essential for these patients.


Electron microscopic findings in non-alcoholic fatty liver disease: is there a difference between hepatosteatosis and steatohepatitis?
Non-alcoholic fatty liver disease has long been accepted as benign; however, recent evidence suggests that the disease may progress to cirrhosis and hepatocellular carcinoma, although the natural course of the disease is still unclear. This study was designed to comparatively evaluate electron microscopic features of non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Quantitative and semi-quantitative ultrastructural evaluations were performed on liver biopsies from 23 patients, 10 with NAFL and 13 with NASH. No statistically significant difference was noted between NAFL and NASH patients in ultrastructural features of hepatocytes including megamitochondria, intramitochondrial crystalline inclusions, mitochondrial matrix granules, foamy cytoplasmic appearance, electron-lucent and glycogen-containing nuclear regions, lipofuscin granules, or an increased frequency of vesicles containing electron-dense material in peribiliary Golgi zone; however, the mitochondrial diameter was significantly higher in the NASH patients. Intercellular distance and microvilli between hepatocytes, collagen and electron-dense material accumulation in the space of Disse, electron-dense material accumulation and microvillus density in bile canaliculi did not differ significantly between the groups. Our data show that, although NAFL and NASH can be distinguished by their distinct light microscopic features, ultrastructural characteristics are similar, which suggests that NAFL may also have the potential to progress to fibrosis and cirrhosis like NASH.


Sedative, hypnotic and anticonvulsant activities of the ethanol fraction from Rhizoma Pinelliae Praeparatum.
Rhizoma Pinelliae Praeparatum is the product of raw Rhizoma Pinellia processed with alkaline solution and Licorice, which had been widely used for treatment of insomnia in traditional Chinese medicine. The present study aimed to investigate the sedative, hypnotic and anticonvulsant activities of ethanol fraction from Rhizoma Pinelliae Praeparatum (EFRP) and to determine whether these effects were related to GABAergic mechanism. The sedative, hypnotic and anticonvulsant activities of EFRP were investigated with locomotion activity, pentobarbital-induced sleeping and nikethamide (NKTM)-induced convulsion tests, respectively. Additionally, the effects of flumazenil (an antagonist of GABA(A) receptor) and L-malic acid (blocker of synthetic enzyme for GABA) on the hypnotic activity of EFRP were evaluated. EFRP at dose of 12 g/kg significantly inhibited the locomotion activity of mice. EFRP showed synergic effect on pentobarbital-induced sleeping by increased numbers of mice falling asleep, reduced the sleep latency and prolonged the sleeping time. L-malic acid and flumazenil inhibited the augment effects of EFRP on pentobarbital-induced sleeping. EFRP promoted a significant protection to NKTM-induced convulsion, by prolonged the death latency and decreased mortality. EFRP possessed sedative, hypnotic and anticonvulsant activities and these activities may be related to the GABAergic system.


Risk factors for death in children with visceral leishmaniasis.
Despite the major public health importance of visceral leishmaniasis (VL) in Latin America, well-designed studies to inform diagnosis, treatment and control interventions are scarce. Few observational studies address prognostic assessment in patients with VL. This study aimed to identify risk factors for death in children aged less than 15 years admitted for VL treatment in a referral center in northeast Brazil. In a retrospective cohort, we reviewed 546 records of patients younger than 15 years admitted with the diagnosis of VL at the Instituto de Medicina Integral Professor Fernando Figueira between May 1996 and June 2006. Age ranged from 4 months to 13.7 years, and 275 (50%) were male. There were 57 deaths, with a case-fatality rate of 10%. In multivariate logistic regression, the independent predictors of risk of dying from VL were (adjusted OR, 95% CI): mucosal bleeding (4.1, 1.3-13.4), jaundice (4.4, 1.7-11.2), dyspnea (2.8, 1.2-6.1), suspected or confirmed bacterial infections (2.7, 1.2-6.1), neutrophil count <500/mm³ (3.1, 1.4-6.9) and platelet count <50,000/mm³ (11.7, 5.4-25.1). A prognostic score was proposed and had satisfactory sensitivity (88.7%) and specificity (78.5%). Prognostic and severity markers can be useful to inform clinical decisions such as whether a child with VL can be safely treated in the local healthcare facility or would potentially benefit from transfer to referral centers where advanced life support facilities are available. High risk patients may benefit from interventions such as early use of extended-spectrum antibiotics or transfusion of blood products. These baseline risk-based supportive interventions should be assessed in clinical trials.


Infection prevention measures and its determinants in childcare facilities during the COVID-19 pandemic: A nationwide survey (2022-2023).
The coronavirus disease-2019 (COVID-19) pandemic presented an unprecedented challenge to societies, necessitating adaptations in infection prevention measures. While there is ample data on infection prevention practices in workplace and healthcare settings, comprehensive data specific to childcare facilities has been lacking. We conducted a nationwide web-based survey capturing responses from various childcare facilities (N = 549). This aimed to understand the adaptation in infection prevention measures between fiscal years 2022 and 2023, the status of events and activities, and the factors influencing decision-making related to infection prevention. From 2022 to 2023, most childcare facilities reduced infection prevention practices like mandatory mask-wearing (46.9 %-7.5 %) and eating without conversing (56.5 %-7.4 %), whereas they continued high levels of hand sanitization and checking child's health condition before attendance. The frequency of events and activities (e.g., athletic meets, field trips) increased, with many being held without restrictions. Surprisingly, 62.8 % of facilities used items not recommended for infection prevention. The influence of local government guidelines (risk ratio, 0.69; 95%CI, 0.53-0.90) and the input from junior teachers (risk ratio, 0.85; 95%CI, 0.72-0.99) were associated with reduced risk of using inappropriate items. Furthermore, childcare facilities emphasized the need to collaborate with public health and medical professionals for more accurate and efficient decision-making during pandemics. The survey provides insights into the evolving practices of Japanese childcare facilities during the COVID-19 pandemic. It underscores the importance of refining information sources, enhancing decision-making processes, and fostering collaboration with the medical community for future pandemics and natural disasters.


CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials.
Central nervous system (CNS) involvement in patients with newly diagnosed acute myeloid leukemia (AML) is rare, and systematic data regarding outcome are scarce. This retrospective study summarized data from 11 consecutive Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) clinical trials for patients with newly diagnosed AML. In all, 3240 patients with AML were analyzed, and 36 (1.11%) were found to have CNS involvement at diagnosis. The incidence of CNS disease among the 5 studies with per protocol mandatory lumbar puncture (LP) was similar to the incidence among studies in which LP was performed at the discretion of the investigator (0.86% vs 1.41%; P = .18). There was no significant difference in the rate of complete remission (CR) among patients with CNS involvement and those with other extramedullary disease (EMD) sites or those with no EMD (52.8% vs 59.3%-60%). The median overall survival (OS) for patients who were CNS positive, who had other EMD, or who had no EMD was 11.4, 11.3, and 12.7 months, respectively. There was no difference in OS among patients with CNS involvement, those with other EMD (hazard ratio [HR], 0.96; adjusted P = .84), and those with no EMD (HR, 1.19; adjusted P = .44). In conclusion, the reported incidence of CNS involvement in patients with newly diagnosed AML is low (1.1%), irrespective of whether an LP is mandatory or not. The presence of CNS disease at diagnosis in and of itself does not seem to portend a poor prognosis for achieving an initial CR or for OS.


Iodinated contrast media electro-degradation: process performance and degradation pathways.
The electrochemical degradation of six of the most widely used iodinated contrast media was investigated. Batch experiments were performed under constant current conditions using two DSA® electrodes (titanium coated with a proprietary and patented mixed metal oxide solution of precious metals such as iridium, ruthenium, platinum, rhodium and tantalum). The degradation removal never fell below 85% (at a current density of 64 mA/cm(2) with a reaction time of 150 min) when perchlorate was used as the supporting electrolyte; however, when sulphate was used, the degradation performance was above 80% (at a current density of 64 mA/cm(2) with a reaction time of 150 min) for all of the compounds studied. Three main degradation pathways were identified, namely, the reductive de-iodination of the aromatic ring, the reduction of alkyl aromatic amides to simple amides and the de-acylation of N-aromatic amides to produce aromatic amines. However, as amidotrizoate is an aromatic carboxylate, this is added via the decarboxylation reaction. The investigation did not reveal toxicity except for the lower current density used, which has shown a modest toxicity, most likely for some reaction intermediates that are not further degraded. In order to obtain total removal of the contrast media, it was necessary to employ a current intensity between 118 and 182 mA/cm(2) with energy consumption higher than 370 kWh/m(3). Overall, the electrochemical degradation was revealed to be a reliable process for the treatment of iodinated contrast media that can be found in contaminated waters such as hospital wastewater or pharmaceutical waste-contaminated streams.


Sacral nerve stimulation in the elderly.
Increasing life expectancy will increase the number of elderly patients with faecal incontinence. The study aimed to assess the safety and efficacy of sacral nerve stimulation (SNS) in patients over the age of 65 years. Patients aged over 65 years, who underwent temporary SNS from 1996 for faecal incontinence unresponsive to conservative treatment, were followed prospectively. Between January 1996 and December 2009, 30 patients [mean age 69.3 years (SD, 3.4)] underwent temporary SNS. Twenty-three (77%) had a >50% improvement in the St Mark's Continence Score and progressed to permanent SNS implantation. Their mean (±SD) score increased from 19 (3.2) at baseline to 8 (3.4) during temporary SNS and to 9 (3.4) 3 months after permanent SNS and 10 (3.7) at the latest median follow up (IQR) of 44 (20-150) months. The corresponding values at the same intervals for urgency [mean (±SD) min] were 1 (1.4), 8 (5.2), 8 (5) and 8 (5.4) and for incontinence episodes per 2 weeks [median (±IQR)] were 10 (7-14), 1 (0-5), 2 (0-5) and 0 (0-6). SNS is an effective treatment for faecal incontinence in patients over 65 years.


Outcomes of second-line oral antidiabetic drugs in persons with young-onset type 2 diabetes.
People with young-onset diabetes (YOD) exhibit a higher risk of morbidity and mortality than those with late-onset diabetes. Few studies have explored the preferred management of diabetes in such patients. We compared the risks of hospitalization and mortality among people with YOD to whom second-line oral antidiabetic drugs (OADs) were administered. 7257 people taking second-line OADs after initial metformin therapy were enrolled during 2009-2014. Using add-on sulfonylureas (SUs) as a reference, the multivariable Cox regression model was used to compare the hospitalization and mortality risks among 5 categories of second-line OADs: alpha-glucosidase inhibitors, meglitinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, SUs, and thiazolidinediones. After baseline characteristics, comorbidities, duration of diabetes, and drug use were controlled, the adjusted hazard ratios and 95% confidence interval for all-cause, cardiovascular, and non-infection hospitalization and all-cause mortality for metformin plus DPP-4 inhibitors were 0.62 (0.52-0.73), 0.49 (0.29-0.85), 0.64 (0.54-0.76), and 0.50 (0.27-0.92), respectively, when compared with the data for metformin plus SUs. Among people with YOD, taking add-on DPP-4 inhibitors was associated with lower risks of all-cause hospitalization and mortality than taking add-on SUs. DPP-4 inhibitors thus seem to be a suitable second-line OAD for such patients.


Tethered cord syndrome and transitional vertebrae.
Tethered cord syndrome (TCS) usually presents with low-lying conus medullaris and thickened filum terminale. Spinal cord anomalies usually accompany congenital malformations and variations of the vertebral column. Transitional vertebrae (TV) are common variant, especially in the lumbosacral region. Accurate definition of the spine level is essential for proper radiological diagnosis and treatment. In this study, congenital spinal cord and vertebral anomalies and the relation with TV groups and types were evaluated in TCS patients. The study was performed in 97 patients. Radiological imaging findings [computed tomography (CT), magnetic resonance imaging (MRI), and radiography] and medical records were evaluated. Spine bony malformation, spinal cord malformation, and spinal level of malformation were compared with TV and non-TV groups in TCS patients. In addition, TV groups and types were compared with each other for these anomalies. There was no statistically significant difference between TV and non-TV group in terms of the presence of vertebral bone and spinal cord anomalies. There were some significant differences in some of the spine bone and spinal cord anomalies among the groups and types of TV. Sixty-two point nine percent TCS patients had TV. Although these findings indicate that TV is common in patients with TCS, no significant difference is observed in most of the studied anomalies. However, there were some differences among the TV groups and TV types in relation to congenital malformations. It can be concluded that TV anomaly could be a distinct malformation apart from all the other anomalies that were studied. Transitional vertebrae may cause pain due to biomechanical changes in addition to progressive neurological symptoms which are usually seen with TCS.