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pubmed_832_18368 | OBJECTIVES
To determine the association between ABO/Rh-D blood types and susceptibility to SARS-CoV-2 infection in Pakistan.
METHODS
In this cross-sectional study, 1935 confirmed cases of COVID-19 were included using consecutive sampling. Age and gender-matched sample of 1935 blood donors was used as a comparison group. Chi-square test and binary logistic regression were used for inferential statistics.
RESULTS
Significantly higher proportion of blood type-B was observed in COVID-19 group (35.9% vs 31.9%, p=0.009). Blood type-AB was found more frequently (14.2% vs 11.8%, p=0.03) in the comparison group. The Rh-D Positive blood types were 93.3% in COVID-19 group and 94.9% in comparison group (p=0.03). The odds of blood type-B, AB and Rh-D positive to test positive for SARS-CoV-2 were 1.195 (95% CI 1.04 - 1.36, p=0.009), 0.80 (95% CI 0.66 - 0.97, p=0.03) and 0.75 (95% CI 0.57- 0.98, p = 0.03), respectively. Blood types A and O did not have significant association with SARS-CoV-2 PCR result (p = 0.22 and 0.88, respectively).
CONCLUSIONS
There is significant association between blood types B & AB and susceptibility to COVID-19. There is no association between blood types A and O with COVID-19. Rh- D positive blood types are less susceptible to COVID-19. | 10.12669/pjms.37.1.3655 |
pubmed_588_3054 | We investigated variation in the gene encoding the agouti signaling protein (ASIP) in relation to coat color evolution in primates. We found little evidence that mutations in the coding region of ASIP have been involved in color changes among closely related primate species. Among many closely related species with differing coat color, the coding region of ASIP was identical. In two cases (Sulawesi macaque and black lion tamarin) where species with almost completely black coat color had derived point mutations in exon 4 of the ASIP coding sequence, the same mutations did not alter coloration in other mammals and so probably do not affect ASIP function. Evolutionary reconstructions of two key phenotypes that are typically related to ASIP function--transverse phaeomelanin bands on hairs and pale ventral coloration--showed that these usually evolved concurrently, suggesting that loci acting downstream of ASIP may be involved. Analysis of dN/dS ratios revealed a likely change in functional constraint on ASIP following loss of agouti-banded hairs + pale ventral coloration, particularly in catarrhine primates (humans, apes, and Old World monkeys). Together with previous results on a lack of association of coat color with MC1R variation, these results suggest that other loci probably have an important role in primate coat color evolution. | 10.1007/s00335-006-0056-0 |
pubmed_560_5167 | Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical and nonmedical settings for opioid detoxification and other substance use indications. All available autopsy, toxicological, and investigative reports were systematically reviewed for the consecutive series of all known fatalities outside of West Central Africa temporally related to the use of ibogaine from 1990 through 2008. Nineteen individuals (15 men, four women between 24 and 54 years old) are known to have died within 1.5-76 h of taking ibogaine. The clinical and postmortem evidence did not suggest a characteristic syndrome of neurotoxicity. Advanced preexisting medical comorbidities, which were mainly cardiovascular, and/or one or more commonly abused substances explained or contributed to the death in 12 of the 14 cases for which adequate postmortem data were available. Other apparent risk factors include seizures associated with withdrawal from alcohol and benzodiazepines and the uninformed use of ethnopharmacological forms of ibogaine. | 10.1111/j.1556-4029.2011.02008.x |
pubmed_539_2920 | Dyslipidemia is a significant risk factor for the progression of cardiovascular disease, particularly when associated with other risk factors. An understanding of the pathophysiology and risks for patients with atherosclerotic diseases of undertreated dyslipidemia is essential for the healthcare provider. In this article, a review of epidemiologic data regarding the role of lipid levels in cardiovascular disease prognosis is presented. A familiarity with current dietary and drug treatment of lipid disorders is at the core of an evidence-based approach to dyslipidemia management in the patient with established cardiovascular diseases. | 10.1097/00044067-200102000-00006 |
pubmed_265_21476 | The final color of all-ceramic restorations is mainly dependent on the light-transmission characteristics of the different components of the ceramic material. This article is a report on the improvement in light reflection and light transmission possible with the new In-Ceram Spinell crown system, which provides a natural-looking appearance. | pubmed_265_21476 |
pubmed_759_8617 | Crohn's disease not only affects the gastrointestinal tract but also causes skeletal complications. Arthritis and ankylosing spondylitis are among the best known of these, while periostal new bone formation in patients with Crohn's disease is rare. A report is presented on a patient who developed this complication after Crohn's disease of many year's standing. | pubmed_759_8617 |
pubmed_386_11127 | In the present study, we describe the synthesis and physicochemical properties of a novel pH- and thermoresponsive micellar drug delivery system for an anticancer ellipticinium derivative based on the triblock copolymer poly(ethylene oxide)-block-[tert-butylacrylamide-co-6-(N-methacryloylamino)hexanoic acid hydrazide]-block-poly(ethylene oxide). The system was designed to meet the basic criteria required for drug carrier systems, namely, solubility in water (overcoming the insolubility of ellipticine), satisfactory drug loading, particle size suitable for an efficient enhanced permeability and retention effect and adequate stability in blood plasma (pH 7.4) followed by rapid drug release in tumors or tumor cell endosomes (pH<6.5). The copolymer in the form of a unimer can be eliminated by kidneys because the weight-average molecular weight of 21 kDa is sufficiently below the renal threshold. The half-life of drug release in a pH 5.0 buffer solution (pH of a late endosome) was ~45 h, but a negligible amount of the free ellipticine derivative was detected at pH 7.4 (pH of blood). Consequently, this supramolecular polymer conjugate is a good candidate for the delivery of ellipticine-based drugs and will therefore be subjected to more detailed studies. | pubmed_386_11127 |
pubmed_905_21666 | BACKGROUND
The release of the Center for Medicare and Medicaid Service's (CMS) latest quality measure, Severe Sepsis/Septic Shock Early Management Bundle (SEP-1), has intensified the long-standing debate over optimal care for severe sepsis and septic shock. Although the last decade of research has demonstrated the importance of comprehensive bundled care in conjunction with compliance mechanisms to reduce patient mortality, it is not clear that SEP-1 achieves this aim. The heterogeneous and often cryptic presentation of severe sepsis and septic shock, along with the multifaceted criteria for the definition of this clinical syndrome, pose a particular challenge for fitting requirements to this disease, and implementation could have unintended consequences.
OBJECTIVE
Following a simulated reporting exercise, in which 50 charts underwent expert review, we aimed to detail the challenges of, and offer suggestions on how to rethink, measuring performance in severe sepsis and septic shock care.
DISCUSSION
There were several challenges associated with the design and implementation of this measure. The ambiguous definition of severe sepsis and septic shock, prescriptive fluid volume requirements, rigid reassessment, and complex abstraction logic all raise significant concern.
CONCLUSIONS
Although SEP-1 represents an important first step in requiring hospitals to improve outcomes for patients with severe sepsis and septic shock, the current approach must be revisited. The volume and complexity of the currently required SEP-1 reporting elements deserve serious consideration and revision before they are used as measures of accountability and tied to reimbursement. | 10.1016/j.jemermed.2016.08.009 |
pubmed_101_10028 | In the past decade, policy-makers in science have been concerned with harmonizing research integrity standards across Europe. These standards are encapsulated in the European Code of Conduct for Research Integrity. Yet, almost every European country today has its own national-level code of conduct for research integrity. In this study we document in detail how national-level codes diverge on almost all aspects concerning research integrity-except for what constitutes egregious misconduct. Besides allowing for potentially unfair responses to joint misconduct by international collaborations, we argue that the divergences raise questions about the envisaged self-regulatory function of the codes of conduct. | 10.1111/bioe.12851 |
pubmed_592_4299 | To evaluate the possible role of catalase in gastric ethanol metabolism in rats, we studied acetaldehyde formation from ethanol by gastric mucosal homogenate under various in vitro conditions. Homogenized rat gastric mucosa produced significant amounts of acetaldehyde in a time and ethanol concentration-dependent manner, even in the absence of added NAD. Both acetaldehyde formation and catalase activity peaked around the physiological pH, whereas alcohol dehydrogenase (ADH) activity was in that pH range low and reached peak values only at a higher pH of 9 to 10. Catalase inhibitors sodium azide (SA) and 3-amino-1,2,4-triazole (3-AT) had little effect on ADH activity but markedly decreased catalase activity and acetaldehyde formation (1 mM of SA to 56 +/- 13% of control, 5 mM of 3-AT to 67 +/- 3% of control; mean +/- SE). 4-Methylpyrazole decreased ADH activity significantly, but did not affect acetaldehyde formation. Heating of the homogenate at 60 degrees C for 5 min decreased ADH activity only slightly, but totally abolished catalase activity and reduced acetaldehyde formation to 39 +/- 3% of control. Addition of a H2O2 generating system (beta-D(+)-glucose + glucose oxidase] increased acetaldehyde formation in a concentration-dependent manner up to 8-fold of the control value. Our results strongly suggest that, in addition to ADH, catalase may play a significant role in gastric ethanol metabolism in rats. | 10.1111/j.1530-0277.1996.tb01939.x |
pubmed_234_1577 | By definition, congenital spine deformities-scoliosis, kyphosis, and lordosis-are due to abnormal vertebral development. Thus, affected children tend to have a curvature noted much earlier in life than typical patients with idiopathic scoliosis. This early development of the deformity has resulted in a tendency for the young child with congenital deformities to receive less than optimal care. These curves must not be allowed to progress. In many cases, early fusion is necessary, which is preferable to allowing severe curves to develop. | 10.1016/s0030-5898(05)70094-8 |
pubmed_536_5320 | Driving anxiety can have a significant impact on everyday functioning and usually results in some kind of avoidance behaviour. The Driving and Riding Avoidance Scale (DRAS; Stewart, A. E., & St. Peter, C. C. (2004). Driving and riding avoidance following motor vehicle crashes in a non-clinical sample: psychometric properties of a new measure. Behaviour Research and Therapy, 42, 859-879) shows promise in the self-report assessment of the degree of such avoidance. The present study investigated the psychometric properties of the DRAS in a sample of 301 university students. Internal consistency for the DRAS was 0.89 and temporal stability over two months was 0.71. The factor structure of the DRAS supported the use of the general and traffic avoidance subscales but not the weather and riding avoidance subscales in the present non-clinical sample. However, a significant limitation of the DRAS is that it does not assess the reasons for driving avoidance, and is therefore not a measure of avoidance that is due to driving anxiety. Some items may be rated highly for practical reasons, such as avoidance because of increasing fuel and other costs associated with driving. Modified instructions for the DRAS should ensure that it measures anxiety-related avoidance behaviour. | 10.1016/j.janxdis.2008.10.006 |
pubmed_32_6369 | Insufficient milk is a poorly understood problem that is often identified as a major reason for early discontinuation of breastfeeding. This study explored the relationship between anemia and insufficient milk in 630 first-time mothers. The frequency of anemia (postpartum hemoglobin < 10 g/dL) was 22 percent. Anemic mothers reported a higher level of symptomatology associated with insufficient milk and were more frequently classified as having insufficient milk syndrome. Mothers with the syndrome reported a shorter period of full breastfeeding, and weaned at an earlier age. They identified not having enough milk, baby nursing too often, and baby not gaining enough weight as the main reasons for discontinuing breastfeeding, compared with baby's disinterest and conflicts with school or work as main reasons among mothers not reporting symptoms related to insufficient milk syndrome. The study results suggest that anemia is associated with the development of insufficient milk, which in turn, is related to duration of full breastfeeding and to age at weaning. | 10.1111/j.1523-536x.1995.tb00565.x |
pubmed_1051_22246 | AIMS
A meta-analysis was carried out to review and identify correlates of stigma in poststroke patients.
BACKGROUND
Patients suffer from impaired physical functions and sequelae of stroke. Stroke-related stigma hinders the recovery process and produces poorer clinical outcomes of stroke, leading to compromised quality of life.
DESIGN
A systematic review and meta-analysis was reported by following PRISMA 2020 guidelines.
REVIEW METHODS
Nine databases were searched from their inception to May 2021 to identify studies focused on the relationships among demographics, disease-related factors, psychosocial factors and poststroke stigma. Included studies were assessed by using the Agency for Healthcare Research and Quality (AHRQ) scale. The statistical software R studios were used to perform statistical analysis.
RESULTS
Nineteen studies were included in the meta-analysis. Four demographic factors (age, caregiver, residence, monthly income), seven stroke-related characteristics (type of stroke, mRS, ADLs, stroke duration, recurrence, sequelae, chronic disease comorbidity) and three psychosocial factors (depression, social support, quality of life) showed significant associations with stroke-related stigma.
CONCLUSIONS
The results of our study can serve as a foundation for designing interventions to reduce stigma and improve the overall quality of life of poststroke patients and may produce positive clinical outcomes. Healthcare professionals should be aware of stroke patients who are characterised by correlates of stigma. Relevance to clinical practice Poststroke patients showed a moderate-to-high level of stigma, and this issue warrants more attention. This review provides a preliminary foundation for healthcare professionals to develop interventions to address stroke-related stigma by focusing on demographic, disease-related and psychosocial factors. Additionally, stigma identification should be a part of clinical nursing evaluation. The involvement of clinical and community nursing is very important to screen stroke-related stigma and pay attention to this population. | 10.1111/jocn.16250 |
pubmed_319_12714 | BACKGROUND
Mutations in the Planar Cell Polarity (PCP) core gene Vangl2 cause the most severe neural tube defects (NTD) in mice and humans. Genetic studies show that the Vangl2 gene genetically interacts with a close homologue Vangl1. How precisely Vangl2 and Vangl1 proteins interact and crosstalk has remained a difficult issue to address, with the main obstacle being the accurate discrimination of the two proteins, which share close sequence homology. Experimental evidence previously presented has been sparse and addressed with ectopically expressed proteins or with antibodies unable to biochemically discriminate Vangl1 from Vangl2, therefore giving rise to unclear results.
METHODOLOGY AND MAIN FINDINGS
A highly specific monoclonal anti-Vangl2 antibody was generated and rigorously tested on both recombinant and extracted Vangl2 using surface plasmon resonance (SPR) analysis, western blot, and immunoprecipitation experiments. This antibody efficiently affinity-purified Vangl2 from cell lysates and allowed the unambiguous identification of endogenous Vangl2 by proteomic analysis. Vangl1 was also present in Vangl2 immunoprecipitates, establishing the first biochemical evidence for the existence of Vangl2/Vangl1 heterodimers at an endogenous level. Epitope-tagged Vangl2 and Vangl1 confirmed that both proteins interact and colocalize at the plasma membrane. The Vangl2 antibody is able to acutely assess differential expression levels of Vangl2 protein in culture cell lines, as corroborated with gene expression analysis. We characterised Vangl2 expression in the cochlea of homozygous and heterozygous Lp mutant mice bearing a point mutation within the C-terminal Vangl2 region that leads to profound PCP defects. Our antibody could detect much lower levels of Vangl2(Lp) protein in mutant mice compared to the wild type mice.
CONCLUSION
Our results provide an in-depth biochemical characterisation of the interaction observed between Vangl paralogues. | 10.1371/journal.pone.0046213 |
pubmed_106_17602 | The liver is the major site of drug metabolism in the body. However, many drugs undergo metabolism in extrahepatic sites and in the gut wall and lumen. In this study, the distribution and activity of reductases in rat that reduced potential cytostatic oracin to its principal metabolite 11-dihydrooracin (DHO) were investigated. The extension and stereospecificity of oracin reduction to DHO were tested in microsomal and cytosolic fractions from the liver, kidney, heart, lung and wall of small intestine, caecum and large intestine. Intestinal bacterial reduction of oracin was studied as well. The amount of DHO enantiomers was measured by HPLC with Chiralcel OD-R as chiral column. Reductive biotransformation of oracin was mostly stereospecific for (+)-DHO, but the enantiomeric ratio differed significantly among individual tissues and subcellular fractions (from 56% (+)-DHO in heart microsomes to 92% (+)-DHO in liver cytosol). Stereospecificity for (-)-DHO (60%) was observed in bacterial oracin reduction in the lumen of small intestine, caecum and large intestine. Shift of the (+)-DHO/(-)-DHO enantiomeric ratio from 90:10 (in liver subcellular fractions) to 60:40 (in-vivo) clearly demonstrated the importance of the contribution of extrahepatic metabolism to the total biotransformation of oracin to DHO. | 10.1211/0022357021260 |
pubmed_616_22555 | Most plant leaves exhibit bilateral symmetry, which has been hypothesized as an inevitable consequence of the existence of the proximodistal and dorsoventral axes. No gene has been described that affects leaf bilateral symmetry but not dorsoventrality in Arabidopsis thaliana. We screened for viable insertional mutations that affect leaf morphology, and out of more than 700 mutants found only one, desigual1-1 (deal1-1), that exhibited bilateral symmetry breaking but no obvious defects in dorsoventrality. We found that deal1-1 is an allele of VASCULATURE COMPLEXITY AND CONNECTIVITY (VCC). Several overlapping regulatory pathways establish the interspersed lobes and indentations along the margin of Arabidopsis thaliana leaves. These pathways involve feedback loops of auxin, the PIN-FORMED1 (PIN1) auxin efflux carrier, and the CUP-SHAPED COTYLEDON2 (CUC2) transcriptional regulator. Early vcc (deal1) leaf primordia fail to acquire bilateral symmetry and instead form ectopic lobes and sinuses. The vcc leaves show aberrant recruitment of marginal cells expressing properly polarized PIN1, resulting in misplaced auxin maxima. Normal PIN1 polarization requires CUC2 expression and CUC2 genetically interacts with VCC; VCC also affects CUC2 expression. VCC has a domain of unknown function, DUF1218, and localizes to the endoplasmic reticulum membrane. VCC acts partially redundantly with its two closest paralogs, DEAL2 and DEAL3, in early leaf margin patterning and is required for bilateral symmetry, but its loss of function does not visibly affect dorsoventrality. | 10.1111/nph.14898 |
pubmed_1044_11129 | Introduction
Taxanes are associated with a distal sensory neuropathy, significantly affecting cancer survivor quality of life. However, chemotherapy-induced peripheral neuropathy (CIPN) assessments are primarily based on clinical symptoms rather than objective neurophysiologic findings. Therefore, we investigated neurophysiologic changes in symptomatic subjects, comparing them with symptom severity.
Materials and Methods
Medical charts of 111 subjects who were referred for CIPN diagnosis after chemotherapy for breast or ovarian cancer between May 1, 2016, and December 31, 2019, were retrospectively reviewed. Demographics, anthropometric parameters, and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale data were collected. The nerve conduction study (NCS) results, including sensory nerve action potentials recorded from sural nerves, were analyzed relative to clinical symptoms. To optimize follow-up (FU) NCS diagnostic sensitivity, relative references of FU sural amplitude reductions to >30% and an absolute reference <10 μV were used.
Results
Eighty-eight female patients met the criteria, and 20 underwent FU NCS. Baseline and FU sural amplitudes showed significant positive correlation with respective LANSS scores (p < 0.01). FU sural amplitude was significantly lower than the initial result (p < 0.05). The FU LANSS score was not different from the initial score. Initial NCS sensitivity and specificity for clinically suspected CIPN diagnoses with LANSS were 69.7 and 47.3%, respectively. All 20 subjects with FU evaluation were clinically compatible with CIPN (LANSS >12) at initial and FU assessments. Among them, only six (30.0%) had abnormal sural amplitudes (<10μV for ≤50 s, <3 μV for 60 s, <1 μV for 70 s) in the initial NCS. In the FU NCS, sural amplitude became abnormal in five additional subjects. Between the initial and FU NCS, sural amplitude was reduced by > 30% in eight subjects (40.0%). NCS sensitivity increased to 65.0% when including either abnormal sural amplitudes or a > 30% reduction in sural amplitude in FU studies.
Conclusions
Although clinical symptoms and NCS results were positively correlated, a single NCS point had limited value for suspected CIPN electrophysiological diagnoses. Serial NCS during chemotherapy might help assess the degree of chemotherapy-induced nerve damage, attain evidence of CIPN prior to symptom aggravation, and monitor the progression of CIPN. Further study is needed to find specific relative references for variable patient factors to increase the sensitivity of electrophysiological studies of clinically suspected CIPN. | 10.3389/fneur.2022.838302 |
pubmed_592_2343 | This article explains the basic principles of lasers from their historical beginnings to their use specifically in otolaryngology. The operation of the laser is shown in clear, easy-to-understand steps with the basics of laser delivery, laser optics, and laser-tissue interactions also presented. This article aims to give the surgeon enough information and understanding to help in deciding which laser to use for which purpose. | pubmed_592_2343 |
pubmed_480_22402 | Protein breakdown and mobilization from old or stressed tissues to growing and sink organs are some of the metabolic features associated with abiotic/biotic stresses, essential for nutrient recycling. The massive degradation of proteins implies numerous proteolytic events in which cysteine-proteases are the most abundant key players. Analysing the role of barley C1A proteases in response to abiotic stresses is crucial due to their impact on plant growth and grain yield and quality. In this study, dark and nitrogen starvation treatments were selected to induce stress in barley. Results show that C1A proteases participate in the proteolytic processes triggered in leaves by both abiotic treatments, which strongly induce the expression of the HvPap-1 gene encoding a cathepsin F-like protease. Differences in biochemical parameters and C1A gene expression were found when comparing transgenic barley plants overexpressing or silencing the HvPap-1 gene and wild-type dark-treated leaves. These findings associated with morphological changes evidence a lifespan-delayed phenotype of HvPap-1 silenced lines. All these data elucidate on the role of this protease family in response to abiotic stresses and the potential of their biotechnological manipulation to control the timing of plant growth. | 10.1093/jxb/erw212 |
pubmed_361_12105 | The degree of extracorporeal platelet sequestration in 32 patients undergoing cardiopulmonary bypass has been assessed using 111In labelled platelets and both a shadow shield whole body monitor and a standard gamma camera. The effects of ZK 36374, a prostacyclin analogue, on deposition of platelets in the oxygenator and atrial line filter were also investigated. Total platelet deposition in the placebo group ranged from 2.2% to 31.7%, mean 13.9 +/- 7.8%; n = 15, and was significantly higher than the deposition in the treatment group, range 0.7% to 9.4%, mean 3.9 +/- 2.6%; n = 16, P less than 0.001. There was also a highly significant correlation between the gamma camera and whole body monitor measurements, r = 0.99, P less than 0.001, with no systematic difference between the techniques. This study demonstrates that accurate quantitative assessment of platelet deposition can be achieved with either the gamma camera or whole body monitor. In addition, significant reduction in platelet sequestration in the extracorporeal circuit can be achieved by using ZK 36374 during the bypass operation. | 10.1007/BF00254624 |
pubmed_502_44 | Lincomycin, or the closely related derivative clindamycin, was used to treat six patients with bacteroides infection. In five of the six there was a rapid clinical response to the treatment. Lincomycin and clindamycin seem to be the antibiotics of choice for such infections. | 10.1136/bmj.1.5795.280 |
pubmed_456_5750 | The aim of this study was to demonstrate the state of diabetic foot ulcer (DFU) research in the past 10 years by bibliometric analysis, especially by performing document co-citation and co-word visualization analysis to reveal the research hotspots, frontiers, and core literature. The literature in connection with DFUs from 2007 to 2018 was retrieved from the Web of Science Core Collection database (WoSCC). We used the WoSCC and CiteSpace to analyze publication outcomes, journals, research direction, research hotspots, and frontiers. Overall, 4580 publications on DFUs were retrieved until March 22, 2018. The number of publications from the United States accounts for approximately one third of all publications from the top 10 countries. Surgery accounted for the largest proportion of the publications we retrieved from the WoSCC in terms of research areas. Results of this analysis indicated that DFU research has been in a stable, mature stage. Developed countries pay more attention to DFU research field than do developing countries, especially the United States. The complications of DFUs, such as lower extremity amputation and diabetic foot infection, are the hotspots. Diabetic foot infection, wound management, prediction studies on DFU, and diseases related to DFU are the research frontiers that should be observed closely in the future. | 10.1053/j.jfas.2018.08.052 |
pubmed_950_3664 | Huangshui (HS), the by-product of Chinese Baijiu, has attracted considerable attention due to its nutrient and microbial composition; however, none of the studies has explored the polysaccharides in HS yet. Here, from HS, we isolated a novel polysaccharide, HSP-3, with an average molecular weight of 26.40 kDa. The structure was elucidated based on monosaccharide composition and methylation analysis, NMR, FT-IR, and AFM analysis. It is mainly composed of mannose (46.6%), galactose (17.3%), arabinose (11.2%), glucose (10.5%), xylose (8.2%), fucose (5.2%), and rhamnose (1.0%). The backbone of HSP-3 was made up of → 2)-β-d-Manp-(1 → 2,6)-β-d-Manp-(1 → 6)-β-d-Galp-(1 → 3,6)-β-d-Galp-(1 → 4)-α-l-Rhap-(1 → 3,4)-α-l-Rhap-(1 → . Moreover, stimulation of the production of ROS, NO, TNF-α and IL-6, upregulation of the mRNA and protein expression levels of TNF-α and IL-6 in THP-1 cells, and enhanced the pinocytic and phagocytic capacities of THP-1 cells exhibited significant immunomodulatory properties of HSP-3. Altogether, this study suggests that HSP-3 could be used as an active component in functional foods. | 10.1016/j.foodchem.2020.127257 |
pubmed_508_2662 | OBJECTIVE
To examine the development of subjective symptoms and heart rate variability (HRV) during motion sickness induced by virtual reality (VR).
METHODS
Subjects were 10 healthy young volunteers. During VR immersion, subjects were immersed in a visual-vestibular conflict produced by VR. The levels of the subjective symptoms were assessed by Graybiel's and Hamilton's criteria. HRV was determined by measuring microvascular blood flow or electrocardiogram.
RESULTS
Subjective symptoms evaluated by Graybiel's and Hamilton's criteria were gradually worsened during VR. Power spectrum analysis of HRV demonstrated a gradual increase in the low frequency but no change in the high frequency during VR. In this study, individual subjective symptoms were not correlated with the individual result of power spectrum analysis.
CONCLUSION
These findings indicate that there was an increase in sympathetic nervous activity, but no change in parasympathetic nervous activity during motion sickness induced by VR. Given the large inter-individual variability and the reliability of subjective measures, it is not surprising that there is scarcely a relation between the subjective symptoms and the results of power spectrum analysis. | 10.1016/j.anl.2007.01.002 |
pubmed_444_10874 | The association between proximal tibiofibular joint (PTFJ) and knee osteoarthritis (OA) has been understudied. The objective of this study was to determine whether the morphology of PTFJ has predictive value for the risk of total knee replacement (TKR). Case knees from Osteoarthritis Initiative participants with TKR at 24-60 months follow up (cases) were 1:1 matched with control knees (no TKR throughout 60 months) by baseline age, sex, and Kellgren-Lawrence grade. PTFJ morphological parameters, including coronal inclination angle (angle α), sagittal inclination angle (angle β), fibular contacting area (S), load-bearing area (Sτ), lateral stress-bolstering area (Sφ), and posterior stress-bolstering area (Sυ) were assessed using coronal and sagittal magnetic resonance imaging (MRI), respectively. Associations of the morphological measures at baseline and the time point before TKR (T0 ) and their changes with TKR risks were examined using conditional logistic regression analyses. Two hundred and twenty-three knees of 193 participants received TKR between 12 and 60 months and therefore were matched with 223 control knees. Of these, 173 paired knees had MRI readings available both at baseline and T0 time point. While baseline angle α was positively associated with TKR risk, other measures at baseline and all measures at T0 were not significantly associated with TKR risk. Changes in S, Sτ, and Sυ were significantly and negatively associated with the risk of TKR (ΔS, odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.19-0.76; ΔSτ, OR = 0.37, 95% CI: 0.16-0.87; ΔSυ, OR = 0.22, 95% CI: 0.08-0.62, respectively). This data shows that morphological changes of PTFJ predict the risk of TKR, suggesting PTFJ may play a role in knee OA. | 10.1002/jor.24862 |
pubmed_583_9458 | In postmenopausal obese women often is observed increase bone mineral density in relation to slim women. Dominate the view that positive influence of adipose tissue on state of skeleton in postmenopausal women can be consequence of the boost to load carrying bone, may also result from the role of adipose tissue as endocrine organ. Interaction existence between somatotrophic axis and bone tissue suggests that revealing itself changes of constituents concentration of this axis in obesity individuals may have significance in bone tissue remodeling modification after menopause. It has been demonstrated that GH and IGF-I secretion decrease with age and this changes are major in obesity persons, particularly in women, and they depend on BMI and the percentage of body fat content. GH as well as IGF-I may directly and indirectly modulate bone remodeling, stimulating both bone formation and bone resorption. In the light of latest data this last effect is realized through their influence on expression of OPG and/or RANKL, cytokines belonging to the family of tumor necrosis factor alpha, which provide important controlling process element of the numbers of activated osteoclasts through osteoblasts. | pubmed_583_9458 |
pubmed_432_3583 | Newborn status, ratings of temperament, and heretofore neglected experiential (parenting) antecedents of hyperactivity were evaluated in a prospective, longitudinal investigation. The experiential variables were derived from a developmental theory of arousal modulation in the early years. Patterns of maternal intrusive care, seductive behavior, and overstimulation were assessed at 6 months, 2 years, and 3 1/2 years, respectively. 2 of these 3 variables significantly predicted hyperactivity in kindergarten at age 5 or 6, as determined by clinically validated ratings made by teachers. Of the 38 early child variables, which included neonatal behavioral assessments and ratings of activity level by parents and observers on many occasions during the first 2 1/2 years, only the motor maturity factor from 2 composited Brazelton exams yielded a significant relation. In addition, a measure of distractibility at 42 months was predictive of hyperactivity. Although other child measures may prove to be more powerful than those we tested, it will remain the case that prospective data are a critical arbiter of etiological factors in hyperactivity. Such data have important implications for both diagnosis and treatment. | 10.1111/j.1467-8624.1987.tb03862.x |
pubmed_232_21182 | A 34-year-old man was admitted to our hospital with the chief complaints of back pain and epigastralgia. The physical examinations on admission disclosed no abdominal tumor. The serum concentration of total bilirubin was 1.4 mg/dl. The serum elastase-1 level was elevated to 526 ng/dl. Computed tomography showed a cystic lesion, 1 cm in diameter, in the head of the pancreas, without dilatation of the main pancreatic duct. Endoscopic retrograde cholangiopancreatography via the papilla of Vater and the accessory papilla revealed an enlarged ventral pancreatic duct and pancreas divisum. The preoperative diagnosis was mucin-producing pancreatic tumor in the ventral pancreas of a patient with pancreas divisum. A pylorus-preserving pancreatoduodenectomy was performed. The gross findings of the cut surface of the resected specimen disclosed mural nodules in the dilated duct of the ventral pancreas. A histological examination of the mural nodules in the ventral pancreas revealed mucin and intraductal papillary adenoma. Benign tumors associated with pancreas divisum are rare; to the best of our knowledge, only three cases have been reported. Although in these three patients the tumor developed in the dorsal pancreas, the tumor developed in the ventral pancreas in our patient. | 10.1007/s00534-004-0906-7 |
pubmed_238_14829 | Introduction and importance
Dropped gallstones are an uncommon complication of laparoscopic cholecystectomy. Few reports have described dropped gallstones that were found accidently. Here, we encountered two cases of dropped gallstones that were unexpectedly found during surgery.
Case presentation
Case 1 involved a 54-year-old woman who has undergone a total abdominal hysterectomy with bilateral salpingo-oophorectomy for endometrioid cancer in the right ovary which was confirmed by histology. During surgery, a small firm nodule was seen in the omentum. An omentectomy is done for histological evaluation. Case 2 involved a 29-year-old woman admitted for an elective Caesarean section. During surgery, a firm nodule in the vesicouterine pouch was found. The nodule was carefully removed and sent to the pathology department. Microscopically, both cases revealed a fibrous wall enclosing gallstone associated with a foreign body-type granulomatous reaction.
Clinical discussion
Dropped gallstones (DGs), also referred to as spilled gallstones, into the peritoneal cavity are an uncommon complication of laparoscopic cholecystectomy. Clinically spilled gallstones usually remain silent for months or years after laparoscopic cholecystectomy and can be found during imaging or surgery.
Conclusion
Clinicians should keep in mind that mass-forming lesions within the peritoneal cavity, due to dropped gallstones, may mimic neoplasia. | 10.1016/j.amsu.2022.104557 |
pubmed_1038_17091 | The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1, and in the AUC from 23 to 65 nmol.h.l-1. The change in AUC corresponded to an increase in the systemic availability of felodipine from 15 to 45%, assuming no change in its clearance. This change was probably caused by inhibition of the oxidation of felodipine to the inactive dehydrofelodipine by flavonoids in grapefruit juice. The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the dihydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs. The higher plasma concentrations of felodipine taken with grapefruit juice resulted in a greater change in blood pressure measured in the morning 3 h after dosing (-9%) than did water (0%). | 10.1007/BF00266354 |
pubmed_822_5581 | This article reviews the current literature supporting the use of botulinum toxin in producing symmetric facial features and reducing unwanted, involuntary movements. Methods, protocols, and adverse events are discussed. Additionally, the authors suggest that using botulinum toxin A therapy in postparalytic facial synkinesis can provide long-term results when used in conjunction with other treatment modalities. | pubmed_822_5581 |
pubmed_1093_20416 | BACKGROUND
Asbestos is classified as a human carcinogen, and studies have consistently demonstrated that workplace exposure to it increases the risk of developing lung cancer. Few studies have evaluated risks in population-based settings where there is a greater variety in the types of occupations, and exposures.
METHODS
This was a population based case-control study with 1,681 incident cases of lung cancer, and 2,053 controls recruited from 8 Canadian provinces between 1994 and 1997. Self-reported questionnaires were used to elicit a lifetime occupational history, including general tasks, and information for other risk factors. Occupational hygienists, who were blinded to case-control status, assigned asbestos exposures to each job on the basis of (i) concentration (low, medium, high), (ii) frequency (<5%, 5-30%, and >30% of the time in a normal work week), and (iii) reliability (possible, probable, definite). Logistic regression was used to estimate odds ratios (ORs) and their corresponding 95% confidence intervals (CI).
RESULTS
Those occupationally exposed to (i) low, and (ii) medium or high concentrations of asbestos had ORs for lung cancer of 1.17 (95% CI=0.92 - 1.50) and 2.16 (95% CI=1.21-3.88), respectively, relative to those who were unexposed. Medium or high exposure to asbestos roughly doubled the risk for lung cancer across all three smoking pack-year categories. The joint relationship between smoking and asbestos was consistent with a multiplicative risk model.
CONCLUSIONS
Our findings provide further evidence that exposure to asbestos has contributed to an increased risk of lung cancer in Canadian workplaces, and suggests that nearly 3% of lung cancers among Canadian men are caused by occupational exposure to asbestos. | 10.1186/1471-2407-12-595 |
pubmed_1121_25676 | We have investigated the effects that iron limitation provokes in Saccharomyces cerevisiae exponential cultures. We have demonstrated that one primary response is the induction of bulk autophagy mediated by TORC1. Coherently, Atg13 became dephosphorylated whereas Atg1 appeared phosphorylated. The signal of iron deprivation requires Tor2/Ypk1 activity and the inactivation of Tor1 leading to Atg13 dephosphorylation, thus triggering the autophagy process. Iron replenishment in its turn, reduces autophagy flux through the AMPK Snf1 and the subsequent activity of the iron-responsive transcription factor, Aft1. This signalling converges in Atg13 phosphorylation mediated by Tor1. Iron limitation promotes accumulation of trehalose and the increase in stress resistance leading to a quiescent state in cells. All these effects contribute to the extension of the chronological life, in a manner totally dependent on autophagy activation. | 10.1042/BCJ20200849 |
pubmed_542_15975 | The release of prostacyclin (PGI2) as measured by the production of 6-keto-PGF1 alpha was assessed in vitro in rat tail artery segments after exposure to norepinephrine (NE). Time course studies demonstrated a three fold increase in 6-keto-PGF1 alpha production in response to 6 X 10(-5) M NE that persisted for approximately one hour. This production was almost completely prevented by the cyclooxygenase inhibitors indomethacin and ibuprofen and the phospholipase inhibitor mepacrine. Vigorous rubbing of the vessel intima did not prevent the response to NE. Previously stimulated tissues were unresponsive to further addition of NE. However, the addition of arachidonic acid following NE resulted in further increases in PGI2 production which exceeded that of the addition of arachidonic acid alone. NE stimulation was significantly inhibited by phentolamine and prazosin pretreatment of the tissues but was not affected by yohimbine or propranolol. Alpha-1 adrenergic agonists (cirazoline, methoxamine, and phenylephrine) were stimulatory whereas alpha-2 agonists in high doses (tramazoline, BHT-920, xylazine, and UK-14304) were without effect. It is concluded that norepinephrine stimulates PGI2 production in the rat tail artery via an alpha-1 adrenergic receptor. NE also enhances the conversion of arachidonic acid to PGI2. Exhaustion of the response appears to be due to consumption of available arachidonic acid. The fact that procedures which generally remove most of the endothelium did not prevent NE-induced stimulation points to the vascular smooth muscle as the likely source of adrenergically mediated prostacyclin generation in this tissue. | 10.1016/0262-1746(85)90152-0 |
pubmed_20_6235 | Bariatric surgery is the most effective weight loss treatment available for morbidly obese patients. The majority of bariatric surgery cases are now performed on reproductive-aged women. The pregnant bariatric surgery patient is unique, with specific care needs that often require a multidisciplinary approach. Here, we will review the rationale for bariatric surgery and contemporary surgical modalities. We will then consider the obstetric and neonatal implications following these procedures and discuss the tenets of pregnancy care in the patient after bariatric surgery. | 10.1097/GRF.0000000000000178 |
pubmed_408_12472 | The synthesis via a phosphotriester method of the octadecaribonucleotide AUG(UUC)5 (19) is reported. The octadecanucleotide is meant to serve as a synthetic messenger in a ribosomal protein synthesizing system. A fully protected octadecamer intermediate (18a) was prepared by a block coupling procedure. For the introduction of the desired 3'-5'-internucleotide bonds a 3'-O-(2,2,2-trichloroethyl 2-chlorophenyl phosphate) function was incorporated into the monomeric building blocks which were applied in the synthesis of 18a. Monomeric and oligomeric compounds with a thus protected 3'-O-phosphotriester function can be selectively deblocked to give 3'-O-phosphodiester derivatives suitable for condensation with 5'-hydroxyl (oligo)nucleotides. Conversion of fully protected oligomers to 5'-hydroxyl derivatives, suitable for further coupling at the 5' end, was effected by selective removal of the levulinyl function at the 5' end. The fully protected octadecanucleotide 18a was deblocked with fluoride ions, followed by ammonia and acid to give the required octadecamer 19. The condensing agent 1-(2,4,6-triisopropyl-phenylsulfonyl)-3-nitro-1,2,4-triazole, which was applied to effect the formation of fully protected 3'-5'-internucleotide phosphotriester functions, may give rise to side reactions with the heterocylic bases uracil and guanine. The consequences of these side reactions for the synthesis of octadecamer 19 are reported. | 10.1021/bi00534a028 |
pubmed_984_24945 | OBJECTIVE
To study the extent of retinal vascular development and influencing factors at birth and the relation between retinal vascularization and retinopathy of prematurity (ROP).
METHODS
From October, 2006 to December 2006, retinal vascularization was screened and evaluated in 84 neonates at different weeks of gestation and birth weights (BWs), had dilated fundus evaluation for zone of retinal vascularization by the 130 degrees lens of a digital fundus camera. The infants' pupils were dilated with 2.5% phenylephrine and 0.5% cyclopentolate eye drops. The study cohort was divided into subgroups depending on the weeks of gestation and birth weights. The control group consisted of healthy term infants. Maternal and neonatal factors were ascertained and analysed.
RESULTS
Vascularization up to zone I and II was considered to be immature retina; vascularization up to zone III or beyond was considered to be mature retina. In this study, 11 of 12 infants who were born at < 30 weeks of gestation, 12 of 26 infants who were born at < 31 approximately 33 weeks of gestation, 1 of 26 babies who were born at < 34 approximately 36 weeks of gestation and none of 20 babies who were born at < 37-40 weeks of gestation had immature retina; 12 of 15 babies at < 1500 g BW, 8 of 14 infants at 1500 g < BW < 1700 g, 4 of 11 infants at 1700 g < BW < 2000 g and of 44 infants at > 2000 g BW had immature retina. Those infants who were born at > 34 weeks of gestational age and at > 2000 g BW had mature retina. Infants who were born between 31 to 34 weeks of gestation and at 1501 to 2000 g BW had variable extent of retinal vascularization at birth. Vascularization was associated with postconceptional age (F = 31.9193, P = 0.000), birth weight (F = 32.4532, P = 0.000), anemia (F = 36.9391, P = 0.000), surfactant (F = 24.000, P = 0.0000), poor nutrition (F = 4.184, P = 0.041), RDS (F = 17.6191, P = 0.000), cesarean delivery (F = 10.972, P = 0.0022) and oxygen > 48 h (F = 22.076, P = 0.0000). Vascularization was affected mainly by the postconceptional age (95% CI = 1.57-261.728, P = 0.021). At last, 15/24 infants with immature retina developed ROP while none of the infants with mature retina developed ROP (chi2 = 45.1087, P = 0.000).
CONCLUSION
There is considerable variability in the extent of retinal vascularization in infants who we born between 31 to 34 weeks of gestation. Modifiable maternal and fetal factors could influence extent of vascularization at birth. Immature retina is the critical factor of ROP. Gestational age is the main factor of the immature retina in premature infants. | pubmed_984_24945 |
pubmed_340_2380 | INTRODUCTION
Mutations of the von Hippel-Lindau (VHL) gene are responsible for VHL disease. This is a familial autosomal-dominant syndrome, predisposing to the development of benign and malignant tumors, including CNS and retinal hemangioblastomas, pheochromocytomas, and clear cell renal carcinomas. At least 30% of the disease-causing mutations in the VHL gene involve large alterations. Identification of these mutations is not possible using PCR-based mutational scanning methods. Quantitative Southern blot analysis has been traditionally employed for the detection of complete or partial deletions and more complex rearrangements of the gene.
METHODS
An alternative quantitative method was developed using a combination of quantitative Southern blot analysis and real-time PCR. With this approach, we studied 24 large VHL gene alterations to determine the exact nature of the mutations and to possibly characterize the boundaries of the deleted regions.
RESULTS
This combined molecular approach showed that all the VHL alterations studied were due to deletions, from which the position in the gene could be more precisely mapped. One of the samples that was completely characterized was found to carry an intragenic 2.2kb deletion with both 5' and 3' breakpoints located within Alu-repeat sequences.
CONCLUSION
This is the first report on the molecular analysis of large VHL alterations. The results of our study and the complete characterization of a large deletion lead to the hypothesis that an Alu-mediated mechanism may be responsible for the common occurrence of large alterations in the VHL gene. | 10.1007/BF03256463 |
pubmed_262_18582 | Trypanosomal S-adenoyl-L-homocysteine hydrolase (Tc-SAHH), considered as a target for treatment of Chagas disease, has the same catalytic mechanism as human SAHH (Hs-SAHH) and both enzymes have very similar x-ray structures. Efforts toward the design of selective inhibitors against Tc-SAHH targeting the substrate binding site have not to date shown any significant promise. Systematic kinetic and thermodynamic studies on association and dissociation of cofactor NAD/H for Tc-SAHH and Hs-SAHH provide a rationale for the design of anti-parasitic drugs directed toward cofactor-binding sites. Analogues of NAD and their reduced forms show significant selective inactivation of Tc-SAHH, confirming that this design approach is rational. | 10.1080/15257770903051031 |
pubmed_1017_10884 | This study examined patterns of onset of activity of daily living (ADL) disability in a nationally representative sample of older adults in mainland China. Using longitudinal data from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2008 (N = 5,570), nonparametric methods were used to evaluate median age at onset of various ADL disabilities and differences in the incidence of disabilities according to sex. The sampled older Chinese adults developed ADL disabilities, on average, between the ages of 89 and 94. Women were likely to experience later onset than men. The results also show that the oldest adults generally lose bathing ability, followed by toileting, transferring, dressing, eating, and finally, continence. This order-derived from estimated median age at onset-was also found to be highly prevalent in subsequently disabled respondents in the sample. The disability experience of older adults in China is somewhat similar to that of older adults in Western developed countries; elderly adults tend to lose ability in activities that require lower extremity strength earlier than those that require upper extremity strength. The relative importance of the various ADL items in the hierarchical ordering has implications for early intervention to reduce the risk of functional disability in older adults and those at risk of transitions of care. | 10.1111/jgs.14264 |
pubmed_81_46 | The production of Lactobacillus brevis has been improved by changing the medium composition and the physiological conditions. The cellular concentration reaches 8.2 x 10(10) cells/mL in 21 h with a fed-batch technique in MRS medium. Freeze-drying has been used as technology for drying the cells and survival rates have been improved with different additives such as glycerol, CaCO3, and skimmed-milk powder up to 70%. A model has been developed to predict the stability of freeze-dried cultures during long-term conservation. This model, based on Arrhenius equation, has been confirmed by experimental data. | 10.1007/BF02920164 |
pubmed_1053_5253 | A case of primary diffuse tracheobronchial amyloidosis in a 45-year-old woman is reported. Because of tracheal stenosis immediately beneath the vocal cords, due to amyloid deposits, she was treated with Nd-YAG laser irradiation. Immediately after treatment, symptoms such as cough, wheezing, and shortness of breath on exertion improved. Bronchoscopic Nd-YAG laser irradiation proved useful for the removal of amyloid deposits from the trachea in this patient. | 10.2169/internalmedicine1962.29.620 |
pubmed_683_5654 | BACKGROUND
Nonthoracotomy systems are rapidly becoming the preferred surgical method for implantation of cardioverter defibrillators. Testing is performed at the time of implantation to insure an adequate margin of safety for defibrillation. However, this safety margin may change with lead maturation. This study evaluated changes in defibrillation threshold following implantation of a nonthoracotomy system.
METHODS AND RESULTS
Ten dogs underwent implantation of a nonthoracotomy system consisting of a single catheter with a distal coil electrode in the right ventricular apex and a proximal coil electrode in the superior vena cava forming a common anode with a subcutaneous patch over the left thorax. Defibrillation threshold testing, using a biphasic waveform, was performed on each animal under general anesthesia at implantation (day 1) and subsequently on postoperative days 3, 7, 10, 17, 24, 31, 38, and 45. E50, the energy associated with a 50% likelihood of successful defibrillation, was determined at each setting. The mean E50 was 12.2 +/- 1.1 J at the time of implantation, increasing 36% to 16.8 +/- 2.0 J by day 38 (P < 0.01). Individual increases in E50 of 10-12 J were observed in four animals.
CONCLUSIONS
Energy requirements for defibrillation with a nonthoracotomy system increase during the early postoperative period, with the highest defibrillation threshold observed at 38 days. This increase may be applicable to humans and should be considered when selecting an adequate energy safety margin for defibrillation at time of implantation. | 10.1111/j.1540-8159.1994.tb03744.x |
pubmed_1080_16037 | The primary structure of phospholipase A2 of the major race of Indian cobra has been determined. Together with previous data on other subforms, it establishes subspecies variations at no less than 20 of the 119 positions in the protein. These variations are large, not only in number but in several cases also regarding properties of the residues involved. Nevertheless, all structures are compatible with largely unaltered enzyme properties. | pubmed_1080_16037 |
pubmed_756_23460 | The ionization potential distributions of hydrated hydroxide and hydronium are computed with the many-body approach for electron excitations with configurations generated by ab initio molecular dynamics. The experimental features are well reproduced and found to be closely related to the molecular excitations. In the stable configurations, the ionization potential is mainly perturbed by solvent water molecules within the first solvation shell. On the other hand, electron excitation is delocalized on both proton receiving and donating complex during proton transfer, which shifts the excitation energies and broadens the spectra for both hydrated ions. | 10.1103/PhysRevLett.111.087801 |
pubmed_133_11929 | Matrix metalloproteinase-2 (MMP-2, gelatinase A) and its tissue inhibitor (TIMP-2) are mainly known for their roles in the (patho)physiological remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. A mechanism of action of MMP-2 is the proteolytic breakdown of specific extracellular matrix proteins. The amino acid sequences in interstitial collagen (Gly-Leu/Ile) and laminin-5 (Ala-Leu) that are cleaved by MMP-2 are homologous to a region (Gly(32)-Leu(33)) within human big endothelin-1[1 to 38] (big ET-1). Big ET-1 requires cleavage to an active form to produce vasoconstriction. We tested the hypothesis that vascular MMP-2 can cleave big ET-1, thus generating a vasoconstrictor peptide. In perfused rat mesenteric arteries with an intact endothelium, inhibition of vascular MMP-2 with TIMP-2 reduced (by 16.2+/-4.2%) the vasoconstrictor effects of big ET-1 (50 pmol). However, when the endothelium was mechanically removed, TIMP-2 abolished (>90%) the vasoconstriction of big ET-1, and this effect was mimicked by an anti-MMP-2 antibody. Incubation of big ET-1 with recombinant human MMP-2 resulted in the specific cleavage of the Gly(32)-Leu(33) bond of big ET-1. Moreover, the resultant peptide ET-1[1 to 32] exerted greater vasoconstrictor effects than big ET-1. We conclude that vascular MMP-2 contributes to the vasoconstrictor effects of big ET-1 by cleaving big ET-1 to yield a novel and potent vasoconstrictor, ET-1[1 to 32]. These data implicate, for the first time, the endogenous MMP-2/TIMP-2 system in the regulation of vascular reactivity. | 10.1161/01.res.85.10.906 |
pubmed_734_14172 | PURPOSE
To evaluate choroidal vascularity index (CVI) among normal subjects using image binarization of swept source optical coherence tomography (SS-OCT).
MATERIALS AND METHODS
Four hundred and sixty eyes of 230 normal participants were included. Total circumscribed choroidal area, luminal area, stromal area (SA), and CVI were derived from SS-OCT scans using open-source software (ImageJ) with the modified Niblack method. Both CVI and subfoveal choroidal thickness (SFCT) were correlated with age, refractive error, intraocular pressure, and mean ocular perfusion pressure (MOPP) using mixed linear model analysis. Pearson's correlation coefficient was used to determine the relationship between age and each dependent factor. Analyses were performed using the SPSS software version 20.0 (IBM Corp., Armonk USA) and statistical significance was tested at 5%.
RESULTS
The mean age was 42.1 (±17.6) years. Mean SFCT was 307 ± 79 μm. Mean CVI was 66.80 (±3.8)%. There was statistically significant positive correlation between CVI and increasing age (r = 0.259, P < 0.0001) and statistically significant negative correlation between SFCT and age (r = -0.361, P < 0.0001). There was positive linear correlation between refractive error and CVI (r = 0.220, P < 0.0001) and negative correlation between SFCT and refractive error. There was no significant effect of MOPP on both CVI (P = 0.07) and SFCT (P = 0.7).
CONCLUSION
CVI and SFCT are significantly correlated with age and refractive error in normal Indian eyes. | 10.4103/ojo.ojo_207_21 |
pubmed_1054_12616 | The effect of route of administration, dosage, and number of boosts employed during immunization with the polymyxin-release form of Escherichia coli heat-labile (LT) enterotoxin on the degree and duration of protection afforded was evaluated in rats which were challenged by the ligated loop technique. Increasing the boosting dosage by fivefold from 50 to 250 mug resulted in a marked increase in protection against challenge with toxin in rats immunized either just by the parenteral route (i.p./i.p.) or by a parenteral prime, followed by peroral boosts (i.p./p.o.) in rats pretreated with cimetidine to ablate gastric secretions; such was not the case, however, even with a 50-fold increase in dosage in rats immunized just by the peroral route (p.o./p.o.). Four weekly peroral boosts were required to achieve the strongest degree of protection. Increasing the boosting dosage also increased the degree of protection against challenge with viable LT(+)/ST(-) and LT(+)/ST(+) strains (ST indicates heat-stable enterotoxin) in rats immunized by the i.p./p.o., but not by the i.p./i.p., route; no protection was evident against an LT(-)/ST(+) strain. Protection was lost within 3 weeks after immunization in rats immunized by the i.p./i.p. route. In contrast, protection was extended over the 3-month observation period in those immunized by the i.p./p.o. route; the degree of protection was enhanced in rats which received an additional boost at 2 months. These observations establish the fact that immunization with LT is similar to that with cholera toxin in that arousal of the local immune intestinal response by means of peroral immunization provides maximal extended protection. | 10.1128/iai.27.1.81-86.1980 |
pubmed_644_11217 | An ortho-metalation method for free ferrocenyl alcohols has been developed, which allows preparation of planar chiral ferrocene derivatives with high yields and diastereoselectivities. | 10.1039/b807895e |
pubmed_786_19403 | Africa is severely affected by a resurgence of human African trypanosomiasis (HAT) at epidemic proportions. We report the results of the first 5 years of a HAT control programme in northern Angola run by the non-governmental organization (NGO) ANGOTRIP. In the period between 1996 and 2001, 13 426 patients were screened for HAT. The mortality rate of patients in stage II who were treated with melarsoprol fell from 7.5% to 2.9%, possibly as a result of training and the standardization of treatment protocols. A total of 191,578 people in three provinces of Angola were screened for HAT. Vector control activities were initiated using Lancien traps. Our experiences reflect the connection between war and the increasing incidence of disease, but also demonstrate that HAT control is possible by dedicated NGOs in close cooperation with national institutions even under extremely difficult circumstances. | 10.1046/j.1365-3156.2003.01152.x |
pubmed_935_747 | A young man who presented initially with a ureteral stone was found to have toluene-induced renal tubular acidosis. Persistent toluene sniffing resulted in recurrent calculi and life-threatening hypokalemic paralysis. The pathophysiology, classification and treatment of renal tubular acidosis are discussed. | 10.1016/s0022-5347(17)55792-4 |
pubmed_959_18331 | We firstly discover the enhanced catalytic activity of magnetic noble metal nanoparticles mediated by surface plasmon resonance. Under light irradiation with certain wavelength, the catalytic performance of magnetic noble metal nanoparticles shows changes with different degrees and directions that are associated with the surface plasmon resonance (SPR) of the noble metal. Moreover, the coupling of silver and gold allows the catalytic performance of magnetic bimetallic Ag-Au nanoparticles to show more positive response to surface plasmon resonance. The magnetic bimetallic Ag-Au nanoparticles show excellent catalytic performance toward the reduction reaction of aromatic nitro group, and corresponding rate constant of the catalytic reduction reaction increases about three times with light irradiation. | 10.1166/jnn.2021.19281 |
pubmed_841_19956 | Recovery of the magnetic dipolar interaction between nuclei bearing the same gyromagnetic ratio in rotating solids can be promoted by synchronous rf irradiation. Determination of the dipolar interaction strength can serve as a tool for structural elucidation in polycrystalline powders. Spinning frequency dependent narrow-band (nb) RFDR and SEDRA experiments are utilized as simple techniques for the determination of dipolar interactions between the nuclei in coupled homonuclear spin pairs. The magnetization exchange and coherence dephasing due to a fixed number of rotor-synchronously applied pi-pulses is monitored at spinning frequencies in the vicinity of the rotational resonance (R(2)) conditions. The powder nbRFDR and nbSEDRA decay curves of spin magnetizations and coherences, respectively, as a function of the spinning frequency can be measured and analyzed using simple rate equations providing a quantitative measure of the dipolar coupling. The effects of the phenomenological relaxation parameters in these rate equations are discussed and an improved methodology is suggested for analyzing nbRFDR data for small dipolar couplings. The distance between the labeled nuclei in the 1,3-(13)C(2)-hydroxybutyric acid molecule is rederived using existing nbRFDR results and the new simulation procedure. A nbSEDRA experiment has been performed successfully on a powder sample of singly labeled 1-(13)C-L-leucine measuring the dipolar interaction between the labeled carboxyl carbon and the natural abundant beta-carbon. Both narrowband techniques are employed for the determination of the nuclear distances between the side-chain carbons of leucine and its carbonyl carbon in a tripeptide Leu-Gly-Phe that is singly (13)C-labeled at the leucine carbonyl carbon position. | 10.1006/jmre.2001.2463 |
pubmed_814_628 | In this study we investigated the efficacy and safety of very short duration (1-month) dual antiplatelet therapy (DAPT) followed by prasugrel monotherapy. In particular, we compared intrastent conditions using optical coherence tomography (OCT) after second-generation drug-eluting stent implantation between standard-duration and 1-month DAPT followed by prasugrel monotherapy. Between May 2015 and February 2018, 120 consecutive patients who underwent elective Resolute zotarolimus-eluting stent implantation were enrolled and divided into those receiving standard-duration or 1-month (1M) DAPT followed by prasugrel monotherapy; 47 patients (n=55 stents) and 46 patients (n=54 stents) in the standard and 1M groups, respectively, completed the protocol. The primary endpoint was the prevalence of abnormal intrastent tissue at the 9-month examination, as observed by OCT. The secondary endpoint was the presence of composite adverse events, including all-cause death, myocardial infarction, stent thrombosis, target lesion and vessel revascularization, and major and minor bleeding. The prevalence of abnormal intrastent tissue was similar between the standard and 1M groups (1.6% vs. 1.5%, respectively; non-inferiority P<0.01). There was a tendency for fewer composite events in the 1M than standard group at the 30-month follow-up examination (28.3% vs. 44.7%, respectively; P=0.41). In conclusion, 1M DAPT followed by prasugrel monotherapy after second-generation drug-eluting stent implantation was not inferior to standard-duration DAPT in terms of intrastent thrombus formation and composite adverse events. | 10.1253/circrep.CR-20-0126 |
pubmed_857_20883 | We isolated cDNAs encoding a mouse interleukin 10 receptor (mIL-10R) from mouse mast cell and macrophage cell lines. The two cDNAs are substantially identical and express an approximately 110-kDa polypeptide in COS7 cells, which binds mIL-10 specifically. A mouse pro-B-cell line (Ba/F3) expressing transfected recombinant mIL-10R binds IL-10 with high affinity (approximately 70 pM) and proliferates in response to mIL-10. mIL-10R is structurally related to interferon receptors (IFNRs). Since IL-10 inhibits macrophage activation by IFN-gamma, a possible implication of this relationship interaction of IL-10R and IFN-gamma R or their signaling pathways. | 10.1073/pnas.90.23.11267 |
pubmed_894_5906 | The binding of (3H)5-hydroxytryptamine ([3H]5-HT, serotonin) to crude homogenates of brains from three different strains of mice has been studied. The strains, C57/BL, DBA and BALB did not show significant differences in the binding characteristics, with Kd values around 6-7 nM and Bmax 270-310 fmoles/mg protein. Various methodological aspects were investigated and found to be important for the binding assay. The presence of ascorbic acid (5.7 mM) thus caused a significant increase in Bmax by 30% without any change in the Kd values. This increase seemed to be due to a decrease in the non-specific binding rather than to an increase in the total binding of serotonin. The presence of a specific MAO-A inhibitor, clorgyline (10 microM), during the assay, resulted in a significant reduction of Bmax by 20% without any change in the affinity for serotonin, when tissue which had been frozen was used. Less than 2% of added serotonin was metabolized during the binding procedure in the absence of clorgyline. Thus, the decrease in binding capacity caused by clorgyline, may be due to a non-competitive blocking effect of the serotonin binding structure. These results indicate that the use of MAO inhibitors in (3H)5-HT binding assays on frozen tissue, rather than being necessary, might negatively affect the result. Neither storage of the brains at -70 degrees nor postmortem storage of the animals for 60 hours at 4 degrees resulted in obvious changes in the (3H)5-HT binding characteristics. | 10.1007/BF01243494 |
pubmed_1013_8105 | Background Drug-induced liver injury (DILI) refers to liver damage caused by drugs. DILI poses a significant challenge in the development of new drugs. The management of DILI mainly involves the withdrawal of the offending drug, and there is a lack of specific therapy. This study sought to evaluate the efficacy and safety of compound glycyrrhizin (CG) injections in DILI patients. Aim To evaluate the efficacy and safety of compound glycyrrhizin injections in DILI treatment. Methods The clinical data of DILI patients were collected from a nationwide DILI database. Patients were divided into two groups: the compound glycyrrhizin (CG) group who received CG injections, and the control group who received no treatment. The propensity score matching (PSM) method was applied to obtain an even distribution of characteristics between the two groups. The efficacy of the CG injections was assessed by the analysis of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels between the two groups. Results There were 152 patients in the compound glycyrrhizin group and 512 patients in the control group. The PSM method was used to acquire 152 matched pairs. The compound glycyrrhizin group had a significantly higher overall ALT and AST normalization rate than the control group (43.42% vs. 24.34%, p = 0.0004 and 63.82% vs. 38.82%, p ≤ .0001). There was no difference in the levels of renal and serum biochemical parameters between the two groups. Conclusions CG injections are effective in reducing ALT and AST levels in DILI patients, and their safety is comparable to the control group. | 10.1007/s11096-022-01402-x |
pubmed_539_3967 | The human cytomegalovirus (HCMV) has dedicated a significant part of its genome to genes encoding molecules that modulate the host immune response. Many of these genes have homologues in the host genome. Others, however, are unique in the sense that no obvious primary sequence identity is found in the available databases. The HCMV gene products interfere with the activation of MHC class I and class II restricted T cells and NK cells, modify the function of cytokines and their receptors, interact with complement factors and modulate signal transduction and transcription factor activity, in addition to interference with many other cellular functions. Investigation of these evasion strategies has not only improved our understanding of HCMV pathogenesis, but has also provided unexpected, novel insights into basic cell biological and immunological processes. | 10.1006/smim.2001.0294 |
pubmed_735_25322 | The intima-media thickness (IMT) of carotid arteries is a marker of subclinical atherosclerosis associated with risk factors for atherosclerosis and a predictor of vascular disease. The aim of the research was to determine the correlation of IMT and age, and above normal IMT values in healthy adults in Slavonia (eastern Croatia). The study included 275 subjects of both sexes, aged between 20 and 79, who had no clinical manifestations of vascular disease or presence of major risk factors for atherosclerosis (hypertension, hypercholesterolemia, diabetes mellitus, cigarette smoking). Ultrasonic measurement of IMT in the B-mode was performed on far walls of the carotid arteries on both sides at three locations (common and internal carotid artery, carotid bifurcation). At all three sites of measurement a high correlation between the IMT values and age was found in both sexes, including the maximum for IMT of carotid bifurcation (men r=0.92, women 0.91). Upper normal values (75th percentile) IMT of common carotid arteries were determined for the ten year age groups. It is the same for both men and women in age groups both 20-29 and 30-39 (0.41, 0.46 mm). On the other hand, in age groups 40-49, 50-59, 60-69 and 70-79 upper normal values for men are 0.57, 0.62, 0.77 and 0.96 mm, and for women 0.50, 0.57, 0.71 and 0.81 mm. Our study in healthy adults in Slavonia (eastern Croatia) established a clear con- nection between carotid IMT and age, which implies a need for taking the age as an essential factor into account when conducting researches that involve the IMT. | pubmed_735_25322 |
pubmed_731_11566 | A spontaneous diaphragmatic hernia (SDH) occurs when intra-abdominal contents extend into the thoracic cavity through a defect in the diaphragm after a sudden increase in intra-abdominal pressure. SDH is one of the rarest surgical emergencies with less than 30 reported cases in the literature.1,2 In our case a 94-year-old female presented to the emergency department in respiratory distress with unilateral breath sounds and was diagnosed with a SDH. The only treatment option for a SDH is surgical.3,11 However, nasogastric tube decompression of the gastrointestinal tract and supplemental oxygen can be used to alleviate symptoms until definitive operative management is performed. | 10.5811/cpcem.2018.5.38587 |
pubmed_486_21119 | Photodynamic therapy (PDT) has been used in the treatment of cancers and other benign diseases for several years in clinic. However, the hypoxia of tumors and the penetration limitation of excitation light to tissues can dramatically reduce the efficacy of PDT to cancers. To overcome these drawbacks, various assembled nanocarriers such as nanoparticles, nanocapsules, nanocrystals, and so on were introduced. The assembled nanocarriers have the ability of loading photosensitizers, delivering O2 into tumors, generating O2 in situ in tumors, as well as turning near-infrared (NIR) light, X-rays, and chemical energy into ultraviolet or visible light. Therefore, it is easy for the nanocarriers to improve the hypoxia microenvironment or increase the treatment depth of cancers, which will improve the efficiency of PDT to some degree. In recent years, a number of investigations were focused on these subjects. We will summarize the advances of nanocarriers in PDT, especially in O2 introduction PDT and deep PDT. The perspectives, challenges, and potential in translation of PDT will also be discussed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease. | 10.1002/wnan.1583 |
pubmed_764_2342 | A number of novel and important observations have recently arisen that emphasize the interaction between sleep apnea and cardiovascular function. New evidence of a role for obstructive sleep apnea as an independent factor in the genesis of hypertension and nocturnal myocardial ischemia has been described. Advances have been made in the understanding of the acute impact of sleep-disordered breathing on hemodynamic function, and a better understanding of the interaction between sleep-disordered breathing and congestive heart failure is now emerging. There is now strong evidence that reversal of sleep-related breathing disorders by nasal continuous positive airway pressure leads to improvements in markers of cardiovascular outcome in selected patients with congestive heart failure. These findings augur well for the development of new diagnostic approaches and treatment strategies for patients with sleep apnea and coexisting cardiovascular disease. | 10.1097/00063198-199511000-00014 |
pubmed_81_11611 | Isolated post-traumatic basal ganglia or brainstem lesions secondary to direct injury resulting in movement disorders, such as tremor or dystonia, are extremely rare. We report an unusual case with a 4-5 Hz rest and postural tremor and focal action-induced dystonia of the left arm. The movement disorder developed within 2 years of the patient sustaining a right-sided mesencephalic-diencephalic lesion due to a penetrating thrust injury with a screwdriver. Magnetic resonance imaging demonstrated involvement of the cerebral peduncle, the substantia nigra, the subthalamic region and the thalamus. | 10.1016/s1353-8020(96)00043-0 |
pubmed_731_26437 | Isolated adrenal tuberculosis accounts for less than 2% of adrenal incidentalomas. This is the most frequent infectious cause of adrenal insufficiencies. We report the case of a 53-year old patient with no previous medical history presenting with adrenal insufficiency with slow progression over six months. Physical examination didn't show any mass or hepatosplenomegaly. Blood pressure was 120/60 mmHg. Laboratory tests didn't show inflammatory syndrome. LDH level was normal. CT scan showed bilateral hypertrophy of the adrenal glands characterized by calcifications. Intradermo tuberculin reaction was positive at 25mm. The analyses to detect Koch's bacillus in the sputum and in the urine were negative. Quantiferon® test was positive. Trial antibacillar treatment was started with clinical improvement and 5kg weight gain in 12 months. Hormonal assays were low. | 10.11604/pamj.2018.29.212.15459 |
pubmed_113_3232 | We present a 29-month-old male patient in follow-up due to pyelocaliceal dilation with a prostatic nodule incidentally found during ultrasound evaluation. Cysto video endoscopy was performed and a prostate biopsy, obtained. Microscopic evaluation showed a haphazardly distributed population of muscular cells with cross striations without evidence of mitosis or necrosis. Immunohistochemistry was positive for myogenin and desmin and negative for smooth muscle actin. Next generation sequencing was performed without finding any pathogenic variant or fusion in the tumor RNA. The patient received no further treatment, remained asymptomatic and continues in follow up, 3 years after initial diagnosis. We report a case of prostate rhabdomyoma in a toddler, an exceptional location that raises concern about differential diagnosis with its malignant counterpart, rhabdomyosarcoma, especially at this age. | 10.1177/10935266211046926 |
pubmed_98_2415 | A series of mesoporous CeZrTiO catalysts were prepared by a facile hydrothermal method. Compared with CeTiO catalysts synthesized under the same conditions, the catalytic activity and anti-SO2 performance of the Ce1Zr1TiO catalyst are greatly improved, and at the gas hourly space velocity (GHSV) of 60 000 h-1, the NO removal efficiency is maintained at 90% in the temperature range of 290-500 °C. The catalytic effect of ZrO2 on the Ce-Ti catalyst NH3-SCR activity was elucidated through a series of characterizations. The results revealed that the doping of Zr could significantly improve and optimize the structure of Ce-Ti catalysts. At the same time, due to the doping of Zr, the synergistic effect between Ce and Zr in the CeZrTiO catalyst can effectively increase oxygen mobility, total acid content, and surface adsorbed oxygen species and lead to a larger pore volume. In addition, the introduction of ZrO2 made the transformation of Ce4+ into Ce3+ more obvious, and the 2Ce4+ + Zr2+ ↔ 2Ce3+ + Zr4+ reaction greatly improved the reducibility of Ce1Zr1TiO. Among them, the improvement of SCR performance and H2O/SO2 tolerance is due to the electronic interaction between Zr and Ce. | 10.1021/acs.langmuir.1c02597 |
pubmed_151_1619 | Left main coronary artery (LMCA) stenosis has long been recognized as a marker of increased morbidity and mortality. Current treatment algorithms for LMCA stenosis consider both percutaneous coronary intervention (PCI) with drug eluting stents (DES) and coronary bypass surgery, each with advantages based on individual patient characteristics. Since the LMCA is the largest artery in the coronary tree, plaque volume and calcification is greater than other coronary segments and often extends to the distal bifurcation segment. In LMCA bifurcation lesions, larger minimal stent area is strongly associated with better outcome in the DES era. Plaque modification strategies such as rotational, orbital, or laser atherectomy are effective mechanisms to reduce plaque volume and alter compliance, facilitating stent delivery and stent expansion. We present a case of a calcified, medina class 1,1,1 LMCA lesion where intravascular ultrasound (IVUS) and orbital atherectomy were employed for optimal results. In this context, we review the evidence of plaque modification devices and the rationale for their use in unprotected left main PCI. | 10.3390/jcm7070180 |
pubmed_565_22303 | BACKGROUND
Due to worldwide migration to Western countries, physicians are increasingly encountering patients with different ethnic backgrounds. Communication problems can arise as a result of differences in cultural backgrounds and poor language proficiency.
AIMS
To assess the effectiveness of an educational intervention on intercultural communication aimed to decrease inequalities in care provided between Western and non-Western patients.
DESIGN OF STUDY
A randomised controlled trial with randomisation at the GP level and outcome measurements at the patient level.
SETTING
General practice in Rotterdam.
METHOD
Thirty-eight Dutch GPs in the Rotterdam region, with at least 25% of inhabitants of non-Western origin, and 2407 visiting patients were invited to participate in the study. A total of 986 consultations were finally included. The GPs were educated about cultural differences and trained in intercultural communication. Patients received a videotaped instruction focusing on how to communicate with their GP in a direct way. The primary outcome measure was mutual understanding and the secondary outcomes were patient's satisfaction and perceived quality of care. The intervention effect was assessed for all patients together, for the 'Western' and 'non-Western' patients, and for patients with different cultural backgrounds separately.
RESULTS
An intervention effect was seen 6 months after the intervention, as improvement in mutual understanding (and some improvement in perceived quality of care) in consultations with 'non-Western' patients.
CONCLUSIONS
A double intervention on intercultural communication given to both physician and patient decreases the gap in quality of care between 'Western' and 'non-Western' patients. | pubmed_565_22303 |
pubmed_1040_663 | This paper employs a rhetorical form designed to clarify and sharpen the focus of the very special stance required--which must be painstakingly learned under careful supervision--in order to effectively tune in to communications coming from the unconscious of the patient. This is the hardest task that must be mastered to become truly empathic and sensitive in dyadic relationships, a unique expertise that marks the psychiatrist as a genuine specialist in medical practice. Regardless of theoretical orientation, neither the form or content of any therapeutic intervention can be appropriate unless it is empathically based. Clinical vignettes illustrate the lack of such empathy, and readings are suggested that enhance our approach to learning this skill, borrowing especially from Kohut and Bion. The great importance of the often ignored "background" of the patient's communication is emphasized, and is illustrated from the field of music in the work of John Cage and Anton Webern. The congruence between this clinical psychiatric problem and the main thrust of Continental philosophy, which attempts to put man back in touch with himself, is described. Suggestions are offered to supervisors how to develop these skills in the novice. Finally, a discussion is presented of the effect on the professional and personal life of the therapist who has not developed these skills, emphasizing the dangers of "burn-out" in therapists and the implicit philosophy of life in a money-oriented practice of psychotherapy. The dangers of not attending to such matters even during residency training are pointed out, in an attempt to raise the consciousness level of the therapist to the extreme importance of background practices both in the patient and the therapist. | 10.1176/appi.psychotherapy.1985.39.1.30 |
pubmed_61_12865 | The quadrupolar Carr-Purcell Meiboom-Gill (QCPMG) and double frequency sweep (DFS)/QCPMG pulse sequences are applied in order to acquire the first solid-state 39K NMR spectra of organometallic complexes, the polymeric main group metallocenes cyclopentadienyl potassium (CpK) and pentamethylcyclopentadienyl potassium (Cp*K). Piecewise QCPMG NMR techniques are used to acquire a high S/N 39K spectrum of the broad central transition of Cp*K, which is ca. 200 kHz in breadth. Analytical and numerical simulations indicate that there is a significant quadrupolar interaction present at both potassium nuclei (C(Q)(39K) = 2.55(6)/2.67(8) MHz and 4.69(8) MHz for CpK (static/MAS) and Cp*K, respectively). Experimental quadrupolar asymmetry parameters suggest that both structures are bent about the potassium atoms (eta(Q)(39K) = 0.28(3)/0.29(3) for CpK (static/MAS) and eta(Q)(39K) = 0.30(3) for Cp*K). Variable-temperature (VT) 39K NMR experiments on CpK elucidate temperature-dependent changes in quadrupolar parameters which can be rationalized in terms of alterations of bond distances and angles with temperature. 13C CP/MAS NMR experiments are conducted upon both samples to quantify the carbon chemical shielding anisotropy (CSA) at the Cp' ring carbon atoms. Ab initio carbon CSA and 39K electric-field gradient (EFG) and CSA calculations are conducted and discussed for the CpK complex, in order to correlate the experimental NMR parameters with molecular structure in CpK and Cp*K. 39K DFS/QCPMG and 13C CP/MAS experiments prove invaluable for probing molecular structure, temperature-dependent structural changes, and the presence of impurities in these systems. | 10.1021/jp058059l |
pubmed_335_20168 | Chronic myeloid leukemia (CML), which is characterized by the Philadelphia translocation, which fuses breakpoint cluster region (BCR) sequences from chromosome 22 upstream of the Abelson murine leukemia viral oncogene homolog (ABL) on chromosome 9, requires specific and efficient treatment. The CRISPR/Cas9 system, with its mechanism of specific DNA complementary recognition by engineered guide RNA (gRNA), allows the development of novel therapeutics for CML. To achieve targeted therapy of CML with the CRISPR/Cas9 system, we encapsulated a CRISPR/Cas9 plasmid (pCas9) expressing gRNA targeting the overhanging fusion region of the BCR-ABL gene (pCas9/gBCR-ABL) with poly(ethylene glycol)-b-poly(lactic acid-co-glycolic acid) (PEG-PLGA)-based cationic lipid-assisted polymeric nanoparticles (CLANs), which specifically disrupted the CML-related BCR-ABL gene while sparing the BCR and ABL genes in normal cells. After intravenous injection, CLANs carrying pCas9/gBCR-ABL (CLANpCas9/gBCR-ABL) efficiently knocked out the BCR-ABL fusion gene of CML cells and improved the survival of a CML mouse model, indicating that the combination of the CRISPR/Cas9 system with nanocarriers is a promising strategy for targeted treatment of CML. | 10.1039/c8bm00263k |
pubmed_543_19718 | Retinoids play an important role as differentiating agents in a variety of normal and neoplastic cells and have been reported to induce ICAM-1 levels in melanomas, a phenomenon that we confirm in this paper. The effects of retinoids on gene expression usually involve the binding of specific retinoic acid receptor trans-acting factors (RARs) with their ligands, which then interact with specific target sites, the retinoic acid responsive elements (RAREs) present in the promoters of responsive genes. In the case of ICAM-1, we have cloned and analyzed the proximal regulatory region of the human gene. We show that the ICAM-1 promoter is RA-inducible, that it contains a putative consensus RARE (GGGTCATCGCCCTGCC), which binds in vitro RAR alpha complemented with RXRs, and that mutation of the RARE abrogates promoter responsiveness to RA. These studies allow ICAM-1 to be added to the list of genes transcriptionally activated by RA acting through an RARE element. | 10.1006/excr.1995.1155 |
pubmed_682_16155 | Evidence that Colletotrichum fragariae causes disease on hosts other than strawberry is limited. In the fall of 2006, fungal isolates from silver date palm with leaf spot symptoms and from cyclamen with leaf spot and stem rot symptoms were identified as C. fragariae. After confirming the pathogenicity of the isolates on their host of origin, a representative isolate from each host was compared to C. fragariae and to C. gloeosporioides/Glomerella cingulata isolates from strawberry. Date palm and cyclamen isolates bore conidia on setae, and conidia were tapered and in the size range of C. fragariae reference isolates. Sequence data from the combined internal transcribed spacer (ITS) regions 1 and 2 and the gene for the 5.8 ribosomal RNA from the cyclamen and date palm isolates matched the sequence for C. fragariae reference isolates. Based on these characteristics, it was concluded that the C. fragariae species designation was correct for both isolates. However, the date palm isolate was a weak pathogen on strawberry compared with other isolates and had a distinct AT-rich DNA banding pattern. The ability of the cyclamen isolate to cause crown rot on strawberry was comparable with the strawberry reference isolates, and the AT-rich DNA banding pattern of the cyclamen isolate was identical to the C. fragariae isolates from strawberry. The results indicate that C. fragariae is a pathogen on hosts other than strawberry and that there is more diversity among C. fragariae isolates than previously reported. | 10.1094/PDIS-92-10-1432 |
pubmed_602_21405 | Medical informatics is a specific and interdisciplinary science which involves many participants of the health system like: patients, physicians, nurses, managers, administrators, computer experts, students, with the different level of education and understanding, different approaches and expectations. Education of medical informatics requests organization solutions of high quality and necessary equipment for its realization. Educational programs are also limited by student's basic knowledge of informatics from secondary schools. For assessment of this knowledge we have conducted special designed questionnaire at the first year of undergraduate study which results confirm our thesis that great number of students entered the faculty with the lack of basic knowledge from informatics area. In this paper was presented level of organization and education of medical informatics at the Medical faculty and University Clinical Center of Tuzla, with its characteristics through which this system has been passed since 1990. | pubmed_602_21405 |
pubmed_1026_24502 | BACKGROUND
High levels of circulating neutrophil extracellular traps (NETs) are associated with a poor prognosis in influenza A infection. It remains unclear whether NETs in the plasma or bronchoalveolar lavage fluid (BALF) can predict clinical outcomes in influenza.
METHODS
One hundred eighteen patients who were diagnosed with H1N1 influenza in 2017-2018 were recruited. The NETs were assessed in plasma and BALF samples by quantifying cell-free deoxyribonucleic acid (cfDNA) and protein-DNA complexes. Predictions of severe illness and 60-day mortality were analyzed with receiver operating characteristic curves.
RESULTS
The NET levels were significantly elevated in the BALF and contributed to the pathology of lungs, yet it was not associated with disease severity or mortality in patients severely infected with H1N1. Plasma NET levels were significantly increased in the patients with severe influenza and positively correlated with the oxygen index and sequential organ failure assessment scores. High levels of plasma cfDNA (>286.6 ng/mL) or histone-bound DNA (>9.4 ng/mL) discriminated severe influenza from mild, and even higher levels of cfDNA (>306.3 ng/mL) or histone-bound DNA (>23.1 ng/mL) predicted fatal outcomes in severely ill patients.
CONCLUSIONS
The cfDNA and histone-bound DNA in plasma represent early predictive biomarkers for the prognosis of influenza. | 10.1093/infdis/jiaa241 |
pubmed_64_19653 | The kinetics of l-phenylalanine ammonia-lyase (PAL) penetration into the monolayer of liver cells after its release from capsules was studied. The studies showed the absence of the effect of the capsule shell based on plant hydrocolloids on the absorption of l-phenylalanine ammonia-lyase in systems simulating the liver surface. After 120 min of incubation, in all variants of the experiment, from 87.0 to 96.8% of the enzyme penetrates the monolayer of liver cells. The combined analysis of the results concludes that the developed encapsulated form of l-phenylalanine ammonia-lyase is characterized by high efficiency in correcting the disturbed catabolism of phenylalanine in phenylketonuria, which is confirmed by the results of experiments carried out on in vitro model systems. PAL is approved for the treatment of adult patients with phenylketonuria. The encapsulated l-phenylalanine ammonia-lyase form can find therapeutic application in the phenylketonuria treatment after additional in vitro and in vivo studies, in particular, the study of preparation safety indicators. Furthermore, it demonstrated high efficacy in tumor regression and the treatment of tyrosine-related metabolic disorders such as tyrosinemia. Several therapeutically valuable metabolites biosynthesized by PAL via its catalytic action are included in food supplements, antimicrobial peptides, drugs, amino acids, and their derivatives. PAL, with improved pharmacodynamic and pharmacokinetic properties, is a highly effective medical drug. | 10.3390/pharmaceutics13030383 |
pubmed_1112_19296 | A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay for the ALK inhibitor crizotinib was developed and validated. Plasma samples were pre-treated using protein precipitation with acetonitrile containing crizotinib-(13)C(2)-(2)H(5) as internal standard. The extract was directly injected into the chromatographic system after dilution with water. This system consisted of a sub-2 μm particle, trifunctional bonded octadecyl silica column with a gradient using 0.1% (v/v) of ammonium hydroxide in water and methanol. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 10-10,000 ng/ml calibration range with r(2)=0.99980±0.00014 for double logarithmic linear regression (n=5). Within day precisions (n=6) were 3.4-4.8%, between day (3 days; n=18) precisions 3.6-4.9%. Accuracies were between 107% and 112% for the whole calibration range. The drug was sufficiently stable under all relevant analytical conditions. Oxidative metabolites of crizotinib were monitored semi-quantitatively. Finally, the assay was successfully used to assess drug pharmacokinetics in mice. | 10.1016/j.jchromb.2012.08.021 |
pubmed_101_12252 | One of the most well-known cancer subtypes worldwide is triple-negative breast cancer (TNBC) which has reduced prediction due to its antagonistic biotic actions and target's deficiency for the treatment. The current work aims to discover the countenance outlines and possible roles of lncRNAs in the TNBC via computational approaches. Long non-coding RNAs (lncRNAs) exert profound biological functions and are widely applied as prognostic features in cancer. We aim to identify a prognostic lncRNA signature for the TNBC. First, samples were filtered out with inadequate tumor purity and retrieved the lncRNA expression data stored in the TANRIC catalog. TNBC sufferers were divided into two prognostic classes which were dependent on their survival time (shorter or longer than 3 years). Random forest was utilized to select lncRNA features based on the lncRNAs differential expression between shorter and longer groups. The Stochastic gradient boosting method was used to construct the predictive model. As a whole, 353 lncRNAs were differentially transcribed amongst the shorter and longer groups. Using the recursive feature elimination, two lncRNAs were further selected. Trained by stochastic gradient boosting, we reached the highest accuracy of 69.69% and area under the curve of 0.6475. Our findings showed that the two-lncRNA signs can be proved as potential biomarkers for the prognostic grouping of TNBC's sufferers. Many lncRNAs remained dysregulated in TNBC, while most of them are likely play a role in cancer biology. Some of these lncRNAs were linked to TNBC's prediction, which makes them likely to be promising biomarkers. | 10.3389/fbioe.2020.523127 |
pubmed_148_4958 | In confirmation and extension of observations by Carp and his associates, brain tissue and sera from patients with multiple sclerosis (MS) were found to harbor an agent which induces a transitory depression in polymorphonuclear leukocytes (PMN) in mice as well as in rats, hamsters, and guinea pigs. All of eight MD brains contained this agent at titers as high as 10(-9)/g of brain tissue. The agent was found in MS sera at titers up to 10(-3)/ml of serum, but its presence depended to some extent on the clinical status of the patients; it was observed more frequently in sera of patients with active disease (73%) thatn in sera of patients with quiescent disease (31%). Control brain tissues or sera failed to induce PMN depression. The apparently MS-associated agent (MSAA) passed through 50-nm but not 25-nm membrane filters (Millipore Corp.) and was largely sedimented at 105,000 X g but not at 50,000 X g for 1 h. It multiplied to high titers in the central nervous tissue of the inoculated animals and could be serially transmitted from animal to animal by passage of brain homeganates. Various observations and considerations appear to preclude that MS-associated agent represents an indigenous animal virus. Although its role in MS remains to be determined, it should be considered a candidate for the etiology of this disease. | 10.1128/iai.12.6.1355-1366.1975 |
pubmed_896_20950 | INTRODUCTION
Post-partum depression (PPD) affects up to 19.1% of pregnancies and is associated with increased levels of proinflammatory cytokines, inflammation, and reductions in brain-derived neurotrophic factor (BDNF). Previous work by our team suggests that environmental toxins such as polybrominated diphenyl ethers (PBDEs) enhance placental inflammation and reduce BDNF production. Nearly, 100% of studied women in California have some level of exposure to these compounds due to extensive use of the flame retardants. High levels of exposure to PBDEs has been linked to increased risk of adverse pregnancy complications associated with placental inflammation such as preterm birth and gestational diabetes but their effects on risk of PPD is unclear.
OBJECTIVE
To determine if PPD is associated with higher levels of PBDE-47, the most common PBDE congener in maternal plasma.
METHODS
PBDE-47 was quantified in first trimester plasma samples collected from a cohort of 367 asymptomatic pregnant women that were routinely screened for depressive symptoms for 1 year post-partum. Data were analyzed using general linear models and multivariable logistic regression to determine if higher levels of PBDE-47 in the first trimester are associated with development of PPD.
RESULTS
Women who developed PPD (n = 22) had significantly higher PBDE-47 levels in their plasma (p=.031) relative to those in which PPD was not diagnosed. Logistic regression analysis suggested that each two-fold increase in PBDE-47 concentrations increased the risk of PPD by 22% (OR = 1.22, 95% CI: 1.03, 1.47). Groups were similar regarding PTB rate, race-ethnicity, parity, child's sex, maternal pre-pregnancy obesity status, maternal age, family income, and study center. Results remained significant after adjustment for these possible confounding factors.
CONCLUSIONS
These results suggest that PBDE-47 exposure in the first trimester is associated with increased risk of PPD. | 10.1080/14767058.2021.1974386 |
pubmed_851_20353 | According to the Centers for Disease Control and Prevention, approximately 25 million Americans suffer from asthma. The disease total annual cost is about $56 billion and includes both the direct and indirect costs of medications, hospital stays, missed work, and decreased productivity. Air pollution with xenobiotics, bacterial agents, and industrial nanomaterials, such as carbon nanotubes, contribute to the exacerbation of this condition and are a point of particular attention in environmental toxicology as well as in occupational health and safety research. Mast cell degranulation and activation of Th2 cells triggered either by allergen-specific immunoglobulin E (IgE) or by alternative mechanisms, such as locally produced neurotransmitters, underlie the pathophysiological process of airway constriction during an asthma attack. Other immune and non-immune cell types, including basophils, eosinophils, Th1, Th17, Th9, macrophages, dendritic cells, and smooth muscle cells, are involved in the inflammatory and allergic responses during asthma, which, under chronic conditions, may progress without mast cells, the key trigger of the acute asthma attack. To decipher complex molecular, cellular, and genetic mechanisms, many researchers have attempted to develop in vitro and in vivo models to study asthma. Herein, we summarize the advantages and disadvantages of various models and their applicability to nanoparticle evaluation in asthma research. We further suggest that a framework for both in vitro and in vivo methods should be used to study the impact of engineered nanomaterials on asthma etiology, pathophysiology, and treatment. | 10.1021/acsnano.7b04916 |
pubmed_821_21741 | The regulatory-targeting subunit (RGL), also called GM) of the muscle-specific glycogen-associated protein phosphatase PP1G targets the enzyme to glycogen where it modulates the activity of glycogen-metabolizing enzymes. PP1G/RGL has been postulated to play a central role in epinephrine and insulin control of glycogen metabolism via phosphorylation of RGL. To investigate the function of the phosphatase, RGL knockout mice were generated. Animals lacking RGL show no obvious defects. The RGL protein is absent from the skeletal and cardiac muscle of null mutants and present at approximately 50% of the wild-type level in heterozygotes. Both the level and activity of C1 protein are also decreased by approximately 50% in the RGL-deficient mice. In skeletal muscle, the glycogen synthase (GS) activity ratio in the absence and presence of glucose-6-phosphate is reduced from 0.3 in the wild type to 0.1 in the null mutant RGL mice, whereas the phosphorylase activity ratio in the absence and presence of AMP is increased from 0.4 to 0.7. Glycogen accumulation is decreased by approximately 90%. Despite impaired glycogen accumulation in muscle, the animals remain normoglycemic. Glucose tolerance and insulin responsiveness are identical in wild-type and knockout mice, as are basal and insulin-stimulated glucose uptakes in skeletal muscle. Most importantly, insulin activated GS in both wild-type and RGL null mutant mice and stimulated a GS-specific protein phosphatase in both groups. These results demonstrate that RGL is genetically linked to glycogen metabolism, since its loss decreases PP1 and basal GS activities and glycogen accumulation. However, PP1G/RGL is not required for insulin activation of GS in skeletal muscle, and rather another GS-specific phosphatase appears to be involved. | 10.1128/MCB.21.8.2683-2694.2001 |
pubmed_753_3974 | INTRODUCTION
The number of overweight and obese patients undergoing renal transplantation has increased dramatically over the past two decades. Studies on graft survival and posttransplantation complications have often yielded conflicting results. Some authors have reported similar results for graft and patient survivals between obese and normal weight patients, but with a marginally increased rate of postoperative complications. In contrast, other reports note higher percentage of graft losses as well as increased mortality. In our study, we analyzed early- and long-term outcomes among obese versus nonobese kidney transplant recipients.
PATIENTS AND METHODS
Between January 2000 and December 2008, we performed 563 cadaveric kidney transplantations. Recipients were classified in 1 of 5 groups based on their body mass index (BMI) at the time of transplantation: group A (n = 68; BMI < 18.5); group B (n = 310; 18.6 < BMI < 24.9); group C (n = 143; 25 < BMI < 29.9); group D (n = 32; 30 < BMI < 34.9); and group E (n = 10; BMI ≥ 35). The comparative analysis included patient and graft survivals, postoperative complications, onset of delayed graft function (DGF), acute rejection episodes, hospital stay, and serum creatinine values in the first 3 years posttransplantation.
RESULTS
At a mean follow-up of 53 months (range, 3-112 months), DGF was observed in 20 patients in group A (29.4%), 82 in group B (26.4%), 43 in group C (30%), 16 in group D (50%), and 4 in group E (40%). Nevertheless, obese patients (groups D and E) showed higher mean serum creatinine values and worse renal function at 6 months (P = .001), 1 year (P < .001), and 3 years (P = .001). Moreover, they were at increased risk of an acute rejection episode (P = .01) and more susceptible to cardiovascular and metabolic complications (P = .01). Morbidly obese patients displayed a higher incidence of postsurgical complications (P = .002). There were no differences in the incidences of chronic allograft nephropathy (CAN) or infectious complications. Despite the differences in morbidity among the 5 groups, we failed to observe significant differences in patient or graft survivals at 6, 12, 36, or 60 months.
CONCLUSION
Our findings suggested that obese patients should not be discriminated against simply based on the BMI. At our center, obese (BMI >35) transplantation candidates undergo a thorough cardiac evaluation, as well as pulmonary, endocrine, and nutritional counseling seeking to minimize medical and surgical complications and improve survival and quality of life. | 10.1016/j.transproceed.2010.12.022 |
pubmed_933_12325 | Accumulating evidence suggests that Sonic hedgehog (Shh) signaling plays a crucial role in eye vesicle patterning in vertebrates. Shh promotes expression of Pax2 in the optic stalk and represses expression of Pax6 in the optic cup. Shh signaling contributes to establishment of both proximal-distal and dorsal-ventral axes by activating Vax1, Vax2, and Pax2. In the dorsal part of the developing retina, Bmp4 is expressed and antagonizes the ventralizing effects of Shh signaling through the activation of Tbx5 expression in chick and Xenopus. To examine the roles of Shh signaling in optic cup formation and optic stalk development, we utilized the Smoothened (Smo) conditional knockout (CKO) mouse line. Smo is a membrane protein which mediates Shh signaling into inside of cells. Cre expression was driven by Fgf15 enhancer. The ventral evagination of the optic cup deteriorated from E10 in the Smo-CKO, whereas the dorsal optic cup and optic stalk develop normally until E11. We analyzed expression of various genes such as Pax family (Pax2/Pax6), Vax family (Vax1/Vax2) and Bmp4. Bmp4 expression was greatly upregulated in the optic vesicle by the 21-somite stage. Then Vax1/2 expression was decreased at the 20- to 24-somite stages. Pax2/6 expression was affected at the 27- to 32-somite stages. Our data suggest that the effects of the absence of Shh signaling on Vax1/Vax2 are mediated through increased Bmp4 expression throughout the optic cup. Also unchanged patterns of Raldh2 and Raldh3 suggest that retinoic acid is not the downstream to Shh signaling to control the ventral optic cup morphology. | 10.1016/j.mod.2009.10.006 |
pubmed_133_5990 | AIM
The aim of this study was to evaluate the prevalence of vertical root fractures (VRF) in extracted endodontically treated teeth and to correlate the findings to previous studies and surveys.
METHODOLOGY
Root-canal-treated teeth were referred for extraction from a public dental clinic. The endodontic therapy had been completed by a variety of dentists. Each tooth was evaluated following extraction by the oral surgeon who performed the procedure: the exact aetiology for the clinical diagnosis that led to the extraction was recorded.
RESULTS
The major reasons for extraction were restorative (43.5%) and endodontic (21.1%), followed by vertical root fractures (10.9%).
CONCLUSIONS
The relatively high prevalence of vertical root fractures in this survey compared with previous clinical and radiographic surveys was probably related to the difficulties in making a clinical diagnosis of vertical fractures before extraction. | 10.1046/j.1365-2591.1999.00208.x |
pubmed_822_10148 | In this study we present the distribution and colocalization pattern of cocaine- and amphetamine-regulated transcript (CART) and three calcium-binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV) in the subicular complex (SC) of the guinea pig. The subiculum (S) and presubiculum (PrS) showed higher CART-immunoreactivity (-IR) than the parasubiculum (PaS) as far as the perikarya and neuropil were concerned. CART- IR cells were mainly observed in the pyramidal layer and occasionally in the molecular layer of the S. In the PrS and PaS, single CART-IR perikarya were dispersed, however with a tendency to be found only in superficial layers. CART-IR fibers were observed throughout the entire guinea pig subicular neuropil. Double-labeling immunofluorescence showed that CART-IR perikarya, as well as fibers, did not stain positively for any of the three CaBPs. CART-IR fibers were only located near the CB-, CR-, PV-IR perikarya, whereas CART-IR fibers occasionally intersected fibers containing one of the three CaBPs. The distribution pattern of CART was more similar to that of CB and CR than to that of PV. In the PrS, the CART, CB and CR immunoreactivity showed a laminar distribution pattern. In the case of the PV, this distribution pattern in the PrS was much less prominent than that of CART, CB and CR. We conclude that a heterogeneous distribution of the CART and CaBPs in the guinea pig SC is in keeping with findings from other mammals, however species specific differences have been observed. | pubmed_822_10148 |
pubmed_1037_24714 | The bicyclic amido-substituted silicon(I) ring compound Si4 {N(SiMe3 )Mes}4 2 (Mes=Mesityl=2,4,6-Me3 C6 H2 ) features enhanced zwitterionic character and different reactivity from the analogous compound Si4 {N(SiMe3 )Dipp}4 1 (Dipp=2,6-i Pr2 C6 H3 ) due to the smaller mesityl substituents. In a reaction with the N-heterocyclic carbene NHC (1,3,4,5-tetramethyl-imidazol-2-ylidene), we observe adduct formation to give Si4 {N(SiMe3 )Mes}4 ⋅ NHC (3). This adduct reacts further with the Lewis acid BH3 to yield the Lewis acid-base complex Si4 {N(SiMe3 )Mes}4 ⋅ NHC ⋅ BH3 (4). Coordination of AlBr3 to 2 leads to the adduct 5. Calculated proton affinities and fluoride ion affinities reveal highly Lewis basic and very weak Lewis acidic character of the low-valent silicon atoms in 1 and 2. This is confirmed by protonation of 1 and 2 with Brookharts acid yielding 6 and 7. Reaction with diphenylacetylene only occurs at 111 °C with 2 in toluene and is accompanied by fragmentation of 2 to afford the silacyclopropene 8 and the trisilanorbornadiene species 9. | 10.1002/chem.202103101 |
pubmed_469_13255 | We characterize living systems as resilient "chemical organizations", i.e. self-maintaining networks of reactions that are able to resist a wide range of perturbations. Dissipative structures, such as flames or convection cells, are also self-maintaining, but much less resilient. We try to understand how life could have originated from such self-organized structures, and evolved further, by acquiring various mechanisms to increase resilience. General mechanisms include negative feedback, buffering of resources, and degeneracy (producing the same resources via different pathways). Specific mechanisms use catalysts, such as enzymes, to enable reactions that deal with specific perturbations. This activity can be regulated by "memory" molecules, such as DNA, which selectively produce catalysts when needed. We suggest that major evolutionary transitions take place when living cells of different types or species form a higher-order organization by specializing in different functions and thus minimizing interference between their reactions. | 10.1016/j.biosystems.2022.104720 |
pubmed_660_22807 | Determining whether power outages have significant fertility effects is an important policy question in developing countries, where blackouts are common and modern forms of family planning are scarce. Using birth records from Zanzibar, this study shows that a month-long blackout in 2008 caused a significant increase in the number of births 8 to 10 months later. The increase was similar across villages that had electricity, regardless of the level of electrification; villages with no electricity connections saw no changes in birth numbers. The large fertility increase in communities with very low levels of electricity suggests that the outage affected the fertility of households not connected to the grid through some spillover effect. Whether the baby boom is likely to translate to a permanent increase in the population remains unclear, but this article highlights an important hidden consequence of power instability in developing countries. It also suggests that electricity imposes significant externality effects on rural populations that have little exposure to it. | 10.1007/s13524-014-0316-7 |
pubmed_769_20908 | OBJECTIVE
Treatment of primary spinal infection includes medical management with or without surgical intervention. The objective of this study was to identify risk factors for the eventual need for surgery in patients with primary spinal infection on initial presentation.
METHODS
From January 2010 to July 2019, 275 patients presented with primary spinal infection. Demographic, infectious, imaging, laboratory, treatment, and outcome data were retrospectively reviewed and collected. Thirty-three patients were excluded due to insufficient follow-up (≤ 90 days) or death prior to surgery.
RESULTS
The mean age of the 242 patients was 58.8 ± 13.6 years. The majority of the patients were male (n = 130, 53.7%), White (n = 150, 62.0%), and never smokers (n = 132, 54.5%). Fifty-four patients (22.3%) were intravenous drug users. One hundred fifty-four patients (63.6%) ultimately required surgery while 88 (36.4%) never needed surgery during the duration of follow-up. There was no significant difference in age, gender, race, BMI, or comorbidities between the surgery and no-surgery groups. On univariate analysis, the presence of an epidural abscess (55.7% in the no-surgery group vs 82.5% in the surgery group, p < 0.0001), the median spinal levels involved (2 [interquartile range (IQR) 2-3] in the no-surgery group vs 3 [IQR 2-5] in the surgery group, p < 0.0001), and active bacteremia (20.5% in the no-surgery vs 35.1% in the surgery group, p = 0.02) were significantly different. The cultured organism and initial laboratory values (erythrocyte sedimentation rate, C-reactive protein, white blood cell count, creatinine, and albumin) were not significantly different between the groups. On multivariable analysis, the final model included epidural abscess, cervical or thoracic spine involvement, and number of involved levels. After adjusting for other variables, epidural abscess (odds ratio [OR] 3.04, 95% confidence interval [CI] 1.64-5.63), cervical or thoracic spine involvement (OR 2.03, 95% CI 1.15-3.61), and increasing number of involved levels (OR 1.16, 95% CI 1.01-1.35) were associated with greater odds of surgery. Fifty-two surgical patients (33.8%) underwent decompression alone while 102 (66.2%) underwent decompression with fusion. Of those who underwent decompression alone, 2 (3.8%) of 52 required subsequent fusion due to kyphosis. No patient required hardware removal due to persistent infection.
CONCLUSIONS
At time of initial presentation of primary spinal infection, the presence of epidural abscess, cervical or thoracic spine involvement, as well as an increasing number of involved spinal levels were potential risk factors for the eventual need for surgery in this study. Additional studies are needed to assess for risk factors for surgery and antibiotic treatment failure. | pubmed_769_20908 |
pubmed_786_22789 | Almost all coal based thermal power plants (CTPP) in India use electrostatic precipitator (ESP) for reduction of particulate matter (PM) in flue gas generated due to the combustion of Indian coal. This coal is characterized by high ash content, low calorific value and low sulfur content resulting in the generation of a very large amount of highly electrically-resistive fly-ash; thereby requiring a very large size ESP to minimize the fly-ash emissions. However, the flue-gas particle size distribution analysis showed that 60% of the particles are above 15 microm size, which can be conveniently removed using a low-cost inertial separator such as a cyclone separator. It is proposed that a cyclone be used, as a pre-cleaner to ESP so that the large size fraction of fly-ash can be removed in the pre-cleaning and the remaining flue-gas entering the ESP will then contain only small size particles with low dust loading, thereby requiring a small ESP, and improving overall efficiency of dust removal. A low efficiency (65%), high throughput cyclone is considered for pre-cleaning flue gas and the ESP is designed for removal of the remaining 35% fly-ash from the flue gas. It is observed that with 100% dust load, the ESP requires six fields per pass, whereas with cyclone as a pre-cleaner, it requires only five fields per pass. Introducing cyclone into the flue gas path results in additional head loss, which needs to be overcome by providing additional power to induced draft (ID) fan. The permissible head loss due to the cyclone is estimated by comparing the power requirement in the bag filter control unit and cyclone-ESP combined unit. It is estimated that a head loss of 10 cm of water can be permitted across the cyclone so as to design the same for 65% efficiency. | 10.1080/09593330309385686 |
pubmed_67_24021 | Microglia are important immune cells in the central nervous system (CNS) that undergo turnover throughout the lifespan. If microglial debris is not removed in a timely manner, accumulated debris may influence CNS function. Clearance of microglial debris is crucial for CNS homeostasis. However, underlying mechanisms remain obscure. We here investigate how dead microglia are removed. We find that although microglia can phagocytose microglial debris in vitro, the territory-dependent competition hinders the microglia-to-microglial debris engulfment in vivo. In contrast, microglial debris is mainly phagocytosed by astrocytes in the brain, facilitated by C4b opsonization. The engulfed microglial fragments are then degraded in astrocytes via RUBICON-dependent LC3-associated phagocytosis (LAP), a form of noncanonical autophagy. Interference with C4b-mediated engulfment and subsequent LAP disrupt the removal and degradation of microglial debris, respectively. Together, we elucidate the cellular and molecular mechanisms of microglial debris removal in mice, extending the knowledge on the maintenance of CNS homeostasis. | 10.1038/s41467-022-33932-3 |
pubmed_27_14950 | Acetylcholinesterases (AChEs) very sensitive to fasciculin inhibition (KiS in picomolar range) have a distinctive group of aromatic amino acids in the peripheral region (Y70, Y121, W279 in Torpedo AChE). Enzymes that lack these amino acids like butyrylcholinesterases (BChEs) or one or two of them like cobra venom, insect and chicken AChEs are 1000 to 1,000,000 times less sensitive. Fasciculin is a non-competitive inhibitor of the hydrolysis of choline and neutral esters by very sensitive AChEs. For the other group of enzymes, differences arise according to the type of substrate. Fasciculin still behaves as a non-competitive inhibitor with choline esters. In contrast, hydrolysis of phenylacetate was unaffected or slightly increased with BChEs and a partial competitive inhibition was observed with cobra venom and chicken enzymes. | 10.1016/0041-0101(96)00035-9 |
pubmed_223_22902 | Soybean is an important oilseed crop grown globally. However, two examples of environmental stresses that drastically regulate soybean growth are low light and high-temperature. Emerging evidence suggests a possible interconnection between these two environmental stimuli. Low light and high-temperature as individual factors have been reported to regulate plant hypocotyl elongation. However, their interactive signal effect on soybean growth and development remains largely unclear. Here, we report that gibberellins (GAs) and auxin are required for soybean hypocotyl elongation under low light and high-temperature interaction. Our analysis indicated that low light and high-temperature interaction enhanced the regulation of soybean hypocotyl elongation and that the endogenous GA3 , GA7 , indole-3-acetic acid (IAA), and indole-3-pyruvate (IPA) contents significantly increased. Again, analysis of the effect of exogenous phytohormones and biosynthesis inhibitors treatments showed that exogenous GA, IAA, and paclobutrazol (PAC), 2, 3, 5,-triiodobenzoic acid (TIBA) treatments significantly regulated soybean seedlings growth under low light and high-temperature interaction. Further qRT-PCR analysis showed that the expression level of GA biosynthesis pathway genes (GmGA3ox1, GmGA3ox2 and GmGA3) and auxin biosynthesis pathway genes (GmYUCCA3, GmYUCCA5 and GmYUCCA7) significantly increased under (i) low light and high-temperature interaction and (ii) exogenous GA and IAA treatments. Altogether, these observations support the hypothesis that gibberellins and auxin regulate soybean hypocotyl elongation under low light and high-temperature stress interaction. | 10.1111/ppl.13158 |
pubmed_590_12070 | The aim of this study was to verify the influence of hyperlactemia and blood acidosis induction on lactate minimum intensity (LMI). Twenty recreationally trained males who were experienced in cycling (15 cyclists and 5 triathletes) participated in this study. The athletes underwent 3 lactate minimum tests on an electromagnetic cycle ergometer. The hyperlactemia induction methods used were graded exercise test (GXT), Wingate test (WAnT), and 2 consecutive Wingate tests (2 × WAnTs). The LMI at 2 × WAnTs (200.3 ± 25.8 W) was statistically higher than the LMI at GXT (187.3 ± 31.9 W) and WAnT (189.8 ± 26.0 W), with similar findings for blood lactate, oxygen uptake, and pulmonary ventilation at LMI. The venous pH after 2 × WAnTs was lower (7.04 ± 0.24) than in (p ≤ 0.05) the GXT (7.19 ± 0.05) and WAnT (7.19 ± 0.05), whereas the blood lactate response was higher. In addition, similar findings were observed for bicarbonate concentration [HCO3] (2 × WAnTs lower than WAnT; 15.3 ± 2.6 mmol·L and 18.2 ± 2.7 mmol·L1, respectively) (p ≤ 0.05). However, the maximal aerobic power and total time measured during the incremental phase also did not differ. Therefore, we can conclude that the induction mode significantly affects pH, blood lactate, and [HCO3] and consequently they alter the LMI and physiological parameters at LMI. | 10.1519/JSC.0000000000000490 |
pubmed_311_8663 | AZD9291 is one of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) induced by AZD9291 is very seldom. We provide a case of NSCLC treated with AZD9291 who developed ILD and died in order to improve the knowledge on AZD9291. | 10.4103/0973-1482.199380 |
pubmed_398_4517 | Administration of hepatocarcinogens aflataxin B1 (AFB1) and N-nitrosodimethylamine (NDMA) to rats caused single-strand breaks in hepatic nuclear DNA. The damage was found to be maximum at 4 hours following AFB1 administration and at 2 hours following NDMA administration. These damages were repaired after 17 and 4 hours, respectively in cases of AFB1 and NDMA. The activity of poly(ADP-ribose)polymerase (PARP), an enzyme known to use single-strand breaks of DNA as cofactor, was observed to increase with increasing damage to DNA and decrease as and when this damage got repaired. DNA polymerase beta and DNA ligase activities were also seen to increase and decline in a way analogous to PARP. In contrast, DNA topoisomerase activity declined corresponding to an increase in PARP activity. These observations suggest a possible role of PARP in coordinating the activities of other enzymes involved in DNA repair. It is also envisaged that these parameters can be utilized to devise strategies to counteract the deleterious effects of chemical carcinogens. | pubmed_398_4517 |
pubmed_383_4559 | PURPOSE
To evaluate corneal endothelial cell density (ECD) in the eyes with different grades of late spontaneous in-the-bag intraocular lens (IOL) dislocation.
METHODS
A prospective study included seventy-eight patients who applied for IOL dislocation. Overall 80 eyes were divided into four grades based on the in-the-bag IOL dislocation classification. All eyes underwent a complete ophthalmological examination. ECD was evaluated using in vivo corneal confocal microscopy.
RESULTS
Median corneal ECD was 1929 (1022-2958) cells/mm2 of all the patients. The lowest number of ECD was in grade 2 (grade 1 median ECD 1990.33 (1182-2425.33) cells/mm2, grade 2-1577.0 (1022-2958) cells/mm2, grade 3-2205.84 (1259-2807.67) cells/mm2 and grade 4-2072.17 (1045-2581.0) cells/mm2). A statistically significant difference was observed between the median of ECD of grade 2nd and 3rd (p = 0.023). By grouping cases into those with and without glaucoma, we found that corneal ECD was significantly lower in eyes with glaucoma compared with eyes without glaucoma in grades 3 and 4 (p < 0.05), while in other grades, the difference did not reach the significance level. We divided the corneal ECD of all eyes into two categories ≤ 1500 cells/mm2 and > 1500 cells/mm2. Logistic regression demonstrated that the odds of having corneal ECD less than 1500 cells/mm2 increased by 3.5-fold if patients with IOL dislocation had been diagnosed with glaucoma previously.
CONCLUSION
Late spontaneous in-the-bag IOL dislocation reduced corneal ECD. Previously diagnosed glaucoma was the most common comorbidity. This condition has a significant impact on corneal ECD for patients with IOL dislocation. | 10.1007/s10792-021-01702-7 |
pubmed_592_15612 | A variety of forces are reshaping the traditional relationship between physicians and their patients. One consequence of this reform movement will be increased responsibility of the pediatrician to evaluate children with surgical diseases. Pediatricians also will be encouraged to do more of the minor surgical procedures themselves. It is not clear how academic pediatric surgeons should adapt to these changes to assure that the general pediatrician is equipped with the skills to handle this increased responsibility. One obvious solution would be to have the pediatrician in training rotate on the pediatric surgery service. The authors have considered these issues at their institution, and thus became interested in learning the status of pediatric surgical rotations by pediatric house staff in this country. A survey was distributed to the 221 accredited pediatric training programs in this country, and 143 individuals responded. Only thirty-five of these programs require a rotation on pediatric surgery. Eighty-six programs offer it as an elective, but only a minority of house staff takes it. The most disturbing aspect of the survey was the 28 of the programs had required a pediatric surgical rotation in the past but had eliminated it. The most common reasons given for this action were the poor educational content of the rotation and the labor requirements of the pediatric service. Based on the survey, the authors believe that it is unlikely that mandatory rotations on pediatric surgery will be begun in pediatric training curriculums. If pediatric surgeons wish to be involved in training pediatricians, they will need to address the educational content of their electives to meet the changing educational needs of the pediatricians. | 10.1016/s0022-3468(96)90828-3 |
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