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Interspecies hybridization is an important evolutionary mechanism in yeasts. The genus Zygosaccharomyces in particular contains numerous hybrid strains and/or species. Here, we investigated the genome of Zygosaccharomyces strain MT15, an isolate from Maotai-flavor Chinese liquor fermentation. We found that it is an interspecies hybrid and identified it as Zygosaccharomyces pseudobailii. The Z. bailii species complex consists of three species: Z. bailii, which is not a hybrid and whose 10 Mb genome is designated 'A', and two hybrid species Z. parabailii ('AB' genome, 20 Mb) and Z. pseudobailii ('AC' genome, 20 Mb). The A, B and C subgenomes are all approximately 7%-10% different from one another in nucleotide sequence, and are derived from three different parental species. Despite being hybrids, Z. pseudobailii and Z. parabailii are capable of mating and sporulating. We previously showed that Z. parabailii regained fertility when one copy of its MAT locus became broken into two parts, causing the allodiploid hybrid to behave as a haploid gamete. In Z. pseudobailii, we find that a very similar process occurred after hybridization, when a deletion of 1.5 kb inactivated one of the two copies of its MAT locus. The half-sibling species Z. parabailii and Z. pseudobailii therefore went through remarkably parallel but independent steps to regain fertility after they were formed by separate interspecies hybridizations. | Zygosaccharomyces |
Mycoplasmas are the smallest and simplest organisms known. They form a large group of bacteria that can infect humans, animals, and plants. Even though several techniques have been proposed to enumerate mycoplasmas in broth medium, the determination of mycoplasma growth still remains a difficult task. The potential of using flow cytometry (FC) for rapidly estimating several species of mycoplasmas, M. agalactiae (Ma), M. putrefaciens (Mp), M. capricolum subsp. capricolum (Mcc), M. bovis (Mb), M. capricolum subsp. capripneumoniae (Mccp) and M. hyopneumoniae (Mh) in broth medium was examined. The FC analysis was performed by staining the mycoplasma cells with a fluorescent dye, SYBR green-I (SYBR), and the results were compared with plate count (Colony Forming Units--CFU) or Colour Changing Units (CCU) methods, depending on the mycoplasma species. There was a good correlation between mycoplasma counts determined by FC (cells ml(-1)) and by traditional plate count (CFU) or CCU methods. A correlation of 0.841, 0.981, 0.960, 0.913, 0.954, and 0.844 was obtained for Ma, Mp, Mcc, Mb, Mccp and Mh, respectively. FC method allowed results in 20-30 min, while 24-72 h was necessary for plate count method and 15 days for CCU method. FC was found to be a very useful, practical and fast technique to count mycoplasmas. These findings suggest that FC can be a good alternative to replace other time-consuming techniques that are currently used to enumerate mycoplasmas in broth medium. | Mycoplasmataceae |
Intravenous contrast agents are frequent adjuncts used in diagnostic imaging. Despite the well-recognized complications of contrast media extravasation, its treatment remains an enigma to many. This article reviews the recognition, prevention and treatment options, with a summary of the contrast media extravasation policy implemented in our department." | Extravasation of Diagnostic and Therapeutic Materials |
p-Dichlorobenzene (p-DCB) and naphthalene are classified as hazardous air pollutants and rank highly among chronic chemical hazards in US. residences. Sources of p-DCB and naphthalene include moth repellents and deodorizers typically used in closets, garment bags, and toilet bowls. Nearly pure concentrations of p-DCB and naphthalene are found in these products. p-DCB and naphthalene mass emission rates were determined for four different products placed in well-ventilated laboratory chambers as well as closets in a test house and in a garment bag. Concentrations were measured in bedrooms adjacent to closets where products were used. Emission rates varied considerably between products that contain p-DCB, primarily due to product packaging, and were generally suppressed when the product was used in closed closet or garments bags relative to products placed in well-ventilated chambers. This reduction appears to be due to lower air speeds in closets and garment bags as opposed to chemical accumulation. Variations in air temperature within typical ranges observed in homes can significantly influence emission rates of p-DCB and naphthalene. Concentrations of p-DCB and naphthalene in bedrooms adjacent to closets where moth repellents are used can exceed or approach odor thresholds. For this study, the concentrations exceeded or were within the upper few percentiles of those previously reported in residential indoor air. Based on a comparison of whole-house emission rates derived in a previous study, it appears that somewhere between 2% and 12% of homes in that study had active sources of p-DCB and between 5% and 15% had active sources of naphthalene. IMPLICATIONS: Inhalation of p-DCB and naphthalene has been linked to several health effects. Several off-the-shelf consumer products are nearly pure p-DCB or naphthalene, thus leading to potential for high emission rates and gas-phase concentrations in indoor environments where such products are used. Knowledge of p-DCB and naphthalene emission rates and variability in emissions with environmental conditions should provide for improvements in predictions of indoor concentrations of these compounds, which are in turn needed to complete exposure and inhalation risk assessments. | Chlorobenzenes |
The data presented here indicate that rodents metabolize and excrete delayed neurotoxic organophosphorus esters with great efficiency. By contrast, the adult chicken seems to have difficulty carrying out these processes. The cat is intermediate between rodents and chickens. Although further studies are needed, these results suggest that the hen model may exaggerate the effect of neurotoxic organophosphorus esters. Extrapolation of findings from the chicken may thus overestimate the risk or hazard of organophosphorus esters to humans. This may explain why no human case of EPN-induced delayed neurotoxicity has been reported despite the fact that it has been in use for over a quarter of a century. Other neurotoxicity data from our laboratory seem to support the suggestion that the cat may be a better model to extrapolate neurotoxicity results to humans. The data presented in this review suggest that the pharmacokinetics and metabolism of organophosphorus esters may play a prominent role in species and age sensitivities for OPIDN. Animals that are sensitive to delayed neurotoxicity have a higher accumulation rate, coupled with slower elimination of the neurotoxic agent. These studies, however, do not rule out the possibility that the target tissue of organophosphorus delayed neurotoxicity itself is species or age specific." | Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester |
With the recent advent of facial transplant (FT) treatment, patients who live with facial disfigurement have a new hope of improved facial aesthetics and quality of life. However, FT has been the subject of intense ethical debate, and there are numerous important ethical considerations surrounding FT that require further in-depth exploration. In the present review, the numerous ethical issues surrounding FT are elucidated, especially the weighty psychosocial impacts of FT, issues surrounding patients' consent, selection and donor matching, and current challenges with postoperative complication management and the facial reconstruction of donors. These are discussed with a key focus on stakeholders' perspectives including recipients, donors' families, and the medical teams involved. This review found that a number of key ethical questions remain unanswered in the field of FT, and further consideration is needed for this novel surgical procedure to have the same evidence-based ethical backing as conventional surgical procedures. | Facial Transplantation |
The role of magnetic resonance imaging (MRI) in prostate cancer evaluation is controversial and likely underestimated. Technological advances over the past 5 years have demonstrated that multiparametric MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI, can evaluate the actual tumor burden of a newly diagnosed prostate cancer more accurately than sextant biopsy protocols. Tumor risk, defined by the D'Amico criteria, hence can be re-evaluated by multiparametric MRI. As a result, there is increasing evidence that MRI before repeat or even initial biopsy can accurately select patients who require immediate biopsies and those in whom biopsy could be deferred. Also, a relationship between apparent diffusion coefficient (ADC), calculated from DWI, and Gleason score was found. Thus, MRI before biopsy helps to detect high-grade tumors to target biopsies within areas of low ADC values. To achieve good targeting accuracy, transrectal ultrasound (TRUS)-MRI image registration is necessary. Three-dimensional deformable registration is sufficiently accurate to match TRUS and MRI volumes with a topographic precision of 1 mm. Real-time MRI-guided biopsy is another technique under evaluation. Both approaches will allow for increasing acceptance of focal therapies, should these techniques be validated in the future. | Neoplasm Grading |
PURPOSE: This study examines how voice quality and multitalker babble noise affect immediate passage comprehension and the efficiency of information encoding into long-term memory in children with normal hearing. METHOD: Eighteen children (mean age = 9 years) with normal hearing participated. Immediate passage comprehension performance and delayed performance (after 5 to 8 days) were assessed for 4 listening conditions: a typical voice in quiet, a typical voice in noise, a dysphonic voice in quiet, and a dysphonic voice in noise. RESULTS: Multitalker babble noise had a significant effect on immediate and delayed performance. This effect was more pronounced for delayed performance. No significant main effect of voice quality was seen on immediate or delayed performance. CONCLUSIONS: Multitalker babble noise impairs immediate passage comprehension and encoding of information into long-term memory for later recall in children with normal hearing. In learning situations where competing speech signals are present, background noise may reduce the prerequisites for optimal learning. | Voice Quality |
Bioassay guided fractionation and separation of the EtOH extract of the kernels of Palaquium formosanum against PC-3 cells via Sephadex LH-20 and reverse phase C-18 columns led to the isolation of 13 protobassic saponins. One of these saponins is new and was characterized as 3'''-O-rhamnopyranosyl-arganin C, a bisdesmoside of 16alpha-hydroxyprotobassic acid at the C-3 and C-28 positions. The structures of these compounds were determined on the basis of 1D NMR ((1)H, (13)C), 2D NMR ((1)H-(1)H COSY, HSQC, HMBC, and NOESY), and selectively excited 1D TOCSY spectroscopic analyses and MS data, and comparison with literature data. Bioassay of these compounds and five additional compounds, isolated from Planchonella obovata leaf, against PC-3 prostate cancer cells indicated arganin C to be the most potent one with the IC(50) value of 13.8 muM. Some structure and activity relationships were also drawn. | Palaquium |
In vitro differentiation of pleomorphic blood-stream forms of Trypanosoma brucei to procyclic culture forms occurred rapidly and at high rates at 27 degrees C in a culture medium containing 1 mM cis-aconitate as the transformation-inducing agent. Citrate was required at a much higher concentration (10 mM) to produce a similar transformation rate. The highest percentage of transformed cells was obtained when bloodstream-form trypanosomes were treated with pronase in the absence of a feeder-cell layer. However, under these conditions, the amount of procyclic forms obtained after 72 h was lower than that obtained in the presence of cis-aconitate. Trypsin was also capable of inducing transformation in the absence of a feeder-cell layer, but this treatment again resulted in low numbers of transformed cells. Blood-stream-form trypanosomes were incapable of taking up citrate to any significant extent and the citrate content of these stages was negligible. After 72 h of exposure to citrate (3 mM), intracellular levels of this compound remained very low (< 1 nmol (10(9) cells)-1), increasing in established procyclic stages to approximately 1.7 nmol (10(9) cells)-1. These observations suggest that the tricarboxylic acid (TCA)-cycle metabolite-dependent transformation may be initiated externally to the trypanosome cell membrane. The ability of both citrate and cis-aconitate to bind calcium and, thus, to reduce the concentration of this cation in the culture medium was found not to be responsible for the triggering effect on trypanosome transformation.(ABSTRACT TRUNCATED AT 250 WORDS) | Aconitic Acid |
BACKGROUND: Correlation network analysis has become an integral tool to study metabolite datasets. Networks are constructed by omitting correlations between metabolites based on two thresholds-namely the r and the associated p-values. While p-value threshold settings follow the rules of multiple hypotheses testing correction, guidelines for r-value threshold settings have not been defined. RESULTS: Here, we introduce a method that allows determining the r-value threshold based on an iterative approach, where different networks are constructed and their network topology is monitored. Once the network topology changes significantly, the threshold is set to the corresponding correlation coefficient value. The approach was exemplified on: (i) a metabolite and morphological trait dataset from a potato association panel, which was grown under normal irrigation and water recovery conditions; and validated (ii) on a metabolite dataset of hearts of fed and fasted mice. For the potato normal irrigation correlation network a threshold of Pearson's |r|>/= 0.23 was suggested, while for the water recovery correlation network a threshold of Pearson's |r|>/= 0.41 was estimated. For both mice networks the threshold was calculated with Pearson's |r|>/= 0.84. CONCLUSIONS: Our analysis corrected the previously stated Pearson's correlation coefficient threshold from 0.4 to 0.41 in the water recovery network and from 0.4 to 0.23 for the normal irrigation network. Furthermore, the proposed method suggested a correlation threshold of 0.84 for both mice networks rather than a threshold of 0.7 as applied earlier. We demonstrate that the proposed approach is a valuable tool for constructing biological meaningful networks. | Correlation of Data |
The extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) are the focus of many studies due to their involvement in numerous physiological and pathological processes, such as cell proliferation and differentiation, and oncogenic transformation, respectively. ERK1/2 belong to the mitogen-activated protein kinase (MAPKs) family, which are serine/threonine kinases that participate in signal transduction and are activated by dual phosphorylation in the Thr-X-Tyr motif located in their activation loop. In addition, ERK activation induces its dimerization and translocation into the nucleus. On the basis of this knowledge, different assays and tools have been developed to determine ERK activity or monitor its activation. In this chapter, we describe methods to assay ERK activity based on the ability of ERK immunocomplexes to phosphorylate a substrate, as well as on immunoblot analysis using antibodies that recognize ERK1/2 phosphorylated in the Thr-X-Tyr motif. In addition, we describe an immunocytochemistry procedure to reveal stimuli-induced nuclear translocation of ERK1/2." | Extracellular Signal-Regulated MAP Kinases |
Artificial insemination using the husband's semen (AIH) has always seemed more acceptable than the same procedure using donor semen. However, the layman may not even have thought of the legal problems or the moral dilemma if in fact a woman is inseminated using her husband's frozen semen after his death. In the USA there are already sperm banks set up by private individuals, generally for the use of those marriage partners when the husband has had a vasectomy and afterwards a child is desired. If such private sperm banks were set up in Britain complex legal problems would follow, quite apart from the moral issue as to whether it was desirable to bring a child into the world deliberately having deprived him of a father from the start. These are the issues which Mr Cusine thinks should be carefully considered before doctors, lawyers and the women potentially concerned are confronted with a new dilemma." | Insemination, Artificial, Homologous |
Papillary lesions of the breast represent a heterogeneous group of neoplasm featuring fibrovascular cores covered by epithelial cells with or without intervening myoepithelial cells. According to the World Health Organization classification of breast tumors, papillary lesions of the breast are further classified into intraductal papilloma (including intraductal papilloma with atypical ductal hyperplasia /ductal carcinoma in situ), papillary ductal carcinoma in situ, encapsulated papillary carcinoma, solid papillary carcinoma (in situ and invasive) and invasive papillary carcinoma. The overlapping morphological features and immunohistochemical profiles make accurate diagnosis of breast papillary lesion a challenge for pathologists. In this review, the morphological and relevant immunohistochemical features of papillary lesions are discussed, with further emphasis on some commonly encountered practical diagnostic issues. A simple diagnostic algorithm will be established. The relevant molecular characteristics will be discussed as well." | Neoplasms, Ductal, Lobular, and Medullary |
Although the production of national spaces, citizens, and populations through enumerative practices has been well explored in a variety of disciplines, anthropological methods and analysis can help to illuminate the everyday practices of enumeration, their unexpected consequences, and the co-construction of identities through these processes by both the counted" and the "counters." The authors in this special issue illustrate how enumeration inflects lived experiences, produces subjectivities, and reconfigures governance. Focusing on the spatial, temporal, ideological, and affective dimensions of the techniques of enumeration, the authors also provide insights into the multiple forms of biopolitical expertise and knowledge that accumulate legitimacy through numerical discourse. They also highlight the ways in which governing structures, institutional and cultural norms, market logics, and rational-technical interventions influence the relationship among numerical categories, subjectivity, and everyday experience." | Anthropology |
CONTEXT: Utilization review (UR) seeks to improve quality and cost-efficiency of health care. However, how well the process works in practice has not been assessed. OBJECTIVE: To describe the outcomes of a sample of physician reviews in terms of the explicit criteria that the UR was designed to implement. DESIGN: Retrospective analysis of transcripts of precertification reviews. PARTICIPANTS AND SETTING: California physicians employed by a UR firm conducted 96 interviews from April 1990 to July 1991 with attending physicians who had proposed to insert tympanostomy tubes on a patient younger than 16 years and whose proposals had been found to be inappropriate on an initial screen. MAIN OUTCOME MEASURES: The appropriateness rating assigned to each case by the physician-reviewer and by the investigators using explicit criteria. Logistic regression identified factors associated with the reviewers' recommendations to perform surgery and with recommendations at variance from the criteria. RESULTS: The reviewers recommended 78% of cases for surgery, of which only 29% were supported by the criteria or had extenuating circumstances. The criteria concurred with all 30 of the reviewers' recommendations against surgery. Two factors, female sex (odds ratio [OR], 8.2; 95% confidence interval [CI], 1.2-53.8) and previous tympanostomy tube insertion (OR, 30.9; 95% CI, 2.4-394.8) were associated with reviewer recommendations in favor of surgery that were at variance from the criteria, despite the lack of evidence for either as a mitigating circumstance. CONCLUSION: Physician reviewers were more lenient than the explicit criteria that the reviews were designed to implement. In no cases did the reviewers depart from the criteria's recommendations in favor of surgery. | Drug Utilization Review |
Clostridium chauvoei is the etiologic agent of blackleg in cattle, inducing fever, severe myonecrosis, oedemic lesions and ultimately death of infected animals. The pathogen often results in such rapid death that antibiotic therapy is futile and thus vaccination is the only efficient strategy in order to control the disease. The beta-barrel pore forming leucocidin Clostridium chauvoei toxin A (CctA) is one of the best characterised toxins of C. chauvoei and has been shown to be an important virulence factor. It has been reported to induce protective immunity and is conserved across C. chauvoei strains collected from diverse geographical locations for more than 50 years. The aim of this study was to identify the location of the CctA toxin during liquid culture fermentation and to use CctA to develop an in vitro assay to replace the current guinea pig challenge assay for vaccine potency in standard batch release procedures. We report that CctA is fully secreted in C. chauvoei culture and show that it is found abundantly in the supernatant of liquid cultures. Sera from cattle vaccinated with a commercial blackleg vaccine revealed strong haemolysin-neutralizing activity against recombinant CctA which reached titres of 1000 times 28 days post-vaccination. Similarly, guinea pig sera from an official potency control test reached titres of 600 times 14 days post-vaccination. In contrast, ELISA was not able to specifically measure anti-CctA antibodies in cattle serum due to strong cross-reactions with antibodies against other proteins present pre-vaccination. We conclude that haemolysin-neutralizing antibodies are a valuable measurement for protective immunity against blackleg and have the potential to be a suitable replacement of the guinea pig challenge potency test, which would forego the unnecessary challenge of laboratory animals. | Clostridium chauvoei |
A patient is described in whom the Dubin-Johnson syndrome was diagnosed after an attack of acute hepatitis at the age of 21. In the eight years following the hepatitis Dubin-Johnson pigment, initially scanty, developed to classical proportions. The defect in intracellular transport of bilirubin was thought to precede the attack of acute hepatitis. | Jaundice, Chronic Idiopathic |
BACKGROUND: Common vetch (Vicia sativa L.) is a forage grain legume of high protein content and high nitrogen fixation, relevant in sustainable agriculture systems. Drought is the main limiting factor of this crop yield. Genetic resources collections are essential to provide genetic variability for breeding. The analysis of drought associated parameters has allowed us to identify drought tolerant and sensitive ecotypes in a vetch core collection. RESULTS: To understand the mechanisms involved in drought response we analysed transcriptomic differences between tolerant and sensitive accessions. Polymorphic variants (SNPs and SSRs) in these differential expressed genes (DEGs) have also been analysed for the design of drought-associated markers. A total of 1332 transcripts were commonly deregulated in both genotypes under drought. To know the drought adaptive response, we also analysed DEGs between accessions. A total of 2646 transcripts are DEG between sensitive and tolerant ecotypes, in watered and drought conditions, including important genes involved in redox homeostasis, cell wall modifications and stress-response. The integration of this functional and genetic information will contribute to understand the molecular mechanisms of drought response and the adaptive mechanisms of drought tolerance in common vetch. The identification of polymorphic variants in these DEGs has also been screened for the design of drought-associated markers that could be used in future breeding program strategies. CONCLUSIONS: Our studies shed light for the first time in common vetch about the genes and pathways associated with drought tolerance. In addition, we identify over 100 potential drought associated polymorphism, as SNPs or SSRs, which are differently present in drought and tolerant genotypes. The use of these molecular markers for trait prediction would enable the development of genomic tools for future engineering strategies by screening of germplasm crop collections for traits related with crop drought resilience, adaptability or yield in vetch. | Vicia |
BACKGROUND: Recent evidence has demonstrated the efficacy of Virtual Reality (VR) for stroke rehabilitation nonetheless its benefits and limitations in large population of patients have not yet been studied. OBJECTIVES: To evaluate the effectiveness of non-immersive VR treatment for the restoration of the upper limb motor function and its impact on the activities of daily living capacities in post-stroke patients. METHODS: A pragmatic clinical trial was conducted among post-stroke patients admitted to our rehabilitation hospital. We enrolled 376 subjects who had a motor arm subscore on the Italian version of the National Institutes of Health Stroke Scale (It-NIHSS) between 1 and 3 and without severe neuropsychological impairments interfering with recovery. Patients were allocated to two treatments groups, receiving combined VR and upper limb conventional (ULC) therapy or ULC therapy alone. The treatment programs consisted of 2 hours of daily therapy, delivered 5 days per week, for 4 weeks. The outcome measures were the Fugl-Meyer Upper Extremity (F-M UE) and Functional Independence Measure (FIM) scales. RESULTS: Both treatments significantly improved F-M UE and FIM scores, but the improvement obtained with VR rehabilitation was significantly greater than that achieved with ULC therapy alone. The estimated effect size of the minimal difference between groups in F-M UE and FIM scores was 2.5 +/- 0.5 (P < 0.001) pts and 3.2 +/- 1.2 (P = 0.007) pts, respectively. CONCLUSIONS: VR rehabilitation in post-stroke patients seems more effective than conventional interventions in restoring upper limb motor impairments and motor related functional abilities. TRIAL REGISTRATION: Italian Ministry of Health IRCCS Research Programme 2590412." | Virtual Reality Exposure Therapy |
BACKGROUND: Anorectal manometry (ARM) is conventionally used to assess patients with fecal incontinence (FI). This review aims to establish the diagnostic accuracy of ARM for FI. METHOD: A search of MEDLINE, EMBASE, Science Citation Index Expanded and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library was performed. Studies examining the sensitivity and specificity of ARM measures, either individually or combined, in the diagnosis of FI, were included. Data analysis was conducted using the bivariate statistical method. RESULTS: Seven studies were included out of an initial search of 1499 studies. The summary sensitivity and specificity for ARM as an overall test were 0.80 (95% confidence interval (CI): 0.69-0.88) and 0.80 (95% CI: 0.65-0.90), respectively. The diagnostic odds ratio (DOR) for ARM was found to be 16.61 (95% CI: 5.52-50.03). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) for ARM were found to be 4.09 (95% CI: 2.11-7.94) and 0.25 (95% CI: 0.14-0.42), respectively. Subgroup analysis based on four studies reporting on maximum resting pressure (MRP) demonstrated a sensitivity, specificity, DOR, PLR and NLR of 0.60 (95% CI: 0.38-0.79), 0.93 (95% CI: 0.80-0.97), 20.0 (95% CI: 4.00-91.00), 8.60 (95% CI: 3.00-24.30) and 0.43 (95% CI: 0.24-0.76), respectively. CONCLUSION: ARM has been shown to be an accurate test for diagnosing FI. Further studies are required to establish the diagnostic accuracy of individual ARM measures. | Fecal Incontinence |
We present a case of a 58-year-old man for surgical myectomy due to recurrent left ventricular outflow tract (LVOT) obstruction, who had prior transaortic septal myectomy and embolization of the septal branch. On admission, transthoracic echocardiography showed a typical hypertrophic obstructive cardiomyopathy (HOCM) with asymmetric septal hypertrophy, significant LVOT obstruction and severe mitral regurgitation due to the systolic anterior movement of the anterior mitral valve leaflet. We performed a novel procedure of the transapical beating-heart septal myectomy, following which the LVOT obstruction was resolved. And a decreased grade of systolic anterior movement and a reduction in the severity of mitral regurgitation were observed." | Ventricular Outflow Obstruction, Left |
Replication of minute virus of mice (MVM) induces a sustained cellular DNA damage response (DDR) which the virus then exploits to prepare the nuclear environment for effective parvovirus takeover. An essential aspect of the MVM-induced DDR is the establishment of a potent premitotic block, which we previously found to be independent of activated p21 and ATR/Chk1 signaling. This arrest, unlike others reported previously, depends upon a significant, specific depletion of cyclin B1 and its encoding RNA, which precludes cyclin B1/CDK1 complex function, thus preventing mitotic entry. We show here that while the stability of cyclin B1 RNA was not affected by MVM infection, the production of nascent cyclin B1 RNA was substantially diminished at late times postinfection. Ectopic expression of NS1 alone did not reduce cyclin B1 expression. MVM infection also reduced the levels of cyclin B1 protein, and RNA levels normally increased in response to DNA-damaging reagents. We demonstrated that at times of reduced cyclin B1 expression during infection, there was a significantly reduced occupancy of RNA polymerase II and the essential mitotic transcription factor FoxM1 on the cyclin B1 gene promoter. Additionally, while total FoxM1 levels remained constant, there was a significant decrease of the phosphorylated, likely active, forms of FoxM1. Targeting of a constitutively active FoxM1 construct or the activation domain of FoxM1 to the cyclin B1 gene promoter via clustered regularly interspaced short palindromic repeats (CRISPR)-enzymatically inactive Cas9 in MVM-infected cells increased both cyclin B1 protein and RNA levels, implicating FoxM1 as a critical target for cyclin B1 inhibition during MVM infection.IMPORTANCE Replication of the parvovirus minute virus of mice (MVM) induces a sustained cellular DNA damage response (DDR) which the virus exploits to prepare the nuclear environment for effective takeover. An essential aspect of the MVM-induced DDR is establishment of a potent premitotic block. This block depends upon a significant, specific depletion of cyclin B1 and its encoding RNA that precludes cyclin B1/CDK1 complex functions necessary for mitotic entry. We show that reduced cyclin B1 expression is controlled primarily at the level of transcription initiation. Additionally, the essential mitotic transcription factor FoxM1 and RNA polymerase II were found to occupy the cyclin B1 gene promoter at reduced levels during infection. Recruiting a constitutively active FoxM1 construct or the activation domain of FoxM1 to the cyclin B1 gene promoter via CRISPR-catalytically inactive Cas9 (dCas9) in MVM-infected cells increased expression of both cyclin B1 protein and RNA, implicating FoxM1 as a critical target mediating MVM-induced cyclin B1 inhibition. | Minute Virus of Mice |
Bone grafting is frequently conducted to treat bone defects caused by trauma and tumor removal, yet with significant medical and socioeconomic burdens. Space-occupying bone substitutes remain challenging in the control of osteointegration, and meanwhile activation of endogenous periosteal cells by using non-space-occupying implants to promote new bone formation becomes another therapeutic strategy. Here, we fabricated a magnesium-based artificial bandage with optimal micropatterns for activating periosteum-associated biomineralization. Collagen was self-assembled on the surface of magnesium oxide nanoparticles embedded electrospun fibrous membranes as a hierarchical bandage structure to facilitate the integration with periosteum in situ. After the implantation on the surface of cortical bone in vivo, magnesium ions were released to generate a pro-osteogenic immune microenvironment by activating the endogenous periosteal macrophages into M2 phenotype and, meanwhile, promote blood vessel formation and neurite outgrowth. In a cortical bone defect model, magnesium-based artificial bandage guided the surrounding newly formed bone tissue to cover the defected area. Taken together, our study suggests that the strategy of stimulating bone formation can be achieved with magnesium delivery to periosteum in situ and the proposed periosteal bandages act as a bioactive media for accelerating bone healing. | Periosteum |
Closed-circuit anesthesia is safe and physiologic. It allows normoventilation and avoids hypo or hyperventilation. Respiratory gases remain warm and humid. No anesthetic pollution of the room occurs. It allows early detection of metabolic abnormalities (malignant hyperthermia, pulmonary or tissue underperfusion). Closed-circuit anesthesia is economical. | Anesthesia, Closed-Circuit |
A 10-year-old boy developed progressive dystonia and dementia. His symptoms had begun at age 2 1/2 years, and he had been unable to walk by 8 years. At age 10 he was severely dystonic, unable to use his hands to feed himself, and almost anarthric . He had dysphagia and urinary incontinence, and functioned at a 4-year-old level of mental development. The mean percentages of beta-hexosaminidase A measured in serum, leukocytes, and fibroblasts by the heat denaturation method, each on three separate assays, were 5.9, 9.8, and 13.0%, respectively. These values are higher than in Tay-Sachs disease but are similar to levels seen in late-onset or adult cases of GM2 gangliosidosis. This patient appears to represent a new phenotype of juvenile GM2 gangliosidosis having dystonia as the dominant symptom. | G(M2) Ganglioside |
Public health institutes have an important role in promoting and protecting the health and well-being of populations. A key focus of such institutes are the wider determinants of health, embracing the need to advocate for 'Health in All Policies' (HiAP). A valuable tool to support this is the health impact assessment. This study aims to support public health institutes to advocate more successfully for the use of health impact assessments and HiAP in order to promote and protect health, well-being and equity. During July 2021, a quantitative online survey was undertaken across international networks with 17 valid responses received. Semi-structured interviews were also administered with nine expert representatives and analysed thematically. In total, 64.7% (n = 11) of survey respondents were aware of health impact assessments and 47.1% (n = 8) currently conducted health impact assessments. It was noted that there are differing approaches to HIAs, with a need for a clear set of standards. Barriers to use included lack of knowledge, training and resources. Overall, 64.7% (n = 11) of survey respondents would like to do more to develop knowledge and capacity around health impact assessments. The results from this study can serve as a platform to help build knowledge, networks and expertise, to help support a 'Health in All Policies' approach and address inequalities which exist in all societies. | Health Impact Assessment |
Multidimensional forced-choice (MFC) testing has been proposed as a way of reducing response biases in noncognitive measurement. Although early item response theory (IRT) research focused on illustrating that person parameter estimates with normative properties could be obtained using various MFC models and formats, more recent attention has been devoted to exploring the processes involved in test construction and how that influences MFC scores. This research compared two approaches for estimating multi-unidimensional pairwise preference model (MUPP; Stark et al., 2005) parameters based on the generalized graded unfolding model (GGUM; Roberts et al., 2000). More specifically, we compared the efficacy of statement and person parameter estimation based on a two-step" process, developed by Stark et al. (2005), with a more recently developed "direct" estimation approach (Lee et al., 2019) in a Monte Carlo study that also manipulated test length, test dimensionality, sample size, and the correlations between generating person parameters for each dimension. Results indicated that the two approaches had similar scoring accuracy, although the two-step approach had better statement parameter recovery than the direct approach. Limitations, implications for MFC test construction and scoring, and recommendations for future MFC research and practice are discussed." | Monte Carlo Method |
The tolerance to degradation processes in meat of nine Trichinella genotypes was studied in mouse and fox tissue, respectively. Minced muscle tissue with Trichinella larvae of different age was stored at room temperature at 100% relative humidity. During storage weekly sub samples of the minced meat were digested and released larvae were inoculated in mice to evaluate the Reproductive Capacity Index (RCI). The RCI decreased with the length of storage, but the larvae from older infections appeared better adapted to tolerate the degradation processes. The African species T. nelsoni had a relative higher tolerance to elevated temperature during storage and the unencysted species T. pseudospiralis was the most vulnerable genotype. | Trichuroidea |
Antivenom immunotherapy is the mainstay of treatment for snakebite envenoming. Most parts of the world affected by snakebite envenoming depend on broad-spectrum polyspecific antivenoms that are known to contain a low content of case-specific efficacious immunoglobulins. Thus, advances in toxin-specific antibodies production hold much promise in future therapeutic strategies of snakebite envenoming. We report anti-3FTxs monoclonal antibodies developed against N. ashei venom in mice. All the three test mAbs (P4G6a, P6D9a, and P6D9b) were found to be IgG antibodies, isotyped as IgG1. SDS-PAGE analysis of the test mAbs showed two major bands at approximately 55 and 29 kDa, suggestive of immunoglobulin heavy and light chain composition, respectively. The immunoaffinity-purified test mAbs demonstrated higher binding efficacy to the target antigen compared to negative control. Similarly, a cocktail of the test mAbs was found to induce a significantly higher inhibition (p-value < 0.0001) compared to two leading commercial brands of antivenoms on the Kenyan market, implying a higher specificity for the target antigen. Both the test mAbs and 3FTxs polyclonal antibodies induced comparable inhibition (p-value = 0.9029). The inhibition induced by the 3FTxs polyclonal antibodies was significantly different from the two antivenoms (p-value < 0.0001). Our results demonstrate the prospects of developing toxin-specific monoclonal-based antivenoms for snakebite immunotherapy. | Three Finger Toxins |
Endometriosis is a benign condition of the female genital system, characterized by endometrial tissue external to the uterine cavity. Of all cases with endometriosis, the incidence of umbilical endometriosis is only 0.29%. Umbilical endometriosis typical presents with symptoms including cyclical pain, bleeding, and swelling of the nodule. Morphological changes in the epidermis, as in this case, simulating a seborrheic keratosis both clinically and microscopically, can initially mask the underlying endometriosis and prolong the course of treatment. A thorough anamnesis and examination revealing the characteristic symptoms and findings coupled with a representative biopsy is essential to correctly diagnose umbilical endometriosis. | Keratosis, Seborrheic |
Untreated transgender men face serious negative health care outcomes. Effective medical, surgical, and mental health treatment ameliorates these risks. Although the research is not as robust as would be ideal, hormone treatment is effective and generally well tolerated with few serious medical risks. Surgeries carry serious risks; but for most transgender men, the benefits outweigh the risks. This review describes current evidence-based medical treatments for transgender men and provides an overview of surgical therapy to enable practitioners to discuss these options with their transgender male patients. | Hormone Replacement Therapy |
To help combat prescription drug misuse, most states have implemented Prescription Drug Monitoring Programs (PDMPs)-electronic databases that collect and track prescription data and flag suspected diversion activities. Equipped with expanding prescriptive authority, NPs are now poised to become vital change agents in expanding the potential effectiveness of PDMPs. | Drug Monitoring |
BACKGROUND: Epidemiological studies suggest a link between the melanoma-related pigmentation gene melanocortin 1 receptor (MC1R) and risk of Parkinson's disease (PD). We previously showed that MC1R signaling can facilitate nigrostriatal dopaminergic neuron survival. The present study investigates the neuroprotective potential of MC1R against neurotoxicity induced by alpha-synuclein (alphaSyn), a key player in PD genetics and pathogenesis. METHODS: Nigral dopaminergic neuron toxicity induced by local overexpression of aSyn was assessed in mice that have an inactivating mutation of MC1R, overexpress its wild-type transgene, or were treated with MC1R agonists. The role of nuclear factor erythroid 2-related factor 2 (Nrf2) in MC1R-mediated protection against alphaSyn was characterized in vitro. Furthermore, MC1R expression was determined in human postmortem midbrain from patients with PD and unaffected subjects. RESULTS: Targeted expression of alphaSyn in the nigrostriatal pathway induced exacerbated synuclein pathologies in MC1R mutant mice, which were accompanied by neuroinflammation and altered Nrf2 responses, and reversed by the human MC1R transgene. Two MC1R agonists were neuroprotective against alphaSyn-induced dopaminergic neurotoxicity. In vitro experiments showed that Nrf2 was a necessary mediator of MC1R effects. Lastly, MC1R was present in dopaminergic neurons in the human substantia nigra and appeared to be reduced at the tissue level in PD patients. CONCLUSION: Our study supports an interaction between MC1R and alphaSyn that can be mediated by neuronal MC1R possibly through Nrf2. It provides evidence for MC1R as a therapeutic target and a rationale for development of MC1R-activating strategies for PD." | Receptor, Melanocortin, Type 1 |
Erwinia carotovora is a major cause of potato tuber infection, which results in disastrous failures of this important food crop. There is currently no effective antibiotic treatment against E. carotovora. Recently we reported antibacterial assays of wound tissue extracts from four potato cultivars that exhibit a gradient of russeting character, finding the highest potency against this pathogen for a polar extract from the tissue formed immediately after wounding by an Atlantic cultivar. In the current investigation, antibacterial activity-guided fractions of this extract were analyzed by liquid chromatography-mass spectrometry (LC-MS) utilizing a quadrupole-time-of-flight (QTOF) mass spectrometer. The most active chemical compounds identified against E. carotovora were: 6-O-nonyl glucitol, Lyratol C, n-[2-(4-Hydroxyphenyl)] ethyldecanamide, alpha-chaconine and alpha-solanine. Interactions among the three compounds, ferulic acid, feruloyl putrescine, and alpha-chaconine, representing metabolite classes upregulated during initial stages of wound healing, were also evaluated, offering possible explanations for the burst in antibacterial activity after tuber wounding and a chemical rationale for the temporal resistance phenomenon. | Tissue Extracts |
Mitochondrial DNA (mtDNA) has largely been used for species delimitation. However, mtDNA introgression across species boundaries can lead to inconsistent phylogenies. Partial sequences of the mitochondrial genome in the chamois, genus Rupicapra, show the presence of three well differentiated clades, West (mtW), Central (mtC) and East (mtE), each with a geographically restricted distribution. The complete mtDNAs of the clades mtW and mtE (main representatives of the two currently considered species R. pyrenaica and R. rupicapra respectively) have been reported. In the present study, we sequenced the clade mtC present in populations from both species inhabiting the central area of Europe: the Apennines (R. pyrenaica ornata) and the Chartreuse Mountains (R. rupicapra cartusiana). The phylogenetic comparison with the genomes of Caprini highlights the ancient presence of chamois in Europe relative to the fossil record, and the old age of the chamois clade mtC that was split from the clade mtW in the early Pleistocene. The separation of R. pyrenaica ornata and R. rupicapra cartusiana female lineages was recent, dating of the late Pleistocene. Our data represent an example of mtDNA introgression of resident females of Chartreuse Mountains into immigrant males of R. rupicapra due to male-biased migration and female phylopatry. | Rupicapra |
We have recently described the expression of two pili of different lengths on the surface of Legionella pneumophila (B. J. Stone and Y. Abu Kwaik, Infect. Immun. 66:1768-1775, 1998). Production of long pili requires a functional pilEL locus, encoding a type IV pilin protein. Since type IV pili in Neisseria gonorrhoeae are associated with competence for DNA transformation, we examined the competence of L. pneumophila for DNA transformation under conditions that allowed the expression of type IV pili. We show that L. pneumophila is naturally competent for DNA transformation by isogenic chromosomal DNA and by plasmid DNA containing L. pneumophila DNA. Many different L. pneumophila loci are able to transform L. pneumophila after addition of plasmid DNA, including gspA, ppa, asd, and pilEL. The transformation frequency is reduced when competing DNA containing either L. pneumophila DNA or vector sequences is added to the bacteria, suggesting that uptake-specific sequences may not be involved in DNA uptake. Competence for DNA transformation correlates with expression of the type IV pili, and a pilEL mutant defective in expression of type IV pili is not competent for DNA transformation. Complementation of the mutant for competence is restored by the reintroduction of a cosmid that restores production of type IV pili. Minimal competence is restored to the mutant by introduction of pilEL alone. We conclude that competence for DNA transformation in L. pneumophila is associated with expression of the type IV pilus and results in recombination of L. pneumophila DNA into the chromosome. Since expression of type IV pili also facilitates attachment of L. pneumophila to mammalian cells and protozoa, we designated the type IV pili CAP (for competence- and adherence-associated pili). | Pili, Sex |
A specific polyclonal antiserum directed against the somatostatin-28(1-14) of vertebrates was applied to sections of the planarians Dugesia lugubris and Dendrocoelum lacteum. This made it possible to reveal nerve cells and processes specifically both in cerebral ganglia and in ventral nerve cords. The phylogenetic importance of this demonstration is pointed out. | Neurosecretion |
BACKGROUND: Accurate implant impressions are critical for the achievement of passive fit of an implant prosthesis which in turn contributes to the long-term success of the implant treatment. There is inconclusive evidence on the techniques and materials used for making multi-unit implant impressions. OBJECTIVE: To evaluate the scientific data related to different aspects of multi-unit implant impression accuracy and draw useful conclusions from the review for application in clinical practice. METHOD AND MATERIALS: Studies from 1990 to November 2012 were evaluated. Papers examining implant impression accuracy for two or more implants were selected for review. Case reports, technique articles, and incomplete studies were excluded. Fifty-nine studies were selected in total for evaluation, three among them clinical and the rest in vitro. RESULTS: Fifteen studies compared PVS (polyvinyl siloxane) and PE (polyether), 11 found no differences between the two materials in terms of impression accuracy. Thirty studies analyzed the splint effect, 13 found splinting better and 13 others elicited no differences between splinting and non-splinting. Among the 25 studies examining pickup and transfer impression techniques, 12 favored pickup over transfer and 11 found no differences between the two. Twelve studies assessed implant angulation effects and found significant differences in accuracy for 20- to 25-degree angulation, and no differences for 5- to 15-degree angulation for most studies, except two. CONCLUSION: PVS and PE were the preferred impression materials for multi-unit implant impressions. The evidence on splinting was inconclusive and the data supporting splint to non-splint were neutral. Pickup was the better performing technique than transfer, especially with increased number of implants. Implant angulation of 20 to 25 degrees negatively affected the multi-unit implant impression accuracy. | Periodontal Splints |
This paper reviews the current status of preimplantation genetic diagnosis (PGD), outlining the methods currently in use for the diagnosis of sex and single-gene defects. New approaches under development are described, e.g. fluorescent polymerase chain reaction (PCR), the use of sub-telomeric probes for patients with balanced reciprocal translocations, the analysis of first and second polar bodies, the use of lasers to facilitate the biopsy of embryos, and ways forward for infertile patients. | Preimplantation Diagnosis |
Solanum acaule Bitt., a wild potato species, is closely related to cultivated potato (Solanum. tuberosum L.). Incorporation of desirable traits from allotetraploid [2n=4x=48, 2 endosperm balance number (EBN)] S. acaule (acl) into autotetraploid (2n=4x=48, 4EBN) S. tuberosum (tbr) is difficult due to incongruity boundaries. In this study, three hybrid combinations, each with a specific genome constitution, were produced through protoplast fusion: (1) hexaploid 2x acl (+) 4x tbr, (2) tetraploid 2x acl (+) 2x tbr, and (3) hexaploid 4x acl (+) 2x tbr hybrids. In terms of glycoalkaloid aglycones, the hybrids produced demissidine, tomatidine and solanidine, similarly to the S. acaule parental species, but S. tuberosum synthesised only solanidine. Inoculations with Clavibacter michiganensis ssp. sepedonicus (Cms), which is the causal agent of bacterial ring rot in potato, yielded significantly lower total glycoalkaloid aglycone accumulation both in S. acaule plants and in interspecific hybrids in comparison with the corresponding mock-inoculated plants. However, in S. tuberosum the aglycone levels were either higher or unchanged as a result of infection by Cms. To incorporate the desirable traits of the interspecific somatic hybrids into 4EBN S. tuberosum, sexual backcrosses were carried out. The hexaploid 4x acl (+) 2x tbr hybrids with the hypothetical 4EBN showed the greatest capacity to undergo backcrosses with S. tuberosum. | Solanum tuberosum |
The binding of native rabbit beta-very low density lipoproteins (beta-VLDL) to the low density lipoprotein receptor-related protein (LRP) requires incubation with exogenous apolipoprotein (apo) E. Inclusion of a mixture of the C apolipoproteins in the incubation inhibits this binding. In the present study, the ability of the individual C apolipoproteins (C-I, C-II, and C-III) to block binding of beta-VLDL to the LRP was examined by measuring cholesteryl ester formation in mutant fibroblasts that lack low density lipoprotein receptors or by measuring binding to the LRP using ligand blotting. In each assay, both apoC-I and apoC-II inhibited binding; apoC-I was the more effective inhibitor. Apolipoprotein C-III had no effect on binding activity, regardless of its sialylation level. Binding of human apoE to rabbit beta-VLDL in the absence or presence of human apoC-I, apoC-II, and monosialo-apoC-III was also determined, by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these studies are consistent with a mechanism in which exogenous human apoE displaces the endogenous apoE and the beta-VLDL particle becomes enriched with apoE (by 4.2-fold in this study). At this higher apoE content, the beta-VLDL bound to the LRP. Inclusion of apoC-I, apoC-II, or apoC-III in the incubation mixture resulted in a differential displacement of apoE from the beta-VLDL; however, at the concentrations examined, only apoC-I and apoC-II were capable of displacing sufficient apoE to abolish binding to LRP. | Apolipoprotein C-I |
PURPOSE OF REVIEW: Recipients of allogeneic stem cell transplantations are at risk of acquiring acute hepatitis E virus (HEV) infection, leading to chronicity. We review the incidence, sequela, extrahepatic manifestations, and treatment of hepatitis due to HEV infection in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients. RECENT FINDINGS: HEV infection and progression to chronic HEV in alloHSCT recipients are recently described. Misdiagnosis of HEV in alloHSCT recipients occurs, with liver enzyme abnormalities often attributed to hepatic graft-versus-host disease or drug-induced liver injury. HEV infection may occur in HSCT donors and emphasizes the need for HEV screening not only after HSCT, but also in donors presenting with liver function disturbances. The discussion about HEV screening of blood products will continue. Extrahepatic manifestations of hepatitis E are described. SUMMARY: HEV RNA screening in alloHSCT recipients with elevated liver enzymes is advised. Intervention strategies should be considered in cases of acute or chronic HEV infection. The first-line approach includes reduction of immunosuppressive medication. Oral ribavirin is in experienced hands a reasonable well tolerated treatment option, although the optimal dose, duration, and quantitative goals of ribavirin treatment are still unknown. Further studies are needed to improve our understanding of HEV, including extrahepatic manifestations and evaluation of therapeutic options. | Hepevirus |
BACKGROUND: Practitioners of traditional medicine use the decoction of Ononis natrix L. to treat hyperglycemia. The literature offers no evidence to support the use. OBJECTIVE: To investigate the effect of the decoction of Ononis natrix L. on the blood glucose concentration in Wistar rats (Rattus norvegicus) with streptozotocin-induced diabetes mellitus. METHODS: We obtained 35 Wistar rats from the animal colony of The University of Jordan School of Medicine. We induced diabetes by a single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and 23 rats (66%) survived to allocation. We randomly assigned the rats to one of four groups: negative control (1% Tween 80 in distilled water), positive control (100 mg/kg metformin), high-dose treatment (7.5 mL of the decoction), and low-dose treatment (3.5 mL of the decoction). We administered the doses twice daily by oral gavage for two weeks and measured the tailblood glucose concentration twice daily, once before the first dose and another time after the second dose. We used linear mixed-effects regression to model the change in blood glucose concentration as a function of the experimentation groups, with adjustments for pseudoreplication and temporal variation. RESULTS: The estimated mean change was 1 mmol/L (-30 to 31 mmol/L) for the negative control group, -26 mmol/L (-56 to 5 mmol/L) for the positive control group, -75 mmol/L (-108 to -42) for the low-dose treatment group, and -82 mmol/L (-111 to -53 mmol/L) for the high-dose treatment group. CONCLUSION: In conclusion, we demonstrate, for the first time, the hypoglycemic effect of Ononis natrix L. in an animal model of diabetes. | Ononis |
BACKGROUND: Primary localized amyloidosis is characterized by the deposition of amyloid proteins restricted to one organ, without systemic involvement. Primary nasopharyngeal amyloidosis is an exceedingly rare condition, for which the standard treatment remains unknown. Because of its challenging anatomical position, surgery alone hardly results in complete resection of the localized amyloidosis. Therefore, an interdisciplinary planning board to design optimal treatment is of particular importance. PATIENT AND METHODS: A 39-year-old man presented with a several-week history of nasal obstruction and epistaxis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a retro-odontoid nonenhancing soft tissue mass. RESULTS: The endoscopic biopsy demonstrated that the mass was amyloid in nature. An extensive systemic workup revealed an absence of inflammatory process, systemic amyloidosis, or plasma cell dyscrasia. The patient was treated with a combination of surgery and radiotherapy, showing no evidence of recurrence or progression at his 1âÂÂyear follow-up. CONCLUSION: Primary solitary amyloidosis is a rare form of amyloidosis. To the best of our knowledge, this is the first report of a nasopharyngeal amyloidosis case treated with excision and radiation leading to complete remission. Because of the difficulty for surgeons to achieve radical resection with such lesions, radiotherapy proved to be an excellent adjuvant treatment in this case. | Nasopharyngeal Diseases |
CONTEXT AND OBJECTIVES: The appropriate use of antibiotic prophylaxis in the perioperative period may reduce the rate of infection in the surgical site. The purpose of this review was to evaluate adherence to guidelines for surgical antibiotic prophylaxis. METHODS: The present systematic review was performed according to the Cochrane Collaboration methodology. The databases selected for this review were: Medline (via PubMed), Scopus and Portal (BVS) with selection of articles published in the 2004-2014 period from the Lilacs and Cochrane databases. RESULTS: The search recovered 859 articles at the databases, with a total of 18 studies selected for synthesis. The outcomes of interest analyzed in the articles were as follows: appropriate indication of antibiotic prophylaxis (ranging from 70.3% to 95%), inappropriate indication (ranging from 2.3% to 100%), administration of antibiotic at the correct time (ranging from 12.73% to 100%), correct antibiotic choice (ranging from 22% to 95%), adequate discontinuation of antibiotic (ranging from 5.8% to 91.4%), and adequate antibiotic prophylaxis (ranging from 0.3% to 84.5%). CONCLUSIONS: Significant variations were observed in all the outcomes assessed, and all the studies indicated a need for greater adherence to guidelines for surgical antibiotic prophylaxis. | Guideline Adherence |
Trinucleotide repeat (TNR) diseases are caused by the aberrant expansion of CXG (X = C, A, G and T) sequences in genomes. We have reported two small molecules binding to TNR, NCD, and NA, which strongly bind to CGG repeat (responsible sequence of fragile X syndrome) and CAG repeat (Huntington's disease). The NMR structure of NA binding to the CAG/CAG triad has been clarified, but the structure of NCD bound to the CGG/CGG triad remained to be addressed. We here report the structural determination of the NCD-CGG/CGG complex by NMR spectroscopy and the comparison with the NA-CAG/CAG complex. While the NCD-CGG/CGG structure shares the binding characteristics with that of the NA-CAG/CAG complex, a significant difference was found in the overall structure caused by the structural fluctuation at the ligand-bound site. The NCD-CGG/CGG complex was suggested in the equilibrium between stacked and kinked structures, although NA-CAG/CAG complex has only the stacked structures. The dynamic fluctuation of the NCD-CGG/CGG structure at the NCD-binding site suggested room for optimization in the linker structure of NCD to gain improved affinity to the CGG/CGG triad. | Trinucleotide Repeats |
Partially acetylated generation five polyamidoamine (PAMAM) dendrimer (G5-Ac) was reacted with biotin and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetria minepentaacetic acid (1B4M-DTPA), respectively to form the complex Bt-G5-Ac-1B4M which was further conjugated with avidin to give the conjugate Av-G5-Ac-1B4M. Then both of the conjugates were radiolabeled with technetium-99m ((99m)Tc), respectively. Their in vitro cellular uptake study shows that the conjugate of Av-G5-Ac-1B4M-(99m)Tc exhibits much higher cellular uptake in HeLa cells than that of Bt-G5-Ac-1B4M-(99m)Tc. Accordingly the following evaluation such as in vitro/in vivo stability, biodistribution and micro-SPECT imaging was observed only for the conjugate of Av-G5-Ac-1B4M-(99m)Tc. | Avidin |
This study aimed to determine the main bioactive components of Cornus officinalis vinegar (COV) and assess the effects of COV on the body weight (BW) and hepatic steatosis in a nonalcoholic fatty liver disease (NAFLD) mouse model. Seven-week-old KM female mice were divided into five treatment groups: (1) Normal control (NC) group, (2) high fat diet (HFD) group, (3) low concentration treatment group (3.5% COV), (4) medium concentration treatment group (5.0% COV), and (5) high concentration treatment group (6.5% COV). Mice in the NC group were fed with a normal chow diet, and those in the other four groups were fed with a HFD known for causing obesity for 10 weeks. Then, mice in the three COV treatment groups were orally administered with COV once a day for 6 weeks. Results showed that the contents of loganin and morroniside in COV reached 16.82 and 51.17 microg/ml, respectively, and COV also contained multiple organic acids. COV significantly reduced BW, abdominal fat weight, liver weight, and the levels of glucose, triglyceride, and low-density lipoprotein cholesterol of serum and increased the levels of high-density lipoprotein cholesterol of serum (p < 0.05). COV also improved the liver function and anti-oxidant activity of liver (p < 0.05). COV treatments increased the interleukin-10 expression and reduced the tumor necrosis factor-alpha expression in the liver tissue of NAFLD mice (p < 0.05). Histopathological observation revealed that COV suppressed hepatic lipid accumulation and steatosis. The results suggest that COV may contribute to the alleviation of NAFLD and obesity. | Cornaceae |
BACKGROUND: Breast cancer is currently among the most common causes of mortality in women. Estrogen and its subsequent signaling pathways play an important role in the occurrence of breast cancer relapse. Tamoxifen is the most common breast cancer treatment option in ER+ patients, which acts as an adjuvant endocrinotherapy with X-ray and surgery. This approach is recommended as the first-line treatment and has increased the survival rate of breast cancer patients and reduced the relapse cases. However, we can observe resistance to tamoxifen and relapse cases in one-third of patients treated with this drug, which has become a major concern. OBJECTIVE: The precise mechanisms of relapse and resistance to tamoxifen have not yet been identified and were explored in this study. METHODS: Microarray profiles of relapse and relapse-free patients were investigated to explain the processes leading to relapse and possibly to tamoxifen resistance. RESULTS: According to the preliminary analysis, 1460 genes showed increased expression while 1132 genes showed decreased expression. According to our default for inclusion (-2LogFC>/= + 2), 36 genes had increased expression (upregulated) while 33 genes had decreased expression (down-regulated). CONCLUSION: It seems that the mechanisms of resistance and relapse are multifactorial, and tumor cells induce relapse and resistance to tamoxifen through cell proliferation, survival, invasion, angiogenesis, extracellular matrix secretion, pump and membrane changes, and immune evasion." | Antineoplastic Agents, Hormonal |
Many drugs of abuse, administered repeatedly over time, cause physical dependence which is expressed by a withdrawal syndrome when the drug is removed from the system. These processes can be thought of as adaptations of the neuronal system to an altered pharmacological state. The molecular mechanisms underlying these adaptations are still not known. A considerable amount of evidence is accumulating which implicates alterations in several components of the cAMP signal transduction cascade in these drug-induced processes. The transcription factor cAMP response element binding protein (CREB) in particular has been shown both in vitro and in vivo to be altered in response to several drugs of abuse, including opiates. This review discusses in detail this transcription factor and demonstrates its importance in the signal transduction cascades involving abused substances." | Cyclic AMP Response Element-Binding Protein |
Osteopathic medical schools and hospital-based postgraduate programs have long constituted small but important sources of physicians and surgeons, particularly for traditionally underserved areas of the United States. Though frequently marginalized in or even left out of standard histories and studies of U.S. medical education, these institutions have become much more difficult to ignore, given the rapid expansion of the number of osteopathic medical students in new and existing colleges and the size of their classes. By 2019, upwards of 25% of all U.S. medical school graduates produced annually will be doctors of osteopathic medicine. The author examines the process through which osteopathy was transformed into osteopathic medicine, how osteopathic medical schools achieved their present status as a significant source of U.S. graduates for residency training, and what challenges osteopathic medical education now faces. | Osteopathic Physicians |
Fas-associated death domain-containing protein (FADD), a classical apoptotic signaling adaptor, participates in different nonapoptotic processes regulated by its phosphorylation. However, the influence of FADD on metabolism, especially glucose homeostasis, has not been evaluated to date. Here, using both two-dimensional electrophoresis and liquid chromatography linked to tandem mass spectrometry (LC/MS/MS), we found that glycogen synthesis, glycolysis, and gluconeogenesis were dysregulated because of FADD phosphorylation, both in MEFs and liver tissue of the mice bearing phosphorylation-mimicking mutation form of FADD (FADD-D). Further physiological studies showed that FADD-D mice exhibited lower blood glucose, enhanced glucose tolerance, and increased liver glycogen content without alterations in insulin sensitivity. Moreover, investigations on the molecular mechanisms revealed that, under basal conditions, FADD-D mice had elevated phosphorylation of Akt with alterations in its downstream signaling, leading to increased glycogen synthesis and decreased gluconeogenesis. Thus, we uncover a novel role of FADD in the regulation of glucose homeostasis by proteomic discovery and physiological validation." | Fas-Associated Death Domain Protein |
Mutations in FUS cause amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to neurodegeneration remain obscure. We previously found that U1 snRNP is the most abundant FUS interactor. Here, we report that components of the U1 snRNP core particle (Sm proteins and U1 snRNA), but not the mature U1 snRNP-specific proteins (U1-70K, U1A and U1C), co-mislocalize with FUS to the cytoplasm in ALS patient fibroblasts harboring mutations in the FUS nuclear localization signal (NLS). Similar results were obtained in HeLa cells expressing the ALS-causing FUS R495X NLS mutation, and mislocalization of Sm proteins is RRM-dependent. Moreover, as observed with FUS, knockdown of any of the U1 snRNP-specific proteins results in a dramatic loss of SMN-containing Gems. Significantly, knockdown of U1 snRNP in zebrafish results in motor axon truncations, a phenotype also observed with FUS, SMN and TDP-43 knockdowns. Our observations linking U1 snRNP to ALS patient cells with FUS mutations, SMN-containing Gems, and motor neurons indicate that U1 snRNP is a component of a molecular pathway associated with motor neuron disease. Linking an essential canonical splicing factor (U1 snRNP) to this pathway provides strong new evidence that splicing defects may be involved in pathogenesis and that this pathway is a potential therapeutic target. | Gemini of Coiled Bodies |
A separation and detection scheme is presented for the determination of the antitumor drugs adriamycin and daunorubicin in human urine. Separation is accomplished by reversed-phase high-performance liquid chromatography and the drugs are detected down to the low picogram level by laser excited fluorescence using a unique fiber optic based flow-cell. Excellent detector selectivity and linearity are reported, and some of the factors influencing the performance of the detector are discussed. Possible extension of the procedure to other biologically important determinations are mentioned. | Daunorubicin |
Acanthamoeba spp. are free living amoebae which can give rise to Acanthamoeba keratitis and granulomatous amoebic encephalitis. The surface of Acanthamoeba contains ergosterol which is an important target for drug development against eukaryotic microorganisms. A library of ten functionally diverse quinazolinone derivatives (Q1-Q10) were synthesised to assess their activity against Acanthamoeba castellanii T4. The in-vitro effectiveness of these quinazolinones were investigated against Acanthamoeba castellanii by amoebicidal, excystation, host cell cytopathogenicity, and NADPH-cytochrome c reductase assays. Furthermore, wound healing capability was assessed at different time durations. Maximum inhibition at 50 mug/mL was recorded for compounds Q5, Q6 and Q8, while the compound Q3 did not exhibit amoebicidal effects at tested concentrations. Moreover, LDH assay was conducted to assess the cytotoxicity of quinazolinones against HaCaT cell line. The results of wound healing assay revealed that all compounds are not cytotoxic and are likely to promote wound healing at 10 mug/mL. The excystation assays revealed that these compounds significantly inhibit the morphological transformation of A. castellanii. Compound Q3, Q7 and Q8 elevated the level of NADPH-cytochrome c reductase up to five folds. Sterol 14alpha-demethylase (CYP51) a reference enzyme in ergosterol pathway was used as a potential target for anti-amoebic drugs. In this study using i-Tasser, the protein structure of Acanthamoeba castellanii (AcCYP51) was developed in comparison with Naegleria fowleri protein (NfCYP51) structure. The sequence alignment of both proteins has shown 42.72% identity. Compounds Q1-Q10 were then molecularly docked with the predicted AcCYP51. Out of ten quinazolinones, three compounds (Q3, Q7 and Q8) showed good binding activity within 3 A of TYR 114. The in-silico study confirmed that these compounds are the inhibitor of CYP51 target site. This report presents several potential lead compounds belonging to quinazolinone derivatives for drug discovery against Acanthamoeba infections. | Quinazolinones |
Convection-enhanced delivery (CED) of GDNF and NTN was employed to determine the tissue clearance of these factors from the rat striatum and the response of the dopaminergic system to a single infusion. Two doses of GDNF (15 and 3 microg) and NTN (10 microg and 2 microg) were infused into the rat striatum. Animals were euthanized 3, 7, 14, 21, and 28 days post-infusion. Brains were processed for ELISA, HPLC, and immunohistochemistry (IHC). Both doses of the infused GDNF resulted in a sharp increase in striatal GDNF levels followed by a rapid decrease between day 3 and 7. Interestingly, IHC revealed GDNF in the septum and the base of the brain 14 days after GDNF administration. Dopamine (DA) turnover was significantly increased in a dose-dependent manner for more than 7 days after a single GDNF infusion. NTN persisted in the brain for at least two weeks longer than GDNF. It also had more persistent effects on DA turnover, probably due to its precipitation in the brain at neutral pH after infusion. Our data suggest that daily or continuous dosing may not be necessary for delivering growth factors into the CNS." | Glial Cell Line-Derived Neurotrophic Factors |
The normal blood lactate level is 0-2 mmol/L, and a value above 3-5 mmol/L is variably used to define hyperlactatemia. In cardiac surgical patients, hyperlactatemia can arise from both hypoxic and non-hypoxic mechanisms. The major non-hypoxic mechanism is likely stress-induced accelerated aerobic metabolism, in which elevated lactate results from a mass effect on the lactate/pyruvate equilibrium. The lactate/pyruvate ratio is normal (<20) in this circumstance. Hyperlactatemia can also result from impaired global or regional oxygen delivery, in which case the lactate/pyruvate ratio is typically elevated (>20). Lactate is a strong anion that is virtually fully dissociated at physiological pH. As such, increased lactate concentration reduces the strong ion difference and exerts an acidifying effect on the blood. Hyperlactatemia in cardiac surgery patients has been categorized as either early or late onset. Early-onset hyperlactatemia is that which develops in the operating room or very early following intensive care unit (ICU) admission. Early-onset hyperlactatemia is strongly associated with adverse outcome and probably arises as a consequence of both hypoxic (e.g., microcirculatory shock) and non-hypoxic (accelerated aerobic metabolism) mechanisms. By contrast, late-onset hyperlactatemia is a benign, self-limiting condition that typically arises within 6-12 hours of ICU admission and spontaneously resolves within 24 hours. Late onset hyperlactatemia occurs in the absence of any evidence of global or regional tissue hypoxia. The mechanism of late onset hyperlactatemia is not understood. Hyperlactatemia is a common accompaniment to treatment with beta(2)-agonists such as epinephrine. Epinephrine-induced hyperlactatemia is thought to be due to accelerated aerobic metabolism and requires no specific intervention. Irrespective of the cause, the presence of hyperlactatemia should trigger a search for remedial causes of impaired tissue oxygenation, bearing in mind that normal-or even supranormal-indices of global oxygen delivery may exist despite regional tissue hypoperfusion. | Hyperlactatemia |
The genus Pestivirus, which belongs to the Flaviviridae family, includes ssRNA+ viruses responsible for infectious diseases in pigs, cattle, sheep, goats and other domestic and wild ruminants. Like most of the RNA viruses, pestivirus has high genome variability with practical consequences on disease epidemiology, diagnosis and control. In addition to the officially recognized species in the genus Pestivirus, such as BVDV-1, BVDV-2, BDV and CSFV, other pestiviruses have been detected. Furthermore, most of the ruminant pestiviruses show low or absent species specificity observed in serological tests and are able to infect multiple species. Particularly, small ruminants are receptive hosts of the most heterogeneous group of pestiviruses. The aim of this study was to carry out the molecular characterization of pestiviruses isolated from sheep and goats in Sicily, Italy. Phylogenetic analysis of two viral genomic regions (a fragment of 5'-UTR and the whole N(pro) regions) revealed the presence of different pestivirus genotypes in the analysed goat and sheep herds. Two of five viral isolates were clustered with BVDV-1d viruses, a strain widespread in Italy, but never reported in Sicily. The other three isolates formed a distinct cluster with high similarity to Tunisian isolates, recently proposed as a new pestivirus species. This represents the first evidence for Tunisian-like pestivirus presence in small ruminants in Italy. Furthermore, one of the isolates was collected from a goat, representing the first isolation of Tunisian-like pestivirus from this species. | Pestivirus |
Nitrogen is an essential macronutrient for all living organisms and is critical for crop productivity and quality. In higher plants, inorganic nitrogen is absorbed through roots and then assimilated into amino acids by the highly conserved glutamine synthetase/glutamine:2-oxoglutarate aminotransferase (GS/GOGAT) cycle. How nitrogen metabolism and nitrogen starvation responses of plants are regulated remains largely unknown. Previous studies revealed that mutations in the rice ABNORMAL CYTOKININ RESPONSE1 (ABC1) gene encoding Fd-GOGAT cause a typical nitrogen deficiency syndrome. Here, we show that ARE2 (for ABC1 REPRESSOR2) is a key regulator of nitrogen starvation responses in rice. The are2 mutations partially rescue the nitrogen-deficient phenotype of abc1 and the are2 mutants show enhanced tolerance to nitrogen deficiency, suggesting that ARE2 genetically interacts with ABC1/Fd-GOGAT. ARE2 encodes a chloroplast-localized RelA/SpoT homolog protein that catalyzes the hydrolysis of guanosine pentaphosphate or tetraphosphate (p)ppGpp, an alarmone regulating the stringent response in bacteria under nutritional stress conditions. The are2 mutants accumulate excessive amounts of (p)ppGpp, which correlate with lower levels of photosynthetic proteins and higher amino acid levels. Collectively, these observations suggest that the alarmone (p)ppGpp mediates nitrogen stress responses and may constitute a highly conserved mechanism from bacteria to plants. | Guanosine Pentaphosphate |
OBJECTIVES: A systematic review and meta-analysis were performed to evaluate the risk and intensity of tooth sensitivity (TS) after dental bleaching with a desensitizer-containing and a desensitizer-free bleaching gel in adult patients. Color change and risk of gingival sensitivity was also evaluated. METHODS: A comprehensive search was performed MEDLINE via PubMed, Scopus, Web of Science, Latin American and Caribbean Health Sciences Literature database (LILACS), Brazilian Library in Dentistry (BBO), EMBASE and Cochrane Library, and System for Information on Grey Literature in Europe (SIGLE) without restrictions to identify randomized clinical trials. Abstracts from the annual conference of the International Association for Dental Research (1990-2016), unpublished and ongoing trials registries, dissertations, and theses were also searched. The quality of the evidence was rated using the Grading of Recommendations: Assessment, Development and Evaluation (GRADE) approach. DATA: After duplicates were removed, 1352 articles were identified. After title and abstract screening, only 47 studies remained for qualitative evaluation. Most of the studies had unclear risk of bias. No difference between groups were observed for the risk ratio of TS (risk ratio = 0.99; 95% confidence interval [CI] = 0.74-1.33); intensity of TS (standardized difference in means [SMD] = 0.04; 95% CI = 0.79-0.70); color change in shade guide units (SMD - 0.04; 95% CI = 0.50-0.42); color change in DeltaE* (SMD = 0.41 (95% CI = 0.07-0.89); and risk ratio of gingival irritation (SMD = 1.05; 95% CI = 0.81-1.36). Except for the risk of TS, graded as moderate quality of evidence, all other outcomes were rated as low and very low quality. CONCLUSIONS: Incorporating desensitizers in the bleaching gel did not reduce the risk of TS, and the quality of this evidence was considered moderate. On the other hand, the intensity of TS, color change, and risk of gingival irritation was similar between groups, but the quality of the evidence for these outcomes was graded as low or very low, thus reducing the level of confidence in these outcomes. | Tooth Bleaching Agents |
Homers are adapter proteins that play a significant role in the organization of calcium signaling protein complexes. Previous functional studies linked Homer proteins to calcium influx in nonexcitable cells. These studies utilized calcium imaging or whole-cell current recordings. Because of limited resolution of these methods, an identity of Homer-modulated ion channels remained unclear. There are several types of plasma membrane calcium influx channels in A431 cells. In the present study, we demonstrated that Homer dissociation resulted in specific activation of I(min) channels but not of I(max) channels in inside-out patches taken from A431 cells. In contrast, inositol 1,4,5-trisphosphate activated both I(min) and I(max) channels in inside-out patches. Short (1a) and long (1c) forms of Homer had different effects on I(min) channel activity. Homer 1a but not Homer 1c activated I(min) in the patches. This study indicates that I(min) channels are specifically regulated by Homer proteins in A431 cells. | Homer Scaffolding Proteins |
BACKGROUND: A diverse set of transcripts called 185/333 is strongly expressed in sea urchins responding to immune challenge. Optimal alignments of full-length 185/333 cDNAs requires the insertion of large gaps that define 25 blocks of sequence called elements. The presence or absence of individual elements also defines a specific element pattern for each message. Individual sea urchins were challenged with pathogen associated molecular patterns (PAMPs) (lipopolysaccharide, beta-1,3-glucan, or double stranded RNA), and changes in the 185/333 message repertoire were followed over time. RESULTS: Each animal expressed a diverse set of 185/333 messages prior to challenge and a 0.96 kb message was the predominant size after challenge. Sequence analysis of the cloned messages indicated that the major element pattern expressed in immunoquiescent sea urchins was either C1 or E2.1. In contrast, most animals responding to lipopolysaccharide, beta-1,3-glucan or injury, predominantly expressed messages of the E2 pattern. In addition to the major patterns, extensive element pattern diversity was observed among the different animals before and after challenge. Nucleotide sequence diversity of the transcripts increased in response to beta-1,3-glucan, double stranded RNA and injury, whereas diversity decreased in response to LPS. CONCLUSION: These results illustrate that sea urchins appear to be able to differentiate among different PAMPs by inducing the transcription of different sets of 185/333 genes. Furthermore, animals may share a suite of 185/333 genes that are expressed in response to common pathogens, while also maintaining a large number of unique genes within the population. | Strongylocentrotus purpuratus |
Oncostatin M (OSM) is a 28-kDa glycoprotein produced by stimulated macrophages and T lymphocytes that inhibits the proliferation of a number of different cell lines derived from solid tumors. Analysis of both amino acid sequence and gene structure has demonstrated that OSM is a member of a cytokine family that includes leukemia inhibitory factor (LIF), IL-6, and granulocyte colony-stimulating factor (G-CSF). We demonstrate that, like LIF, IL-6 and G-CSF, OSM can induce the differentiation of the myeloblastic M1 murine leukemia cells into macrophage-like cells. The morphologic and functional changes induced by OSM are more similar to those observed with LIF and IL-6 than those induced with G-CSF. OSM can also induce the differentiation of the histiocytic U937 human leukemia cells in the presence of granulocyte-macrophage CSF, a property shared with LIF and IL-6. In murine M1 cells, binding of labeled OSM is completely inhibited by excess LIF or OSM, reflecting the binding of OSM to the high affinity form of the murine LIF receptor. In contrast, the binding of labeled OSM to human U937 leukemia cells is inhibited by OSM, but the inhibition by LIF is significantly less. These results suggest that, in human leukemia cells, OSM may act through the LIF receptor and an OSM-specific receptor. The existence of an OSM-specific receptor was confirmed by both growth inhibition and competition binding assays on A375 human melanoma cells. The growth of human A375 cells was inhibited by OSM and IL-6 but not LIF or G-CSF. Neither LIF, G-CSF, nor IL-6 could compete with the binding of labeled OSM to A375 cells. | Receptors, OSM-LIF |
Tumor necrosis factor (TNF)-alpha is a potent pro-inflammatory and pathological cytokines in inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases. Anti-TNF-alpha therapy has been established as an efficacious therapeutic strategy in these diseases. In clinical settings, three monoclonal anti-TNF-alpha full IgG1 antibodies infliximab, adalimumab, and golimumab, PEGylated Fab' fragment of anti-TNF-alpha antibody certolizumab pegol, extracellular domain of TNF receptor 2/IgG1-Fc fusion protein etanercept, are almost equally effective for rheumatoid arthritis. Although monoclonal full IgG1 antibodies are able to induce clinical and endoscopic remission in inflammatory bowel diseases, certolizumab pegol without Fc portion has been shown to be less effective for inflammatory bowel diseases compared to full IgG1 antibodies. In addition, there are no evidences that etanercept leads clinical remission in inflammatory bowel diseases. Besides the common effect of anti-TNF-alpha agents on neutralization of soluble TNF-alpha, each anti-TNF-alpha agent has its own distinctive pharmacological properties which cause the difference in clinical efficacies. Here we focus on the distinctions of action of anti-TNF-alpha agents especially in following points; (1) blocking ability against ligands, transmembrane TNF-alpha and lymphotoxin, (2) effects toward transmembrane TNF-alpha-expressing cells, (3) effects toward Fcgamma receptor-expressing cells, (4) degradation and distribution in inflamed tissue. Accumulating evidence will give us the idea how to modify anti-TNF-alpha agents to enhance the clinical efficacy in inflammatory diseases. | Certolizumab Pegol |
Several inhibitors of angiogenesis are being developed for the treatment of cancer. One dominant strategy involves disruption of the vascular endothelial growth factor (VEGF) pathway by inhibition of the receptors for VEGF. Inhibition of the VEGF receptor activity can be accomplished using catalytic RNA molecules known as ribozymes, which downregulate VEGF receptor function by specifically cleaving the mRNAs for the primary VEGF receptors, Flt-1 and KDR. Significant inhibition of angiogenesis using ribozymes against both receptors has been demonstrated. In animal tumor models, antitumor effects are most pronounced with the anti-Flt-1 ribozyme known as Angiozyme (Ribozyme Pharmaceuticals, Boulder, CO). Extensive preclinical studies have demonstrated no significant toxicities. Clinical trials of Angiozyme are currently in progress for patients with advanced malignancy. Preliminary results demonstrate Angiozyme to be well tolerated, without significant side effects. Several phase II trials are underway for patients with advanced malignancy to test therapeutic efficacy. | Receptors, Growth Factor |
OBJECTIVE: To determine the effectiveness of kinesiotaping (KT) with or without co-interventions for clinical outcomes in patients with subacromial impingement syndrome (SIS). DESIGN: Systematic review with meta-analysis of randomized clinical trials. DATA SOURCES: Eight databases (MEDLINE, CENTRAL, EMBASE, PEDro, LILACS, CINAHL, SPORTDiscus, and Web of Science) were searched from inception until March 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Clinical trials that determine the effectiveness of KT with or without co-interventions for clinical outcomes in patients with SIS who are older than 18 years of age. RESULTS: Ten trials for the quantitative analysis were included. For pain intensity at 1-3 weeks, the overall pooled MD was -0.73 cm, 95% CI = -1.50 to 0.04 (p = 0.06), and at 3-6 weeks, it was -0.13 cm, 95% CI = -1.37 to 0.36 (p = 0.25). For shoulder function, the MD was -0.02, 95%CI = -0.30 to 0.26 (p = 0.89). For shoulder Range of Motion (ROM) flexion, the MD was -16.70, 95% CI = -0.52 to 33.92 (p = 0.06). Additionally, there was a low to moderate quality of evidence according to the GRADE rating. CONCLUSION: Kinesiotaping with or without co-interventions was not superior to other interventions for improving shoulder pain intensity, function and ROM flexion in patients with SIS. | Athletic Tape |
Human tumor necrosis factor receptor-associated protein 1 (Trap1) is a mitochondrial protein identical to heat shock protein 75 (HSP75) that plays an important role in protecting cells from oxidative stress and apoptosis. In this study, grass carp (Ctenopharyngodon idella) tumor necrosis factor receptor-associated protein 1 (designated as CiTrap1) was identified through two-dimensional electrophoresis (2-DE) analysis and its pattern of expression was investigated in grass carp kidney (CIK) cells infected with grass carp reovirus (GCRV). The full length cDNA of CiTrap1 contained an opening reading frame of 2157 bp that encoded a peptide of 718 amino acids. Phylogenetic analyses indicated that the CiTrap1 shared 87% identity with its homologue from zebrafish (Danio rerio). The transcriptional level of CiTrap1 in CIK cells was upregulated post virus infection as well as poly (I: C) stimulation. Following virus infection, grass carp PTEN-induced putative kinase 1 (PINK1) and Sorcin, whose coding proteins interact with Trap1 in human, were simultaneously upregulated with CiTrap1. Typical characteristics of apoptosis were observed in CIK cells infected with GCRV by DAPI staining, DNA ladder electrophoresis, TUNEL assay and Annexin âÂ
¤ labeling. RNAi-mediated silencing of CiTrap1 in CIK cells resulted in the increased rate of virus-induced apoptotic cells. The results of this study suggest that CiTrap1 is involved in the host's innate immune response to viral infection possibly through protecting infected cells from apoptosis." | TNF Receptor-Associated Factor 1 |
BACKGROUND: Gitelman syndrome (GS) is a rare autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we report, for the first time, a case of GS overlapping nephrotic syndrome (NS) related to PLA2R-associated membranous nephropathy (MN). CASE PRESENTATION: We described a male patient had a 4-year history of recurrent fatigue. Serum biochemistry revealed hypokalemia with renal potassium wasting, hypomagnesemia, metabolic alkalosis, hyperreninemia, hypocalciuria, as well as nephrotic-range proteinuria, hypoalbuminemia, and elevated serum anti-phospholipase A2 receptor (PLA2R) antibody. Gene sequencing identified compound heterozygous mutations in SLC12A3 [c.536T > A(p.V179D) and c.1456G > A(p.D486N)]. The unusual association of SLTs and nephrotic-range glomerular proteinuria prompted us to perform a renal biopsy. Renal biopsy showed idiopathic MN. Due to the potential to activate the sodium-chloride co-transporter (NCC) and cause hyperkalemia, tacrolimus was selected to treat NS. Following treatment with potassium chloride, magnesium oxide, low-dose glucocorticoid combined with tacrolimus, the fatigue significantly improved, and concurrently hypokalemia, hypomagnesemia were corrected and NS was remitted. CONCLUSIONS: Renal biopsy should be warranted for GS patients with moderate to nephrotic-range proteinuria. Tacrolimus was preferred to the management of GS patients with NS. | Gitelman Syndrome |
PURPOSE: During the last five decades drug and therapeutics committees (DTCs), have evolved from mainly hospital-based groups of experts in pharmacotherapy and drug logistics into an arena for healthcare professionals employing evidence-based methods of promoting rational drug use. The purpose of this study was to suggest a framework for analysing the structure and activities of DTCs. METHODS: A literature search was carried out in the Medline, Cinahl and Web of Sciences databases for the period 1993-2012. RESULTS: A total of 207 articles were included. Based on these articles a framework for the analysis of the DTCs based on the role of the DTC, target groups, budget perspective and type of economic decisions could be suggested. CONCLUSIONS: In order to respond to future demands the DTCs will have to develop their skill in pharmacoeconomics. Their processes will have to be standardised and made more transparent in order to be better adapted to evidence-based decision-making. They will also have to embrace the possibilities created by electronic health records in both influencing the decisions of physicians, and in improving quality assurance programmes and longitudinal follow-up of drug therapy and outcomes. They will have to find new ways of interacting with the public and policy makers in order to get the resources needed for their work. Finally, they will have to handle the conflict among national, regional and local decision-making processes and the relationship between formularies and therapeutic guidelines." | Pharmacy and Therapeutics Committee |
We present a particle-in-cell (PIC) analysis of terahertz (THz) radiation by ultrafast plasma currents driven by relativistic-intensity laser pulses. We show that, while the I(0) [Formula: see text] product of the laser intensity I(0) and the laser wavelength lambda(0) plays the key role in the energy scaling of strong-field laser-plasma THz generation, the THz output energy, W(THz), does not follow the I(0) [Formula: see text] scaling. Its behavior as a function of I(0) and lambda(0) is instead much more complex. Our two- and three-dimensional PIC analysis shows that, for moderate, subrelativistic and weakly relativistic fields, W(THz)(I(0) [Formula: see text]) can be approximated as (I(0)lambda(0)(2))(alpha), with a suitable exponent alpha, as a clear signature of vacuum electron acceleration as a predominant physical mechanism whereby the energy of the laser driver is transferred to THz radiation. For strongly relativistic laser fields, on the other hand, W(THz)(I(0) [Formula: see text]) closely follows the scaling dictated by the relativistic electron laser ponderomotive potential [Formula: see text], converging to W(THz) proportional, variant [Formula: see text] for very high I(0), thus indicating the decisive role of relativistic ponderomotive charge acceleration as a mechanism behind laser-to-THz energy conversion. Analysis of the electron distribution function shows that the temperature T(e) of hot laser-driven electrons bouncing back and forth between the plasma boundaries displays the same behavior as a function of I(0) and lambda(0), altering its scaling from (I(0)lambda(0)(2))(alpha) to that of [Formula: see text], converging to W(THz) proportional, variant [Formula: see text] for very high I(0). These findings provide a clear physical picture of THz generation in relativistic and subrelativistic laser plasmas, suggesting the THz yield W(THz) resolved as a function of I(0) and lambda(0) as a meaningful measurable that can serve as a probe for the temperature T(e) of hot electrons in a vast class of laser-plasma interactions. Specifically, the alpha exponent of the best (I(0)lambda(0)(2))(alpha) fit of the THz yield suggests a meaningful probe that can help identify the dominant physical mechanisms whereby the energy of the laser field is converted to the energy of plasma electrons. | Radiation, Nonionizing |
Bacteria produce protein polymers on their surface called pili or fimbriae that serve either as attachment devices or as conduits for secreted substrates. This review will focus on the chaperone-usher pathway of pilus biogenesis, a widespread assembly line for pilus production at the surface of Gram-negative bacteria and the archetypical protein-polymerizing nanomachine. Comparison with other nanomachines polymerizing other types of biological units, such as nucleotides during DNA replication, provides some unifying principles as to how multidomain proteins assemble biological polymers. | Multienzyme Complexes |
The purpose of the present study was to investigate the histological changes of the periodontal tissues in rats produced by oral administration of dihydrotachysterol (DHT). Forty-five rats, 6 weeks old, were divided equally into 9 groups (Groups A-I). Groups A, D and G, control groups, received an administration of corn oil (0.5 ml) once a day for 1, 2 and 4 weeks, respectively. Groups B, E and H received an administration of DHT (25 micrograms) once a day for 1, 2 and 4 weeks, respectively. Groups C, F and I had an administration of DHT (50 micrograms) once a day for 1, 2 and 4 weeks, respectively. The animals of all groups were killed 24 hours after the last administration. The periodontal tissues of the maxillary first molar of all animals were examined histologically and histometrically. Histological and histometrical findings: 1. In Groups A, D and G, control groups, the periodontal ligament, alveolar bone and cementum appeared normal during the entire experimental period. 2. In Group B, the peridontal tissues were almost similar to those of the control group. 3. In Groups C and E, osteoid tissue was observed in the alveolar bone surface. The thickness of the periodontal ligament decreased and the bone marrow spaces were slightly enlarged. The volmetric density of the alveolar bone decreased compared with that of the control groups. 4. In Groups F, H and I, the thickness of the periodontal ligament decreased significantly. In the periodontal ligament, destruction of collagen fibers was observed, and fibroblasts, collagen fibers and oxytalan fibers decreased in number. Dental ankylosis was also found. An abnormal darkly-stained layes (using the PAS staining method) was observed in the cementum surface. The alveolar bone marrow spaces were enlarged and replaced by fibrous tissue. In the histometrical findings, the thickness of the periodontal ligament and the volumetric density of the alveolar bone had decreased, and the volume of the cementum had increased significantly. The result of the present study suggested that oral administration of dihydrotachysterol to the rats induced the changes of the periodontal tissues similar to those seen in aging humans. | Dihydrotachysterol |
Since the outbreak of COVID-19, one of the strategies used to search for new drugs has been to find inhibitors of the main protease (Mpro) of the virus SARS-CoV-2. Initially, previously reported inhibitors of related proteases such as the main proteases of SARS-CoV and MERS-CoV were tested. A huge effort was then carried out by the scientific community to design, synthesize and test new small molecules acting as inactivators of SARS-CoV-2 Mpro. From the chemical structure view, these compounds can be classified into two main groups: one corresponds to modified peptides displaying an adequate sequence for high affinity and a reactive warhead; and the second is a diverse group including chemical compounds that do not have a peptide framework. Although a drug including a SARS-CoV-2 main protease inhibitor has already been commercialized, denoting the importance of this field, more compounds have been demonstrated to be promising potent inhibitors as potential antiviral drugs. | Coronavirus 3C Proteases |
Urinary tract infection (UTI) is one of the most common bacterial infections in infants less than age 1 year. UTIs frequently recur and result in long-term effects include sepsis and renal scarring. Uropathogenic Escherichia coli (UPEC), the most prevalent organism found in UTIs, can cause host inflammation via various virulence factors including hemolysin and cytotoxic necrotizing factors by inducing inflammatory cytokines such as interleukin (IL)-1beta. However, the ability of each UPEC organism to induce IL-1beta production may differ by strain. Furthermore, the correlation between differential IL-1beta induction and its relevance in pathology has not been well studied. In this study, we isolated UPEC from children under age 24 months and infected bone-marrow derived macrophages with the isolates to investigate secretion of IL-1beta. We found that children with higher concentrations of C-reactive protein (CRP) were more likely to harbor phylotype B2 UPEC strains that induced more IL-1beta production than phylotype D. We also observed a significant correlation between serum CRP level and in vitro IL-1beta induction by phylotype B2 UPEC bacteria. Our results highlight the diversity of UPEC in terms of IL-1beta induction capacity in macrophages and suggest a potential pathogenic role in UTIs by inducing inflammation in infants." | Uropathogenic Escherichia coli |
Sagittaria trifolia is a good model of wetland plants to elucidate the formation of corm. However, few studies have been conducted to uncover the complexity of gene expression involved in corm formation. In this study, high-throughput tag-sequencing based on Solexa Genome Analyzer Platform was applied to monitor the changes in gene expression with three libraries of differentially expressed genes (DEGs) (C1 library: stolon stage, C2 library: initial swelling stage and C3 library: swelling stage) during corm formation in Sagittaria trifolia. Approximately 6.0 million tags were sequenced, and 5854021, 5983454, and 5761079 clean tags including 138319, 116804, and 101739 distinct tags were obtained after removal of low quality tags from each library, respectively. About 46% distinct tags were unambiguous tags mapping to the reference genes, and 33% were unambiguous tag-mapped genes. Totally, 20575, 19807, and 18438 were annotated in C1, C2, and C3 libraries, respectively, after mapping their functions in existing databases. In addition, we found that profiling of gene expression in C1/C2 and C2/C3 libraries were different among most of the selected 20 DEGs. Most DEGs in C1/C2 libraries were relevant to hormone synthesis and response; energy metabolism and stress response, while most of the genes in C2/C3 libraries were involved in carbohydrate metabolism. All up-regulated transcriptional factors and 16 important genes relevant to corm formation in three libraries were also identified. To further analyze the expression of 9 genes, from the results of tag-sequencing, qRT-PCR was applied. In summary, this study provides a comprehensive understanding of gene expression, during the formation of corm in Sagittaria trifolia. | Sagittaria |
Non-exudative age-related macular degeneration (AMD) is an irreversibly progressive retinal degenerative disease characterized by dysfunction and loss of retinal pigment epithelium (RPE). It has been suggested that impaired phagocytosis of the RPE is involved in the progression of non-exudative AMD, but the mechanism is not fully clear. In this study, we investigated the effect of lipid droplet accumulation on RPE function. Compared to young mice, the expression of lipid droplet-associated proteins increased in the RPE-choroidal complex, and lipid droplet in the RPE was observed in aged pigmented mice (12-month-old). Repeated treatment of the photoreceptor outer segment against ARPE-19 resulted in lipid droplets in ARPE-19 cells in vitro. Oleic acid treatment for ARPE-19 cells to form intracellular lipid droplet reduced the POS uptake into the ARPE-19 cells without causing a decrease in cell viability. The suppression of the POS uptake by lipid droplet formation improved by inhibiting lipid droplet formation using triacsin C. Moreover, the amount of intracellular reactive oxygen species was suppressed by the triacsin C treatment. These results indicate that lipid droplet is involved in the RPE dysfunction, and inhibiting lipid droplet formation may be a target for preventing and treating non-exudative AMD. | Lipid Droplets |
This article briefly reviews the history of the inclusion of culture within child and adolescent psychiatry. This history is a reflection of broader trends within medical education and psychiatry, more generally. The authors then present an approach for incorporating culture within the clinical setting termed the cultural sensibility model. In addition to outlining the model and its philosophical basis, they present brief case examples and a sample curriculum in support of this model. | Ethnopsychology |
During the last decades pertussis incidence raised globally. Several vaccination strategies targeting adults to reduce pertussis among young infants have been proposed, including vaccination of healthcare workers (HCWs). The aim of this study was to analyse, by performing a systematic review of literature, published papers that evaluated Tdap coverage among HCWs, variables associated with vaccine uptake and efforts implemented to raise vaccination rates. We searched the MedLine, Embase, SCOPUS, LILACS, Web of Science and Cochrane for full-text studies that evaluated Tdap coverage in HCW. Two independent reviewers screened the articles and extracted the data.Twenty-eight studies published from 2009 to 2018 were reviewed. Most studies were conducted in the USA. Initial Tdap coverage varied from 6.1% to 63.9%. USA and France are the only two countries with studies evaluating Tdap coverage within HCWs using national data. In the USA, Tdap coverage in HCWs raised from 6.1% to 45.1% from 2007 to 2015. In the analysis of French national data, a Tdap coverage of 63.9% was observed. Five studies used interventions to raise Tdap coverage in HCWs. Two intervention studies implemented mandatory vaccination and three used educational strategies. All of them achieved coverages over 86%. Only eleven studies analysed the association of Tdap vaccination with variables of interest. Previous immunization with other vaccines recommended for HCWs (like influenza, hepatitis B and MMR) was positively associated with Tdap uptake in four studies. In conclusion, overall Tdap coverage among HCWs is low, but seems to increase over the years after the vaccine introduction and with implementation of interventions to increase coverage." | Diphtheria-Tetanus-acellular Pertussis Vaccines |
OBJECTIVE: The purpose of this study was to assess the effectiveness of the application of kinesio taping in reducing induced pain after dry needling of active trigger points (TrPs) to the upper trapezius muscle. METHODS: Consecutive patients had mechanical neck pain (n = 34, 44% female) with active TrPs in the upper trapezius muscle. All participants received dry needling into upper trapezius active TrPs. Then, they were randomly divided into a kinesio taping group, which received an adhesive tape (Kinesio Tex), and a control group, which did not receive the taping. The numeric pain rating scale was assessed (0-10) at post-needling; immediately after; and 24 hours, 48 hours, and 72 hours after needling. Neck- and shoulder-related disability was assessed before and 72 hours after needling with the Neck Disability Index (NDI) and the Shoulder Pain and Disability Index, respectively. The pressure pain threshold (PPT) over the TrP was also assessed post-needling, immediately post-intervention, and 72 hours after needling. RESULTS: The analysis of covariance did not find a significant group x time interaction (P = .26) for post-needling soreness: both groups exhibited similar changes in post-needling induced pain (P < .001). No significant group x time interactions were observed for changes in NDI (P = .62), SPADI (P = .41), or PPTs (P = .52): similar improvements were found after the needling procedure for the NDI (P < .001), Shoulder Pain and Disability Index (P < .001), and PPT (P < .001). The number of local twitch responses and sex (all, P > .30) did not influence the effect for any outcome. CONCLUSION: The application of kinesio taping after dry needling of active TrPs in the upper trapezius muscle was not effective for reducing post-needling induced pain in people with mechanical neck pain. Further, the application of kinesio taping as a post-needling intervention did not influence short-term changes in disability. | Dry Needling |
Impedance spectroscopy in the radio frequency range from 100 MHz to 20 GHz can reveal the dielectric relaxations of biological and chemical solutions. S-parameters for a coplanar waveguide are derived. To perform these measurements, a coplanar waveguide device was fabricated on a conventional FR-4 substrate for fluid interrogation. The microfluidic channel was formed by milling conventional waveguides and laser-cutting channels in the dielectric substrate. Measurements using this device were performed on standards: deionized water, isopropyl alcohol, and air. These measurements were compared to those taken with a conventional dielectric probe. The results demonstrate the ability of the fabricated device to extract varying transmission parameters due to changing sample properties. | Dielectric Spectroscopy |
Factitious diseases and pathomimias and particularly Munchausen's syndrome, due to their rarity, are poorly diagnosed by medical teams working in oncology. Consequences can be serious and result in unadapted surgery or non justified implementation of chemotherapy and radiotherapy regimens. These patients simulate diseases in order to attract medical attention. They might become belligerent and are likely to promptly discharge themselves from hospital if they do not get the desired attention or are unmasked. With two following case reports and literature review, we would like to alert clinicians about difficulties encountered in diagnosis and management of factitious disorders. When faced with this diagnosis, the patient will tend to deny reality and break contact with the medical team who exposed him. Medical peregrinating behavior surrounded by conflicts with medical team, past psychiatric illness, history of working in the medical and paramedical field and social isolation can guide the diagnosis. Somaticians and especially surgeons working in the oncologic field must remain vigilant about this diagnosis and collaborate with either the psycho-oncologic team or the consultation-liaison psychiatric team. Some recommendations for medical professionals how to cope with these patients will be suggested. | Factitious Disorders |
Prostaglandin (PG) E2 is produced by mammalian hypothalamus and when administered exogenously prolongs wakefulness. In order to study the relation of endogenous hypothalamic PGE2 to sleep and wakefulness, we have used microdialysis in freely moving rats associated with EEG recording. Male Wistar rats were implanted with three cortical electrodes and with a guide cannula for microdialysis in the space between the paraventricular nucleus (PVN) and the ventromedial hypothalamus (VMH). PGE2 was measured by RIA in 3- or 6-min dialysates 15 days after surgery, when sleep patterns were normal again and PGE2 production stabilised. PGE2 levels were significantly higher during wakefulness (601 +/- 35 pg/ml, 5 experiments, 35 samples) than during slow-wave sleep (487 +/- 24 pg/ml, 5 experiments, 49 samples). Samples corresponding to paradoxical sleep showed a tendency towards higher PGE2 values compared to slow-wave sleep but lower compared to wakefulness. In epochs of wakefulness or sleep lasting at least 12 min, high PGE2 levels in the middle of wakefulness regularly dropped, thus announcing the occurrence of sleep. During sleep, PGE2 first went on dropping and then reincreased towards the values that characterize early periods of wakefulness. In its turn, this reincrease in PGE2 announced the end of sleep and the imminent occurrence of wakefulness. It is the first study to our knowledge showing that the evolvement in endogenous PG profile may predict the occurrence of sleep or wakefulness." | Ventromedial Hypothalamic Nucleus |
It is common to compare life with machines. Both consume fuel and release waste to run. In biology, the engine that drives the living system is referred to as metabolism. However, attempts at deciphering the origins of metabolism do not focus on this energetic relationship that sustains life but rather concentrate on nonenzymatic reactions that produce all the intermediates of an extant metabolic pathway. Such an approach is akin to studying the molecules produced from the burning of coal instead of deciphering how the released energy drives the movement of pistons and ultimately the train when investigating the mechanisms behind locomotion. Theories that do explicitly invoke geological chemical gradients to drive metabolism most frequently feature hydrothermal vent conditions, but hydrothermal vents are not the only regions of the early Earth that could have provided the fuel necessary to sustain the Earth's first (proto)cells. Here, we give examples of prior reports on protometabolism and highlight how more recent investigations of out-of-equilibrium systems may point to alternative scenarios more consistent with the majority of prebiotic chemistry data accumulated thus far. This article is part of the theme issue 'Emergent phenomena in complex physical and socio-technical systems: from cells to societies'. | Extreme Environments |
Panic disorder is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as 0.5 M sodium lactate infusions. Although studied for four decades, the mechanism of lactate sensitivity in panic disorder has not been understood. The dorsomedial hypothalamus/perifornical region (DMH/PeF) coordinates rapid mobilization of behavioral, autonomic, respiratory and endocrine responses to stress, and rats with disrupted GABA inhibition in the DMH/PeF exhibit panic-like responses to lactate, similar to panic disorder patients. Utilizing a variety of anatomical and pharmacological methods, we provide evidence that lactate, via osmosensitive periventricular pathways, activates neurons in the compromised DMH/PeF, which relays this signal to forebrain limbic structures such as the bed nucleus of the stria terminalis to mediate anxiety responses, and specific brainstem sympathetic and parasympathetic pathways to mediate the respiratory and cardiovascular components of the panic-like response. Acutely restoring local GABAergic tone in the DMH/PeF blocked lactate-induced panic-like responses. Autonomic panic-like responses appear to be a result of DMH/PeF-mediated mobilization of sympathetic responses (verified with atenolol) and resetting of the parasympathetically mediated baroreflex. Based on our findings, DMH/PeF efferent targets such as the C1 adrenergic neurons, paraventricular hypothalamus, and the central amygdala are implicated in sympathetic mobilization; the nucleus of the solitary tract is implicated in baroreflex resetting; and the parabrachial nucleus is implicated in respiratory responses. These results elucidate neural circuits underlying lactate-induced panic-like responses and the involvement of both sympathetic and parasympathetic systems. | Sodium Lactate |
AIM: Mild hypothermia is increasingly applied in the intensive care unit. Knowledge on the effects of hypothermia on respiratory parameters during mechanical ventilation is limited. In this retrospective study, we describe the effect of hypothermia on gas exchange in patients cooled for 24 h after a cardiac arrest. METHODS: Respiratory parameters were derived from electronic patient files from 65 patients at the start and end of the hypothermic phase and at every centigrade increase in body temperature until normo-temperature, including tidal volume, positive end expiratory pressure (PEEP), plateau pressure, respiratory rate, exhaled CO(2) concentrations (etCO(2)) and FIO(2). Static compliance was calculated as V(T)/P(plateau)-PEEP. Dead space ventilation was calculated as (PaCO(2)-etCO(2))/PaCO(2). RESULTS: During hypothermia, PaCO(2) decreased, at unchanged PaCO(2)-etCO(2) gap and minute ventilation. During rewarming, PaCO(2) did not change, while etCO(2) increased at unchanged minute ventilation. Dead space ventilation did not change during hypothermia, but lowered during rewarming. During hypothermia, PaO(2)/FIO(2) ratio increased at unchanged PEEP levels. Respiratory static compliance did not change during hypothermia, nor during rewarming. CONCLUSION: Hypothermia possibly improves oxygenation and ventilation in mechanically ventilated patients. Results may accord with the hypothesis that reducing metabolism with applied hypothermia may be beneficial in patients with acute lung injury, in whom low minute ventilation results in severe hypercapnia. | Respiratory Dead Space |
The analysis of a variety of data sets (transcriptome arrays, phylogenetic profiles, etc.) yields groups of functionally related genes. In order to determine their biological function, associated gene groups are often projected onto known pathways or tested for enrichment of known functions. However, these approaches are not flexible enough to deal with variations or novel pathways. During the last decade, we developed and refined an approach that predicts metabolic pathways from a global metabolic network encompassing all known reactions and their substrates/products, by extracting a subgraph connecting at best a set of seed nodes (compounds, reactions, enzymes or enzyme-coding genes). In this review, we summarize this work, while discussing the problems and pitfalls but also the advantages and applications of network-based metabolic pathway prediction. | Transcriptome |
Cichlid fishes' famous diversity in body coloration is accompanied by a highly diverse and complex visual system. Although cichlids possess an unusually high number of seven cone opsin genes, they express only a subset of these during their ontogeny, accounting for their astonishing interspecific variation in visual sensitivities. Much of this diversity is thought to have been shaped by natural selection as cichlids inhabit a variety of habitats with distinct light environments. Also, sexual selection might have contributed to the observed visual diversity, and sexual dimorphism in coloration potentially co-evolved with sexual dimorphism in opsin expression. We investigated sex-specific opsin expression of several cichlids from Africa and the Neotropics and collected and integrated data sets on sex-specific body coloration, species-specific visual sensitivities, lens transmission and habitat light properties for some of them. We comparatively analysed this wide range of molecular and ecological data, illustrating how integrative approaches can address specific questions on the factors and mechanisms driving diversification, and the evolution of cichlid vision in particular. We found that both sexes expressed opsins at the same levels-even in sexually dimorphic cichlid species-which argues against coevolution of sexual dichromatism and differences in sex-specific visual sensitivity. Rather, a combination of environmental light properties and body coloration shaped the diversity in spectral sensitivities among cichlids. We conclude that although cichlids are particularly colourful and diverse and often sexually dimorphic, it would appear that natural rather than sexual selection is a more powerful force driving visual diversity in this hyperdiverse lineage. | Sexual Selection |
BACKGROUND: To investigate the clinical features of corneal opacity and the surgical outcome of penetrating keratoplasty (PK) in eyes with congenital glaucoma. METHODS: A retrospective review was made of the records from 320 eyes of 193 patients who were diagnosed with congenital glaucoma between January 1981 and January 2016. Anterior segment photographs at disease presentation were examined for the presence and severity of corneal opacity. Data on patient demographics, intraocular pressure (IOP), ocular and systemic comorbidities, ocular surgery and its outcome were collected. RESULTS: Overall, corneal opacification was observed in 248 of 320 eyes (77.5%). Out of 248 eyes with corneal opacification, 53 eyes had Haab striae alone, and 195 eyes presented with either nebulomacular corneal opacity (128 eyes, iris details visible through opacity) or leukomatous corneal opacity (67 eyes, iris details invisible through opacity). In 12 eyes with severe leukomatous corneal opacity, PK was performed at the mean age of 18.6 months (range 4-57 months). The grafts failed in 6 eyes (50%) due to endothelial rejection (4 eyes) or graft infection (2 eyes) during the mean 80.6 months of follow-up (range 15-228 months). The median survival time was 36 months. The graft failure was significantly associated with smaller corneal diameter at the time of surgery, but not with the age, IOP, combined aniridia, simultaneous glaucoma or lens surgery. CONCLUSION: Congenital glaucoma was combined with corneal opacity in 77.5%. The corneal transplant survival was 50% in eyes with congenital glaucoma and total corneal opacity. | Corneal Opacity |
Blood vessels, either in insufficient numbers or in excess, contribute to the pathogenesis of many diseases. Agents that stimulate angiogenesis can improve blood flow in patients with ischemic diseases, whereas anti-angiogenic agents are used to treat disorders ranging from macular degeneration to cancer. In this review I describe in vitro assays that can be used to assess the activity of agents that affect angiogenesis. Means of quantifying endothelial cell matrix degradation, migration, proliferation, apoptosis and morphogenesis are discussed, as are embryoid body, aortic ring and metatarsal assays of vessel outgrowth. Strengths and limitations of these techniques are also addressed." | Angiogenesis Modulating Agents |
The Charadriiformes is a large and diverse order of shorebirds currently classified into 19 families, including morphologically aberrant forms that are of uncertain phylogenetic placement within non-passerine birds in general. Recent attempts using morphological characters have failed to recover a well-supported phylogeny depicting higher level relationships within Charadriiformes and the limits to the order, primarily because of inconsistency and homoplasy in these data. Moreover, these trees are incongruent with the relationships presented in the DNA hybridization tapestry of, including the location of the root and the branching order of major clades within the shorebirds. To help clarify this systematic confusion we therefore sequenced the large RAG-1 nuclear exon (2850 bp) from 36 species representing 17 families of shorebirds for which DNA was available. Trees built with maximum parsimony, maximum likelihood or Bayesian methods are topologically identical and fully resolved, with high support at basal nodes. This further attests to the phylogenetic utility of the RAG-1 sequences at higher taxonomic levels within birds. The RAG-1 tree is topologically similar to the DNA hybridization tree in depicting three major subordinal clades of shorebirds, the Charadrii (thick-knees, sheathbills, plovers, oystercatchers, and allies), Scolopaci (sandpipers and jacanas) and the Lari (coursers, pratincoles, gulls, terns, skimmers, and skuas). However, the basal split in the RAG-1 tree is between Charadrii and (Scolopaci+Lari), whereas in the DNA hybridization tree Scolopaci is the sister group to the (Charadrii+Lari). Thus in both of these DNA-based trees the Alcidae (auks, murres, and allies) are not basal among shorebirds as hypothesized in morphological trees, but instead are placed as a tip clade within Lari. The enigmatic buttonquails (Turnicidae), variously hypothesized as being allied to either the Galliformes, Gruiformes, or Charadriiformes, are shown to be a basal lineage in the more conventional Lari clade. Divergence times estimated with rate-smoothing methods and minimum time constraints imposed at nodes with key fossils suggest that Charadriiformes originated in Gondwanaland. | Genes, RAG-1 |
Corynebacterium glutamicum ATCC13032 and Brevibacterium flavum JV16 were engineered for L-valine production by over-expressing ilvEBN ( r ) C genes at 31 degrees C in 72 h fermentation. Different strategies were carried out to reduce the by-products' accumulation in L-valine fermentation and also to increase the availability of precursor for L-valine biosynthesis. The native promoter of ilvA of C. glutamicum was replaced with a weak promoter MPilvA (P-ilvAM1CG) to reduce the biosynthetic rate of L-isoleucine. Effect of different relative dissolved oxygen on L-valine production and by-products' formation was recorded, indicating that 15 % saturation may be the most appropriate relative dissolved oxygen for L-valine fermentation with almost no L-lactic acid and L-glutamate formed. To minimize L-alanine accumulation, alaT and/or avtA was inactivated in C. glutamicum and B. flavum, respectively. Compared to high concentration of L-alanine accumulated by alaT inactivated strains harboring ilvEBN ( r ) C genes, L-alanine concentration was reduced to 0.18 g/L by C. glutamicum ATCC13032MPilvA big up tri, openavtA pDXW-8-ilvEBN ( r ) C, and 0.22 g/L by B. flavum JV16avtA::Cm pDXW-8-ilvEBN ( r ) C. Meanwhile, L-valine production and conversion efficiency were enhanced to 31.15 g/L and 0.173 g/g by C. glutamicum ATCC13032MPilvA big up tri, openavtA pDXW-8-ilvEBN ( r ) C, 38.82 g/L and 0.252 g/g by B. flavum JV16avtA::Cm pDXW-8-ilvEBN ( r ) C. This study provides combined strategies to improve L-valine yield by minimization of by-products' production. | Brevibacterium flavum |
Recently, a new class of oligonucleotides, forming G-quartet structures, has been developed as novel anti-HIV agents. Several critical structure-activity relationships between HIV-1 integrase and G-quartet oligonucleotides have been demonstrated. In addition the mechanism of the inhibition of HIV-1 integrase by G-quartet oligonucleotides, such as T30695 and its derivatives, has been explored. This review summarises the preliminary studies of developing G-quartet oligonucleotides as novel anti-HIV agents in several aspects including structure-activity relationship, stability-activity correlation, mechanism of HIV-1 integrase inhibition, substitution of phosphorothioates and targeting HIV-1 integrase in infected cells, which, hopefully, could help for developing a novel, efficient anti-HIV agent. | Anti-HIV Agents |
Acute neurologic disease associated with intracranial migration of a first instar larva of a warble fly, Hypoderma bovis (Linnaeus), was observed in a 14-year-old Quarter Horse gelding in western Montana. The disease was characterized by incoordination of gait, circling to the left, head tilt to the right, partial paralysis of the right side of the face, and impaired vision in the right eye. Two and one-half hours after it was first noticed sick, the horse collapsed and was euthanized. Massive hemorrhage unaccompanied by necrosis or significant cellular response was present in the right side of the midbrain and pons. | Hypodermyiasis |
Obstructive sleep apnoea syndrome (OSAS), which is characterised by repetitive episodes of pharyngeal collapse during sleep, is gaining much attention because of the important deleterious consequences it might have on the patient's health. We therefore organised a retrospective longitudinal study to report the long-term follow-up of maxillomandibular advancement (MMA) as a treatment for OSAS. A total of 19 patients with severe OSAS was treated during the period 2007-2016. They were followed up six months postoperatively (T1) and after a mean follow up of 6.7 (range 4-10) years (T2, between November 2017 and February 2018) for the polysomnography variables, and the Epworth sleeping scale (ESS) and body mass index (BMI) were recorded. All polysomnographic variables improved significantly from baseline to T1 and from baseline to T2. The ESS significantly improved from baseline to T2. Nearly all patients at T1 and over two-thirds at T2 had a 50% reduction of the apnoea/hypopnoea index when compared with baseline, and a value lower than 20 of the same index. The BMI did not change significantly from T0 to T2. Our long-term follow-up has documented the stability of the outcomes of the MMA for the treatment OSAS. | Cohort Studies |
Senecio fistulosus, an endemic plant in Chile, is highly regarded for its medicinal properties and is popular in alternative medicine. It thrives even in polluted areas, like Puchuncavi Valley, Chile. Therefore, the study aimed to assess the impact of industrial pollution in Puchuncavi Valley, Chile, on the phytoconstituent content, as well as the antioxidant and cytotoxic activities, of S. fistulosus. Phenols, flavonoids, and anthraquinones content were measured, alongside the assessment of antioxidant activities. Additionally, a GC-MS analysis was conducted to profile the phytoconstituents, while the cytotoxic potential was evaluated in HT-29 and MCF-7 and cell line non-tumorigenic MCF-10. The Wild sample exhibited a greater concentration of phytoconstituents (0 to 169.48 mg.L(-1)) compared to the Commercial control (0 to 95.38 mg.L(-1)), directly correlating with its antioxidant activity. While the Wild species showed cytotoxic activity, the Commercial control demonstrated cytotoxic effects on MCF-10 and MCF-7. Noteworthy compounds identified were hexadecanoic acid (12.76 to 19.57% relative area) and (Z,Z,Z)-9,12,15-octadecatrienoic acid (18.36% relative area), with anticancer properties. In conclusion, the abiotic stress experienced by S. fistulosus led to higher phytoconstituent content and improved antioxidant activity when contrasted with the Commercial control. The Commercial species showed increased cytotoxic activity against both tumorigenic and non-tumorigenic cell lines. | Senecio |
Enterovirus 94 (EV-94) is an enterovirus serotype described recently which, together with EV-68 and EV-70, forms human enterovirus D species. This study investigates the seroprevalences of these three serotypes and their abilities to infect, replicate, and damage cell types considered to be essential for enterovirus-induced diseases. The cell types studied included human leukocyte cell lines, primary endothelial cells, and pancreatic islets. High prevalence of neutralizing antibodies against EV-68 and EV-94 was found in the Finnish population. The virus strains studied had wide leukocyte tropism. EV-94 and EV-68 were able to produce infectious progeny in leukocyte cell lines with monocytic, granulocytic, T-cell, or B-cell characteristics. EV-94 and EV-70 were capable of infecting primary human umbilical vein endothelial cells, whereas EV-68 had only marginal progeny production and did not induce cytopathic effects in these cells. Intriguingly, EV-94 was able to damage pancreatic islet beta-cells, to infect, replicate, and cause necrosis in human pancreatic islets, and to induce proinflammatory and chemoattractive cytokine expression in endothelial cells. These results suggest that HEV-D viruses may be more prevalent than has been thought previously, and they provide in vitro evidence that EV-94 may be a potent pathogen and should be considered a potentially diabetogenic enterovirus type. | Enterovirus D, Human |
Stroke and traumatic injuries of the brain and spinal cord are major public health issues. In the last few decades, hundreds of clinical trials with patients suffering from these conditions have been done, however, most of them had not succeeded and there is still the need to develop more effective treatments for these conditions. Astrocytes play critical roles in the development, function and survival of neurons in the central nervous system. These cells are implicated in the pathophysiology and in the response to several neuropathological conditions and may represent potential cell targets for neuroprotective strategies. Progesterone and dehydroepiandrosterone (DHEA) are neuroactive steroids that modulate neuronal and astroglial function and have neuroprotective effects in different experimental models, being potential candidates to the development of new therapeutic approaches for brain and spinal cord injuries. The aim of this review is to discuss the role of astrocytes in the pathophysiology of brain and spinal cord injuries and how they could be modulated by progesterone and DHEA for the treatment of these conditions. | Neuroprotection |
Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Probiotics are one of the most popular dietary supplements for hypercholesterolemia, but there are questions as to whether there are differences between probiotics and cholesterol-lowering drugs like atorvastatin (ATO) both in effectiveness and in the underlying mechanisms. In this study, the hypocholesterolemia effects of 4 probiotic strains were investigated and compared with ATO, focusing on their impacts on the gut microbiota. A hypercholesterolemia model was established via high-fat diet (HFD) in golden hamsters after which ATO and the 4 probiotics were orally administered individually for 8 weeks. All probiotics were effective, but less than ATO, on body weight, serum parameters (TG, TC, LDL, INS, HbA1c) and expression of inflammatory factors (INF-alpha, IL-1beta, CRP), with strain JQII-5 being most significant. Besides, these effects were associated with restoration of microbiota dysbiosis induced by HFD. It was worth noting that ATO and probiotics induced different shifts of the gut microbiota in both structure and key phylotypes. Most interestingly, Allobaculum, a HFD-suppressed genus, reported to be involved in alleviating oxidative stress, was enriched by all tested probiotic strains, but not by ATO. Furthermore, Prevotella, also a HFD-suppressed genus, was uniquely reversed by JQII-5. Importantly, most of the alerted genera and reversed genera were found to be correlated with the inflammatory state and serum lipid level. Compared with ATO, the probiotic strains were less effective on body weight, hypercholesterolemia, and inflammation. However, probiotics exert additional favorable effects on the gut microbiota, making them excellent potential complements to cholesterol-lowering drugs like ATO. | Pediococcus pentosaceus |
The purpose of this study was to evaluate the time to diagnosis and management of hook of hamate fractures in an era of advanced imaging. We performed a retrospective study of 51 patients treated for hook of hamate fractures. Patients were sent a quickDASH questionnaire regarding the outcomes of their treatment. Hook of hamate fractures were diagnosed with advanced imaging at a median of 27 days. Clinical findings of hook of hamate tenderness had better sensitivity than carpal tunnel-view radiographs. Nonunion occurred in 24% of patients with non-operative treatment and did not occur in the operative group. Both treatment groups achieved good clinical results, with a grip strength of 80% compared with the non-injured hand and a median quickDASH score of 2. Advanced imaging improved the time to diagnosis and treatment compared to historical case series. Nonunion is common in patients treated non-operatively. LEVEL OF EVIDENCE: IV. | Hamate Bone |
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