The prevalence of foot-and-mouth disease in Asia.
Foot-and-mouth disease (FMD) is listed among the highly contagious diseases in animals and is endemic throughout the Asian continent. The disease is caused by the Foot-and-mouth disease virus (FMDV) and affects a wide variety of domesticated animals as well as wild ungulates. Clinically, the disease is described as a vesicular lesion on the tongue, muzzle, lips, gum, dental pad, interdigital cleft, coronary band, and heel of the foot. Sometimes these lesions give rise to lameness. Mastitis is also caused due to teat lesions. A biochemical test reveals that during FMD infection, there are elevated levels of interleukin-1 (IL-1), tumor necrosis factor-alpha, interferon-gamma (IFN-γ), interleukin-6, serum amyloid A protein, lactoferrin, mannose-binding lectin, and monocytes chemo-attractant protein-1 in the serum of infected animals. There is no specific treatment for FMD although some antivirals are given as prophylaxis and antibiotics are given to prevent secondary bacterial infection. This review presents comprehensive data on the prevalence of FMD and serotypes of FMDV that are attributable to the cause of FMD from a regional point of view. It also explains the worldwide dynamics of the seven serotypes of FMD and tries to identify epidemiological clusters of FMD in various geographical areas. Furthermore, the pathology associated with the foot and mouth disease virus along with the pathophysiology is discussed. The continent-wide prevalence and diversity patterns of FMD suggest that there is a need for stringent policies and legislation implementation regarding research and development aimed at manufacturing strain-specific vaccination, infection prevention, and control of the disease.


Influence analysis for linear mixed-effects models.
In this paper, we extend several regression diagnostic techniques commonly used in linear regression, such as leverage, infinitesimal influence, case deletion diagnostics, Cook's distance, and local influence to the linear mixed-effects model. In each case, the proposed new measure has a direct interpretation in terms of the effects on a parameter of interest, and collapses to the familiar linear regression measure when there are no random effects. The new measures are explicitly defined functions and do not necessitate re-estimation of the model, especially for cluster deletion diagnostics. The basis for both the cluster deletion diagnostics and Cook's distance is a generalization of Miller's simple update formula for case deletion for linear models. Pregibon's infinitesimal case deletion diagnostics is adapted to the linear mixed-effects model. A simple compact matrix formula is derived to assess the local influence of the fixed-effects regression coefficients. Finally, a link between the local influence approach and Cook's distance is established. These influence measures are applied to an analysis of 5-year Medicare reimbursements to colon cancer patients to identify the most influential observations and their effects on the fixed-effects coefficients.


Temperature-controlled flow switching in nanocapillary array membranes mediated by poly(N-isopropylacrylamide) polymer brushes grafted by atom transfer radical polymerization.
We report actively controlled transport that is thermally switchable and size-selective in a nanocapillary array membrane (NCAM) prepared by grafting poly(N-isopropylacrylamide) (PNIPAAm) brushes onto the exterior surface of a Au-coated polycarbonate track-etched membrane. A smooth Au layer on the membrane surface, which is key to obtaining a uniform polymer film, was prepared by thermal evaporation of approximately 50 nm Au on both exterior surfaces. After evaporation, the inner diameter of the pore is reduced slightly, but the NCAM retains a narrow pore size distribution. PNIPPAm brushes with 10-30 nm (dry film) thickness were grafted onto the Au surface through surface-initiated atom transfer radical polymerization (ATRP) using a disulfide initiator, (BrC(CH3)2COO(CH2)11S)2. Molecular transport through the PNIPAAm polymer brush-modified NCAMs was investigated by real-time fluorescence measurements using fluorescein isothiocyanate (FITC)-labeled dextrans ranging from 4.4 to 282 kDa in membranes with variable initial pore diameters (80, 100, and 200 nm) and different PNIPAAm thicknesses. Manipulating the temperature of the NCAM through the PNIPAAm lower critical solution temperature (LCST) causes large, size-dependent changes in the transport rates. Over specific ranges of probe size, transport is completely blocked below the LCST but strongly allowed above the LCST. The combination of the highly uniform PNIPAAm brush and the monodisperse pore size distribution is critical in producing highly reproducible switching behavior. Furthermore, the reversible nature of the switching raises the possibility of using them as actively controlled filtration devices.


Malignant solitary fibrous tumor in retroperitoneum: A case report and literature review.
Solitary fibrous tumor (SFT) is a rare mesenchymal tumor occurs in various sites. Malignant SFT in retroperitoneum is extremely rare. We report a case of malignant retroperitoneal SFT in a 59-year-old man presented with right flank pain for 1 month. A laparotomy and resection of the tumor were performed, the histopathologic and immunohistochemical findings were consistent with malignant retroperitoneal SFT. No adjuvant treatment was performed, and the patient had no signs of recurrence or metastasis at the 12 months follow-up. Complete surgical excision is the basic treatment principle for malignant retroperitoneal SFT. The histologic features and the Ki-67 label index are helpful for the diagnosis of malignant SFT.


Antisense gets a grip on miR-122 in chimpanzees.
Innovations in antisense drug design have enhanced potency and selectivity, as demonstrated in a recent study by Lanford and colleagues, who treated hepatitis C virus (HCV)-infected chimpanzees with SPC3649. This compound is a second-generation antisense RNA molecule that is complementary to the microRNA miR-122, a major regulatory RNA in liver that fine-tunes the expression of over 100 cellular genes and enhances HCV replication. Serum concentrations of cholesterol and HCV RNA were reduced in chimpanzees treated with 12 weekly intravenous infusions of SPC3649, and no major side effects were noted, paving the way for clinical trials of SPC3649 and other antisense drugs directed against microRNAs. Potential therapeutic uses of SPC3649 include the treatment of HCV infection and liver cancer.


Potential Role of Chemokines in Fracture Repair.
Chemokines are a family of small cytokines that share a typical key structure that is stabilized by disulfide bonds between the cysteine residues at the NH2-terminal of the protein, and they are secreted by a great variety of cells in several different conditions. Their function is directly dependent on their interactions with their receptors. Chemokines are involved in cell maturation and differentiation, infection, autoimmunity, cancer, and, in general, in any situation where immune components are involved. However, their role in postfracture inflammation and fracture healing is not yet well established. In this article, we will discuss the response of chemokines to bone fracture and their potential roles in postfracture inflammation and healing based on data from our studies and from other previously published studies.


[Alternative methods of therapy for comorbid sleep disorders as a method of choice in adult patients with epilepsy].
Systematization and generalization of data from domestic and foreign literature on alternative methods of treatment of sleep disorders in epilepsy. The search for data from domestic and foreign literary sources was carried out in the electronic databases Medline (PubMed), Scopus, Web of Science, eLibrary, CyberLeninka, Google Scholar. The data of modern randomized trials, meta-analyzes on the effectiveness of various non-traditional methods as a method of choice for epilepsy with comorbid sleep disorders have been analyzed. Complementary (alternative) treatments have many advantages over the classical pharmacotherapy of sleep disorders in epilepsy, in the form of non-invasiveness, low incidence of side-effects, ease of use, and lack of a dose-dependent effect. Of course, the targets of most of the above methods are not focused and not very specific, and the sample size is too small to obtain impartial and meaningful clinical conclusions, but this once again emphasizes the urgent need for large-scale clinical trials, which is necessary to develop evidence-based treatments for comorbid sleep disorders in epilepsy.


Immunopathogenesis of lupus and lupus nephritis: recent insights.
Systemic lupus erythematosus is a multisystemic autoimmune disease. The immunopathogenesis is characterized by the loss of tolerance to self. While many abnormalities in the immune system have been detected, genetic factors play a central role in the pathogenesis. The event proximate to target organ involvement appears to be autoantigen-driven, T cell-mediated, B cell activation. High levels of autoantibodies are produced. However, not all autoantibodies are pathogenic to the kidney (i.e. 'nephritogenic'). These nephritogenic autoantibodies appear to share specific physiochemical features that correlate well with patterns of renal injury. While DNA was initially regarded as the inciting autoantigen, this view does not appear to be supported by the prevailing evidence. Nucleosomes, which are structures comprising histones and DNA, have emerged as the more likely candidate autoantigen. Autoantibodies directed against nucleosomes that cross-react with nucleosomal epitopes have been identified. Furthermore, evidence suggests that immunoglobulin-nucleosomal complexes may be important in target organ immune deposition. In-vivo generation of nucleosomes requires apoptosis; in fact, there are several examples of aberrant apoptotic processes that present with autoimmunity. Aberrant apoptosis may also be critical in lupus immunopathogenesis. Indeed, studies on Fas/FasL and Bcl-2 in animal models and in humans have underscored the importance of apoptosis as an etiological factor in lupus. Cytokines, hormonal, infectious and environmental factors have also been found to be important in the pathogenesis of systemic lupus erythematosus. Overall, much progress has been made in elucidating the etiological agents and pathogenic mechanisms by which lupus develops. However, there is still some way to go before arriving at a unifying hypothesis. The reward for a better understanding of lupus immunopathogenesis will be the development of more specific targets for treatment, and the introduction of better and safer treatment modalities.


Differentiation of Brazilian Peppertree (Schinus terebinthifolius Raddi) and Peruvian Peppertree (Schinus molle L.) Fruits by UHPLC-UV-MS Analysis of Their Anthocyanin and Biflavonoid Profiles.
The objectives of this work were to determine the phenolic profile of Schinus terebinthifolius and Schinus molle fruits and to develop a reliable method for the differentiation of these two similar spices both known as pink pepper. Anthocyanins, biflavonoids and gallotannins, some of which are reported for the first time in these species, were identified by UHPLC-UV/vis-MS/MS. Consideration of the relative and absolute amounts of phenolics as well as indicator compounds from 18 samples revealed that the relative amounts of anthocyanins and biflavonoids are the most trustworthy parameters. Principal component analysis and cluster analysis (CA) allowed a grouping of the samples according to their species, showing that the anthocyanins are most important for the identification of species. As a result, authentication of the two Schinus species can be accomplished by UHPLC analysis of the relative amounts of anthocyanins combined with CA.


Transition of phase response properties and singularity in the circadian limit cycle of cultured cells.
The circadian system has been regarded as a limit cycle oscillator constructed by the integrated interaction of clock genes and proteins. Here, we investigated a mammalian circadian oscillation geometrically before and after a perturbation. We detected the singular point and transition from a type 1 to type 0 phase response curve (PRC) and determined the embedding dimension to show how many variables are needed to describe the limit cycle oscillation and relaxation process after a perturbation. As a perturbation, forskolin (FK) was administered to Rat-1 cells expressing the Per2::luc gene. By broadly and finely changing the phase and strength of the perturbation, we detected the transition of the PRC from type 1 to type 0 and a possible singular transition point, the property of which agreed quite well with our numerical simulation of the noisy Goodwin model, a simple yet canonical model for the transcription-translation feedback loop of the core clock genes. Furthermore, we estimated the embedding dimension of the limit cycle before and after the perturbation. The trajectory of the limit cycle was embedded in two dimensions but with the perturbation of the state point moved out of the trajectory, the relaxation process was generally embedded in higher dimensions. The average number of embedding dimensions at each dose of FK increased as the FK dose increased but most of the relaxation process was generally embedded within four dimensions. These findings support the existence of a circadian limit cycle oscillator in mammalian cells and suggest that a small number of variables determine the relaxation process after a perturbation.


Fetal alcohol spectrum disorder: report of one case.
One seven-year-old aboriginal boy visited our outpatient department for survey of study difficulty. The physical examination revealed microcephaly, broad depressed nasal bridge, thin upper lip, smooth philtrum, epicanthal folds and clinodactyly. He also had mild mental retardation and abnormal findings on brain MRI. His mother had confirmed daily alcoholic consumption (72 to 144 gm) during pregnancy. Besides the short stature and microcephaly, the patient had developmental delay in language. According to the history, clinical presentation, and the finding of brain imaging, this case matches the diagnosis of fetal alcohol spectrum disorder. It seems reasonable to consider that some cases with the idiopathic developmental delay may fit in this disorder, thus suggesting the importance of total abstinence from alcohol during pregnancy.


Genetic counseling. An evaluation of public health genetic clinics.
The geographic distribution of County Health Department clinic facilities in the state of California has made it readily possible to establish a regionalized program for genetic counseling services, using public health nurses as a major source of case-finding. From both consumer and health professional standpoints, regionalized satellite genetic counseling clinics have been successful, and in particular, the effectiveness of public health nurses in identifying clinical genetic problems is readily apparent.Long-term follow-up reinforcement of genetic counseling appears to be an important conclusion from these studies. It is our suggestion that reinforcement of counseling would best be accomplished through the health team member (physician, nurse and so forth) following the patient or family rather than through the consulting geneticist.


Influence of compression pressure and velocity on tablet sticking.
A rotary tablet machine fitted with 8-mm diameter flat-faced punches was used to measure scraper pressure (SCR), a type of shear stress, to evaluate sticking behavior. The shear stress between the surfaces of the tablet and lower punch was determined using an SCR detection system. Mean surface roughness (R(a)) of tablets, measured by a scanning laser-microscope, was used to estimate the magnitude of sticking. Tablet tensile strength tended to increase with compression pressure at either of the tablet production velocities tested, which was consistent with previous reports. SCR decreased with increasing compression pressure for samples at all compression velocities, and showed a tendency to increase with binder concentration. SCR also tended to increase with compression velocity for samples at all compression pressures, suggesting that the frequency of tablet sticking increased as compression velocity increased. R(a) associated with sticking increased with SCR, indicating that the adhesive force between the particles of the tablet surface and the lower punch surface plays an important role in sticking.


Prioritization of pesticide environmental transformation products in drinking water supplies.
Receiving waters within catchments may be exposed to many different transformation products following the application of pesticides. As environmental waters are abstracted for drinking water treatment these compounds may pose a risk to human health. This paper describes a prioritization approach for identifying the most important transformation products in drinking water sources. The approach can be applied to different geographical areas that have suitable pesticide usage data. The risk based approach incorporates data on pesticide usage and toxicity as well as transformation product formation, mobility, and persistence. The application of the approach is illustrated for two geographical areas that have good quality pesticide usage data: Great Britain and California. The transformation products with the highest risk index and a complete experimentally derived data set for Great Britain were 3,5,6-trichloro-2-pyridinol, thifensulfuron acid, and kresoxim-methyl acid and for California were carbendazim, aldicarb sulfoxide, and RP30228.


Possible natural hybridization of two morphologically distinct species of Acropora (Cnidaria, Scleractinia) in the Pacific: fertilization and larval survival rates.
Natural hybridization of corals in the Indo-Pacific has been considered rather rare. However, field studies have observed many corals with intermediate interspecific or unusual morphologies. Given that the existence of F1 hybrids with intermediate interspecific morphologies has been proven in the Caribbean, hybrids may also inhabit the Indo-Pacific and occur more frequently than expected. In this study, we focused on two morphologically different species, Acropora florida and A. intermedia, and performed crossing experiments at Akajima Island, Japan. Results showed that these species could hybridize in both directions via eggs and sperm, but that fertilization rates significantly differed according to which species provided eggs. These results are similar to those reported from the Caribbean. Although all embryos developed normally to the planular larval stage, the developmental processes of some hybrid embryos were delayed by approximately 1 h compared with conspecific embryos, suggesting that fertilization occurred 1 h later in interspecific crosses than in intraspecific crosses. More successful hybridization could occur under conditions with low numbers of conspecific colonies. Additionally, a comparison of survival rates between hybrid and intraspecific larvae revealed that intra- and interspecific larvae produced from eggs of A. florida survived for significantly longer than those produced from eggs of A. intermedia. Considering these data, under specific conditions, hybrids can be expected to be produced and survive in nature in the Pacific. Furthermore, we identified one colony with intermediate morphology between A. florida and A. intermedia in the field. This colony was fertilized only by eggs of A. florida, with high fertilization rates, suggesting that this colony would be a hybrid of these two species and might be backcrossed.


Single dose of mirtazapine modulates whole-brain functional connectivity during emotional narrative processing.
The link between neurotransmitter-level effects of antidepressants and their clinical effect remain poorly understood. A single dose of mirtazapine decreases limbic responses to fearful faces in healthy subjects, but it is unknown whether this effect applies to complex emotional situations and dynamic connectivity between brain regions. Thirty healthy volunteers listened to spoken emotional narratives during functional magnetic resonance imaging (fMRI). In an open-label design, 15 subjects received 15mg of mirtazapine two hours prior to fMRI while 15 subjects served as a control group. We assessed the effects of mirtazapine on regional neural responses and dynamic functional connectivity associated with valence and arousal. Mirtazapine attenuated responses to unpleasant events in the right fronto-insular cortex, while modulating responses to arousing events in the core limbic regions and the cortical midline structures (CMS). Mirtazapine decreased responses to unpleasant and arousing events in sensorimotor areas and the anterior CMS implicated in self-referential processing and formation of subjective feelings. Mirtazapine increased functional connectivity associated with positive valence in the CMS and limbic regions. Mirtazapine triggers large-scale changes in regional responses and functional connectivity during naturalistic, emotional stimuli. These span limbic, sensorimotor, and midline brain structures, and may be relevant to the clinical effectiveness of mirtazapine.


Alternol inhibits the proliferation and induces the differentiation of the mouse melanoma B16F0 cell line.
High malignant potential and low susceptibility to treatment are characteristics of malignant melanoma. Alternol, a novel compound purified from microbial fermentation products obtained from the bark of the yew tree, exhibits a variety of antitumor activities. Based on these findings, the aim of the present study was to extend the knowledge on the antineoplastic effect of alternol in the mouse melanoma B16F0 cell line. Alternol significantly inhibited the proliferation and colony formation of B16F0 cells in a dose-dependent manner as detected by MTT and soft agar colony formation assays. NaOH alkaline lysis and oxidation of Dopa indicated that alternol enhanced the melanin content and tyrosinase activity of the B16F0 cells and results also showed a dose‑response relationship. Morphologic changes accompanied by extended dendrites were discovered in the B16F0 cells after treatment with alternol. Furthermore, the mRNA levels of tyrosinase, Trp1 and Trp2 were increased by alternol. Our results confirmed that alternol possesses marked antineoplastic properties against melanoma cells, indicating that this microbial fermentation product is a promising agent for the differentiation therapy of cancer. The inhibition of cell proliferation and colony formation by alternol was associated with both cytotoxicity and induction of differentiation.


Direct Detection of Nucleic Acid with Minimizing Background and Improving Sensitivity Based on a Conformation-Discriminating Indicator.
As is well-known, the nucleic acid indicator-based strategy is one of the major approaches to monitor the nucleic acid hybridization-mediated recognition events in biochemical analysis, displaying obvious advantages including simplicity, low cost, convenience, and generality. However, conventional indicators either hold strong self-fluorescence or can be lighted by both ssDNA and dsDNA, lacking absolute selectivity for a certain conformation, always with high background interference and low sensitivity in sensing; and additional processing (e.g., nanomaterial-mediated background suppression, and enzyme-catalyzed signal amplification) is generally required to improve the detection performance. In this work, a carbazole derivative, EBCB, has been synthesized and screened as a dsDNA-specific fluorescent indicator. Compared with conventional indicators under the same conditions, EBCB displayed a much higher selective coefficient for dsDNA, with little self-fluorescence and negligible effect from ssDNA. Based on its superior capability in DNA conformation-discrimination, high sensitivity with minimizing background interference was demonstrated for direct detection of nucleic acid, and monitoring nucleic acid-based circuitry with good reversibity, resulting in low detection limit and high capability for discriminating base-mismatching. Thus, we expect that this highly specific DNA conformation-discriminating indicator will hold good potential for application in biochemical sensing and molecular logic switching.


A Typology of Violence against Self and Others and Its Associations with Drinking and Other Drug Use among High School Students in a U.S. General Population Survey.
This study examined associations between binge drinking and other substance use and perpetration of violence against self and others. Data were pooled from the 2003, 2005, and was constructed to reflect four categories of behaviors: other-directed violence only, self-directed violence only, combined other- and self-directed violence, and no violence. Results from multinomial logistic regressions show that the frequency of binge drinking and other substance use were significant risk factors for each of the violence categories relative to no-violence. However, the strengths of these associations varied across the violence categories.


High prevalence of Mycoplasma genitalium in the lower genitourinary tract of women attending a sexually transmitted disease clinic in Paris, France.
Previous studies have suggested that Mycoplasma genitalium is associated with cervicitis and may be a cause of pelvic inflammatory disease. This study attempted to investigate further the possible role of M genitalium in genital symptoms of women attending a sexually transmitted disease (STD) clinic. To determine the prevalence of and the association of clinical and microbiologic features with M genitalium in women presenting with genital symptoms. Between April 1994 and June 1996 a prospective study of 170 consecutive women with abnormal vaginal discharge, with or without urethral itching, dysuria, or pelvic pain, was conducted at the STD clinic at Saint-Louis Hospital in Paris. Information was collected on each subject's characteristics, and a clinical vulvar, vaginal, and cervical examination was performed. Cervical, vaginal, and urethral samples were obtained to identify infecting organisms. DNA of M genitalium was identified by polymerase chain reaction (PCR) at one or more genital sites in 65 women (38%; 95% CI, 31-46%) and was statistically more frequently detected in the vagina (39%) than in the cervix (21%) or urethra (28%) (P = 0.001 and 0.048, respectively). PCR inhibitors were detected in 17 specimens (4%). M genitalium was found in 6/14 (43%) positive for Chlamydia trachomatis, but no significant association between M genitalium and any demographic, clinical, or microbiologic data was noted in univariable or multivariable analysis. This study indicates that M genitalium is frequently encountered in the female genital tract and is not associated with cervicitis or any particular clinical or microbiologic data.


Effects of different sulfuric acid etching concentrations on PEEK surface bonding to resin composite.
This study evaluated the effects of surface pretreatment with different concentrations of sulfuric acid etching on surface properties and bonding between Polyetheretherketone (PEEK) and a resin composite. Six groups of surface pretreatment (no pretreatment, etched with 70, 80, 85, 90, and 98% sulfuric acid for 60 s) were treated on PEEK. Surface roughness, scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses were examined. Shear bond strength (SBS) and cross-sectional observations of the interfaces were performed. One-way ANOVA analysis revealed differences in surface roughness and SBS between groups. The 90 and 98% sulfuric acid etching significantly achieved the highest SBS (p<0.05). SEM and AFM demonstrated etched surfaces with wide and deep pores. The 90 and 98% sulfuric acid etching were suggested to be the optimal concentration to improve adhesion between PEEK and the resin composite.


Molecular and clinicopathological characteristics of ERBB2 gene fusions in 32,131 Chinese patients with solid tumors.
ERBB2 amplification is one of the most important and mature targets for HER2-targeted drug therapy. Somatic mutations of ERBB2 in the tyrosine kinase domain have been studied extensively, and play a role in response to anti-HER2 therapy among different cancer types. However, ERBB2 fusion has not been got attention and its relevance to HER2-targeted therapy is unclear. We comprehensively characterized ERBB2 fusions from next-generation sequencing (NGS) data between May 2018 and October 2021 in 32,131 various solid tumors. Among the tumors, 0.28% harbored ERBB2 fusions, which occurred more commonly in gastroesophageal junction cancer (3.12%; 3/96), breast cancer (1.89%; 8/422), urothelial carcinoma (1.72%; 1/58), and gastric cancer (1.60%; 23/1,437). Our population presented with a median age of 65 years (range 28 to 88 years), a high proportion of men (55 men vs 34 women; 61.80%). Among the patients with ERBB2 fusions, TP53 (82%), APC (18%), and CDK4 (15%) were the top3 co-mutant genes. What's more, most patients with ERBB2 fusion also had ERBB2 amplification (75.28%; 67/89), which was similar to the data in the TCGA database (88.00%; 44/50). Furthermore, TCGA database shows that patients with ERBB2 fusions in pan-cancer had a worse prognosis than those without ERBB2 fusions, as well as in breast cancer. Besides, ERBB2 amplification combined with ERBB2 fusion had worse prognosis than those with only ERBB2 amplification. ERBB2 fusion may interfere the effect of anti-HER2-targeted antibody drugs and influence the prognosis of patients with ERBB2 amplification. Prospective clinical trials are warranted to confirm the results in the future.


Health seeking behaviour and self-treatment for common childhood symptoms in rural Guatemala.
This study was conducted in the Guatemalan highland department of Sacatepequez, in a sample of 146 rural women insured by the Social Security system. It examined their health care behaviour when their children presented common childhood symptoms such as diarrhoea, fever, cough and worms. The mothers generally sought help and treatment advice from an older woman in the family, and did so more often for diarrhoea (82%) and fever (64%) than for cough (43%) or worms (28%). Obtaining advice in a pharmacy or from a drug seller ranked second (range: 8%-38%, depending on the symptom), before the procurement of professional help at a medical service (range: 8%-23%). Traditional healers were hardly consulted (range: 0%-3%). In the case of self-treatment the women predominantly relied on Western drugs: around 80% in diarrhoea and fever, and above 50% in cough. Herbs and traditional external remedies were little used, except in cough (27% herbs) and worms (58% external remedies). None of the mothers reported ORS as home treatment for diarrhoea. Problems of geographical or financial accessibility could not explain the low utilisation of the Western health care system. The acceptability of public services, however, was poor. Largely because the Social Security clinic did not prescribe the "potent" modern drugs mothers preferred for the treatment of childhood symptoms--at least, not for uncomplicated illness episodes. Women hence turned to the--partially informal--private sector, which unabashedly responds to their demands. Clear away the discrepancy between the "rational" needs perceived by the official health sector and the demands of the population is one of the bigger challenges to health care planning in transitional communities such as the one studied.


Determinants of specificity in coagulation proteases.
Proteases play diverse roles in a variety of essential biological processes, both as non-specific catalysts of protein degradation and as highly specific agents that control physiologic events. Here, we review the mechanisms of substrate specificity employed by serine proteases and focus our discussion on coagulation proteases. We dissect the interplay between active site and exosite specificity and how substrate recognition is regulated allosterically by Na+ binding. We also draw attention to a functional polarity that exists in the serine protease fold, which sheds light on the structural linkages between the active site and exosites.


Mapping epileptic foci by the dipole tracing method in a brain tumor patient with olfactory seizures: comparison with intraoperative electrocorticograms.
We estimated the position of the epileptic foci in a case of brain tumor with olfactory seizures using the Dipole Tracing Method (DTM) and compared the results with electrocorticograms (ECoGs) recorded during surgical resection. The case was a 24-year-old male. Electroencephalograms (EEG) showed frequent focal spikes in the right temporal area. Magnetic resonance imaging revealed a tumor in the right hippocampus region. We analyzed the spikes using DTM with a CDT-1000 EEG analyzer. The locations of two independent foci were analyzed; one was thought to be in the right hippocampus and the other in the right superior temporal gyrus. When the ECoG was taken, the results were in very close correlation with those of DTM, demonstrating the accuracy of DTM in the estimation of the location of epileptic foci in epileptic seizures with brain lesions.


Cardio-Ankle Vascular Index in a Thai Population.
Arterial stiffness as measured by the cardio-ankle vascular index (CAVI) is a widely available method in Thailand. Data from a large cross-sectional study revealed a significant correlation of CAVI and the presence of coronary artery disease as detected from 64-slice coronary computed tomography arteriography. Futhermore, CAVI was shown to predict long-term cardiovascular events in the patients with intermediate cardiovascular risk.


EMINIM: an adaptive and memory-efficient algorithm for genotype imputation.
Genome-wide association studies have proven to be a highly successful method for identification of genetic loci for complex phenotypes in both humans and model organisms. These large scale studies rely on the collection of hundreds of thousands of single nucleotide polymorphisms (SNPs) across the genome. Standard high-throughput genotyping technologies capture only a fraction of the total genetic variation. Recent efforts have shown that it is possible to "impute" with high accuracy the genotypes of SNPs that are not collected in the study provided that they are present in a reference data set which contains both SNPs collected in the study as well as other SNPs. We here introduce a novel HMM based technique to solve the imputation problem that addresses several shortcomings of existing methods. First, our method is adaptive which lets it estimate population genetic parameters from the data and be applied to model organisms that have very different evolutionary histories. Compared to previous methods, our method is up to ten times more accurate on model organisms such as mouse. Second, our algorithm scales in memory usage in the number of collected markers as opposed to the number of known SNPs. This issue is very relevant due to the size of the reference data sets currently being generated. We compare our method over mouse and human data sets to existing methods, and show that each has either comparable or better performance and much lower memory usage. The method is available for download at http://genetics.cs.ucla.edu/eminim.


Direct regulation of the natural competence regulator gene tfoX by cyclic AMP (cAMP) and cAMP receptor protein (CRP) in Vibrios.
TfoX (Sxy) and CRP are two important competence activators. The link between tfoX and CRP has been shown in H. influenza but lacking evidence of direct interaction. Recently a Sxy-dependent CRP (CRP-S) site autoregulating Sxy was reported in E. coli. Here, we show that the cAMP-CRP complex transcriptionally regulates tfoX expression through multiple canonical CRP (CRP-N) sites in Vibrios. This conclusion is supported by an analysis of the tfoX mRNA levels and tfoX transcriptional reporter fusions. The reduced expression of tfoX(VC) was restored by trans-complementation of crp in ∆crp and by exogenous cAMP in ∆cya. A promoter deletion analysis and the site-directed mutagenesis of the putative CRP-N sites revealed the presence of two functional CRP-N sites. The direct binding of cAMP-CRP to the tfoX(VC)promoter was demonstrated by EMSA assays. Additionally, the transcriptional start site (TSS) of tfoX(VF) in V. fluvialis was determined, and -10/-35 regions were predicted. Further comparison of the tfoX promoter in Vibrios revealed the existence of similar -10 motifs and putative CRP-N sites, indicating the conserved mechanism of CRP regulation on tfoX. Our study demonstrates the direct binding of the cAMP-CRP complex to tfoX promoter, and broadens the understanding of the molecular mechanism regulating tfoX in Vibrios.


Icariin ameliorate Alzheimer's disease by influencing SIRT1 and inhibiting Aβ cascade pathogenesis.
Of all types of dementia, Alzheimer's disease is the type that has the highest proportion of cases and is the cause of substantial medical and economic burden. The mechanism of Alzheimer's disease is closely associated with the aggregation of amyloid-β protein and causes neurotoxicity and extracellular accumulation in the brain and to intracellular neurofibrillary tangles caused by tau protein hyperphosphorylation in the brain tissue. Previous studies have demonstrated that sirtuin1 downregulation is involved in the pathological mechanism of Alzheimer's disease. The decrease of sirtuin1 level would cause Alzheimer's disease by means of promoting the amyloidogenic pathway to generate amyloid-β species and thereby triggering amyloid-β cascade reaction, such as tau protein hyperphosphorylation, neuron autophagy, neuroinflammation, oxidative stress, and neuron apoptosis. Currently, there is no effective treatment for Alzheimer's disease, it is necessary to develop new treatment strategies. According to the theory of traditional Chinese medicine and based on the mechanism of the disease, tonifying the kidneys is one of the principles for the treatment of Alzheimer's disease and Epimedium is a well-known Chinese medicine for tonifying kidney. Therefore, investigating the influence of the components of Epimedium on the pathological characteristics of Alzheimer's disease may provide a reference for the treatment of Alzheimer's disease in the future. In this article, we summarise the effects and mechanism of icariin, the main ingredient extracted from Epimedium, in ameliorating Alzheimer's disease by regulating sirtuin1 to inhibit amyloid-β protein and improve other amyloid-β cascade pathogenesis.


Development of a nano-SiO2 based enzyme-linked ligand binding assay for the determination of ibuprofen in human urine.
The application domains of classic enzyme-linked ligand binding assay (ELBA) is relatively narrow due to the high cost and hardly available binding receptor. In here, we described for the first time the possibility of developing a new ELBA based on silica nanoparticles (nano-SiO2) to assess the ibuprofen in human urine. Nano-SiO2 with a large surface area was introduced as stationary phase to improve the analytical performance. In the experiment, a competitively binding procedure with human serum albumin (HSA) was performed between the ibuprofen presented in sample and horseradish peroxidase labeled ibuprofen (HRP-ibuprofen) subsequently added. After centrifugal separation, the HRP/ibuprofen/nano-SiO2 composite catalyzed the substrate solution (TMB/H2O2) with a color change from colorless to yellow for quantitative measurement via an ultraviolet spectrophotometer. As a validation of the new principle, the developed nano-ELBA method was applied in the determination of ibuprofen excreted in human urine with excellent performance. This detection range only depends on the solubility of ligand and sensitivity of UV spectrophotometer. Our results indicate that this new method demonstrated to be able to rapidly and adequately determine the concentration of components in biological samples and advocate its effectiveness for various applications.


[Clinical value of MR cholangiopancreatography combining with dynamic enhanced MRI in the detection of cholangiocarcinoma].
To evaluate the clinical value of breath-hold magnetic resonance cholangiopancreatography (MRCP) combining with dynamic enhanced MRI in the diagnosis of cholangiocarcinoma. MRCP findings of 88 cholangiocarcinoma patients proved surgically and pathologically were analyzed retrospectively. MRCP examination succeeded in all the 88 patients and the pancreaticobiliary ducts were shown satisfactorily. The accuracy of MRCP in the location of both hilar and extrahepatic cholangiocarcinoma was 100%, and the accuracy of detecting hilar and extrahepatic cholangiocarcinoma were 100% and 52.2%, respectively. Combining with dynamic enhanced MRI, the detecting accuracy of extrahepatic cholangiocarcinoma improved to 91.3%. MRCP examination has a high successful rate and can accurately determine the location of hilar and extrahepatic cholangiocarcinoma, and the accuracy of qualitative diagnosis for the former two is high. Combining with dynamic enhanced MRI, the specificity of determining extrahepatic cholangiocarcinoma is also high.


How much, how often, how well? Adherence to a neuromuscular training warm-up injury prevention program in youth basketball.
Adherence is a key implementation outcome that determines the effectiveness of an intervention. This study, an observational design involving coaches and players from 33 high school basketball teams, evaluated the dimensions of adherence to a basketball-specific neuromuscular training (NMT) warm-up program in youth basketball. Coach adherence (daily report of team adherence) was collected prospectively. Adherence measures: cumulative utilization (proportion of total sessions possible), utilization fidelity (average # of exercises completed per NMT session), utilization frequency (average # of NMT sessions completed per week) were calculated and further evaluated for optimal adherence (≥80%, ≥10.4 exercises/session and ≥2 sessions/week, respectively) per coach. Additionally, exercise fidelity (proportion of players performing individual exercises correctly) was assessed. Coach (n = 31; 27-59 years) median cumulative utilization was 80%, utilization fidelity was 12 (of a possible 13 exercises per session) and utilization frequency was 2.3 sessions per week. Optimal adherence ranged from 52% to 71% across measures of adherence. Player exercise fidelity was 48%. Time constraint (47%) was the most frequently reported adherence barrier. While coach adherence to the NMT warm-up program was reasonably high across measures of adherence, a considerable proportion of coaches did not attain optimal adherence levels and player exercise fidelity was low.


Linking treatment centers with alcoholics anonymous.
Research has explored professional relationships with mutual-help groups but has not paid specific attention to professional coordination with Alcoholics Anonymous. This study surveyed by mail and by means of personal interview professionals and members of A.A. Thirty-six centers reported good relationships with A.A., although some professionals evaluated cooperation as better than did A.A. members. Six centers refrained from cooperating with A.A. Respondents shared methods of coordination and recommended linking practices. Good relationships with A.A. existed when professionals interacted frequently with the fellowship and where these interactions followed certain patterns of activity.


16. Recent studies using a global approach to measuring illness.
Global measures of illness are designed to measure the performance of a health service as a whole and the contribution of its various components. Such measures convert data about the outcome of medical care into information for use in planning at all administrative levels including the highest levels of government. This is achieved by means of a classification of states of illness applicable to all patients, whatever their diagnosis and symptoms, and of a scale which places valuations as perceived by society on the defined states. The valuations of changes in the states of individuals during treatment or over a period of time can then be summed for heterogeneous populations. By adjusting the valuations of future changes for time preferences it may be possible to take into account prognosis, and by placing a valuation on death, mortality and morbidity data can be combined. The properties appropriate to the classification and scale are defined and problems encountered in their derivation are discussed. Examples are presented of the application of one global measure to a group of medical specialists and to population data for the United Kingdom.


Three distinct ribonucleoproteins from tobacco chloroplasts: each contains a unique amino terminal acidic domain and two ribonucleoprotein consensus motifs.
Chloroplasts contain their own genetic system. Eighteen different split genes have been found among approximately 130 chloroplast genes from higher plants. However, little is known about the chloroplast splicing system. Mammalian heterogeneous nuclear ribonucleoproteins (hnRNP proteins) have been shown to be involved in splicing. We applied a purification procedure developed for HeLa cell hnRNP proteins, which uses a single-stranded DNA (ssDNA) affinity column, directly to the tobacco chloroplast lysate to isolate their chloroplast counterparts. Four proteins (mol. wt approximately 30 kd) bound strongly to the column. The amino-terminal sequences of three of them were determined and their cDNA clones were isolated from a tobacco leaf cDNA library. Sequence analysis of these clones revealed that all three proteins contain two ribonucleoprotein consensus sequences (RNP-CS), confirming their ribonucleoprotein (RNP) nature. The presence of putative transit peptides in their predicted protein sequences, and an in vitro import experiment confirmed they are located in the chloroplast. This is the first report of organellar proteins containing RNP-CS. In addition, these three chloroplast proteins have a very acidic amino-terminal domain, a novel feature among RNP proteins identified so far. They are expressed both in leaves and roots; their mRNA levels showed different light modulation in mature leaves. The three proteins might be involved in splicing and/or processing of chloroplast RNAs.


Improvement of vision after a combined midfacial and maxillary distraction with a rigid external distraction device.
We report a rare case of visual improvement in a 19-year-old patient with Apert syndrome after segmental distraction with a rigid external distraction device. We used the Rigid External Distraction Device II System (R.E.D. II, KLS Martin) after Le Fort I and III osteotomies.


Alcohol cue reactivity and mood induction in male and female alcoholics.
The purpose of this study was twofold: to investigate gender differences in alcohol cue reactivity, and to study the effect of individualized mood induction on cue reactivity. Male (n = 38) and female (n = 19) alcoholics were exposed to an alcoholic beverage before and after mood induction to assess their reactivity to the beverage cues. The mood induction was based on a situation the subject had identified as being high risk for relapse. Subjects showed urge and salivary reactivity in response to alcohol beverage cues prior to mood induction, and the induction of mood enhanced urge reactivity in both men and women. Analyses with alcohol urge reactors (subjects that demonstrate an increased urge to drink alcohol in response to an alcoholic beverage cue) suggested that women show more urge reactivity in response to negative moods than do men. No gender differences were seen in reactivity to beverage cues alone. These results identify an important gender difference in the effect of negative moods on cue reactivity and suggest that negative mood situations may place women at a higher risk for relapse than men.


["Modality shift" paradigms and subjective basic symptoms in schizophrenic patients with various developmental biological risk anamnesis].
Clinical experimental research on schizophrenia does not consider maturation processes of brain function in the majority of cases. In the course of neuronal organization and the differentiation phases of cerebral systems, early traumas in functionally important regions of the brain are accompanied by a facultative impairment of complex systems of information processing. Against the background of the comprehensively coherent "integrative psychobiological model of schizophrenia" (Ciompi) with high construct validity, (experimental) psychology investigations are reported on in the context of the "high-risk" concept in 44 young (20-37 years old) and mainly chronic schizophrenic patients with formation of a specific hypothesis for the developmental biology of the condition. In two homogeneous groups with the same structure, it is checked whether a discriminative appraisal concerning a different organization principle of central information processing systems is possible with "crossmodal" choice-reaction times (cCRT) and certain subscales of the Frankfurt symptom questionnaire (FBF) with regard to alternatively distributed and specially operationalized anamnestic biological risk factors. It can be objectively established in terms of experimental psychology that postpsychotically de-actualized "risk-free" schizophrenics differ from the reference group with a high-risk anamnesis in terms of significantly prolonged cCRT, but not from healthy subjects and an "MBD" control group. In addition, the FBF subscores "weakness of selective attention" and "loss of automatized skills" correlate with poor cCRT.(ABSTRACT TRUNCATED AT 250 WORDS)


Lasers for stone lithotripsy: advantages/disadvantages of each laser source.
The purpose of this article was to make a narrative review of the literature in search of all articles regarding thulium:yttrium-aluminium-garnet (YAG), thulium laser fiber (TFL) and holmium:YAG (Ho:YAG) for lithotripsy from 2020 to 2023. A selection of articles of special interest and best evidence was made in order to give a better perspective on their advantages and disadvantages. New Ho:YAG technologies of as high power, high frequency and pulsed modulations have shown promising results for lithotripsy by reducing retropulsion with good ablation efficiency. High peak power makes it particularly good for percutaneous nephrolithotomy. High intrarenal temperatures and correct setting are still concerning points.TFL has arrived to be one of the main players in flexible ureteroscopy. Being highly efficient and quick, and by producing micro-dusting the laser is quickly heading to become a gold standard. The new pulsed Thulium YAG is the newest laser. For now, only in-vitro studies show promising results with efficient lithotripsy. As the peak power lies between Ho:YAG and TFL it may be able to adequately perform when needing and low power lithotripsy. Several new technologies have been developed in the last years for stone lithotripsy. All being efficient and safe if well used. Different advantages and disadvantages of each laser must be taken into consideration to give each laser the proper indication.


Perioperative Physiotherapy in Total Knee Arthroplasty.
Total knee arthroplasty has a high success rate. In the interest of enhancing patient outcomes, numerous perioperative interventions have been studied, including preoperative education, preoperative rehabilitation, postoperative inpatient rehabilitation, continuous passive motion, postoperative outpatient rehabilitation, unsupervised in-home exercises, telerehabilitation, and various combinations of these. This comprehensive review analyzes the existing body of evidence on these perioperative interventions and examines some burgeoning opportunities in rehabilitation after total knee arthroplasty in the interest of improving patient outcomes and ensuring sustainable health care utilization for the future of total knee arthroplasty. [Orthopedics. 2017; 40(5):e765-e773.].


Drug therapy for chronic heart failure due to left ventricular systolic dysfunction: a review. III. Angiotensin-converting enzyme inhibitors.
The role of angiotensin-converting enzyme inhibitors (ACEIs) in heart failure (HF), which act primarily by inhibiting the renin-angiotensin-aldosterone system, has been thoroughly studied in different subgroups. This article reviews the most valid and recent evidence available concerning the use of ACEIs in HF due to left ventricular systolic dysfunction. The administration of ACEIs leads to statistically and clinically significant reductions in mortality (20 to 23%), risk of myocardial infarction (20 to 21%), hospitalization for heart failure (33%) and symptoms (as measured by NYHA classification). The existence of a class effect has been suggested for ACEIs. However, it has not been possible to demonstrate a significant effect on mortality in subgroup analysis for females or blacks. Higher doses of ACEIs are associated with a significant reduction in the combined endpoint of death or hospitalization for any reason and fewer hospitalizations for heart failure, but not in mortality risk or improvement as measured by NYHA class. All patients with HF should be prescribed an ACEI except in cases of contraindication or adverse reactions.


Clinical pharmacokinetics of antipsychotics in pediatric populations: a scoping review focusing on dosing regimen.
Achieving optimal clinical responses and minimizing side effects through precision dosing of antipsychotics in children and adolescents with psychiatric disorders remains a challenge. Identifying patient characteristics (covariates) that affect pharmacokinetics can inform more effective dosing strategies and ultimately improve patient outcomes. This review aims to provide greater insight into the impact of covariates on the clinical pharmacokinetics of antipsychotics in pediatric populations. A comprehensive literature search was conducted, and the main findings regarding the effects of the covariates on the pharmacokinetics of antipsychotics in children and adolescents are presented. Our study highlights significant covariates, including age, sex, weight, CYP2D6 phenotype, co-medication, and smoking habits, which affect the pharmacokinetics of antipsychotics. However, the findings were generally limited by the small sample sizes of naturalistic, open-label, observational studies, and the homogeneous subgroups. Dosing based on weight and preemptive genotyping could prove beneficial for optimizing the dosing regimen in pediatric populations. Future research is needed to refine dosing recommendations and establish therapeutic reference ranges critical for precision dosing and Therapeutic Drug Monitoring (TDM). The integration of individual patient characteristics with TDM can further optimize the efficacy and safety of antipsychotics for each patient.


Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract.
The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time. Eighty-two subjects (50% female, median age 54 years (range 3-73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = -0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = -0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher viral load. In nasal epithelium, only GNLY (granulysin) gene expression showed significant negative correlation with viral load. Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production and administration of interferon alpha-14 may be attractive transmission-blocking interventions.


Terahertz spectroscopy for interpreting the formation and hierarchical structures of silk fibroin oligopeptides.
Determining the configuration and conformation of peptides is crucial for interpreting their structure-property relationships. In this work, we present nondestructive terahertz time-domain spectroscopy combined with density functional theory (DFT) and potential energy distribution (PED) analysis to identify the hierarchical structures of oligopeptides. The characteristic THz spectra of silk fibroin oligopeptides have been measured. Supported by DFT and PED analysis, the intrinsic differences among the dipeptides were identified by the collective vibrational modes of "R" groups and terminal groups linked by molecular chains of amido bonds or benzene rings. For tetrapeptides and hexapeptides, a few weak resonances and intensity differences were distinguished by the vibration mode of the molecular collective network formed by the interaction of amide planes and intramolecular hydrogen bond interactions. According to the THz absorption analyses of amide planes and intramolecular interactions within the molecular chains of silk fibroin oligopeptide isomer pairs, the formation and hierarchical structures were successfully interpreted using THz spectroscopy. This investigation develops a better understanding of the peptide formation mechanism, which further provides guidance in interpreting the formation of silk.


The EAG Voltage-Dependent K+ Channel Subfamily: Similarities and Differences in Structural Organization and Gating.
EAG (ether-à-go-go or KCNH) are a subfamily of the voltage-gated potassium (Kv) channels. Like for all potassium channels, opening of EAG channels drives the membrane potential toward its equilibrium value for potassium, thus setting the resting potential and repolarizing action potentials. As voltage-dependent channels, they switch between open and closed conformations (gating) when changes in membrane potential are sensed by a voltage sensing domain (VSD) which is functionally coupled to a pore domain (PD) containing the permeation pathway, the potassium selectivity filter, and the channel gate. All Kv channels are tetrameric, with four VSDs formed by the S1-S4 transmembrane segments of each subunit, surrounding a central PD with the four S5-S6 sections arranged in a square-shaped structure. Structural information, mutagenesis, and functional experiments, indicated that in "classical/Shaker-type" Kv channels voltage-triggered VSD reorganizations are transmitted to PD gating via the α-helical S4-S5 sequence that links both modules. Importantly, these Shaker-type channels share a domain-swapped VSD/PD organization, with each VSD contacting the PD of the adjacent subunit. In this case, the S4-S5 linker, acting as a rigid mechanical lever (electromechanical lever coupling), would lead to channel gate opening at the cytoplasmic S6 helices bundle. However, new functional data with EAG channels split between the VSD and PD modules indicate that, in some Kv channels, alternative VSD/PD coupling mechanisms do exist. Noticeably, recent elucidation of the architecture of some EAG channels, and other relatives, showed that their VSDs are non-domain swapped. Despite similarities in primary sequence and predicted structural organization for all EAG channels, they show marked kinetic differences whose molecular basis is not completely understood. Thus, while a common general architecture may establish the gating system used by the EAG channels and the physicochemical coupling of voltage sensing to gating, subtle changes in that common structure, and/or allosteric influences of protein domains relatively distant from the central gating machinery, can crucially influence the gating process. We consider here the latest advances on these issues provided by the elucidation of eag1 and erg1 three-dimensional structures, and by both classical and more recent functional studies with different members of the EAG subfamily.


Some Strychnos spinosa (Loganiaceae) leaf extracts and fractions have good antimicrobial activities and low cytotoxicities.
Strychnos spinosa Lam. is a deciduous tree used in traditional medicine to treat infectious diseases. This study is designed to determine the antimicrobial, antioxidant and cytotoxic activities of extracts and fractions from leaves of S. spinosa. Extracts were obtained by maceration with acetone, methanol and dichloromethane/methanol (1/1) while fractions were prepared by liquid-liquid fractionation of the acetone extract. A broth serial microdilution method with tetrazolium violet as growth indicator was used to determine the minimum inhibitory concentration (MIC) against fungi, Gram-positive and Gram-negative bacteria. The antioxidant activity was determined using free-radical-scavenging assays, and the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide reduction assay was used to determine cytotoxicity. Four extracts and five fractions had good to weak antimicrobial activity with MICs ranging from 0.04 to >1.25 mg/ml against both fungi and bacteria. The chloroform and ethyl acetate fractions had an MIC of 0.08 mg/ml against Aspergillus fumigatus. The n-butanol fraction had an MIC of 0.04 mg/ml against Cryptococcus neoformans. The hexane and chloroform fractions had an MIC of 0.08 mg/ml against Staphylococcus aureus. The antioxidant activities were much lower than that of the positive controls. Except for the alkaloid extract, all the extracts and fractions had free-radical-scavenging activity (IC50 ranging from 33.66 to 314.30 μg/ml). The cytotoxicity on Vero cells was reasonable to low with LC50 values ranging between 30.56 and 689.39 μg/ml. The acetone extract and the chloroform fraction had the highest antibacterial activity. By solvent-solvent fractionation it was possible to increase the activity against A. fumigatus and to decrease the cytotoxicity leading to a potentially useful product to protect animals against aspergillosis. Our results therefore support the use of S. spinosa leaves in traditional medicine to treat infectious diseases.


Deficiency in neutrophil elastase does not impair neutrophil recruitment to inflamed sites.
To reach the sites of inflammation, neutrophils traverse the endothelium, its underlying basement membrane, and other barriers depending on the localization of the insulting agent. Whether neutrophil elastase (NE) plays a role in neutrophil recruitment to inflamed sites is still debatable. By exploiting mice deficient in NE (NE(-/-)), we sought to address this dilemma. We recruited neutrophils to the lungs or the peritoneum of wild-type (WT) or NE(-/-) mice by intranasal or intraperitoneal challenge with Pseudomonas aeruginosa or its lipopolysaccharide. At designated times post-inoculation (0, 4, 24, and 48 h), groups of mice were killed to assess changes in leukocyte counts and inflammatory responses. NE(-/-) and WT mice had normal circulating leukocyte numbers including neutrophils and changes in the hemograms in the setting of acute inflammation were indistinguishable. Analyses of lung tissues or fluids from the lungs and peritoneum found that regardless of the inflammatory model, the leukocyte counts including neutrophils and the inflammatory response were similar in NE(-/-) and WT mice at all time points. In vitro, neutrophils isolated from the lungs or the peritoneum of NE(-/-) and WT mice had comparable chemotactic and respiratory-burst functions and migrated normally through Matrigel in response to various stimuli. Interestingly, preincubation of human peripheral blood neutrophils with NE physiologic inhibitors did not alter the migration of the cells through Matrigel. In sum, our findings present the first in vivo description that the absence of NE does not impair neutrophil recruitment to inflamed sites and that NE is not required for basement membrane transmigration of neutrophils.


Effects of some thiol chelators on enzymatic activities in blood, liver and kidneys of acute arsenic (III) exposed mice.
The effects of meso 2, 3-dimercaptosuccinic acid (DMSA), sodium 2, 3-dimercaptopropane 1-sulfonate (DMPS) and S-adenosyl L-methionine (SAM) on the enzymatic activities of mice were studied. The mice were given intraperitoneal (i.p.) injections of these chelating agents (1 mmol/kg) and 3 h later the activity of delta-aminolevulinic acid dehydratase (ALAD) in the blood, and aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase (ALP) in the liver and kidney were determined. The activity of blood ALAD was significantly increased by the administration of DMSA and SAM while DMPS had only a moderate effect. The activities of other hepatic enzymes changed little when the mice were treated with these chelating agents, except for a significant reduction in hepatic ALP activity following DMPS administration. Arsenic (III) administration markedly increased the activities of ALT and ALP in the liver and kidneys. The changes in the enzymatic activities by treatment with arsenic were prevented by injection of DMSA, DMPS and SAM, DMSA being the most effective. These results indicate that DMSA, DMPS and SAM were not toxic to the liver or kidneys of mice and that treatment with DMSA is more effective than DMPS or SAM in protecting mice from acute hepatic or renal toxicity caused by arsenic.


Reduced NOx and PM10 emissions on urban motorways in The Netherlands by 80 km/h speed management.
A speed limit of 80 km/h with "strict enforcement" has been introduced in 2005 on zones of urban motorways in The Netherlands with the aim to improve air quality of NO(2) and PM(10) along these motorways. Strict enforcement means speed control by camera surveillance over the whole trajectory of 2-4 km combined with licence plate recognition and automatic fining in case of exceeding the speed limit. Traffic data measured in Rotterdam and Amsterdam at the zones without and with speed management showed that traffic dynamics have been significantly reduced as a result of speed management with strict enforcement. Reduction of traffic dynamics results in more free-flowing traffic with relatively less NO(x) and exhaust PM(10) emissions compared to congested traffic, i.e., stop-and-go traffic. The actual effect on NO(x) and PM(10) emissions at these speed management zones was studied in the cities Rotterdam and Amsterdam. The study was performed in two different ways: firstly by measurements and by modelling the contribution to NO(x) and PM(10) concentrations on both sides of the motorways, and secondly by estimating the change in traffic dynamics and the effect on emissions. From the results of both approaches in this study, it was concluded that in our case study in the Netherlands emission reduction by speed management is in the range of 5-30% for NO(x) and 5-25% for PM(10). Actual emission reductions by speed management at a specific motorway mainly depend on the ratio of congested traffic prior and after implementation of speed management. The larger this ratio, the larger is the relative emission reduction. The impact on air quality of 80 km/h for NO(x) and PM(10) is largest on motorways with a high fraction of heavy-duty vehicles.


Autophagy regulates the stemness of cervical cancer stem cells.
Cancer stem cells (CSCs) are a rare population of multipotent cells with the capacity to self-renew. It has been reported that there are CSCs in cervical cancer cells. Pluripotency-associated (PA) transcription factors such as Oct4, Sox2, Nanog and CD44 have been used to isolate CSCs subpopulations. In this study, we showed that autophagy plays an important role in the biological behavior of cervical cancer cells. The expression of the autophagy protein Beclin 1 and LC3B was higher in tumorspheres established from human cervical cancers cell lines (and CaSki) than in the parental adherent cells. It was also observed that the basal and starvation-induced autophagy flux was higher in tumorspheres than in the bulk population. Autophagy could regulate the expression level of PA proteins in cervical CSCs. In addition, CRISPR/Cas 9-mediated Beclin 1 knockout enhanced the malignancy of HeLa cells, leading to accumulation of PA proteins and promoted tumorsphere formation. Our findings suggest that autophagy modulates homeostasis of PA proteins, and Beclin 1 is critical for CSC maintenance and tumor development in nude mice. This demonstrates that a prosurvival autophagic pathway is critical for CSC maintenance.


Leptin in the ovine fetus correlates with fetal and placental size.
The purpose of this study was to detect the presence of leptin and its receptor in ovine fetal tissues and to examine the relationship between circulating leptin concentrations and fetal and placental weights on gestational day 138 (GD138) of ovine pregnancy (term, 145 days). Pregnant sheep (n = 18) were instrumented on GD 110 to facilitate measurement and chronic reduction of uterine blood flow and produce intrauterine growth restriction. Four animals that served as controls were euthanized on GD 138 to obtain fetal tissues to determine the presence of ovine leptin and its receptor by reverse transcriptase-polymerase chain reaction. Seven instrumented animals were randomized into the control group, and 7 instrumented animals were randomized into the uterine blood flow restricted group (reduction equaled approximately 50% on GD 138). Maternal and fetal blood samples were obtained on day 138 to measure plasma leptin concentrations, and animals were euthanized for the determination of fetal morphometrics and placental weight. Expression of RNA for ovine leptin and its receptor were observed in fetal liver, skeletal muscle, kidney, heart, and placenta. Fetal body weight, ponderal index, and placental weight were significantly decreased by approximately 40% in the blood flow restricted group as compared with controls. Fetal leptin concentrations were increased by 45% in the uteroplacental blood flow restricted group (P =.01). Maternal leptin concentrations were not significantly different between the 2 groups and did not correlate with fetal concentrations. Fetal leptin concentrations had an inverse relationship with uterine blood flow (r = -0.73; P =.004), fetal body weight (r = -0.78; P =.002), and placental weight (r = -0.68; P =.01). Ovine fetal tissues express RNA for leptin and its receptor. Circulating leptin concentrations in the ovine intrauterine growth restriction fetus were significantly elevated on gestational day 138 compared with controls. Fetal leptin concentrations were inversely related to uterine blood flow and fetal and placental weight. These findings suggest that fetal leptin may be involved in an adaptive response to intrauterine growth restriction.


Fetal malnutrition and adult chronic disease.
Since the fetal origins of adult disease hypothesis was put forward, more than 30 studies around the world have indicated low-birth-weight (LBW) infants have a higher incidence of hypertension and impaired glucose tolerance. India ranks second in incidence of LBW among South East Asian countries and is experiencing a transition of disease pattern from communicable disease to non-communicable disease. Whether this could be explained in part by LBW infants who experienced better nutrition at a later age is explored here. An earlier cohort with accurate birth weights was traced and enrolled into the study. A sample of 50 LBW and 78 normal birth weight (NBW) individuals are reported on here. Though the odds ratio (OR) estimates of risk factors for coronary heart disease and diabetes tended to be higher in LBWs who were better nourished at the time of the study, they were not statistically different. Similarly, OR estimates for risk factors tended to be higher in LBWs who put on more weight than the median of NBWs, but they were not significant. Logistic regressions with several variables indicated significant influence of body mass index on systolic (P <0.007) and diastolic (P <0.004) blood pressures. Since the risk associations are weak, more studies are needed to put the hypothesis on a firm footing.


Protein synthesis in the dendrite.
In neurons, many proteins that are involved in the transduction of synaptic activity and the expression of neural plasticity are specifically localized at synapses. How these proteins are targeted is not clearly understood. One mechanism is synaptic protein synthesis. According to this idea, messenger RNA (mRNA) translation from the polyribosomes that are observed at the synaptic regions provides a local source of synaptic proteins. Although an increasing number of mRNA species has been detected in the dendrite, information about the synaptic synthesis of specific proteins in a physiological context is still limited. The physiological function of synaptic synthesis of specific proteins in synaptogenesis and neural plasticity expression remains to be shown. Experiments aimed at understanding the mechanisms and functions f synaptic protein synthesis might provide important information about the molecular nature of neural plasticity.


[Bronchial cancer--development, diagnosis, therapy, prognosis].
Lung cancer is the most frequent cause of death from cancer in men. In addition its prevalence among women is currently rapidly increasing. Main risk factors are smoking, exposure to asbestos and genetic factors. Current screening methods do not allow early detection and, hence, lung cancer is usually diagnosed at an advanced stage. The stage of the disease affects survival. In non-small cell lung cancer the probability of 5-year survival for patients is about 43% with stage I, 23% with stage II, 17% with stage IIIA and 2% with stage IIIB disease. Surgery plays a major role in patients with non-small cell lung cancer in stages I, II and maybe IIIA. In small cell lung cancer the probability of 5-year survival is about 10% for patients with limited disease and less than 1% for patients with extended disease. Although surgery plays a role in stage I to stage IIIA, chemotherapy remains the most important mode of therapy in small cell lung cancer. In stages I to IIIA, however, combined treatment modalities might improve outcome of the patients with small cell lung cancer.


[Bone Metabolism and Mineral Density in Chronic Heart Failure].
to assess the state of bone metabolism and mineral density in outpatients with chronic heart failure (CHF). We examined 70 outpatients (30 men, 40 women, aged 56-88 years) with CHF and 40 outpatients without CHF (10 men, 30 women, aged 57-88 years). Examination included laboratory assessment, echocardiography, study of bone mineral density (BMD) in the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Osteoporosis was recorded in 61.4 and 32.4%, osteopenia - in 20 and 42.5%, normal BMD - in 18.6 and 25% of patients with and without CHF, respectively. A total of 24.3 and 7.5% of patients with and without CHF, respectively, experienced various bone fractures during mean follow up of 26.5 months. Significant correlation was established between osteoporosis and patient's age (r=0.36; p=0.002), CHF duration (r=0.26; p=0.039), falls (r=0.29; p=0.015), fractures (r=0.42; <0.001), chronic kidney disease - CKD (r=0.24; =0.048), N-proBNP (r=0.52; =0.007), GFR (r=-0.37; =0.010). In unifactorial analysis osteoporosis was associated with CKD (odds ratio [R] 3.1, 95% confidence interval [CI] 1.1-8.8, p=0.032 , N-proBNP (R 9.8, 95% CI 1.1-8.9, =0.043) and frequent alls (R 4.0, 95% CI 1.3-12.7; =0.019). Association of high N-proBNP level and abnormal renal function with lowered BMD allows to suggest that low BMD is an independent marker of CHF severity, and patients with CHF are at high risk of osteoporosis and related fractures.


Quantitative analysis of multiple components based on liquid chromatography with mass spectrometry in full scan mode.
Although liquid chromatography with mass spectrometry in full scan mode can obtain all the signals simultaneously in a large range and low cost, it is rarely used in quantitative analysis due to several problems such as chromatographic drifts and peak overlap. In this paper, we propose a Tchebichef moment method for the simultaneous quantitative analysis of three active compounds in Qingrejiedu oral liquid based on three-dimensional spectra in full scan mode of liquid chromatography with mass spectrometry. After the Tchebichef moments were calculated directly from the spectra, the quantitative linear models for three active compounds were established by stepwise regression. All the correlation coefficients were more than 0.9978. The limits of detection and limits of quantitation were less than 0.11 and 0.49 μg/mL, respectively. The intra- and interday precisions were less than 6.54 and 9.47%, while the recovery ranged from 102.56 to 112.15%. Owing to the advantages of multi-resolution and inherent invariance properties, Tchebichef moments could provide favorable results even in the situation of peaks shifting and overlapping, unknown interferences and noise signals, so it could be applied to the analysis of three-dimensional spectra in full scan mode of liquid chromatography with mass spectrometry.


[Female urethral diverticulum with calculus formation imitating stress incontinence].
A female urethral diverticulum (UD) is a rare condition with a prevalence of 0.6 - 4.7 %. Possible aetiologies include chronic infection of the periurethral glands, childbirth trauma, and iatrogenic lesions after urethral manipulation. The main symptoms are recurrent urinary tract infections, post-void dribbling and leakage of urine or purulent discharge by movement, which is caused by the emptying of the diverticular lumen (paradoxical incontinence). As this may imitate stress urinary incontinence, the final diagnosis is a challenge for urologists. We report the case of a female UD containing multiple calculi, which were diagnosed during diagnostic work-up of incontinence. Based on this case report, we want to present and analyse the symptoms as well as the diagnostic evaluation and treatment of UD as reported in the literature. Also we wish to emphasise that the differential diagnosis between a complicated diverticulum and stress urinary incontinence requires a precise knowledge of the symptoms and the diagnostic algorithm for the detection of a DU because the symptoms of these two conditions are similar.


Ashy Dermatosis in a Two-year-old Child: A Case Report and Mini-review.
Ashy dermatosis, or erythema dyschromicum perstans, is characterized by acquired grey patches distributed on the face, neck, trunk, and extremities with an unknown pathophysiology. Herein, we report a case of ashy dermatosis in a two-year-old child, possibly caused by an infection, with eventual improvement within two years, absent any treatment. To our knowledge, this is the second report of ashy dermatosis in a patient under the age of three years, and the first under the age of two years that was followed-up in the English-language literature from 2000 to 2021. Although the eruptions showed eventual improvement without any treatment in our case, all cases do not improve spontaneously. Further research is necessary to differentiate cases that eventually improve from resistant ones and determine treatment options for resistant cases.


High-risk metastatic gestational trophoblastic neoplasia. Primary management with EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) chemotherapy.
To describe and evaluate the clinical profile and response of patients with metastatic high-risk gestational trophoblastic neoplasia (GTN) to EMA-CO and other adjuvant treatment. A retrospective, descriptive analysis of data was done using charts of diagnosed cases of GTN from 2006-2010. The patients were classified according to the International Federation of Gynecology and Obstetrics anatomic staging and World Health Organization prognostic scoring. Clinical profiles of patients and response to EMA-CO chemotherapy and other surgical procedures in terms of remission rates, toxicities and mortality were evaluated. Seventy-three patients had metastatic high-risk disease. Sixty-seven patients were started on EMA-CO as first-line treatment. Only 56 completed treatment. Of those 56 patients, 30% underwent adjuvant surgical therapy. Primary remission rate with EMA-CO was 72%. Sustained remission rate after chemotherapy and other adjuvant procedures was 80%. Overall survival rate was 86% at the time of this writing. Of the 8 patients who died, 5 had stage IV disease while 3 had stage III disease. Factors that significantly affected response to EMA-CO were pretreatment hCG levels >100,000 mIU/mL and stage IV disease. The most common toxicities associated with the regimen were hematologic in nature. The use of EMA-CO chemotherapy as primary treatment for patients with metastatic high-risk GTN resulted in a primary remission rate of 72% and sustained remission rate of 80%. A survival rate of 86% was seen in this study.


High-temperature seedless synthesis of gold nanorods.
We demonstrate seedless synthesis of gold nanorods at high temperatures up to 97 degrees C. Using the correct silver nitrate concentration is crucial for formation of rod-shaped particles at all temperatures. We observed a decrease of nanorod length with increasing temperature, while the width stays constant throughout the temperature range. From kinetics studies, we show 3 orders of magnitude increase in nanorod growth rate when the temperature is raised from room temperature to 97 degrees C. From the temperature dependence of the growth rate, we obtain a average activation energy for growth on all facets of 90 +/- 10 kJ mol(-1). High-temperature synthesis of gold nanorods presents a more attractive method for scalable flow-based production of gold nanorods.


The soft genome.
Caenorhabditis elegans (C. elegans) nematodes transmit small RNAs across generations, a process that enables transgenerational regulation of genes. In contrast to changes to the DNA sequence, transgenerational transmission of small RNA-mediated responses is reversible, and thus enables "soft" or "flexible" inheritance of acquired characteristics. Until very recently only introduction of foreign genetic material (viruses, transposons, transgenes) was shown to directly lead to inheritance of small RNAs. New discoveries however, demonstrate that starvation also triggers inheritance of endogenous small RNAs in C.elegans. Multiple generations of worms inherit starvation-responsive endogenous small RNAs, and starvation also results in heritable extension of the progeny's lifespan. In this Commentary paper we explore the intriguing possibility that large parts of the genome and many additional traits are similarly subjected to heritable small RNA-mediated regulation, and focus on the potential influence of transgenerational RNAi on the worm's physiology. While the universal relevance of this mechanism remains to be discovered, we will examine how the discoveries made in worms already challenge long held dogmas in genetics and evolution.


Inequalities in size and intensity-dependent growth in a mermithid nematode parasitic in beach hoppers.
Inequality in body sizes is a common feature in populations of helminth parasites, with potential consequences for egg production and population genetics. Inequalities in body lengths and the effects of intraspecific competition on worm length were studied in a species of mermithid nematode parasitic in the crustacean Talorchestia quoyana (Amphipoda: Talitridae). The majority of the 753 worms recovered were relatively small, and an analysis using a Lorenz curve and Gini coefficient suggested that there were no marked inequalities in body lengths among the worms. Total worm length in the 356 infected amphipods (i.e. the sum of the lengths of all the worms in a host) increased steadily as a function of the number of worms per amphipod, whereas the length of the longest worm per amphipod peaked in amphipods harbouring intermediate numbers of worms. This last result was not significantly accounted for by the observed increase in host size with increasing intensity of infection, but resulted from a correlation between worm length and host size. As the number of worms per amphipod increased, the relative sizes of the second-, third-, and fourth-longest worms per host increased markedly. This means that relative inequalities in sizes become less pronounced, i.e. subordinate worms get closer in size to the longest worm, as the number of worms per host increases. The main consequence of this phenomenon is that worm sizes in the mermithid population are more homogeneous than they would be if intraspecific competition had stronger effects on worm growth.


Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications.
Intermediate filaments (IFs), together with actin filaments and microtubules, form the cytoskeleton - a critical structural element of every cell. Normal functioning IFs provide cells with mechanical and stress resilience, while a dysfunctional IF cytoskeleton compromises cellular health and has been associated with many human diseases. Post-translational modifications (PTMs) critically regulate IF dynamics in response to physiological changes and under stress conditions. Therefore, the ability to monitor changes in the PTM signature of IFs can contribute to a better functional understanding, and ultimately conditioning, of the IF system as a stress responder during cellular injury. However, the large number of IF proteins, which are encoded by over 70 individual genes and expressed in a tissue-dependent manner, is a major challenge in sorting out the relative importance of different PTMs. To that end, methods that enable monitoring of PTMs on IF proteins on an organism-wide level, rather than for isolated members of the family, can accelerate research progress in this area. Here, we present biochemical methods for the isolation of the total, detergent-soluble, and detergent-resistant fraction of IF proteins from 9 different mouse tissues (brain, heart, lung, liver, small intestine, large intestine, pancreas, kidney, and spleen). We further demonstrate an optimized protocol for rapid isolation of IF proteins by using lysing matrix and automated homogenization of different mouse tissues. The automated protocol is useful for profiling IFs in experiments with high sample volume (such as in disease models involving multiple animals and experimental groups). The resulting samples can be utilized for various downstream analyses, including mass spectrometry-based PTM profiling. Utilizing these methods, we provide new data to show that IF proteins in different mouse tissues (brain and liver) undergo parallel changes with respect to their expression levels and PTMs during aging.


Functional outcomes after free flap reconstruction of the upper aerodigestive tract.
When the complex structures of the upper aerodigestive tract are disrupted after resection of head and neck tumors, an appropriate reconstructive option should be chosen in an attempt to regain maximum function. Reconstructions using microvascular free tissue transfer offer unparalleled flexibility, both in tissue composition and in placement. This article will examine functional outcomes after free flap reconstruction of the upper aerodigestive tract. With the maturation of free tissue transfer techniques, functional outcomes are being analyzed with increasing frequency. Recent reports show promising results for free flap reconstruction of oral cavity, oropharyngeal, and hypopharyngeal soft tissue defects, as well as for bony mandibular and maxillary defects. For both soft tissue and bony defects of the upper aerodigestive tract, microvascular free flaps provide good functional outcomes. In the future, randomized studies are needed to compare the functional outcomes of microvascular free flaps with those of other reconstructive options.


[Treatment of a case of generalised dystonia using subthalamic stimulation].
Generalised dystonia is an entity that does not usually respond well to medical treatment. Different surgical targets have therefore been used in the treatment of dystonia, including several thalamic nuclei or the internal globus pallidus. The subthalamic nucleus plays a fundamental role in the physiology of the basal ganglia. It could therefore be considered to be a good potential target for stimulation. A patient who was confined to a wheelchair and who had not responded to a number of different medical treatment protocols or to a bilateral thalamotomy was treated with bilateral deep brain stimulation in the subthalamic nucleus. Tetrapolar electrodes were placed in both subthalamic nuclei in two stages. The patient showed a significant improvement from the very beginning of the post-operative period. After six months' progression, the patient was able to walk unaided and the dystonic seizures diminished significantly. Unfortunately, the patient died from choking. We used a bipolar stimulation protocol at 50 Hz with 210 micros pulses, which do not reach the levels of maximum charge density that are considered to be harmful. The subthalamic nucleus can be a good surgical target for deep brain stimulation in cases of generalised dystonia; it responds well to stimulation at intermediate frequencies with safe charge densities.


Benefits, Safety, and Adjunct Modality Prevalences of Long-Term Botulinum Toxin Injections for Cervical Dystonia and Myofascial Neck Pain: A Retrospective Cohort Study.
There is a paucity of long-term treatment benefit and safety data of botulinum toxin A (BTX-A) for cervical dystonia (CD) and myofascial neck pain syndrome (MPS). Additionally, the prevalence of adjunct modality uses during this period is unknown despite evolving practices. To assess and compare treatment benefit, safety, and adjunct modality prevalences of long-term BTX-A injections between CD and MPS patients. Retrospective cohort study. Private practice tertiary care clinics in Toronto. Convenience sample of 37 (52.9%) CD and 33 (47.1%) MPS patients treated for a mean±SD duration of 7.2±4.3 and 8.3±4.7 years, respectively. BTX-A injections administered at least once yearly, for a duration longer than 1 year. Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS) for disability and pain, Patient Global Impression of Change (PGIC) score, time to peak effect, duration of total response, adverse effects, and prevalence of adjunct modalities. CD patients experienced improvements in TWSTRS disability (17.57±6.79 to 9.81±4.35, p<0.001) and pain (14.61±3.08 to 9.05±3.49, p<0.001) scores as well as PGIC score (52.00%±23.60% to 64.80%±23.60%, p=0.007). MPS patients experienced improvements in TWSTRS disability (15.86±7.70 to 10.07±7.01, p=0.01) and pain (15.25±4.09 to 10.85±4.49, p=0.01) scores. In both cohorts, there were no changes in time to peak effect and duration of total response. Adverse effects were minimal and self-limiting. Prevalences of adjunct modalities used by CD versus MPS patients were 28.13% versus 50.00% for anesthetic procedures, 23.08% versus 15.38% for image-guidance, 65.71% versus 56.25% for pectoralis minor injections, and 47.06% versus 53.13% for cannabis-use. There were demonstrated and comparable treatment benefit, safety, and adjunct modality prevalences. Our study is the first to demonstrate that long-term BTX-A injections for MPS, although commonly used off-label, can be effective and safe.


Plasma adrenomedullin in cerebrovascular disease: a possible indicator of endothelial injury.
Cultured vascular endothelial and smooth muscle cells actively produce adrenomedullin, a novel vasodilator peptide discovered in human pheochromocytoma tissue. This present study was designed to determine whether the plasma level of adrenomedullin is a useful indicator for estimating the degree of endothelial injury in patients with atherosclerotic disease. We used a radioimmunoassay to measure plasma adrenomedullin concentrations in 51 patients with chronic cerebrovascular disease (34 infarctions and 17 haemorrhages) and in 10 subjects without symptomatic cerebrovascular disease. We also measured the plasma concentrations of thrombomodulin and endothelin as markers of endothelial injury. The patients were divided into three groups (A, B, and C) on the basis of the number of risk factors for atherosclerosis: hypertension, hyperlipidemia, smoking, low HDL-cholesterol, diabetes mellitus, and hyperuricaemia. Group A (68.7+/-2.7 years) consisted of patients with 0 or 1 risk factors; B (68.3+/-4.2 years) those with 2 risk factors; and C (69.2+/-3.6 years) those with 3 or more risk factors. The plasma concentration of adrenomedullin in these patients showed a significant positive correlation with age (r=0.33, p<0.05), as well as with the plasma concentrations of thrombomodulin (r=0.54, p<0.001) and endothelin (r=0.53, p<0.001). Moreover, the plasma concentrations of adrenomedullin and thrombomodulin (p<0.005 and p<0.02, respectively) tended to be higher in Group B and to be significantly higher in Group C as compared to Group A. Plasma adrenomedullin concentrations did not, however, significantly differ between the infarction and haemorrhage patients. These findings suggest that the plasma adrenomedullin concentrations reflect the degree of endothelial injury in patients with atherosclerotic disease.


Geckos as indicators of mining pollution.
Catastrophic collapse of a mine tailings dam released several million cubic meters of toxic mud and acidic water into the Guadiamar River valley, southern Spain, in 1998. Remediation efforts removed most of the sludge from the floodplain, but contamination persists. Clean-up activities also produced clouds of aerosolized materials that further contaminated the surrounding landscape. Whole-body concentrations of 21 elements in the Moorish wall gecko, Tarentola mauritanica, a common inhabitant of both rural and urban areas, were compared among seven locations. Locations spanned an expected contamination gradient and included a rural and an urban non-mine-affected location, two mine-affected towns, and three locations on the contaminated floodplain. Multivariate analyses of whole-body concentrations identified pollutants that increased across the expected contamination gradient, a trend particularly evident for As, Pb, and Cd. Additionally, higher contaminant concentrations occurred in prey items eaten by geckos from mine-affected areas. Comparison of element concentrations in tails and whole bodies suggests that tail clips are a viable nondestructive index of contaminant accumulation. Our results indicate that areas polluted by the mine continue to experience contamination of the terrestrial food chain. Where abundant, geckos represent useful taxa to study the bioavailability of some hazardous pollutants.


Polarization-Encrypted Orbital Angular Momentum Multiplexed Metasurface Holography.
Metasurface holography has the advantage of realizing complex wavefront modulation by thin layers together with the progressive technique of computer-generated holographic imaging. Despite the well-known light parameters, such as amplitude, phase, polarization, and frequency, the orbital angular momentum (OAM) of a beam can be regarded as another degree of freedom. Here, we propose and demonstrate orbital angular momentum multiplexing at different polarization channels using a birefringent metasurface for holographic encryption. The OAM selective holographic information can only be reconstructed with the exact topological charge and a specific polarization state. By using an incident beam with different topological charges as erasers, we mimic a super-resolution case for the reconstructed image, in analogy to the well-known STED technique in microscopy. The combination of multiple polarization channels together with the orbital angular momentum selectivity provides a higher security level for holographic encryption. Such a technique can be applied for beam shaping, optical camouflage, data storage, and dynamic displays.


Current evidence regarding the value of self-monitored blood glucose testing.
Many people with diabetes are falling short of attaining or maintaining glycemic goals. Self-monitoring of blood glucose (SMBG) is among the many strategies proposed to address the problem. SMBG complements hemoglobin A1c (HbA1c) testing by providing specific information regarding the effects of diet, exercise, and medications on glycemia. Although the importance of self-monitoring is appreciated for insulin-using patients, evidence is still emerging in support of self-monitoring for patients with type 2 diabetes managed with oral agents or diet. Evaluating the available evidence requires a good understanding of the study design and methodology. Although several clinical trials involving SMBG have been insufficiently powered to detect clinically meaningful differences in HbA1c, recent meta-analyses have reproducibly supported the benefit of self-monitoring in non-insulin-treated patients. Although additional work is needed to establish optimal frequency and timing of SMBG, these studies can serve as a basis for conservative recommendations to guide patients and their healthcare providers.