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PubMed1983

Evidence for a neuroactive component in the toxic extract from Gonyaulax monilata.

1. A toxic extract has been isolated from the red-tide dinoflagellate Gonyaulax monilata by a phenol-water extraction. 2. The compound action potential in the desheathed frog sciatic nerve is irreversibly blocked by topical application of the extract in concentrations as low as 40 ppm (w/v) in frog Ringer solution. 3. The toxin liberated by this algae has the potential for causing the neurological symptoms exhibited by animals following the administration of the toxic extract.

Action Potentials↗

PubMed1996

Implications of the emerging home systems technologies for rehabilitation.

This paper gives a review of the current and anticipated developments in Integrated Home Systems and raises the implications these have in the field of rehabilitation. Firstly, the systems under consideration are defined and their development world-wide outlined. An overview of the European Home Systems Specification is given. The implications of this technology for rehabilitation are then raised considering: environmental control in the home; how people with degenerative conditions may be more readily able to remain in their homes as condition progresses; and remote health monitoring. The expectation that the initial impact will be in the area of environment control is stated, and a closer look at this field is made comparing current with anticipated systems. An outline is given of the TIDE Project HS-ADEPT (Home Systems--Access for Disabled and Elderly People to this Technology). The key findings of the survey of users made at the outset of the project, relevant to this paper, are given. The ongoing work of the project is described in brief. The continuing developments in Integrated Home Systems and in particular the issue of standards are noted. Concluding comments are offered in the hope of stimulating the necessary interdisciplinary discussion if this technology is to realize its full potential in the field of rehabilitation.

Electronics, Medical↗

PubMed1996

An integrated approach to Smart House technology for people with disabilities.

It is now commonly accepted that 'Smart House' technology can play a significant part in helping both elderly and disabled people enjoy a greater degree of independence in the near future. In order to realize this aspiration, it is necessary to examine a number of factors: the development of the appropriate Home Bus technologies and supported devices; the development of the appropriate user interfaces that will allow people with a range of special needs use the system; the incorporation of the requirements of the 'Smart House' controller with the other technological needs of the user; and the development of mainstream technologies that will affect the cost and availability of devices to the user. This paper will examine the above points and suggest appropriate actions and trends. It will draw upon the work of a four-member consortium currently finalizing a technical development project under the EC TIDE program, the experience of research and commercial organizations engaged in development work in associated areas and the experiences of the Dublin-based, Central Remedial Clinic and in particular, its Client Technical Services Unit. The CTSU have been actively engaged in the development of systems for clients and direct clinical assessments for the last 12 years.

Biomedical Engineering↗

PubMed2004

New biomedical approaches for sexually transmitted infection prevention: vaccines and microbicides.

STIs are a major global health problem. Biomedical strategies are under development that will help prevent these infections. Vaccines against C. trachomatis and N. gonorrhoeae are in early stages of development. Stage-III trials are underway on prophylactic vaccines for HPV and HSV-2. Strategies focused on immunizing only high-risk individuals are unlikely to stem the tide of STIs. Approaches to widespread immunization require acceptance of such vaccines by health care providers, institutions providing funding, parents, and adolescents. Microbicides offer a female-controlled method for protection from STIs. They use many strategies to prevent infection. These products are at various stages of development. It seems that young women and teenagers would be interested in using microbicides. Correct and consistent use of microbicides will require taking women's preferences into account during product development and marketing.

Administration, Intravaginal↗

PubMed2006

IVF results: optimize not maximize.

The desire to improve in vitro fertilization (IVF) results has led clinicians to replace more than 1 embryo in the uterus. As a result, multiple births have increased over the last 2 decades to epidemic proportions, exposing the field of assisted conception to justified criticism. This review aims to ensure that physicians involved in the field of fertility treatment are aware of the risks and complications related to multiple pregnancies, and to explore possible strategies such as blastocyst culture, preimplantation genetic screening, and embryo cryopreservation, which can help to control and reverse the tide of multiple pregnancies without reducing the good success rate that modern IVF treatment enjoys. A brief overview of the respective UK legislative system is also presented.

Cryopreservation↗

PubMed2004

In situ impact of multiple pulses of metal and herbicide on the seagrass, Zostera capricorni.

Tides and freshwater inflow which influence water movement in estuarine areas govern the exposure-regime of pollutants. In this experiment, we examined the in situ impact of double pulses of copper and the herbicide Irgarol 1051 on the photosynthesis of the seagrass, Zostera capricorni. Despite a 4-day recovery period between the two 10h pulses of toxicant, the effective quantum yield of photosystem II (DeltaF/Fm') and total chlorophyll concentrations indicated that multiple-pulses had a greater impact than a single pulse. During the first exposure period, samples exposed to Irgarol 1051 had DeltaF/Fm' values as low as zero while controls remained around 0.6 relative units. After the second exposure period, treated samples recovered to only 0.4 relative units. Samples exposed to copper had DeltaF/Fm' values around 0.3 relative units during the first exposure period and while these samples recovered before the second dose, they remained below 0.2 relative units after the second exposure period. Alternate samples were also exposed to one toxicant, allowed to recover and then exposed to the other toxicant. DeltaF/Fm' values indicated that copper exposure followed by Irgarol 1051 exposure was more toxic than Irgarol 1051 exposure followed by copper exposure.

Analysis of Variance↗

PubMedDate not supplied

Diabetes mellitus in children and adolescents.

Until recently, diabetes in children was virtually synonymous with type 1 diabetes mellitus, whereas type 2 diabetes was a disease of middle age and the elderly. Over the past 10-20 years, an alarming increase in the prevalence of type 2 diabetes has been reported from pediatric diabetes centers in North America and elsewhere in the world. Lifestyle factors responsible for the worldwide epidemic of overweight and obesity are responsible for the increase in the prevalence of type 2 diabetes in adults and children. This article briefly discusses the diagnosis and major types of diabetes in children but focuses on aspects of type 2 diabetes in children and adolescents, including demographics, pathophysiology, clinical presentation, screening, prevention and treatment. The identification of children at risk for type 2 diabetes and the implementation of community-wide preventive programs will be essential to reverse the tide. The availability of calorie dense "fast foods," candy, and sugared soft drinks must be restricted in schools and other venues frequented by children. Parents must limit the amount of time their children spend watching television and playing computer games. After-school programs that promote physical activity should be a priority of local and central governmental agencies. Prevention will only succeed if governments and local communities recognize that childhood obesity is an important public health problem and provide an environment that promotes changes in lifestyle that prevent and reverse obesity.

Adolescent↗

PubMed2006

Type-2 diabetes mellitus related cardiovascular risk: new options for interventions to reduce risk and treatment goals.

Diabetes represents a state of accelerated cardiovascular risk with data from longitudinal studies suggesting that in patients with well established diabetes the risk is equivalent to those with existing cardiovascular disease. In addition, the prognosis of patients with diabetes who suffer cardiovascular disease (CVD) is much worse. There are therefore dual imperatives for all physicians, particularly those in primary care, to focus on strategies to reduce vascular risk in their patients with diabetes. There are, in parallel, background issues that make this risk modification in diabetes a priority, with the rising prevalence of disease, driven at least in part by the rising tide of obesity, and the rising cost (42% of total expenditure) of treating CVD in diabetics. Evidence for interventions that modify the CVD risk in diabetes is now strong, with unequivocal data to support multifactorial risk modification, particularly for the effective targeting of glycaemia and blood pressure (with primary evidence for bp targets below standard care) from studies such as Steno2 and UKPDS, and lipid modification through the use of statins in both secondary (HPS) and primary (CARDS) prevention of CVD in diabetes. Knowledge of these interventions is high in primary care, but implementation is variable. This is probably at least in part because primary care physicians appear to consider risk factor modification within single risk strategies, rather than adopting lifestyle and therapeutic interventions that influence multiple risks in a systematic package of care and patient follow up.

Cardiovascular Diseases↗

PubMed2003

Rapid regulation of NaCl secretion by estuarine teleost fish: coping strategies for short-duration freshwater exposures.

This review summarizes the mechanism of Cl(-) active secretion and its regulation in estuarine teleost fish. Small estuarine fish such as the killifish, Fundulus heteroclitus, forage in shallow water following advancing tides and are exposed regularly to very dilute microenvironments. Using the killifish opercular epithelium and related teleost membranes containing mitochondria-rich cells, the regulation includes a reduction of active Cl(-) secretion and passive diffusive ion loss in a three-stage process spanning approximately 30 min. There is a combination of sympathetic neural reflex mediated by alpha(2)-adrenoceptors operating via intracellular inositol tris phosphate and intracellular Ca(2+) and a cellular hypotonic shock response, followed by covering over of ion-secreting cells by pavement cells. This effectively minimizes salt loss in dilute media. The upregulation of salt secretion on return to full strength seawater may be via hormones (arginine vasotocin and urotensin I) and neurotransmitter (vasoactive intestinal polypeptide) in combination with hypertonic shock. A hypothetical model includes involvement of protein kinase A and C and protein phosphatases 1 and 2A in regulation of the NKCC1 cotransporter on the basolateral side and protein kinase A regulation of the CFTR-like apical anion channel.

Adaptation, Physiological↗

PubMed2025

Identification and external validation of a prognostic signature based on myeloid-derived suppressor cells-related LncRNAs to evaluate survival prognosis and treatment efficacy in invasive breast carcinoma.

BACKGROUND: Originating in the hematopoietic tissue, myeloid-derived suppressor cells (MDSCs) significantly contribute to tumor-related immunological processes. However, their relationship with long noncoding RNAs (lncRNAs) and breast cancer remains incompletely understood. In this study, we introduced MDSCs-associated lncRNAs as novel prognostic biomarkers to assess outcomes in patients with invasive breast carcinoma (BRCA). METHODS: Information regarding BRCA cases, including clinical and genomic details, was obtained from the TCGA repository. Predictive indicators were discovered, and their reliability underwent thorough verification. A clinically useful nomogram was developed following application-based validation. Additional investigations encompassed functional analysis, TMB assessment, TME profiling, immunotherapy efficacy forecasting, and drug sensitivity testing along with target identification. Long non-coding RNA expression was measured using reverse transcription quantitative PCR. RESULTS: A risk stratification model incorporating eight MDSCs-related lncRNAs effectively predicted patient outcomes. Kaplan-Meier (K-M) survival analysis clearly indicated a much worse prognosis among patients classified as high-risk (p < 0.001). The nomogram accurately forecasted overall survival (OS). Analysis of functional enrichment revealed that pathways associated with epithelial cells showed activity among patients at higher risk. Characterization of the tumor microenvironment showed increased immune cell presence in those classified as low-risk. Conversely, individuals with greater risk displayed higher tumor mutational burden. TIDE and IPS analyses indicated superior immunotherapy responsiveness in the low-risk BRCA subgroup. Among 47 drugs with notable IC50 variations, Ribociclib, PD173074, KU-55933, NU7441, and nutlin-3a exhibited lower IC50 values within the low-risk group, whereas Lapatinib demonstrated greater efficacy among the high-risk group. Moreover, 10 potential therapeutic agents and their targets were predicted for high-risk patients. RT-qPCR validation confirmed the robustness of the model. CONCLUSIONS: We successfully verified a new model of molecular markers of MDSCs-related lncRNAs, offering critical insights for predicting outcomes and guiding therapeutic decisions in BRCA cases.

Bioinformatics↗

PubMed2005

Brevetoxin augments NMDA receptor signaling in murine neocortical neurons.

Brevetoxins (PbTx) are potent allosteric enhancers of voltage-gated sodium channel (VGSC) function and are associated with periodic "red tide" blooms. These neurotoxins produce neuronal injury and death in cerebellar granule cells (CGC) following acute exposure. In murine neocortical neurons, brevetoxin induces Ca(2+) influx that is mediated through both glutamatergic and non-glutamatergic pathways. Inasmuch as Src kinase is capable of upregulating the NMDA subtype of glutamate receptors, we determined whether Src kinase participated in PbTx-2-induced Ca(2+) influx. Inhibition of Src kinase blocked PbTx-2-induced Ca(2+) influx. PbTx-2 treatment moreover increased tyrosine phosphorylation of the NR2B subunit. A rise in intracellular [Na(+)] and phosphorylation of NMDA receptors by Src kinase is known to increase NMDA receptor activity. We therefore explored the influence of brevetoxin on NMDA receptor function. We found that PbTx-2 augments NMDA receptor-mediated Ca(2+) influx in both spontaneously oscillating mature neurons and in non-oscillatory immature neurons. PbTx-2 also enhanced the effect of bath-applied NMDA on extracellular signal-regulated kinase 2 (ERK2) activation. These results suggest that brevetoxin augments NMDA receptor signaling in neocortical neurons, and this upregulation may be mediated by coincidence of an elevation in intracellular [Na(+)] and Src kinase activation.

Animals↗

PubMed2006

Effects of salinity and temperature on the expression of enzymatic biomarkers in Eurytemora affinis (Calanoida, Copepoda).

In order to establish effective enzymatic biomarkers that could provide in situ early warning of contaminant exposure in estuarine ecosystems, the potential effects of the principal abiotic factors (temperature and salinity) were investigated on common biomarkers, the acetylcholinesterase (AChE) and the glutathione S-transferase (GST) in Eurytemora affinis. Short term salinity stress effects simulated during an experimental tide indicated that enzymatic activities of this species are characterized by maximum expression related to an optimal salinity range (between 5 and 15 psu). Moreover, longer time exposure to various salinity tanks confirmed the effects of this factor on both AChE and GST activities. Therefore, optimal AChE activity was measured at 10 psu, while optimal GST activity was measured at 5 psu. Furthermore, significant effects of temperature were also recorded, particularly for AChE expression (slight effects were measured on GST expression) with an optimal condition at 11 degrees C. These experiments indicated a more pronounced effect of salinity over temperature especially on the AChE expression and confirmed the need to standardize sampling procedures in relation with environmental parameters for biomonitoring studies based on enzymatic analyses.

Acetylcholinesterase↗

PubMed2006

The Na+, K+, 2Cl- cotransporter of estuarine pufferfishes (Sphoeroides testudineus and S. greeleyi) in hypo- and hyper-regulation of plasma osmolality.

The pufferfishes Sphoeroides testudineus and Sphoeroides greeleyi are estuarine species that osmoregulate efficiently, but S. testudineus tolerates seawater dilution to a much higher degree than S. greeleyi. This study aimed at testing whether NKCC is involved with their differential tolerance of seawater dilution, through the analysis of in vivo furosemide (NKCC inhibitor) injection both on hypo-regulation (in 35 per thousand salinity) and hyper-regulation (in 5 per thousand salinity). After exposure for 6 h or 5 days to both salinities, blood samples were obtained for determination of plasma osmolality, chloride, sodium and hematocrit, and muscle samples for determination of water content. Furosemide injection led to increased plasma osmolality and sodium in 35 per thousand and decreased osmolality and chloride in 5 per thousand, when compared to saline-injected controls. Furosemide injection led to hematocrit reduction in both salinities, and muscle water content increase in 5 per thousand and decrease in 35 per thousand in S. testudineus. The results are compatible with NKCC working in branchial NaCl secretion in 35 per thousand, in both species, and a higher role in cell volume regulation in blood and muscle cells of S. testudineus, in both salinities, which could partially explain the stronger capacity of S. testudineus to tolerate seawater dilution during low tide.

Animals↗

PubMed2005

Media literacy for clinicians and parents.

Families and children are in the midst of a media revolution. Television, Internet access, instant messaging, cell phones, and interactive video games are delivering more information for more hours than ever in history. Exposure is occurring at younger and younger ages, often without parental oversight or interpretation. The impact on children is just beginning to be studied. Does media exposure prepare children for the world in which they live or deprive them of critical developmental opportunities? Does the steady display of violence contribute to violent behavior? This article presents a developmental context, discusses the research conducted to date, reviews the recommendations of major organizations, and tries to take a balanced perspective in the midst of a rising tide of media, technology, commercialism, and controversy.

Adolescent↗

PubMed2005

Seasonal distribution and contamination levels of total PHCs, PAHs and heavy metals in coastal waters of the Alang-Sosiya ship scrapping yard, Gulf of Cambay, India.

Alang-Sosiya situated on the Gulf of Cambay is one of the largest ship breaking yard in the world. The seasonal distribution and contamination levels of dissolved and/or dispersed total petroleum hydrocarbons (PHCs), total polycyclic aromatic hydrocarbons (PAHs) and heavy metals in seawater during high tide are investigated. The concentrations of petroleum hydrocarbons and heavy metals are higher in the winter than in the monsoon and summer. The concentrations of total PHCs and PAHs are about three times higher in the winter and two times in the monsoon or summer at Along-Sosiya and about twice in all seasons at two stations one on either side 5 km away from it as compared to the reference station at Mahuva, 60 km away towards the south. Further, the levels of PHCs are correlated with salinity and compared with those of other regions. The concentration of all metals is the highest in the winter season followed by the monsoon and summer. We carried out the quantitative analysis of the possible relationships among 13 variables such as Al, Fe, Pb, Mn, Cu, Zn, Cd, Cr, Co, pH, NO3-, NO2 and PO4(3-).

Environmental Monitoring↗

PubMed2005

Arsenosugars and other arsenic compounds in littoral zone algae from the Adriatic Sea.

In 10 different marine algae from the littoral zone (found between the highest and lowest tide marks on the seashore) arsenic compounds were determined by means of a high-performance liquid chromatography (anion and cation exchange)-UV photochemical digestion-hydride generation-atomic fluorescence spectrometry (HPLC-UV-HGAFS) system. Samples (Ceramium sp., Cystoseira barbata, Enteromorpha sp., Fucus virsoides, two different species of Gelidium, Padina pavonica, Polisyphonia sp. and Ulva rigida) were collected along the Adriatic Sea coast of Slovenia. The total arsenic content of the algal samples, as determined by ICP-MS, ranged from 1.35 to 28.1 microg g(-1) (fresh weight). In all algae but two, the most abundant arsenic species found were arsenosugars with minor amounts of other arsenic compounds. Cystoseira barbata and Ceramium sp. contained high amounts of mainly inorganic arsenic. A small quantity of arsenobetaine was detected in most of the investigated Adriatic algae, which probably originates from mesofauna attached to the algae in their natural habitat.

Arsenates↗

PubMed2004

The role and assessment of ventricular peptides in heart failure.

Although heart failure may be diagnosed readily in its advanced stages, it may be difficult to diagnose clinically in its early stages.Thus, there is a critical need for an inexpensive, simple, rapid,and objective test for heart failure. This article discusses the role and assessment of ventricular natriuretic peptides and related pep-tides in heart failure.

Biomarkers↗

PubMed2026

Pan-cancer multi-omics machine learning defines a lactylation-associated immune-excluded tumor state with proteomic and experimental corroboration.

BACKGROUND: Histone lactylation links lactate metabolism to chromatin regulation, but whether lactylation-program-associated transcriptional patterns delineate recurrent pan-cancer tumor states remains unclear. METHODS: We integrated mRNA, lncRNA, and miRNA profiles from 9712 TCGA tumors across 33 cancer types with GTEx references, six GEO cohorts, IMvigor210, and an institutional clear-cell renal cell carcinoma (ccRCC) cohort used for exploratory DIA-NN proteomic corroboration. Random-effects co-expression meta-analysis, multi-omics consensus clustering, regulon inference, immune deconvolution, TIDE, oncoPredict, and SHAP-based machine learning were applied. hsa-miR-431-5p was functionally evaluated as a proof-of-concept CS2-associated miRNA in bladder cancer models. RESULTS: LacCoEx-Atlas comprised 398,491 lactylation-related co-expression pairs across 24,667 RNA features under a random-effects framework (median I² = 88.6%). Consensus clustering identified two subtypes: CS2 showed glycolytic-mesenchymal-immune-excluded features, M2 macrophage enrichment, CD8⁺ T-cell depletion, elevated HDAC4/NSD3/KDM6B activity, and worse survival, whereas CS1 showed oxidative, sirtuin-active programs. CS2 had fewer predicted ICI responders (18.3% vs. 52.0%) and a lower observed ORR in IMvigor210 (15.3% vs. 24.0%). oncoPredict identified NU7441 as a hypothesis-generating CS2-associated sensitivity signal (Hedges' g = 1.17). DIA-NN proteomics in 50 ccRCC specimens provided exploratory support for CS2-associated hypoxia, ECM degradation, and metastasis programs. The 10-feature mRNA LARItools model achieved an apparent AUC of 0.9413, while a separate multi-omics model achieved 0.971; neither was independently validated. LARItools reproduced prognostic separation across six GEO cohorts. miR-431-5p promoted malignant phenotypes and EMT in bladder cancer cells, with concordant CMU4h expression findings. CONCLUSIONS: Lactylation-program-associated transcriptional patterns delineate a recurrent immune-excluded pan-cancer tumor state associated with adverse prognosis, reduced predicted immunotherapy responsiveness, exploratory single-cancer protein-level support, and testable DNA damage response-targeting hypotheses. LacCoEx-Atlas and LARItools provide open resources for lactylation-program-associated tumor-state stratification and future translational research.

Humans↗