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Background and purpose - Low statistical power remains endemic in clinical medicine including orthopedics and manifests as high uncertainty and wide confidence intervals (CI). We evaluated the reporting and correspondence between power calculation and observed data on key parameters of variability and uncertainty in orthopedic randomized controlled trials (RCTs).Material and methods - RCTs with 1:1 allocation published in 8 major orthopedic journals between 2016 and 2017 with one continuous primary outcome were included in the review. The components of power calculation and observed standard deviation (SD), mean difference (MD), and confidence interval (CI) of MD between groups were assessed for primary outcome.Results - 160 RCTs were included, of which 93 (58%) and 138 (86%) studies reported the estimated SD and MD in the power calculation, respectively. The median ratio of the estimated SD and SDs observed in the data was 1.0 (IQR -0.76 to 1.32) for 69 (43%) studies. Only 31 of 138 studies reported the CI of MD in primary outcome. In 42% of the negative studies, the estimated MD was included in the CI of the observed MD.Interpretation - The key parameters of data variability, both in power analyses and in final study results, were poorly reported. Low power in orthopedics may result from too high an estimated effect size due to an overoptimistic estimate of MD between study groups. In almost half of the studies, overlap of the CI of the observed MD and estimated MD suggested that the reported results of these studies were inconclusive." | Randomized Controlled Trials as Topic |
The topography and nature of granulopoietic tissues appearing during the larval period of Rana esculenta have been investigated using light and electron microscopy. The formation of eosinophils and heterophils occurred in the interstices of the pronephros and opisthonephros, in the mesenchymal sheath surrounding the pronephric duct, as well as in the mesentery and mesenchymal coat of the bile duct and hepatic ducts. Developing basophils were very rare, being detectable only in the stroma of the trunk kidneys. The pronephric interstices additionally contained differentiating lymphocytes, the opisthonephric interstices differentiating lymphocytes and erythrocytes. In contrast, the mesenchymal sheath of the pronephric duct as well as the mesentery and the mesenchymatous coat of the bile duct and hepatic ducts were solely granulopoietic. | Rana esculenta |
Chlamydomonas RNase J is the first member of this enzyme family that has endo- but no intrinsic 5' exoribonucleolytic activity. This questions its proposed role in chloroplast mRNA maturation. RNA maturation and stability in the chloroplast are controlled by nuclear-encoded ribonucleases and RNA binding proteins. Notably, mRNA 5' end maturation is thought to be achieved by the combined action of a 5' exoribonuclease and specific pentatricopeptide repeat proteins (PPR) that block the progression of the nuclease. In Arabidopsis the 5' exo- and endoribonuclease RNase J has been implicated in this process. Here, we verified the chloroplast localization of the orthologous Chlamydomonas (Cr) RNase J and studied its activity, both in vitro and in vivo in a heterologous B. subtilis system. Our data show that Cr RNase J has endo- but no significant intrinsic 5' exonuclease activity that would be compatible with its proposed role in mRNA maturation. This is the first example of an RNase J ortholog that does not possess a 5' exonuclease activity. A yeast two-hybrid screen revealed a number of potential interaction partners but three of the most promising candidates tested, failed to induce the latent exonuclease activity of Cr RNase J. We still favor the hypothesis that Cr RNase J plays an important role in RNA metabolism, but our findings suggest that it rather acts as an endoribonuclease in the chloroplast. | RNA, Chloroplast |
A tecnhique of performing metrizamide myelography with the patient supine and using lateral C1-2 puncture is described. Some advantages of this technique are discussed, especially for thoracic myelography. | Metrizamide |
The objective of this study was to determine fractional absorption of exogenous zinc and intestinal excretion of endogenous zinc in women of childbearing age whose habitual dietary zinc intake was marginal. The target population (L group) comprised residents of a remote farming village in northeast China and the control subjects (M group) were residents of Beijing. Mean (+/-SE) calculated dietary zinc intakes were 5.2 +/- 0.2 and 8.1 +/- 0.2 mg/d, respectively. The phytate-zinc molar ratio in the diet of both groups was approximately 10:1. 70Zn was administered intravenously before breakfast and 67Zn orally with three main meals in 1 d. Subsequently, all feces were collected quantitatively until the second visible marker had been excreted and 12-h urine samples were collected on days 3-9. Fractional absorption was determined by measuring cumulative fecal excretion of nonabsorbed 67Zn and endogenous fecal zinc by isotope-dilution technique (70Zn). Fractional absorption values for L and M groups, respectively, were 0.31 +/- 0.03 and 0.34 +/- 0.03 (P=0.45). Corresponding figures for endogenous fecal zinc were 1.30 +/- 0.07 and 2.34 +/- 0.20 mg Zn/d (P<0.001). Both the estimated total size of the pools of zinc that exchange with zinc in plasma within 2 d (r=0.762, P<0.001) and the excretion of endogenous zinc in the feces (r=0.706, P<0.0001) were positively correlated with calculated total daily zinc absorption. We conclude that fractional absorption of zinc does not differ between women consuming marginal and adequate quantities of zinc in their diets, but endogenous zinc is conserved effectively by the intestine in women whose habitual dietary zinc is marginal. | Zinc |
BACKGROUND: Desert dust is assumed to have substantial adverse effects on human health. However, the epidemiologic evidence is still inconsistent, mainly because previous studies used different metrics for dust exposure and its corresponding epidemiologic analysis. We aim to provide a standardized approach to the methodology for evaluating the short-term health effects of desert dust. METHODS: We reviewed the methods commonly used for dust exposure assessment, from use of a binary metric for the occurrence of desert dust advections to a continuous one for quantifying particulate matter attributable to desert dust. We presented alternative time-series Poisson regression models to evaluate the dust exposure-mortality association, from the underlying epidemiological and policy-relevant questions. A set of practical examples, using a real dataset from Rome, Italy, illustrate the different modeling approaches. RESULTS: We estimate substantial effects of desert dust episodes and particulate matter with diameter <10 mum (PM10) on daily mortality. The estimated effect of non-desert PM10 was 1.8% (95% confidence interval [CI] = 0.4, 3.2) for a 10 mug/m rise of PM10 at lag 0 for dust days, 0.4% (95% CI = -0.1, 0.8) for non-dust days, and 0.6% (95% CI = -0.5, 2.1) for desert PM10. CONCLUSION: The standardized modeling approach we propose could be applicable elsewhere, in and near hot spots, which could lead to more consistent evidence on the health effects of desert dust from future studies. | Desert Climate |
Presented herein are the trajectories of four women who can be considered pioneers of microbiology in Spain. Three of them have been studied before, but never presented as pioneers of microbiology, and their lives are briefly reviewed: Zoe Rosinach Pedrol, a pioneering microbiologist in the health care field; Isabel Toran del Carre, in the agri-food sector; and Luz Zalduegui Gabilondo in the veterinary sciences. Nevertheless, Trinidad del Pan Arana is presented from the first time as pioneering microbiologist in the natural sciences area. All of these women developed their professional activity during the first third of the twentieth century, contributing to the establishment of microbiology as a new scientific discipline in Spain. | Food Microbiology |
Thrombotic thrombocytopenic purpura (TTP) is primarily caused by deficiency of ADAMTS13 within the blood stream due to either genetic defects or presence of inhibitory autoantibodies. Preclinical and clinical studies suggest that enzyme replacement therapy with recombinant human ADAMTS13 protein (rhADAMTS13) is effective and safe in treatment of TTP. However, frequent dosing would be required due to the relatively short half-life of rhADAMTS13 in circulation as well as the presence of inhibitory autoantibodies that collectively result in the poor pharmacological profile of rhADAMTS13. With technical breakthroughs in exploring mRNA as therapeutics, we hypothesized that restoration of ADAMTS13 activity for a prolonged duration of time can be achieved through systemic dosing of mRNA, wherein the dosed mRNA would utilize hepatic cells as bioreactors for continuous production of ADAMTS13. To test this hypothesis, mRNA encoding human ADAMTS13 WT or an ADAMTS13 variant, that had demonstrated resistance to predominant clinical TTP autoantibodies, was formulated in lipid nano-particles for liver-targeted delivery. In both ADAMTS13-sufficient and -deficient mice, a single dose of the formulated mRNAs at 1 mg/kg resulted in expression of hADAMTS13 at or above therapeutically relevant levels in mice for up to five days. This proof-of-concept study suggests that mRNA therapy could provide a novel approach for TTP treatment. | ADAMTS13 Protein |
BACKGROUND: Osteoarthritis (OA) is associated with cartilage destruction. Maintenance of differentiated chondrocyte biomarkers is important in prevention of degeneration. Selective estrogen receptor modulators (SERMs) such as raloxifene (Ral) and phytoestrogens like enterolactone (Ent) which have structural and functional homologies with estrogen can mime their action. This study was undertaken to evaluate in vitro the possible effects of Ral and Ent on the expression of differentiated, dedifferentiated and hypertrophic biomarkers in human articular chondrocytes (HAC). METHODS: Chondrocytes of osteoarthritic patients, harvested from one passage cell culture, were treated with Ral (0.1 and 1 microM) and Ent (1 and 5 microM) for 10 and 12 days in two- (2D) and three-dimensional (3D) models. Genes expression of type I collagen (COL1A1), type II collagen (COL2A1), type X collagen (COL10A1), aggrecan (ACAN) and small novel rich in cartilage (SNORC), were detected by real-time PCR and by Western-Blotting. RESULTS: Our study revealed that Ral increased COL2A1, ACAN and SNORC and decreased concomitantly COL1A1 and COL10A1 genes expression when compared to untreated OA chondrocytes. Ent increased COL2A1 and decreased genes expression of the other biomarkers cited above like COL1A1. Our results demonstrated that low doses of 17beta-oestradiol (E2), Ral and Ent had positive effects on the expression of differentiated chondrocyte markers such as COL2A1, ACAN and SNORC whereas high dose of these compounds inhibited their effects. Our results showed that 1microM of Ral induced an up-regulation of COL2A1, ACAN and SNORC expression and a down-regulation of COL1A1 and COL10A1 expression in HAC incubated in 3D for 12 days. CONCLUSIONS: This study showed that SERMs like Ral and a phyto-estrogen like Ent induced the expression of differentiated chondrocyte markers of hyaline cartilage: COL2A1, ACAN and SNORC and decreased COL1A1 and COL10A1 genes expression on HAC of osteoarthritis patients. | Aggrecans |
Fires raged once again across Indonesia in the latter half of 2015, creating a state of emergency due to poisonous smoke and haze across Southeast Asia as well as incurring great financial costs to the government. A strong El Nino-Southern Oscillation (ENSO) led to drought in many parts of Indonesia, resulting in elevated fire occurrence comparable with the previous catastrophic event in 1997/1998. Synthetic Aperture Radar (SAR) data promise to provide improved detection of land use and land cover changes in the tropics as compared to methodologies dependent upon cloud- and haze-free images. This study presents the first spatially explicit estimates of burned area across Sumatra, Kalimantan, and West Papua based on high-resolution Sentinel-1A SAR imagery. Here, we show that 4,604,569 hectares (ha) were burned during the 2015 fire season (overall accuracy 84%), and compare this with other existing operational burned area products (MCD64, GFED4.0, GFED4.1s). Intersection of burned area with fine-scale land cover and peat layer maps indicates that 0.89 gigatons carbon dioxide equivalents (Gt CO(2) e) were released through the fire event. This result is compared to other estimates based on nonspatially explicit thermal anomaly measurements or atmospheric monitoring. Using freely available SAR C-band data from the Sentinel mission, we argue that the presented methodology is able to quickly and precisely detect burned areas, supporting improvement in fire control management as well as enhancing accuracy of emissions estimation. | El Nino-Southern Oscillation |
Muller glia (MG) in mammalian retinas are incapable of regenerating neurons after damage, whereas the MG in lower vertebrates regenerate functional neurons. Identification of cell signaling pathways and gene regulatory networks that regulate MG-mediated regeneration is key to harnessing the regenerative potential of MG. Here, we study how NFkB-signaling influences glial responses to damage and reprogramming of MG into neurons in the rodent retina. We find activation of NFkB and dynamic expression of NFkB-associated genes in MG after damage, however damage-induced NFkB activation is inhibited by microglia ablation. Knockout of NFkB in MG suppressed the accumulation of immune cells after damage. Inhibition of NFkB following NMDA-damage significantly enhanced the reprogramming of Ascl1-overexpressing MG into neuron-like cells. scRNA-seq of retinal glia following inhibition of NFkB reveals coordination with signaling via TGFbeta2 and suppression of NFI and Id transcription factors. Inhibition of Smad3 signal transducer or Id transcription factors increased numbers of neuron-like cells produced by Ascl1-overexpressing MG. We conclude that NFkB is a key signaling hub that is activated in MG after damage, mediates the accumulation of immune cells, and suppresses the neurogenic potential of MG. | Ependymoglial Cells |
Telemedicine in Armenia began with the US Telemedicine Space Bridge programme, which was introduced following the disastrous earthquake in 1988. More recently educational programmes have been established between the School of Medicine at Boston University and the Emergency Hospital in Yerevan. There are also telemedicine activities involving the Internet, for example at the Diagnostica Medical Centre in Yerevan. The future integration of telemedicine and telehealth services within the health services in Armenia will produce significant benefits. Current telemedicine activities in Armenia represent models for collaborative projects in other former Soviet republics with the aim of providing greater access to health-care at higher quality and lower cost. | Telemedicine |
Self-generated body movements have reliable visual consequences. This predictive association between vision and action likely underlies modulatory effects of action on visual processing. However, it is unknown whether actions can have generative effects on visual perception. We asked whether, in total darkness, self-generated body movements are sufficient to evoke normally concomitant visual perceptions. Using a deceptive experimental design, we discovered that waving one's own hand in front of one's covered eyes can cause visual sensations of motion. Conjecturing that these visual sensations arise from multisensory connectivity, we showed that grapheme-color synesthetes experience substantially stronger kinesthesis-induced visual sensations than nonsynesthetes do. Finally, we found that the perceived vividness of kinesthesis-induced visual sensations predicted participants' ability to smoothly track self-generated hand movements with their eyes in darkness, which indicates that these sensations function like typical retinally driven visual sensations. Evidently, even in the complete absence of external visual input, the brain predicts visual consequences of actions. | Kinesthesis |
Four new alleles at the rabbit (Oryctolagus cuniculus) mannose-6-phosphate isomerase (E.C. 5.3.1.8, MPI) locus are proposed to account for phenotypes observed after starch gel electrophoresis and enzymatic staining of red cell lysates and tissues. Population data from various wild and domestic rabbit populations are presented. | Mannose-6-Phosphate Isomerase |
Fractographic analysis of clinically failed dental ceramics can provide insights as to the failure origin and related mechanisms. One anterior 6-unit all-ceramic zirconia fixed partial denture (FPD) (Cercon) has been clinically recovered and examined using qualitative fractography. The purpose was to identify the fracture origin and to state the reasons for failure. The recovered parts of the zirconia FPD were microscopically examined to identify classic fractographic patterns such as arrest lines, hackle, twist hackle and wake hackle. The direction of crack propagation was mapped and interpreted back to the origin of failure at the interface of the occlusal-palatal tip of the core and the veneering ceramic. An inappropriate core drop design favoring localized stress concentration combined with a pore cluster in the veneering ceramic at the core tip interface were the reasons for this premature through-the-core thickness failure. | Dental Prosthesis Design |
CONTEXT: Cervical cancer screening in women younger than 30 years relies on cervical cytology because of the poor performance of human papillomavirus (HPV) DNA testing in this age group. OBJECTIVES: To determine the performance of in-cell HPV E6, E7 mRNA quantification (HPV OncoTect) for the detection of high-grade cervical intraepithelial neoplasia in women younger than 30 years. DESIGN: We analyzed 3133 cytology specimens from a screening population of women aged 19-75 years investigate HPV OncoTect as a triage/secondary screening test for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology in women younger than 30 years. Test results were compared to histology in 246 cases. RESULTS: The sensitivity of E6, E7 mRNA was 89% for CIN 2+ and 100% for CIN 3+ lesions in women 30 years and older. In women younger than 30 years, the sensitivity of E6, E7 mRNA for CIN 2+ lesions was 88% for CIN 2+ and 92% for CIN 3+ lesions. Abnormal cytology (>/=ASCUS) exhibited a sensitivity of 89% for CIN 2+ and 100% for CIN 3+ in women 30 years and older and 96% sensitivity for CIN 2+ and 93% sensitivity for CIN 3+ in women younger than 30. The specificity of E6, E7 mRNA was >80% for CIN 2+ and CIN 3+ in both groups of women compared to a specificity of abnormal cytology of <10% for CIN 2+ and CIN 3+ in both groups. CONCLUSIONS: HPV OncoTect demonstrates a performance that would be effective for ASCUS/LSIL triage in women including those younger than 30 years. | Gammapapillomavirus |
Sulfur mustard is a chemical warfare agent which was widely used during World War I and more recently in conflicts in the Middle East. This highly toxic compound causes severe dermal, gastrointestinal, respiratory and ocular injuries. It acts as an alkylating agent that induces structural changes and, hence, destruction of nucleic acids and proteins, impairing the cell's normal homeostasis and eventually causing its death. Sulfur mustard reacts rapidly with ocular tissues, and after a latent period of a few hours the patient starts suffering from severe eye pain, photophobia, excessive lacrimation and blindness. The injury, which is restricted to the anterior segment of the eye, may cause long-lasting incapacity in large numbers of casualties. Approximately 0.5% of the severely wounded victims may develop late complications which require prolonged ophthalmologic observation and therapy. In light of the ever-present threat of mustard chemical warfare against military and civilians, physicians worldwide should be aware of its grave effects and know how to care for its victims. | Mustard Gas |
Neuropsychiatric disorders represent a substantial social and health care issue. The National Institutes of Health estimates that greater than 2 million adults suffer from neuropsychiatric disorders in the USA. These individuals experience symptoms that can include auditory hallucinations, delusions, unrealistic beliefs and cognitive dysfunction. Although antipsychotic medications are available, suboptimal therapeutic responses are observed for approximately one-third of patients. Therefore, there is still a need to explore new pharmacotherapeutic strategies for the treatment of neuropsychiatric disorders. Many of the medications that are used clinically to treat neuropsychiatric disorders have a pharmacological profile that includes being an antagonist at D2-like (D2, D3 and D4) dopamine receptor subtypes. However, dopamine receptor subtypes are involved in a variety of neuronal circuits that include movement coordination, cognition, emotion, affect, memory and the regulation of prolactin. Consequently, antagonism at D2-like receptors can also contribute to some of the adverse side effects associated with the long-term use of antipsychotics including the a) adverse extrapyramidal symptoms associated with the use of typical antipsychotics and b) metabolic side effects (weight gain, hyperglycemia, increased risk of diabetes mellitus, dyslipidemia and gynecomastia) associated with atypical antipsychotic use. Preclinical studies suggest that D3 versus D2 dopamine receptor selective compounds might represent an alternative strategy for the treatment of the symptoms of schizophrenia. In this review we discuss a) how bitropic Nphenylpiperazine D3 dopamine receptor selective compounds have been developed by modification of the primary (orthosteric) and secondary (allosteric or modulatory) pharmacophores to optimize D3 receptor affinity and D2/D3 binding selectivity ratios and b) the functional selectivity of these compounds. Examples of how these compounds might be modified to develop bivalent ligands capable of interacting with receptor dimers or oligomers are also provided. Preclinical studies using bitropic D3 dopamine receptor selective ligands are also discussed as strategy to pharmacologically dissect the role of the D2 and D3 dopamine receptor subtypes in animal models of neuropsychiatric, neurological and substance abuse disorders. This research has the potential to a) advance the understanding of the role of the D2 and D3 dopamine receptor subtypes in neuropsychiatric disorders and b) lead to new treatment strategies for neuropsychiatric disorders. | Receptors, Dopamine D3 |
PURPOSE: To test whether the oxygen uptake ([Formula: see text]) plateau at [Formula: see text] is simply a calculation artifact caused by the variability of [Formula: see text] or a clearly identifiable physiological event. METHODS: Forty-six male participants performed an incremental ramp and a [Formula: see text] verification test. Variability of the difference between adjacent sampling intervals (difference) and of the slope of the [Formula: see text]-workload relationship (slope) in the submaximal intensity domain were calculated. Workload defined sampling intervals used for the calculation of the difference and slope were systematically increased from 20 to 100 W until the expected risk of false plateau diagnoses based on the Gaussian distribution function was lower than 5%. Overall, more than 1500 differences and slopes were analyzed. Subsequently, frequencies of plateau diagnoses in the submaximal and maximal intensity domains were compared. RESULTS: Variability of the difference and slope decreased with increasing sampling interval (p < 0.001). At a sampling interval of 50 W, the predefined acceptable risk of false plateau diagnoses (</= 5%) was achieved. At this sampling interval, the actual frequency (1.4%) of false-positive plateau diagnoses did not differ from the expected frequency in the submaximal intensity domain (1.6%; p = 0.491). In contrast, the actual frequency at maximal intensity (35.7%) was significantly higher compared to the submaximal intensity domain (p < 0.001) and even higher than the expected frequency of false-positive diagnoses (p < 0.001). CONCLUSION: The [Formula: see text] plateau at [Formula: see text] represents a physiological event and no calculation artifact caused by [Formula: see text] variability. However, detecting a [Formula: see text] plateau with sufficient certainty requires large sampling intervals. | Physical Conditioning, Human |
PURPOSE OF REVIEW: The objectives of this article are to review the major changes in the staging of head and neck cancers and the rationale for the modifications. RECENT FINDINGS: Information gathered from various institutional reports lead to a better understanding of the clinical and biological behavior of head and neck tumors, resulting in distinct outcomes, which were used to update the staging system. This article reviews the changes in the staging of head and neck cancers published in the 8th edition of the AJCC/UICC TNM staging system. | Medical Oncology |
This commentary is intended to start a discussion about whether people should be allowed to modify, translate, adapt or sell copyrighted questionnaires without the permission of the developer (copyright-holder). | Copyright |
The author of this essay comments on the thematic block New Medical Ethics," which appeared in the journal Drustvena istrazivanja (23-24, vol. 5, 3-4/1996), and enters upon an extended discussion on the methodological and philosophical aspects of bioethics (also called biomedical ethics and new medical ethics). The essay represents an attempt to explain the origins of the new medical ethics that is arising out of the new medical situation due to scientific-technological progress. The author distinguishes between positive and negative aspects of bioethics and reconstructs (taking into account the suppositions of Peter Singer) the structure of bioethical methods. He defines bioethics--based on the claim that it is necessarily affiliated with philosophy--as a specific, relational and multiperspectival ethics. Such an approach is formulated as an alternative to deductivist conceptions which consider bioethics as a part of applied ethics, but also as an alternative to bioethical trends (casuistry, principles of biomedical ethics, etc.) that do not permit openness to ethical and philosophical theory." | Casuistry |
Dengue is a mosquito-borne viral disease of expanding geographical range and increasing incidence. The vast majority of dengue cases are children less than 15 years of age. Dengue causes a spectrum of illness from mild fever to severe disease with plasma leakage and shock. Infants and children with secondary heterologous dengue infections are most at risk for severe dengue disease. Laboratory diagnosis of dengue can be established within five days of disease onset by direct detection of viral components in serum. After day five, serologic diagnosis provides indirect evidence of dengue. Currently, no effective antiviral agents are available to treat dengue infection. Therefore, treatment remains supportive, with emphasis on close hematological monitoring, recognition of warning signs of severe disease and fluid-replacement therapy and/or blood transfusions when required. Development of a dengue vaccine is considered a high public health priority. A safe and efficacious dengue vaccine would also be important for travelers. This review highlights the current understanding of dengue in children, including its clinical manifestations, pathogenesis, diagnostic tests, management and prevention. | Dengue |
Islet transplantation can restore lost glycemic control in type 1 diabetes subjects but is restricted in its clinical application by a limiting supply of islets and the need for heavy immune suppression to prevent rejection. TNFAIP3, encoding the ubiquitin editing enzyme A20, regulates the activation of immune cells by raising NF-kappaB signaling thresholds. Here, we show that increasing A20 expression in allogeneic islet grafts resulted in permanent survival for ~45% of recipients, and > 80% survival when combined with subtherapeutic rapamycin. Allograft survival was dependent upon Tregs and was antigen specific, and grafts showed reduced expression of inflammatory factors. Transplantation of islets with A20 containing a loss-of-function variant (I325N) resulted in increased RIPK1 ubiquitination and NF-kappaB signaling, graft hyperinflammation, and acute allograft rejection. Overexpression of A20 in human islets potently reduced expression of inflammatory mediators, with no impact on glucose-stimulated insulin secretion. Therapeutic administration of A20 raises inflammatory signaling thresholds to favor immune tolerance and promotes islet allogeneic survival. Clinically, this would allow for reduced immunosuppression and support the use of alternate islet sources." | Tumor Necrosis Factor alpha-Induced Protein 3 |
PURPOSE: Respiratory gating has been used in PET imaging to reduce the amount of image blurring caused by patient motion. Optimal binning is an approach for using the motion-characterized data by binning it into a single, easy to understand/use, optimal bin. To date, optimal binning protocols have utilized externally driven motion characterization strategies that have been tuned with population-derived assumptions and parameters. In this work, we are proposing a new strategy with which to characterize motion directly from a patient's gated scan, and use that signal to create a patient/instance-specific optimal bin image. METHODS: Two hundred and nineteen phase-gated FDG PET scans, acquired using data-driven gating as described previously, were used as the input for this study. For each scan, a phase-amplitude motion characterization was generated and normalized using principle component analysis. A patient-specific "optimal bin" window was derived using this characterization, via methods that mirror traditional optimal window binning strategies. The resulting optimal bin images were validated by correlating quantitative and qualitative measurements in the population of PET scans. RESULTS: In 53% (n = 115) of the image population, the optimal bin was determined to include 100% of the image statistics. In the remaining images, the optimal binning windows averaged 60% of the statistics and ranged between 20% and 90%. Tuning the algorithm, through a single acceptance window parameter, allowed for adjustments of the algorithm's performance in the population toward conservation of motion or reduced noise-enabling users to incorporate their definition of optimal. In the population of images that were deemed appropriate for segregation, average lesion SUV max were 7.9, 8.5, and 9.0 for nongated images, optimal bin, and gated images, respectively. The Pearson correlation of FWHM measurements between optimal bin images and gated images were better than with nongated images, 0.89 and 0.85, respectively. Generally, optimal bin images had better resolution than the nongated images and better noise characteristics than the gated images. DISCUSSION: We extended the concept of optimal binning to a data-driven form, updating a traditionally one-size-fits-all approach to a conformal one that supports adaptive imaging. This automated strategy was implemented easily within a large population and encapsulated motion information in an easy to use 3D image. Its simplicity and practicality may make this, or similar approaches ideal for use in clinical settings." | Respiratory-Gated Imaging Techniques |
Intracellular Ca(2+)-transport ATPases exert a pivotal role in the endoplasmic reticulum and in the compartments of the cellular secretory pathway by maintaining a sufficiently high lumenal Ca(2+) (and Mn(2+)) concentration in these compartments required for an impressive number of vastly different cell functions. At the same time this lumenal Ca(2+) represents a store of releasable activator Ca(2+) controlling an equally impressive number of cytosolic functions. This review mainly focuses on the different Ca(2+)-transport ATPases found in the intracellular compartments of mainly animal non-muscle cells: the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pumps. Although it is not our intention to treat the ATPases of the specialized sarcoplasmic reticulum in depth, we can hardly ignore the SERCA1 pump of fast-twitch skeletal muscle since its structure and function is by far the best understood and it can serve as a guide to understand the other members of the family. In a second part of this review we describe the relatively novel family of secretory pathway Ca(2+)/Mn(2+) ATPases (SPCA), which in eukaryotic cells are primarily found in the Golgi compartment. | Ca(2+) Mg(2+)-ATPase |
Crude rice bran oils from different rice cultivars and extraction methods bear different contents of nutraceuticals. The health benefits of lowering cholesterol activity of rice bran oil being confirmed by many reports are partly attributed to non-nutrient nutraceuticals, especially gamma-oryzanol, phytosterols, and policosanols. As the world has been facing the global warming crisis, green extraction technology is gaining attention from many sectors. The current study aims to compare the nutraceutical composition with respect to gamma-oryzanol, phytosterol, and policosanol content as well as the antioxidant properties of crude rice bran oils extracted from white and red rice bran using three green technologies, comparing with conventional hexane extraction. The data show that the traditional solvent extraction gave the highest oil yield percentage (26%), but it was not significantly different from subcritical liquefied dimethyl ether extraction (24.6%). Subcritical liquefied dimethyl ether extraction gave higher oil yield than supercritical CO(2) extraction (15.5-16.2%). The crude rice bran oil extracted using subcritical liquefied dimethyl ether extraction produced the highest total phenolic contents and antioxidant activities. The highest gamma-oryzanol content of the crude rice bran oil was found in oil extracted by conventional cold press (1370.43 mg/100 g). The gamma-oryzanol content of the oil obtained via subcritical liquefied dimethyl ether extraction was high (1213.64 mg/100 g) compared with supercritical CO(2) extraction. The red rice bran yielded the crude rice bran oil with the highest total phytosterol content compared with the white bran, and the oil from red rice bran extracted with subcritical liquefied dimethyl ether generated the highest total phytosterol content (1784.17 mg/100 g). The highest policosanol content (274.40 mg/100 g) was also found in oil obtained via subcritical liquefied dimethyl ether extraction. | Rice Bran Oil |
BACKGROUND: Although rates have declined, hysterectomy is still a frequent gynaecological procedure. To date, there has been no systematic quantification of the relationships between early/mid-life exposures and hysterectomy. We performed a systematic review and meta-analyses to quantify the associations between age at menarche, education level, parity and hysterectomy. METHODS: Eligible studies were identified by searches in PubMed and Embase through March 2015. Study-specific estimates were summarised using random effects meta-analysis. Heterogeneity was explored using sub-group analysis and meta-regression. RESULTS: Thirty-two study populations were identified for inclusion in at least one meta-analysis. Each year older at menarche was associated with lower risk of hysterectomy-summary hazard ratio 0.86 (95% confidence interval: 0.78, 0.95; I2 = 0%); summary odds ratio 0.88 (95% confidence interval: 0.82, 0.94; I2 = 61%). Low education levels conferred a higher risk of hysterectomy in the lowest versus highest level meta-analysis (summary hazard ratio 1.87 (95% confidence interval: 1.25, 2.80; I2 = 86%), summary odds ratio 1.51 (95% confidence interval: 1.35, 1.69; I2 = 90%)) and dose-response meta-analysis (summary odds ratio 1.17 (95% confidence interval: 1.12, 1.23; I2 = 85%) per each level lower of education). Sub-group analysis showed that the birth cohort category of study participants, the reference category used for level of education, the year the included article was published, quality of the study (as assessed by the authors) and control for the key variables accounted for the high heterogeneity between studies in the education level meta-analyses. In the meta-analyses of studies of parity and hysterectomy the results were not statistically significant. CONCLUSIONS: The present meta-analyses suggest that the early life factors of age at menarche and lower education level are associated with hysterectomy, although this evidence should be interpreted with some caution due to variance across the included studies. | Parity |
1. The studies were designed to investigate the changes in responsiveness to beta-adrenoceptor agonists induced by chronic administration of beta-adrenoceptor antagonists and agonists. 2. Dose-response curves for dopexamine, isoprenaline, noradrenaline and impromidine on heart rate, blood pressure and myocardial contractility (dP/dt:integrated isometric tension) were obtained in untreated dogs and compared to those measured in dogs which had been pretreated with propranolol (8 mg kg-1 day-1), atenolol (6 mg kg-1 day-1), isoprenaline (0.5 microgram kg-1 min-1) or noradrenaline (0.5 microgram kg-1 min-1) for 14 days. 3. Propranolol pretreatment significantly enhanced the inotropic and chronotropic responses to isoprenaline. There were noticeable, but non-significant increases in inotropic sensitivity to noradrenaline and dopexamine, especially at higher dose levels. In the atenolol treatment group, there were significant increases in inotropic responses to dopexamine and isoprenaline and in depressor responses to isoprenaline. 4. Thus, chronic administration of propranolol increased responses mediated by both beta 1- and beta 2-adrenoceptors, whereas, atenolol selectively enhanced the inotropic responsiveness to dopexamine, which is mediated mainly by beta 2-adrenoceptors. 5. Isoprenaline pretreatment caused a significant decrease in inotropic sensitivity to dopexamine, isoprenaline and noradrenaline and a significant reduction in chronotropic responses to dopexamine. The tendency to reduced depressor responses to isoprenaline and dopexamine failed to reach significance. Pretreatment with noradrenaline decreased only the inotropic response to noradrenaline. 6. Thus, chronic isoprenaline treatment reduced the responsiveness of both beta 1- and beta 2-adrenoceptors, while chronic noradrenaline infusion only reduced beta 1-adrenoceptor-mediated responses. 7. There was no significant change in any of the dose-response curves to impromidine after any beta-adrenoceptor antagonist or agonist treatment. This indicates that there was no non-specific alteration in responsiveness and that the observed changes were likely to be associated with specific alterations in beta-adrenoceptor number or function. | Impromidine |
The number and the pharmacological activities of drugs featuring a guanidine group is actually amazing. Many synthetic guanidine derivatives have attracted pharmacologists in search of new antihypertensive drugs for their ability to block adrenergic nerve activity through central and/or peripheral mechanisms. As a result, compounds such as guanethidine, guanabenz, guanfacine, and pinacidil have been introduced in antihypertensive drug therapy. A crude methanol extract of the Venezuelan plant Verbesina caracasana Fries (Compositae), intravenously administered to mice, was found to induce biological effects such as erection of hair, initial stimulation and subsequent blockade of breathing. Biologically controlled purification yielded a series of active guanidine derivatives, namely G1-G7, which were extensively studied with the focus on the following items: (1) The structure determination of the active compounds by spectral data and a set of reactions; (2) The confirmation of the structures by a biogenetically oriented synthesis; (3) The study of the pharmacological profiles of the isolated drugs; (4) The synthesis of analogous and homologous products in the effort to shed some light on the structure-activity relationship. The metabolites of V. caracasana were characterized, in anesthetized rats, as hypotensive drugs of high (G2), mild (G1, G7) and low (G3,G5,G6) potency, devoid of consistent actions in heart rate, and provided with moderate stimulatory effects on cardiac inotropism and breathing (at selected non-toxic intravenous doses). Autonomic neurogenic components and/or peripheral adrenergic and cholinergic receptor-related pathways were involved in the cardiovascular effects. Synthetic analogs and homologs of G1 and G5 were all shown to be hypotensive drugs of low-mild potency, not affecting appreciably cardiac inotropism and/or breathing. The pharmacodynamic differences among the studied compounds were likely to depend on their ability to cross the blood-brain barrier, lipophilicity and pharmacokinetics. Since most of the compounds did not induce reflex tachycardia and depression of myocardial contractility as the majority of the antihypertensive drugs, they might be useful in the treatment of arterial hypertension of various genesis. | Verbesina |
Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disease characterized by IgG autoantibodies to type VII collagen, a major component of anchoring fibrils. Most patients with EBA are adult and develop autoantibodies to the noncollagenous (NC) 1 domain of type VII collagen. We describe a 4-year-old Japanese boy presenting pruritic vesicles and tense blisters over his whole body. Immunofluorescence studies revealed linear IgG/C3 deposits along the dermal-epidermal junction of the patient's skin, and circulating IgG autoantibodies mapping to the dermal side of 1 M NaCl-split skin. By immunoblotting analysis using dermal extracts as a substrate, the patient's IgG antibodies labelled a 290-kDa protein corresponding to type VII collagen. Immunoblotting studies using recombinant proteins demonstrated that the patient's circulating autoantibodies recognized not only the NC1 but also the NC2 domain of type VII procollagen. Review of the previously reported cases and the present case suggested that patients with EBA with autoantibodies to regions other than the NC1 domain are all children younger than 10 years of age with clinical features of an inflammatory phenotype." | Epidermolysis Bullosa Acquisita |
Serine- and arginine-rich (SR) proteins constitute a highly conserved family of pre-mRNA splicing factors that play key roles in the regulation of splice site selection, and thereby in the control of alternative splicing processes. In addition to conserved sequences at the splice junctions, splice site selection also depends upon different sets of auxiliary cis regulatory elements known as exonic and intronic splicing enhancers (ESEs and ISEs) or exonic and intronic silencers (ESSs and ISSs). Specific binding of SR proteins to their cognate splicing enhancers as well as binding of splicing repressor to silencer sequences serve to enhance or inhibit recognition of weak splice sites by the splicing machinery. Given that the vast majority of human genes contain introns and that most pre-mRNAs containing multiple exons undergo alternative splicing, mutations disrupting or creating such auxiliary elements can result in aberrant splicing events at the origin of various human diseases. In the past few years, numerous studies have reported several approaches allowing correction of such aberrant splicing events by targeting either the mutated sequences or the splicing regulators whose binding is affected by the mutation. The aim of the present review is to highlight the different means by which it is possible to modulate the activity of SR splicing factors and to bring out those holding the greatest promises for the development of therapeutic treatments. | Aclarubicin |
Fluocinonide and halcinonide are class II topical corticosteroids that are indicated for the relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and generally are applied to affected skin at least twice daily. This pilot study compared the absorption kinetics of cream formulations of fluocinonide and halcinonide in the stratum corneum within a 9-hour period following application. A dermal tape-stripping protocol was used to quantify corticosteroid concentration at 6 sequential depths in the skin of 4 sites on the forearm. Halcinonide and fluocinonide were extracted from the strips and concentrations were measured using liquid chromatography-mass spectrometry. Results demonstrated the immediate absorption of fluocinonide and halcinonide into the stratum corneum within 1 hour of application followed by a sustained release of halcinonide and a steady decline of fluocinonide after peaking. | Fluocinonide |
Hyponatraemia is the most common electrolyte disorder seen in clinical practice and the consequences can range from minor symptoms to life-threatening complications including seizures and cardiorespiratory distress. These effects occur as a result of fluid shifts due to deranged serum tonicity and subsequent cerebral oedema. The appropriate assessment and management of patients with hyponatraemia is not always achieved in clinical practice, which is partly related to challenges in teaching with limited clinical guidance. Recently, the European Society of Endocrinology, European Society of Intensive Care Medicine and European Renal Association-European Dialysis and Transplant Association produced clinical practice guidelines to focus on appropriate investigation and management of these patients. Within this manuscript, we highlight the key points from these guidelines, which are most pertinent to doctors of all specialties to improve the care of patients with this common electrolyte disorder. | Hyponatremia |
Although orthopedic injury has been reported to be the most frequent injury associated with facial trauma, their relationship has not been sufficiently evaluated in the literature. To evaluate this relationship, we compared 263 patients with concomitant facial and orthopedic injuries with 2006 patients with facial injuries alone. The rate of associated orthopedic injuries was 11.5%. Motor vehicle accidents, falls, mandibular fractures, and Le Fort I fractures increased the chance of sustaining orthopedic injuries nearly 17-, 15-, 10-, 4.4-, and 4.5-fold, respectively. Most fractures occurred in large bones with their inherent potential to cause severe, life-threatening complications. The high rates of mortality and morbidities associated with orthopedic injuries and the frequent occurrence of these injuries in patients with facial trauma emphasize upon the fact that maxillofacial surgeons, residents, and trauma nurses need more training in early diagnosis and appropriate management of associated orthopedic injuries. | Maxillofacial Injuries |
In recent years, there has been a return to the use of electron probe X-ray microanalysis for biological studies but this has occurred at a time when the Hall programme which acted as the mainstay for biological microanalysis is no longer easily available. Commercial quantitative routines rely on the Cliff-Lorimer method that was originally developed for materials science applications. Here, the development of these two main routines for obtaining quantitative data from thin specimens is outlined and the limitations that are likely to be met when the Cliff-Lorimer routine is applied to biological specimens is discussed. The effects of specimen preparation on element content is briefly summarized and the problems encountered when using quantitative analysis on resin-embedded materials emphasized. | Electron Probe Microanalysis |
Comparison of pA2 values for antagonism of clonidine induced inhibition of the electrically evoked contraction of the rat isolated vas deferens (alpha 2-adrenoceptor) and antagonism of contractions to methoxamine on the rat isolated anococcygeus (alpha 1-adrenoceptor) showed a group of substituted benzoquinolizines (Wy 25309, 26392 and 26703) to be more potent and more selective alpha 2-adrenoceptor antagonists than yohimbine. The benzoquinolizines and yohimbine enhanced stimulation-evoked overflow of tritium from rabbit isolated pulmonary arteries preloaded with [3H]-noradrenaline, as expected for alpha 2-adrenoceptor antagonists. In contrast to the results on the rat vas deferens, yohimbine was more potent than the benzoquinolizines. At higher concentrations all the alpha-adrenoceptor antagonists reduced the stimulation-evoked contraction of the pulmonary artery. The benzoquinolizines were competitive antagonists of 5-hydroxytryptamine on the rat isolated ileum. Wy 25309 showed only weak activity (pA2 = 5.21) whereas Wy 26703 was more potent (pA2 = 7.25). Yohimbine was a potent antagonist of 5-hydroxytryptamine. Wy 26703 was the only compound to have histamine antagonist effects in the guinea pig isolated ileum and to antagonise the chronotropic effect of isoprenaline on the isolated atria of the guinea pig and in both instances activity was weak (pA2 values 5.3 and 5.5 respectively). Yohimbine reduced the spontaneous beating of the atria at 3 X 10(-6) M. No compound at 10(-5) M antagonised acetylcholine on the guinea pig ileum. These novel substituted benzoquinolizines should be useful experimental compounds for the study of alpha 2-adrenoceptor mediated responses." | 2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- |
Lampreys represent the most primitive vertebrate class of jawless fish and serve as an evolutionary model of the vertebrate visual system. Transducin-alpha (G alpha(t)) subunits were investigated in lamprey Petromyzon marinus in order to understand the molecular origins of rod and cone photoreceptor G proteins. Two G alpha(t) subunits, G alpha(tL) and G alpha(tS), were identified in the P. marinus retina. G alpha(tL) is equally distant from cone and rod G proteins and is expressed in the lamprey's long photoreceptors. The short photoreceptor G alpha(tS) is a rod-like transducin-alpha that retains several unique features of cone transducins. Thus, the duplication of the ancestral transducin gene giving rise to rod transducins has already occurred in the last common ancestor of the jawed and jawless vertebrates. | Petromyzon |
We used data from a population-based case-control study to explore the relation between certain life events during the periconceptional period and several types of congenital anomalies. We ascertained cases from pregnancies ending in 1987-1989 and randomly selected controls from eligible liveborn infants. In telephone interviews, women reported deaths of anyone close to them. They also reported job losses or separations/divorces, for themselves or anyone close to them. Experiencing at least one stressful event during the periconceptional period was associated with a prevalence odds ratio of 1.4-1.5 for the delivery of infants with conotruncal heart defects, neural tube defects, and isolated cleft lip with or without palate. These associations tended to be restricted to women who were not obese and women with less than or equal to a high school education. This study suggests that women who experience stressful life events around the time of conception or early gestation may be at increased risk of delivering infants with certain congenital anomalies." | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
A review of the literature about angio-immunoblastic lymphadenopathy since 1972 Flandrin's first description, attempts to define the main clinical, biological characteristics and clinical course of this disease. Clinically adenopathy, fever, weight loss, often hepatosplenomegaly of the appear as being constant. Hemolytic anemia and polyclonal hyperglobulinemia are the most common biological signs of this immunological disorder. In despite of spontaneous remissions, prognosis is severe. Infections complications are common and often fatal. Transformation in immunoblastic sarcoma is possible. | Immunoblastic Lymphadenopathy |
Peripheral (muscle) aspects of fatigue are well documented. However, little is known about the central aspects of fatigue that could influence, in particular, multijoint coordination. To investigate the central aspects of fatigue, we compared the multijoint kinematics of non-fatigued and fatigued individuals while sawing. Muscle fatigue was associated with decreases in sawing force and movement amplitude at the elbow whereas the basic characteristics of the saw trajectory, including the movement direction, extent and duration, remained invariant. This invariance was maintained by increasing the movement amplitude at the wrist, shoulder and trunk. The system thus takes advantage of the redundancy of the motor apparatus to maintain the endpoint trajectory despite fatigue. | Muscle Fatigue |
It can be seen that, although psychoanalytic pluralism is widespread, there is still a spirit of intolerance among the different theoretical schools. Matte Blanco's work allows us to think about these questions in a fresh way. Direct psychic experience, felt to be an indivisible whole, is characterized by the symmetrical mode (close to the unconscious) and projects itself in a multiple and decondensed manner on to the asymmetrical mode (consciousness, thought). Thus, psychical facts (for example, what the patient says and feels during the session) can be accounted for by multiple conscious representations which, however, are not mutually contradictory (e.g. in different theoretical approaches). Affective factors linked to the hope of reviving 'oceanic feelings' of fusion with a unified and unifying theory of the subject-analyst are also explored insofar as they lead to the tendency of analysts to exclude one another. | Unconscious, Psychology |
Purine nucleosides on position 9 of eukaryal and archaeal tRNAs are frequently modified in vivo by the post-transcriptional addition of a methyl group on their N1 atom. The methyltransferase Trm10 is responsible for this modification in both these domains of life. While certain Trm10 orthologues specifically methylate either guanosine or adenosine at position 9 of tRNA, others have a dual specificity. Until now structural information about this enzyme family was only available for the catalytic SPOUT domain of Trm10 proteins that show specificity toward guanosine. Here, we present the first crystal structure of a full length Trm10 orthologue specific for adenosine, revealing next to the catalytic SPOUT domain also N- and C-terminal domains. This structure hence provides crucial insights in the tRNA binding mechanism of this unique monomeric family of SPOUT methyltransferases. Moreover, structural comparison of this adenosine-specific Trm10 orthologue with guanosine-specific Trm10 orthologues suggests that the N1 methylation of adenosine relies on additional catalytic residues. | RNA, Transfer, Met |
We investigated the real-time cascade of postural, visual, and manual actions for object prehension in 38 6- to 12-month-old infants (all independent sitters) and eight adults. Participants' task was to retrieve a target as they spun past it at different speeds on a motorized chair. A head-mounted eye tracker recorded visual actions and video captured postural and manual actions. Prehension played out in a coordinated sequence of postural-visual-manual behaviors starting with turning the head and trunk to bring the toy into view, which in turn instigated the start of the reach. Visually fixating the toy to locate its position guided the hand for toy contact and retrieval. Prehension performance decreased at faster speeds, but quick planning and implementation of actions predicted better performance. | Psychomotor Performance |
Thirteen patients presenting with symptomatic pathologic variations or congenital deformities of the subtalar joint are presented. These variations included: four abnormal posterior talar processes, five patients with asymmetric subtalar joint development, and four congenital complete subtalar coalitions with a secondary ball-and-socket joint. In each case these adult patients had been unaware of the variation and had been symptom free until awakening" sprain or fracture trauma brought about symptoms. The nonoperative and operative management of these variations is reviewed." | Tarsal Joints |
The possibility that bacteria other than Geobacter species might contain genes for electrically conductive pili (e-pili) was investigated by heterologously expressing pilin genes of interest in Geobacter sulfurreducens. Strains of G. sulfurreducens producing high current densities, which are only possible with e-pili, were obtained with pilin genes from Flexistipes sinusarabici, Calditerrivibrio nitroreducens and Desulfurivibrio alkaliphilus. The conductance of pili from these strains was comparable to native G. sulfurreducens e-pili. The e-pili derived from C. nitroreducens, and D. alkaliphilus pilin genes are the first examples of relatively long (>100 amino acids) pilin monomers assembling into e-pili. The pilin gene from Candidatus Desulfofervidus auxilii did not yield e-pili, suggesting that the hypothesis that this sulfate reducer wires itself with e-pili to methane-oxidizing archaea to enable anaerobic methane oxidation should be reevaluated. A high density of aromatic amino acids and a lack of substantial aromatic-free gaps along the length of long pilins may be important characteristics leading to e-pili. This study demonstrates a simple method to screen pilin genes from difficult-to-culture microorganisms for their potential to yield e-pili; reveals new sources for biologically based electronic materials; and suggests that a wide phylogenetic diversity of microorganisms may use e-pili for extracellular electron exchange. | Deltaproteobacteria |
The Solid Phase Adsorption Toxin Tracking (SPATT) technology, first introduced in 2004, uses porous synthetic resins capable of passively adsorbing toxins produced by harmful microalgae or cyanobacteria and dissolved in the water. This method allows for the detection of toxic compounds directly in the water column and offers numerous advantages over current monitoring techniques (e.g., shellfish or fish testing and microalgae/cyanobacteria cell detection), despite some limitations. Numerous laboratory and field studies, testing different adsorbent substrates of which Diaion(®) HP20 resin appears to be the most versatile substrate, have been carried out worldwide to assess the applicability of these passive monitoring devices to the detection of toxins produced by a variety of marine and freshwater microorganisms. SPATT technology has been shown to provide reliable, sensitive and time-integrated sampling of various aquatic toxins, and also has the potential to provide an early warning system for both the occurrence of toxic microalgae or cyanobacteria and bioaccumulation of toxins in foodstuffs. This review describes the wide range of lipophilic and hydrophilic toxins associated with toxin-producing harmful algal blooms (HABs) that are successfully detected by SPATT devices. Implications in terms of monitoring of emerging toxic risks and reinforcement of current risk assessment programs are also discussed. | Water Pollutants |
Hypercholesterolemia drives the development of cardiovascular disease, the leading cause of mortality in western society. Supplementation with probiotics that interfere with cholesterol metabolism may provide a contribution to disease prevention. Lactobacillus plantarum CUL66 (NCIMB 30280) has been assessed in vitro for its ability to impact cholesterol absorption. L. plantarum CUL66 tested positive for bile salt hydrolase activity and the ability to assimilate cholesterol from culture media. RT-qPCR analysis showed that the bacterium significantly decreased the expression of Niemann-Pick C1-like 1 and ATP-binding cassette transporter-1 in polarised Caco-2 cells after 6 h exposure. Conversely, the expression of ATP-binding cassette sub-family G member (ABCG)-5 and ABCG-8, and 3-hydroxy-3-methylglutaryl-CoA reductase were significantly increased. Using a radiolabelled assay, we also observed significant reductions in the uptake and basolateral efflux of cholesterol by Caco-2 cells exposed to L. plantarum CUL66. This in vitro study identified L. plantarum CUL66 as a cholesterol lowering bacteria by highlighting its ability to beneficially regulate multiple in vitro events associated with intestinal cholesterol metabolism and provides evidence of efficacy for its inclusion in future in vivo studies. | Lactobacillus plantarum |
Conscious sedation is recommended, together with behaviour management techniques, to facilitate treatment of dental fear or dental phobia patients. In this article the authors focus on inhalation sedation by means of nitrous oxide. The procedures and indications are explained and illustrated with clinical cases. On the strength of the literature and their own experience the authors reach the conclusion that Inhalation sedation is a kind of pharmacological behaviour management and an important additional tool to increase patient cooperation. Inhalation sedation can only be performed by trained practitioners under internationally accepted safety conditions. Inhalation sedation has a future in Belgium providing the appropriate law is adapted. This technique deserves a place in the dental curriculum. | Gas Scavengers |
OBJECTIVES: The study aims to establish a peri-implant dehiscence-type bone defect in a diabetic animal model of human bone repair and to quantify the influence of diabetes on peri-implant bone regeneration. MATERIAL AND METHODS: Experimental diabetes was induced in three domestic pigs by streptozotocin. Three animals served as healthy controls. After 12 months four standardized peri-implant dehiscence bone defects were surgically created in the ramus mandibulae. The animals were sacrificed after 90 days. Samples were histologically analyzed to quantify new bone height (NBH), bone-to-implant-contact (BIC), area of newly formed bone (NFB), bone-density (BD), and bone mineralization (BM) in the prepared defect (-D) and in a local control region (-L). RESULTS: After 90 days, diabetic animals revealed a significantly lower BIC (p = 0.037) and BD (p = 0.041) in the defect area (-D). NBH and BM-D differences within the groups were not significant (p > 0.05). Significant more NFB was measured in the healthy control group (p = 0.046). In the region of local bone BIC-L was significant less in the diabetic group (p = 0.028). In the local control region BD-L and BM-L was lower in the diabetic group compared to the healthy control animals (p > 0.05). CONCLUSION: Histological evidence indicates impaired peri-implant defect regeneration in a diabetic animal model." | Maxillofacial Prosthesis Implantation |
There has been great research progress on hypertensive disorders in pregnancy (HDP) in the last few decades. Failure of placentation, especially a lack of uterine spiral artery remodeling, is the main pathological finding of HDP. Currently, members of the vascular endothelial growth factor family are used as markers for the early prediction of onset of HDP. Epidemiologic research has also shown that HDP can have effects on the next generation infants, representing a Development Origins of Health and Disease-related disease. However, the precise pathogenic mechanism and the effect of HDP on the offspring remain unclear. The group of strong pro-inflammatory molecules known as danger signals" have been shown to be released from the placental trophoblast surface and increase in the maternal circulation in HDP, which are then possibly transported into the fetal circulation. These signals, including fatty acids or adipocytokines, may alter the offspring's health in later life. Moreover, a hypoxic condition alters placental methylation, and the change may be passed onto the fetus. Although the genetic origin of the disease is still unknown, a hypothesis has been put forward that a paternal-maternal genetic conflict, mainly at imprinting lesion sites, may be a key factor for disease initiation. In particular, an imbalance in paternal and maternal factors may impede proper placentation, trophoblast invasion, decidualization or immune moderation so as to achieve better nutrition for the fetus (paternal) versus ensuring safe delivery and further pregnancy (maternal). Here, we review this research progress on HDP and focus on this novel genetic conflict concept, which is expected to provide new insight into the cause, pathophysiology, and multi-generational effects of HDP." | Maternal Inheritance |
Idiopathic pulmonary fibrosis is an interstitial lung disease of unknown etiology resulting in progressive interstitial fibrosis, with a known predilection in West Highland white terriers. In humans, computed tomography (CT) is a standard method for providing diagnostic and prognostic information, and plays a major role in the idiopathic pulmonary fibrosis staging process. Objectives of this retrospective, analytical, cross-sectional study were to establish descriptive criteria for reporting CT findings and test correlations among CT, clinical findings and survival time in West Highland white terriers with idiopathic pulmonary fibrosis. Inclusion criteria for affected West Highland white terriers were a diagnosis of idiopathic pulmonary fibrosis and available CT, bronchoscopy, bronchoalveolar lavage, echocardiography, and routine blood analysis findings. Clinically normal West Highland white terriers were recruited for the control group. Survival times were recorded for affected dogs. The main CT lung pattern and clinical data were blindly and separately graded as mild, moderate, or severe. Twenty-one West Highland white terriers with idiopathic pulmonary fibrosis and 11 control West Highland white terriers were included. The severity of pulmonary CT findings was positively correlated with severity of clinical signs (rho = 0.48, P = 0.029) and negatively associated with survival time after diagnosis (rho = -0.56, P = 0.025). Affected dogs had higher lung attenuation (median: -563 Hounsfield Units (HU)) than control dogs (median: -761 HU), (P < 0.001). The most common CT characteristics were ground-glass pattern (16/21) considered as a mild degree of severity, and focal reticular and mosaic ground-glass patterns (10/21) considered as a moderate degree of severity. Findings supported the use of thoracic CT as a method for characterizing idiopathic pulmonary fibrosis in West Highland white terriers and providing prognostic information for owners. | Idiopathic Pulmonary Fibrosis |
PURPOSE: This study aimed to develop a prediction model to identify risk factors for post-operative acute pancreatitis (POAP) in children with pancreaticobiliary maljunction (PBM) by pre-operative analysis of patient variables. METHODS: Logistic regression (LR), support vector machine (SVM), and extreme gradient boosting (XGBoost) models were established using the prospectively collected databases of patients with PBM undergoing surgery which was reviewed in the period comprised between August 2015 and August 2022, at the Children's Hospital of Soochow University. Primarily, the area beneath the receiver-operating curves (AUC), accuracy, sensitivity, and specificity were used to evaluate the model performance. The model was finally validated using the nomogram and clinical impact curve. RESULTS: In total, 111 children with PBM met the inclusion criteria, and 21 children suffered POAP. In the validation dataset, LR models showed the highest performance. The risk nomogram and clinical effect curve demonstrated that the LR model was highly predictive. CONCLUSION: The prediction model based on the LR with a nomogram could be used to predict the risk of POAP in patients with PBM. Protein plugs, age, white blood cell count, and common bile duct diameter were the most relevant contributing factors to the models." | Pancreaticobiliary Maljunction |
Rational design of modifications to the interior and exterior surfaces of virus-like particles (VLPs) for future therapeutic and materials applications is based on structural information about the capsid. Existing cryo-electron microscopy-based models suggest that the C-terminus of the bacteriophage P22 coat protein (CP) extends toward the capsid exterior. Our biochemical analysis through genetic manipulations of the C-terminus supports the model where the CP C-terminus is exposed on the exterior of the P22 capsid. Capsids displaying a 6xHis tag appended to the CP C-terminus bind to a Ni affinity column, and the addition of positively or negatively charged coiled coil peptides to the capsid results in association of these capsids upon mixing. Additionally, a single cysteine appended to the CP C-terminus results in the formation of intercapsid disulfide bonds and can serve as a site for chemical modifications. Thus, the C-terminus is a powerful location for multivalent display of peptides that facilitate nanoscale assembly and capsid modification. | Bacteriophage P22 |
Persistent infection with high-risk human papillomaviruses (HPVs) is the major risk factor associated with development of anogenital and oropharyngeal cancers. Initial infection by HPVs occurs into basal epithelial cells where viral genomes are established as nuclear episomes and persist until cleared by the immune response. Productive replication or amplification occurs upon differentiation and is dependent upon activation of the ataxia-telangiectasia mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) DNA damage repair (DDR) pathways. In addition to activating DDR pathways, HPVs must escape innate immune surveillance mechanisms by antagonizing sensors, adaptors, interferons and antiviral gene expression. Both DDR and innate immune pathways are key host mechanisms that crosstalk with each other to maintain homeostasis of cells persistently infected with HPVs. Interestingly, it is still not fully understood why some HPV infections get cleared while others do not. Targeting of these two processes with antiviral therapies may provide opportunities for treatment of cancers caused by high-risk HPVs. | Alphapapillomavirus |
RATIONALE: Ingested esophageal foreign bodies are commonly seen in adult population. In very few instances, esophageal foreign body may pass through the mucosal surface, re-epithelialize or migrate into surrounding soft tissues. PATIENT CONCERNS: A 55-year-old Chinese male was admitted to our hospital with a 10-day history chest and upper abdominal pain without dysphasia, cough or other symptoms. DIAGNOSES: We initially suspected chronic gastritis, and thoracic computed tomography and endoscopy ultrasonography (EUS) were used to identify a fish bone completely embedded within the lower esophageal wall. INTERVENTIONS: Under the EUS-guidance, we marked the foreign body using methylene blue with saline solution, which was followed by successful thoracoscopy and surgical removed of the foreign body. OUTCOMES: The patient recovered well and was discharged 1 week postoperatively. One month postoperatively, the patient was symptom free and the chest wound was complete healed. LESSONS: Our case showed that computed tomography is necessary to diagnose the esophageal foreign body, and EUS may help confirm the position of foreign body, especially those embedded in the esophageal submucosa. We advocate necessary surgery at the first accurate diagnosis in patient with esophageal foreign body when endoscopy is not possible. | Esophageal Perforation |
Potassium glutamate accumulates upon hyper-osmotic shock and serves as a temporary osmoprotectant. This salt leads to transcriptional activation of sets of genes that allow the cell to achieve long-term adaptation to high osmolarity. The current experiments show that potassium glutamate also acts as an inhibitor of bulk cellular transcription. It can do so independent of the involvement of macromolecular repressors or activators by virtue of its ability to directly inhibit RNA polymerase binding to ribosomal promoters. Thus, potassium glutamate mediates a global transcription switch by acting differentially on RNA polymerase at sets of genomic promoters that differ in their built-in direct response to this salt. | Potassium Acetate |
After having briefly reviewed the different subjective and objective procedures for interpreting Bone Marrow Biopsies from the standpoint of evaluating Bone Marrow Cellularity, the authors propose a method for overall morphological examination, controlled by a rapid evaluation by means of an integrator ocular. This simple, reliable and easily reproducible semi-subjective" technique seems useful in routine pathological diagnosis, particularly to compare successive Bone Marrow Biopsies from the same patient when treated by antimitotics, or to study the changes of the hematopoietic tissue in the area of medullary metastasis." | Bone Marrow Examination |
In an open, random, cross-over trial, 8 young healthy volunteers were given standard doses of lymecycline and doxycycline for 2 days to achieve steady state. The pharmacokinetics of each tetracycline in serum and dermal, suction blister fluid were determined after oral doses of 300 mg lymecycline or 100 mg doxycycline on the 3rd day. Serum concentrations were higher for lymecycline than for doxycycline, the difference being statistically significant from 3 to 9 h after dosing. Also blister concentrations were higher for lymecycline than for doxycycline, though the difference was not statistically significant. The serum half-life for lymecycline was close to 10 h, for doxycycline 12 h. According to our results, both lymecycline and doxycycline should be regarded as 'intermediate-acting' tetracyclines, and each should consequently be dosed twice daily. | Lymecycline |
Myasthenia gravis (MG) is a T cell-dependent antibody-mediated autoimmune neuromuscular disease. Antibodies to the nicotinic acetylcholine receptor (AChR) destroy the AChR, thus leading to defective neuromuscular transmission of electrical impulse and to muscle weakness. This unit is a practical guide to the induction and evaluation of experimental autoimmune myasthenia gravis (EAMG) in the mouse, the animal model for MG. Protocols are provided for the extraction and purification of AChR from the electric organs of Torpedo californica, or the electric ray. The purified receptor is used as an immunogen to induce autoimmunity to AChR, thus causing EAMG. The defect in neuromuscular transmission can also be measured quantitatively by electromyography. In addition, EAMG is frequently characterized by the presence of serum antibodies to AChR, which are measured by radioimmunoassay and by a marked antibody-mediated reduction in the number of muscle AChRs. AChR extracted from mouse muscle is used in measuring serum antibody levels and for quantifying muscle AChR content. Another hallmark of the disease is complement and IgG deposits located at the neuromuscular junction, which can be visualized by immunofluorescence techniques." | Myasthenia Gravis, Autoimmune, Experimental |
One hundred thirty-two children with tuberculous meningitis were admitted over a period of 1 year to the L. T. Municipal Medical College Hospital, Bombay. It was found that the most important single factor influencing the prognosis was a developing hydrocephalus. Of the 132 patients, 50 showed hydrocephalus and had to be operated. The operation markedly improved the sensorium, the vision and the neurological deficit of the patients. A plea is made for early detection and treatment of hydrocephalus. | Tuberculosis, Meningeal |
1. A simple design for partial dentures has been presented using cobalt samarium (Co5Sm) magnets as both retention and reciprocation units. 2. The magnets are totally enclosed within a thin veneer such as hard dental gold so that the magnet alloy is completely isolated from the oral and tissue fluids. 3. The magnets are arranged in attracting pairs, one member is cemented into a standing abutment tooth while the other member is processed into the denture base directly opposite. 4. Retention is positive, inconspicuous, and oral hygiene problems are minimized. | Dental Prosthesis |
Tungiasis (sand flea disease) is caused by the penetration of females of Tunga penetrans into the skin of the feet. Within 2 weeks of penetration the burrowed flea increases its volume by a factor of 2,000. This is paralleled by intense inflammation of the surrounding tissue. Acute and chronic inflammation leads to the development of painful and debilitating clinical pathology. This results in impaired physical fitness and mobility. The social implications of tungiasis-associated morbidity are multifold. Children with tungiasis are teased and ridiculed, adults feel ashamed and stigmatized. There is anecdotal evidence that tungiasis negatively affects educational achievements. Impaired mobility and physical fitness will have a negative impact on household economics. Sand flea disease is common in resource-poor communities in South America and in sub-Saharan Africa with prevalence in the general population of up to 60%. In East Africa, it has re-emerged in epidemic dimensions in recent years. Hitherto, no effective drug treatment has been at hand. Traditional treatment, i.e., the manipulation of burrowed sand fleas with blunt and inappropriate instruments may facilitate the transmission of blood-derived pathogens. Prevention is feasible through regular application of a repellent based on coconut oil. Owing to its strong association with poverty, sand flea disease would be an excellent starting point for a community-based fight against rural poverty. | Tungiasis |
BACKGROUND: Although the saphenous vein is the most commonly used conduit for coronary artery bypass surgery occlusion rates are high, with more than 50% grafts failing within 10 years. Nitric oxide, a potent vasodilator, also inhibits platelet aggregation, thrombus formation and vascular smooth muscle cell proliferation, is implicated in various vascular pathologies, including graft failure. METHODS: Saphenous veins were obtained from patients undergoing bypass surgery harvested by conventional methods and with minimal handling, using a no-touch" technique. Tissue distribution and protein expression of endothelial nitric oxide synthase was compared using immunohistochemistry and Western blot analysis. Nitric oxide generation was assessed using the citrulline assay. RESULTS: There was injury to conventional compared with no-touch vein segments, in particular to the lumenal endothelium and tunica adventitia. This injury was accompanied by an absence of endothelial nitric oxide synthase immunostaining at regions of endothelial denudation and damaged adventitial layer of conventional veins and a significant reduction (p < 0.05) in endothelial nitric oxide synthase protein expression. Furthermore, nitric oxide release from conventional tissue extracts was significantly (p < 0.05) lower than no-touch vein segments. CONCLUSIONS: Our results show that there is a reduction in endothelial nitric oxide synthase and nitric oxide release in saphenous veins harvested by conventional surgical methods compared with those prepared atraumatically. These observations may influence graft performance." | Saphenous Vein |
A key part of the ecological theory of adaptive radiation is disruptive selection during periods of sympatry. Some insight into this process might be gained by studying populations that are bimodal for dual-context traits, i.e. those showing adaptive divergence and also contributing to reproductive isolation. A population meeting these criteria is the medium ground finch (Geospiza fortis) of El Garrapatero, Santa Cruz Island, Galapagos. We examined patterns of selection in this population by relating individual beak sizes to interannual recaptures during a prolonged drought. Supporting the theory, disruptive selection was strong between the two beak size modes. We also found some evidence of selection against individuals with the largest and smallest beak sizes, perhaps owing to competition with other species or to gaps in the underlying resource distribution. Selection may thus simultaneously maintain the current bimodality while also constraining further divergence. Spatial and temporal variation in G. fortis bimodality suggests a dynamic tug of war among factors such as selection and assortative mating, which may alternatively promote or constrain divergence during adaptive radiation. | Finches |
Plant secondary (or specialized) metabolites determine multitrophic interaction dynamics. Herbivore natural enemies exploit plant volatiles for host location and are negatively affected by plant defense chemicals that are transferred through herbivores. Recent work shows that herbivore natural enemies can evolve resistance to plant defense chemicals, and that generating plant defense resistance through forward evolution enhances their capacity to prey on herbivores. Here, we discuss how this knowledge can be used to engineer better biocontrol agents. We argue that herbivore natural enemies which are adapted to plant chemistry will likely enhance the efficacy of future pest control efforts. Detailed phenotyping and field experiments will be necessary to quantify costs and benefits of optimizing chemical links between plants and higher trophic levels. | Herbivory |
The archaeolipids (lipids extracted from archaebacterias) are non saponificable molecules that form self sealed mono or bilayers (archaeosomes-ARC). Different to liposomes with bilayers made of conventional glycerophospholipids, the bilayer of ARC posses a higher structural resistance to physico chemical and enzymatic degradation and surface hydrophobicity. In this work we have compared the binding capacity of ARC exclusively made of archaeols containing a minor fraction of sulphoglycophospholipids, with that of liposomes in gel phase on M-like cells in vitro. The biodistribution of the radiopharmaceutical (99m)Tc-DTPA loaded in ARC vs that of liposomes upon oral administration to Wistar rats was also determined. The fluorescence of M-like cells upon 1 and 2h incubation with ARC loaded with the hydrophobic dye Rhodamine-PE (Rh-PE) and the hydrophilic dye pyranine (HPTS) dissolved in the aqueous space, was 4 folds higher than upon incubation with equally labeled liposomes. Besides, 15% of Rh-PE and 13 % of HPTS from ARC and not from liposomes, were found in the bottom wells, a place that is equivalent to the basolateral pocket from M cells. This fact suggested the occurrence of transcytosis of ARC. Finally, 4 h upon oral administration, ARC were responsible for the 22.3 % (3.5 folds higher than liposomes) shuttling of (99m)Tc-DTPA to the blood circulation. This important amount of radioactive marker in blood could be a consequence of an extensive uptake of ARC by M cells in vivo, probably favored by their surface hydrophobicity. Taken together, these results suggested that ARC, proven their adjuvant capacity when administered by parenteral route and high biocompatibility, could be a suitable new type of nanoparticulate material that could be used as adjuvants by the oral route. | Glyceryl Ethers |
Ladybird beetles (Coleoptera: Coccinellidae), with broad morphological diversity, wide geographic distribution and substantial agricultural significance, are a challenging group for taxonomists and phylogenetics. As a promising tool to identify and discover new species, DNA barcoding might offer significant potential for identification, taxonomy and phylogeny of ladybird beetles. In the present study, a total of 1364 COI (cytochrome C oxidase subunit I) sequences representing 128 species from 52 genera of ladybird beetles were screened for barcoding evaluation and phylogenetic analysis. Our results from the barcoding analysis revealed that COI displays a similar level of species identification efficiency (nearly 90%) either based on Kimura two-parameter (K2P) distances calculation or on simplified neighbour-joining (NJ) tree construction. The phylogenetic relationships within the family Coccinellidae was analyzed by Bayesian-inference (BI) method. The phylogenetic results confirmed the monophyly of the subfamilies Microweisinae and Coccinellinae sensu Slipinski (2007), and suggested that the subfamilies Coccidulinae, Chilocorinae and Scymninae are paraphyletic. However, the phylogenetic relationships among different subfamilies are not clearly defined and thus remain to be thoroughly studied. Overall, our study confirmed the usefulness of DNA barcoding for coccinellid species identification and phylogenetic inference. | DNA Barcoding, Taxonomic |
The myelin sheath is a multilayered membrane in the nervous system, which has unique biochemical properties. Myelin carries a set of specific high-abundance proteins, the structure and function of which are still poorly understood. The proteins of the myelin sheath are involved in a number of neurological diseases, including autoimmune diseases and inherited neuropathies. In this review, we briefly discuss the structural properties and functions of selected myelin-specific proteins (P0, myelin oligodendrocyte glycoprotein, myelin-associated glycoprotein, myelin basic protein, myelin-associated oligodendrocytic basic protein, P2, proteolipid protein, peripheral myelin protein of 22 kDa, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and periaxin); such properties include, for example, interactions with lipid bilayers and the presence of large intrinsically disordered regions in some myelin proteins. A detailed understanding of myelin protein structure and function at the molecular level will be required to fully grasp their physiological roles in the myelin sheath. | Myelin Proteolipid Protein |
Carotenoids are lipophilic isoprenoid compounds synthesized by photosynthetic organisms and some non-photosynthethic prokaryotes and fungi [...]. | Dietary Exposure |
Flavonoids are plant specialized metabolites that consist of one oxygenated and two aromatic rings. Different flavonoids are grouped according to the oxidation degree of the carbon rings; they can later be modified by glycosylations, hydroxylations, acylations, methylations, or prenylations. These modifications generate a wide collection of different molecules which have various functions in plants. All flavonoids absorb in the UV wavelengths, they mostly accumulate in the epidermis of plant cells and their biosynthesis is generally activated after UV exposure. Therefore, they have been assumed to protect plants against exposure to radiation in this range. Some flavonoids also absorb in other wavelengths, for example anthocyanins, which absorb light in the visible part of the solar spectrum. Besides, some flavonoids show antioxidant properties, that is, they act as scavengers of reactive oxygen species that could be produced after high fluence UV exposure. However, to date most reports were based on in vitro studies, and there is very little in vivo evidence of how their roles are carried out. In this review we first summarize the biosynthetic pathway of flavonoids and their characteristics, and we describe recent advances on the investigation of the role of three of the most abundant flavonoids: flavonols, flavones, and anthocyanins, protecting plants against UV exposure and high light exposure. We also present examples of how using UV-B supplementation to increase flavonoid content, is possible to improve plant nutritional and pharmaceutical values. | Sunlight |
Studied was the effect of lactoplasmin, gamma-globulin, a tissue preparation of swine embryos after Filatov, and a hyperimmune rabbit serum on the hemopoieis, the white blood picture, and the morbidity rate in calves with bronchopneumonia. It was found that these preparations influence favourably the white blood picture, the clotting time of blood, and the resistance of calves. With the test calves the morbidity rate was lower than in the controls. Best prophylactic effect was produced with use of tissue preparations and lactoplasmin. | Tissue Therapy, Historical |
Because of the pandemic of COVID-19, the federal government of Nigeria has instituted a mandatory policy requiring everyone going out in public to wear face masks. Unfortunately, the Nigeria media is awash with images of misuse and abuse of face masks by the public, government officials, and healthcare workers. Medical masks are used widely in community settings amid reported scarcity within healthcare facilities. It is observed that some people wear face masks on their chin and neck, and mask wearers give no attention to covering their mouth and nose, especially when talking. Used face masks are kept with personal belongings or disposed indiscriminately in public spaces, leading to self and environmental contamination. Inappropriate use and disposal of face masks in Nigeria could promote the spread of the novel coronavirus in the country and negate the country's efforts to contain the COVID-19 pandemic. In the implementation of the universal masking policy in Nigeria, federal and state governments ought to consider local applicability, feasibility, and sustainability, as well as identify and mitigate all potential risks and unintended consequences. Also critical is the need for intensive public sensitization and education on appropriate use and disposal of face masks in the country. | Masks |
Intracranial malignant tumors during pregnancy are rare. Primary meningeal sarcoma with leiomyoblastic differentiation during pregnancy has not been reported. We present the case of a 25-year-old woman in the third trimester of pregnancy with a large intracranial tumor destructing the parietal calvaria and invasion of soft tissues. Histological examination revealed primary meningeal sarcoma with leiomyoblastic differentiation. A gross macroscopical resection of the tumor with removal of the infiltrated parietal calvaria was performed after delivery of a healthy baby through caesarean section. A mass on the head rapidly enlarging during pregnancy should be considered for a malignancy of intracranial origin. Early radiological exams as well as tumor resection followed by staging and multimodality treatment should be urgently performed. | Leiomyoma, Epithelioid |
BACKGROUND: Vascular rings, including right aortic arch with aberrant left subclavian artery (RAA-ALSCA), double aortic arch (DAA) and pulmonary artery sling (PAS), are congenital anomalies that may cause airway and oesophageal compression. As prenatal detection has improved, literature comparing clinical outcomes of antenatally versus postnatally diagnosed cases continues to emerge. The aim is to define a statewide tertiary paediatric institution's clinical profile and outcomes of prenatal versus postnatally diagnosed isolated vascular rings. METHOD: A retrospective single-centre review of isolated RAA-ALSCA, DAA and PAS between 1 January 1999 and 31 December 2020 was conducted. Clinical characteristics, surgical and follow-up information were collected. Antenatal and postnatally diagnosed groups were compared. RESULTS: Out of 123 cases diagnosed with isolated vascular rings, 98 (79.7%) cases had RAA-ALSCA, 21 (17.1%) with DAA, 4 (3.3%) with PAS. The antenatal detection rate was 73.6% in the past decade; 20.3% had a genetic disorder, of which 48% had 22q11.21 microdeletion. Of prenatally diagnosed cases, 31.3% developed symptoms, commonly stridor and dysphagia, at a median age of 2.0 months (IQR 0.0-3.0), compared to a median age of diagnosis for the postnatal cohort of 9 months (IQR 1.0-40.7). Postnatally diagnosed cases were more likely to present with symptoms, primarily respiratory distress, than prenatally diagnosed cases (p=0.006). Fifty-nine (59) cases (50% antenatally diagnosed) required vascular ring division; 6.8% had residual symptoms following surgery. DISCUSSION: Antenatal diagnosis has improved and leads to better parental awareness and more timely, appropriate intervention. Postnatally diagnosed patients were older, more likely to be symptomatic, underwent more investigations and were commenced on more medications for symptom management prior to diagnosis. One in five cases of isolated vascular ring anomalies carried a genetic diagnosis, which has important implications on prenatal counselling and genetic testing. | Vascular Ring |
Lipoprotein(a) [Lp(a)] is a quantitative trait in human plasma. Lp(a) consists of a low-density lipoprotein and the plasminogen-related apolipoprotein(a) [apo(a)]. The apo(a) gene determines a size polymorphism of the protein, which is related to Lp(a) levels in plasma. In an attempt to gain a deeper insight into the genetic architecture of this risk factor for coronary heart disease, we have investigated the basis of the apo(a) size polymorphism by pulsed field gel electrophoresis of genomic DNA employing various restriction enzymes (SwaI, KpnI, KspI, SfiI, NotI) and an apo(a) kringle-IV-specific probe. All enzymes detected the same size polymorphism in the kringle IV repeat domain of apo(a). With KpnI, 26 different alleles were identified among 156 unrelated subjects; these alleles ranged in size from 32 kb to 189 kb and differed by increments of 5.6 kb, corresponding to one kringle IV unit. There was a perfect match between the size of the apo(a) DNA phenotypes and the size of apo(a) isoforms in plasma. The apo(a) DNA polymorphism was further used to estimate the magnitude of the apo(a) gene effect on Lp(a) levels by a sib-pair comparison approach based on 253 sib-pairs from 64 families. Intra-class correlation of log-transformed Lp(a) levels was high in sib-pairs sharing both parental alleles (r = 0.91), significant in those with one common allele (r = 0.31), and absent in those with no parental allele in common (r = 0.12). The data show that the intra-individual variability in Lp(a) levels is almost entirely explained by variation at the apo(a) locus but that only a fraction (46%) is explained by the DNA size polymorphism. This suggests further heterogeneity relating to Lp(a) levels in the apo(a) gene. | Lipoprotein(a) |
OBJECTIVES: To investigate the ratio of Crown to Chin length (CCL) to Crown-rump length (CRL) between triploid and normal fetuses at first trimester and establish a reference range of fetal CCL/CRL ratio. METHODS: Three hundred and twenty-five normal and 12 triploid fetuses were reviewed in this study. The image of fetal Crown-rump length (CRL) was acquired retrospectively. CCL and CRL were measured offline by two experienced sonographers, we obtained each averaged value of CCL and CRL as the final data for analysis. A normal range of CCL was established and CCL/CRL ratio was analyzed in normal and triploid fetuses. RESULTS: In 325 normal fetuses, CCL increased with gestational age following a linear trend from 20 mm at a CRL of 45-36 mm at a CRL of 84 mm (CCL (mm) = 3.65 + 0.38 CRL, R(2) = 0.821, P = .000). The CCL/CRL ratio decreased with gestational age from a mean of 0.46 at a CRL of 45 mm to 0.41 at a CRL of 84 mm (PML/CRL = 0.502-0.001 CRL, R(2) = 0.093, P = .000). All 12 triploid fetuses had a CCL/CRL ratio above the 95th percentile. When the 95th percentile are used as cutoff values, the detection rate, false-positive rate, and the positive likelihood ratio are 100%, 5%, and 20, respectively. CONCLUSIONS: The present study demonstrates that fetal CCL/CRL ratio can be used and effective ultrasound marker in screening for triploidy during the first trimester. | Triploidy |
In 96 patients with pleural exudates of known origin the authors assessed different cytological, biochemical and immunological parameters in the fluid and serum. In 44 patients the pleural effusions were malignant, in 26 tuberculosis, in 17 bacterial and 9 of viral nature. Statistical analysis was carried on mean values of studied parameters. The results indicate that only bacterial effusions differ significantly from the other pleural effusions. In effusions of malignant, tuberculous and viral nature the studied parameters did not differ significantly and cannot be used as differentiating criteria. | Pleural Effusion |
Linear accelerator workloads for each available photon energy are important quantities to know for radiation safety considerations, and presented is a technique to measure the workload using paired detectors. The signals from the two detectors can give sufficient information to separate the signal contributions from 6 and 18 MV photon fields and, combined with a signal-per-monitor-unit calibration factor, yields the number of monitor units delivered for each energy. CR-39 NTD is a neutron detector chosen for its ability to discriminate between 6 MV and 18 MV radiation fields. TLD-100 is a detector responsive to both 6 MV and 18 MV fields. These appeared to be a good choice for a detector pair. This experiment had both failures and successes to report. The CR-39 NTD and TLD-100 were not a successful pairing. The CR-39 NTD signals saturated under this experiment's exposure conditions. The TLD-100 had a combination of detector noise and detector sensitivity that made extracting the 6 MV signal from the total signal impractical, unless the total exposure was overwhelmingly 6 MV. Nevertheless, the TLD-100 proved to be excellent for determining workloads when it was exposed to a single energy with 1% accuracy and 3% precision. The theory and data analysis showed the importance of understanding the noise contributions for the more general problem of pairing any two detector types. This experiment indicated the TLD-100 could be an excellent detector choice if paired with a suitable second detector. | Thermoluminescent Dosimetry |
IMPORTANCE: Almost 1 in 4 women older than 65 years is unable to walk 2 to 3 blocks, and mobility disability is a key factor associated with loss of independence. Lack of moderate to vigorous-intensity physical activity is associated with mobility disability, but whether lighter physical activity is associated with mobility disability is unknown. OBJECTIVE: To determine the association of light-intensity physical activity and incident mobility disability among older women. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included women enrolled in the Objectively Measured Physical Activity and Cardiovascular Health study, an ancillary study of the Women's Health Initiative, between March 2012 and April 2014, with follow-up through March 31, 2018. The Women's Health Initiative was a population-based, multisite study that recruited from 40 clinical sites across the US. Participants in the present analysis included 5735 of 7058 ambulatory, community-dwelling women aged 63 years and older who returned an accelerometer with usable data, were free of mobility disability, and had follow-up data on mobility status. Data were analyzed from August 2018 to May 2019. EXPOSURES: Light-intensity physical activity, defined as movement requiring energy expenditure between 1.6 and 2.9 metabolic equivalents, captured using an accelerometer over 7 days. MAIN OUTCOMES AND MEASURES: Incident mobility disability, defined as the first self-reported inability to walk 1 block or up a flight of stairs at annual follow-up, and persistent incident mobility disability, defined as incident mobility loss that persisted through the end of follow-up. RESULTS: A total of 5735 participants were included for primary analysis of all incident mobility disability (mean [SD] age, 78.5 [6.6] years [range, 63-97 years]; 2811 [49.0%] White participants). Compared with women in the lowest quartile of light-intensity physical activity, lower risk of incident mobility disability was observed in quartile 2 (multivariable hazard ratio [HR], 0.78; 95% CI, 0.67-0.90), quartile 3 (HR, 0.60; 95% CI, 0.51-0.71), and quartile 4 (HR, 0.60; 95% CI, 0.51-0.71) (P < .001). This beneficial association was stronger for persistent mobility disability in quartile 2 (multivariable HR, 0.72; 95% CI, 0.60-0.85), quartile 3 (HR, 0.55; 95% CI, 0.46-0.67), and quartile 4 (HR, 0.52; 95% CI, 0.42-0.63) (P < .001). Stratified analyses showed the association was stronger among women with a body mass index of less than 30.0 (HR, 0.73; 95% CI, 0.66-0.82) compared with women with a body mass index of 30.0 or higher (HR, 0.91; 95% CI; 0.79-1.04; P = .04 for interaction). CONCLUSIONS AND RELEVANCE: In this cohort study, increased time spent in light-intensity physical activity was associated with reduced incident mobility disability. These findings support placing greater emphasis on promoting light-intensity physical activity for preserving mobility in later life. | Metabolic Equivalent |
Anastomotic leakage (AL) remains one of the most severe complications following colorectal cancer (CRC) surgery. Indeed, leaks that may occur after any type of intestinal anastomosis are commonly associated with a higher reoperation rate and an increased risk of postoperative morbidity and mortality. At first, our review aims to identify specific preoperative, intraoperative and perioperative factors that eventually lead to the development of anastomotic dehiscence based on the current literature. We will also investigate the role of several biomarkers in predicting the presence of ALs following colorectal surgery. Despite significant improvements in perioperative care, advances in surgical techniques, and a high index of suspicion of this complication, the incidence of AL remained stable during the last decades. Thus, gaining a better knowledge of the risk factors that influence the AL rates may help identify high-risk surgical patients requiring more intensive perioperative surveillance. Furthermore, prompt diagnosis of this severe complication may help improve patient survival. To date, several studies have identified predictive biomarkers of ALs, which are most commonly associated with the inflammatory response to colorectal surgery. Interestingly, early diagnosis and evaluation of the severity of this complication may offer a significant opportunity to guide clinical judgement and decision-making. | Anastomotic Leak |
Upon pathogen invasion, bacteria and archaea activate an RNA-interference-like mechanism termed CRISPR (clustered regularly interspaced short palindromic repeats). A large family of Cas (CRISPR-associated) proteins mediates the different stages of this sophisticated immune response. Bioinformatic studies have classified the Cas proteins into families, according to their sequences and respective functions. These range from the insertion of the foreign genetic elements into the host genome to the activation of the interference machinery as well as target degradation upon attack. Cas7 family proteins are central to the type I and type III interference machineries as they constitute the backbone of the large interference complexes. Here we report the crystal structure of Thermofilum pendens Csc2, a Cas7 family protein of type I-D. We found that Csc2 forms a core RRM-like domain, flanked by three peripheral insertion domains: a lid domain, a Zinc-binding domain and a helical domain. Comparison with other Cas7 family proteins reveals a set of similar structural features both in the core and in the peripheral domains, despite the absence of significant sequence similarity. T. pendens Csc2 binds single-stranded RNA in vitro in a sequence-independent manner. Using a crosslinking - mass-spectrometry approach, we mapped the RNA-binding surface to a positively charged surface patch on T. pendens Csc2. Thus our analysis of the key structural and functional features of T. pendens Csc2 highlights recurring themes and evolutionary relationships in type I and type III Cas proteins. | Thermofilaceae |
The United States Internal Revenue Service (IRS) and some states require nonprofit hospitals to demonstrate that they provide a substantial community benefit in order to get or maintain their tax-exempt status. This places every nonprofit hospital at risk. This article is about certain common factors that impact the management of all nonprofit hospitals and their ability to comply with such laws. | Capital Expenditures |
Electroconvulsive therapy (ECT) remains an important treatment of geriatric patients. ECT treats severe depression, mania, psychosis, catatonia, and comorbid depression and agitation in dementia. ECT also serves a crucial role in treating urgent illness requiring expedient recovery, such as catatonia, or in patients with severe suicidal ideation or intent. ECT is even more effective in the elderly than in mixed-age adult populations. ECT is a safe treatment option with few medical contraindications. Cognitive effects are largely transient, even in patients with preexisting cognitive impairment. | Geriatric Psychiatry |
In trypanosomatid protozoa, all mRNAs obtain identical 5'-ends by trans-splicing of the 5'-terminal 39 nucleotides of a small spliced leader RNA to appropriate acceptor sites in pre-mRNA. Although this process involves spliceosomal small nuclear (sn) RNAs, it is thought that trypanosomatids do not contain a homolog of the cis-spliceosomal U1 snRNA. We show here that a trypanosomatid protozoon, Crithidia fasciculata, contains a novel small RNA that displays several features characteristic of a U1 snRNA, including (i) a methylguanosine cap and additional 5'-terminal modifications, (ii) a potential binding site for common core proteins that are present in other trans-spliceosomal ribonucleoproteins, (iii) a U1-like 5'-terminal sequence, and (iv) a U1-like stem/loop I structure. Because trypanosomatid pre-mRNAs do not appear to contain cis-spliced introns, we argue that this previously unrecognized RNA species is a good candidate to be a trans-spliceosomal U1 snRNA. | RNA, Nuclear |
STUDY DESIGN: A systematic review reporting on the efficacy of an ERAS protocol in patients undergoing spinal fusion for AIS. OBJECTIVE: To systematically evaluate the relevant literature pertaining to the efficacy of ERAS protocols with respect to the length of stay, complication, and readmission rates in patients undergoing posterior spinal corrective surgery for AIS. ERAS is a multidisciplinary approach aimed at improving outcomes of surgery by a specific evidence-based protocol. The rationale of this rapid recovery regimen is to maintain homeostasis so as to reduce the postoperative stress response and pain. No thorough review of available information for its use in AIS has been published. METHODS: A systematic review of the English language literature was undertaken using search criteria (postoperative recovery AND adolescent idiopathic scoliosis) using the PRISMA guidelines (Jan 1999-May 2020). Isolated case reports and case series with < 5 patients were excluded. Length of stay (LOS), complication and readmission rates were used as outcome measures. Statistical analysis was done using the random effects model. RESULTS: Of a total of 24 articles, 10 studies met the inclusion criteria (9 were Level III and 1 of level IV evidence) and were analyzed. Overall, 1040 patients underwent an ERAS-type protocol following posterior correction of scoliosis and were compared to 959 patients following traditional protocols. There was a significant reduction in the length of stay in patients undergoing ERAS when compared to traditional protocols (p < 0.00001). There was no significant difference in the complication (p = 0.19) or readmission rates (p = 0.30). Each protocol employed a multidisciplinary approach focusing on optimal pain management, nursing care, and physiotherapy. CONCLUSION: This systematic review demonstrates advantages with ERAS protocols by significantly reducing the length of stay without increasing the complications or readmission rates as compared to conventional protocols. However, current literature on ERAS in AIS is restricted largely to retrospective studies with non-randomized data, and initial cohort studies lacking formal control groups. LEVEL OF EVIDENCE: 3." | Enhanced Recovery After Surgery |
Research indicates that anxiety before surgical intervention in paediatric patients negatively affects on post hospital recovery. Numerous investigations are, therefore, conducted to alleviate anxiety through different psychological techniques at this critical moment that the child is undergoing in surgery. In our case, we have considered one of the resources of the Sant Joan de Deu Hospital: a voluntary team that works in the anteroom of the operating theatre to keep the children company. The aim of our research has been to train these volunteers (who previously did not have any specific training for their task) and to observe the effect on the children's anxiety. The subjects of our study were 140 boys and girls between the ages of 0 and 18 years old. Results indicate that training not only produces significative changes on volunteers' behaviour, but also has resulted in the children's presurgical anxiety behaviour. In this way, we recommend that all children be accompanied by a trained volunteer. | Hospital Volunteers |
Recent decades provide mounting evidence for the continual increase in global temperatures, now termed global warming," to the point of drastic worldwide change in the climate. Climatic change is a long-term shift in temperatures and weather patterns, including increased frequency and intensity of extreme environmental events such as heat waves accompanied by extreme temperatures and high humidity. Climate change and global warming put several challenges to the livestock industry by directly affecting the animal's production, reproduction, health, and welfare. The broad impact of global warming, and in particular heat stress, on-farm animals' performance has been comprehensively studied. It has been estimated that the US livestock industry's loss caused by heat stress is up to $2.4 billion annually. However, the long-term intergenerational and transgenerational effects of climatic change and global warming on farm animals are sparse. Transgenerational effects, which are mediated by epigenetic mechanisms, can affect the animal's performance regardless of its immediate environment by altering its phenotypic expression to fit its ancestors' environment. In many animal species, environmental effects are epigenetically encoded within a narrow time interval during the organism's gametogenesis, and these epigenetic modifications can then be intergenerationally transmitted. Several epigenetic mechanisms mediate intergenerational transmission of environmental effects, typically in a parent-dependent manner. Therefore, exposure of the animal to an extreme climatic event and other environmental stressors during gametogenesis can undergo epigenetic stabilization in the germline and be passed to the offspring. As a result, the offspring might express a phenotype adjusted to fit the stressors experienced by their ancestors, regardless of their direct environment. The purpose of this perspective is to review current evidence for intergenerational and transgenerational transmission of environmental stress effects, specifically in the context of global warming and climate change, and to offer viewpoints on the possible impacts on the livestock industry." | Climatic Processes |
The first asymmetric total synthesis of the marine natural product apratoxin D, a highly potent inhibitor of H-460 human lung cancer cell growth (IC(50) value of 2.6 nM), is described. Asymmetric N-amino cyclic carbamate (ACC) alpha,alpha-bisalkylation was utilized to establish the isolated C-37 methyl group with excellent selectivity. Other key asymmetric transformations employed were an Evans syn-aldol and a Paterson anti-aldol, both of which also proceeded with excellent stereoselectivity. | Depsipeptides |
Dehydroepiandrosterone (DHEA) is a metabolic intermediate in the biosynthesis of estrogens and androgens with a past clouded in controversy and bold claims. It was once touted as a wonder drug, a fountain of youth that could cure all ailments. However, in the 1980s DHEA was banned by the FDA given a lack of documented health benefits and long-term use data. DHEA had a revival in 1994 when it was released for open market sale as a nutritional supplement under the Dietary Supplement Health and Safety Act. Since that time, there has been encouraging research on the hormone, including randomized controlled trials and subsequent meta-analyses on various conditions that DHEA may benefit. Bone health has been of particular interest, as many of the metabolites of DHEA are known to be involved in bone homeostasis, specifically estrogen and testosterone. Studies demonstrate a significant association between DHEA and increased bone mineral density, likely due to DHEA's ability to increase osteoblast activity and insulin like growth factor 1 (IGF-1) expression. Interestingly, IGF-1 is also known to improve fracture healing, though DHEA, a potent stimulator of IGF-1, has never been tested in this scenario. The aim of this review is to discuss the history and mechanisms of DHEA as they relate to the skeletal system, and to evaluate if DHEA has any role in treating fractures. | Androstenes |
This analysis of interviews with Dutch oncologists investigates the outcomes of second-opinion requests for physician-patient and physician-colleague relationships. | Oncologists |
We describe a patient with pituitary apoplexy causing sudden visual loss and light-near dissociation of the pupils but minimal ophthalmoplegia. Good visual recovery occurred despite an 8-day delay in neurosurgical treatment. | Adenoma, Chromophobe |
The autopsy--as the lesson of death--should be an integrated constituent of our affairs of health services. Beside its task for teaching and training as well as the post-autopsy follow-up with families, the autopsy plays a vital role for the quality assessment and the health statistics as the basis for the health care policy. By the introduction of the DRG system (diagnosis related groups), as a lump sum based charging system of inpatients regardless of diagnostic procedures and therapy and the equalization of costs for similar services calculations, should also include the costs of autopsy. The quality assurance is garanteed and independently attained by the autopsy service. Moreover, this is the only way to overcome the danger of abolishing essential diagnostic and therapeutic procedures because of economic pressure. However, the impact of the autopsy service is widely neglected. Therefore, widespread information about this matter in the medical profession, in the general public and in politics is mandatory. | Autopsy |
PURPOSE OF REVIEW: Advances in the field of intestinal failure continue to reduce mortality rates of this complex syndrome. Over the last 20 months (January 2021- October 2022), several important papers were published that relate to the nutritional and medical management of intestinal failure and rehabilitation. RECENT FINDINGS: New reports on the epidemiology of intestinal failure have shown that short bowel syndrome (SBS) remains the most common cause of intestinal failure worldwide in both adults and children. Advances in the provision of parenteral nutrition (PN), the advent of Glucagon-like peptide-2 (GLP-2) analogs, and the development of interdisciplinary centers have allowed for safer and longer courses of parenteral support. Unfortunately, rates of enteral anatomy continue to lag behind these advancements, requiring greater focus on quality of life, neurodevelopmental outcomes, and management of sequalae of long-term PN such as Intestinal Failure Associated Liver Disease (IFALD), small bowel bacterial overgrowth (SBBO), and Metabolic Bone Disease (MBD). SUMMARY: There have been significant advances in the nutritional and medical approaches in intestinal failure, including advances in PN, use of GLP-2 analogs, and key developments in the medical management of this condition. As children with intestinal failure increasingly survive to adulthood, new challenges exist with respect to the management of a changing population of patients with SBS. Interdisciplinary centers remain standard of care for this complex patient population. | Intestinal Failure |
OBJECTIVES: The objectives of this study were to compare the amount of fluoride delivered via a topical application of 38% silver diamine fluoride (SDF) solution and 5% sodium fluoride (NaF) varnish as well as to determine the amount of 38% SDF solution delivered using various micro-applicators. METHODS: The weights of 38% SDF (Saforide) and 5% NaF (Duraphat) applied to the occlusal surface of an extracted human upper first premolar with a regular-size (2.50-mm tip diameter) micro-applicator were measured using an electronic-analytical balance. Afterwards, the weight of 38% SDF applied to a premolar using the micro-applicators of 5 common brands (Premium Plus, 3M, Dentsply, Elevate Oral Care, and SDI) were studied. The tip diameter of each micro-applicator was measured under a microscope. The weights of the delivered fluoride and silver were also calculated. RESULTS: The mean weights of the fluoride delivered via the SDF solution and NaF varnish were 0.25 +/- 0.07 mg and 0.49 +/- 0.08 mg, respectively (P < .001). In addition, the tip diameters of the micro-applicators ranged from 1.89 +/- 0.03 mm to 2.76 +/- 0.02 mm. The mean weights of the fluoride delivered per application of 38% SDF using different applicators ranged from 0.13 +/- 0.06 mg to 0.30 +/- 0.09 mg, whereas the mean weights of the silver ranged from 0.76 +/- 0.32 mg to 1.68 +/- 0.50 mg. The weights of the delivered 38% SDF solution varied with the brand and with the tip diameters of the dental micro-applicators (P < .001). CONCLUSIONS: The fluoride of the 38% SDF solution delivered topically was significantly less than that of 5% NaF varnish. Moreover, the amount of SDF solution delivered depends on the brand and size of the micro-applicators. | Hydrofluoric Acid |
The contribution of the two major cytosolic chaperone systems, Hsp70 and the cylindrical chaperonins, to cellular protein folding has been clarified by a number of recent papers. These studies found that, in vivo, a significant fraction of newly synthesized polypeptides transit through these chaperone systems in both prokaryotic and eukaryotic cells. The identification and characterization of the cellular substrates of chaperones will be instrumental in understanding how proteins fold in vivo. | Prokaryotic Cells |
BACKGROUND: Cortex Phellodendri (C. Phellodendri), the dried trunk bark of Phellodendron amurense Ruprecht, has been known as a traditional herbal medicine, showing several bioactivities. However, antiviral activity of C. Phellodendri aqueous extract (CP) not reported in detail, particularly aiming the prophylactic effectiveness. METHODS: In vitro CP antiviral activity evaluated against Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Newcastle Disease Virus (NDV), Herpes Simplex Virus (HSV), Coxsackie Virus (H3-GFP) and Enterovirus-71 (EV-71) infection on immune (RAW264.7) and epithelial (HEK293T/HeLa) cells. Such antiviral effects were explained by the induction of antiviral state which was determined by phosphorylation of signal molecules, secretion of IFNs and cytokines, and cellular antiviral mRNA expression. Furthermore, Compounds present in the aqueous fractions confirmed by HPLC analysis and evaluated their anti-viral activities. Additionally, in vivo protective effect of CP against divergent influenza A subtypes was determined in a BALB/c mouse infection model. RESULTS: An effective dose of CP significantly reduced the virus replication both in immune and epithelial cells. Mechanically, CP induced mRNA expression of anti-viral genes and cytokine secretion in both RAW264.7 and HEK293T cells. Furthermore, the main compound identified was berberine, and shows promising antiviral properties similar to CP. Finally, BALB/c mice treated with CP displayed higher protection levels against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). CONCLUSION: CP including berberine play an immunomodulatory role with broad spectrum antiviral activity, due to induction of antiviral state via type I IFN stimulation mechanism. Consequently, C. Phellodendri could be a potential source for promising natural antivirals or to design other antiviral agents for animal and humans. | Phellodendron |
Oxygen utilization by the autotrophic nitrifiers Nitrosomonas and Nitrobacter was studied. Experimental evidence is presented which reflects the effect of carbon dioxide fixation on overall oxygen utilization in autotrophic nitrification. Measurement of dissolved oxygen and inorganic nitrogen changes indicates that oxygen-nitrogen ratios in inorganic nitrogen oxidation are equal to 3.22 parts (expressed in milligrams per liter) of oxygen per part of ammonia nitrogen oxidized to nitrite nitrogen and 1.11 parts of oxygen per part of nitrite nitrogen oxidized to nitrate nitrogen. These values rather than the stoichiometric ratios should be used in nitrogenous oxygen demand calculations. | Nitrosomonadaceae |
N,N',N -triethylenethiophosphoramide (thioTEPA) is a trifunctional alkylating agent with a broad spectrum of antitumour activity developed in the 1950s. The drug is now experiencing renewed interest as it appears to be one of the most effective anticancer drugs in high dose regimens. Despite many years of experience with thioTEPA, pharmacologic data are incomplete and controversy remains with respect to the dose-dependent pharmacokinetics of thioTEPA. In recent years greater insight has been obtained into the metabolism of thioTEPA, but there is still a gap between the total urinary excretion of thioTEPA and metabolites and the alkylating activity. In vivo and in vitro studies show that alkylation of DNA by thioTEPA can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action. The currently available sensitive analytical methods for thioTEPA and its metabolites can be used to elucidate the many questions that still exist even so many years after its introduction. An overview is given of the chemistry, pharmacology, clinical use and toxicity of thioTEPA as well as its pharmacokinetics and analytical methods for thioTEPA and its metabolites." | Phosphoramides |
PURPOSE: As a result of multilateral migration and globalization in times of humanitarian crises, western countries face a possible increase in the incidence of central nervous system tuberculosis (CNS TB). The diagnosis of CNS TB is challenging and often delayed due to the manifold and often non-specific presentation of the disease. The aim of this review is to analyze and summarize imaging features and correlated clinical findings of CNS TB. METHODS: The different manifestations of CNS TB are explained and illustrated by characteristic neuroradiological as well as neuropathological findings. An overview on diagnostic and therapeutic approaches is provided. For clarity, tables summarizing the lesion patterns, differential diagnoses and diagnostic hints are added. RESULTS: The CNS TB can be manifested (1) diffuse as tuberculous meningitis (TBM), (2) localized as tuberculoma or (3) tuberculous abscess or (4) in extradural and intradural spinal infections. Information on clinical presentation, underlying pathology and the distinguishing features is demonstrated. The TBM is further described, which may lead to cranial nerve palsy, hydrocephalus and infarction due to associated arteritis of the basal perforators. The differential diagnoses are vast and include other infections, such as bacterial, viral or fungal meningoencephalitis, malignant causes or systemic inflammation with CNS. Complicating factors of diagnosis and treatment are HIV coinfection, multi-drug resistance and TB-associated immune reconstitution inflammatory syndrome (IRIS). CONCLUSIONS: Neurologists and (neuro-)radiologists should be familiar with the neuroradiological presentation and the clinical course of CNS TB to ensure timely diagnosis and treatment." | Tuberculosis, Central Nervous System |
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