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At least 235 records · Page 13Linked to original sources
PubMed2006

Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1.

During mammalian embryogenesis, precise coordination of progenitor cell proliferation and differentiation is essential for proper organ size and function. The involvement of TLX (NR2E1), an orphan nuclear receptor, has been implicated in ocular development, as Tlx-/- mice exhibit visual impairment. Using genetic and biochemical approaches, we show that TLX modulates retinal progenitor cell proliferation and cell cycle re-entry by directly regulating the expression of Pten and its target cyclin D1. Additionally, TLX finely tunes the progenitor differentiation program by modulating the phospholipase C and mitogen-activated protein kinase (MAPK) pathways and the expression of an array of cell type-specific transcriptional regulators. Consequently, Tlx-/- mice have a dramatic reduction in retina thickness and enhanced generation of S-cones, and develop severe early onset retinal dystrophy. Furthermore, TLX interacts with atrophin1 (Atn1), a corepressor that is involved in human neurodegenerative dentatorubral-pallidoluysian atrophy (DRPLA) and that is essential for development of multiple tissues. Together, these results reveal a molecular strategy by which an orphan nuclear receptor can precisely orchestrate tissue-specific proliferation and differentiation programs to prevent retinal malformation and degeneration.

Animals↗
PubMed2025

miss-SNF: a multimodal patient similarity network integration approach to handle completely missing data sources.

MOTIVATION: Precision medicine leverages patient-specific multimodal data to improve prevention, diagnosis, prognosis, and treatment of diseases. Advancing precision medicine requires the non-trivial integration of complex, heterogeneous, and potentially high-dimensional data sources, such as multi-omics and clinical data. In the literature, several approaches have been proposed to manage missing data, but are usually limited to the recovery of subsets of features for a subset of patients. A largely overlooked problem is the integration of multiple sources of data when one or more of them are completely missing for a subset of patients, a relatively common condition in clinical practice. RESULTS: We propose miss-Similarity Network Fusion (miss-SNF), a novel general-purpose data integration approach designed to manage completely missing data in the context of patient similarity networks. miss-SNF integrates incomplete unimodal patient similarity networks by leveraging a non-linear message-passing strategy borrowed from the SNF algorithm. miss-SNF is able to recover missing patient similarities and is "task agnostic", in the sense that can integrate partial data for both unsupervised and supervised prediction tasks. Experimental analyses on nine cancer datasets from The Cancer Genome Atlas (TCGA) demonstrate that miss-SNF achieves state-of-the-art results in recovering similarities and in identifying patients subgroups enriched in clinically relevant variables and having differential survival. Moreover, amputation experiments show that miss-SNF supervised prediction of cancer clinical outcomes and Alzheimer's disease diagnosis with completely missing data achieves results comparable to those obtained when all the data are available. AVAILABILITY AND IMPLEMENTATION: miss-SNF code, implemented in R, is available at https://github.com/AnacletoLAB/missSNF.

Humans↗
PubMedDate not supplied

Diabetic complications and their prevention or reversal.

Patients with Type I, i.e., insulin-deficient diabetes, Type II or non-insulin-deficient diabetes, and impaired glucose tolerance or so-called chemical diabetes are variably predisposed to develop macroangiopathy, i.e., atherosclerosis, microangiopathy or basement membrane thickening, and neuropathy. Once these morphologic changes appear, they in all probability will remain irreversible even when precise regulation is attained. Hence prevention is the only realistic goal.

Aging↗
PubMed2004

Protein biomarkers for breast cancer prevention.

Protein biomarkers suitable for the prevention of breast cancer must be extremely sensitive, easily detectable and highly correlated with the disease. They should be expressed in the reversible phase of carcinogenesis. Among the large number of candidate tumour-associated proteins, those related to the oestrogen/chorionic gonadotropin/insulin pathway seem to be of most interest because these can be causally implicated. They presumably are the first to express differently and are open to hormonal treatments. The biomarkers that give information on membrane receptor-modulated signal transduction should be considered as well. Up to now, only tamoxifen has shown some preventive activity, suggesting that the oestrogen pathway is useful indeed. Fenretinide and recombinant human chorionic gonatotropin (hCG) are also promising. But the financial requirements and the very long assessment periods largely prevent current research. This is precisely why we badly need to give priority to molecular biology research, in particular in the protein compartment There is widespread belief that advanced proteomics together with increased informatics can provide specific combinations of disease-related expression profiles that could identify high-risk groups with much more reliability and allow us to monitor preventive strategies.

Adult↗
PubMed2001

[Endoscopic surveillance of precancerous changes in the stomach].

Undoubtedly, one of the most important achievements of gastroenterology is the demonstration that, for many pathological conditions with future neoplastic degeneration risk, a periodical endoscopic surveillance is a determining element for the restraining of possible evolutive complications. Nonetheless, it is to be considered how, during the last years, the prevention and follow-up procedures for the stomach disease have been sometimes emphasized. In fact, various recent evidences originated from precise scientific evaluations have contained same prevention strategic attitudes so as to reach the best cost-benefit ratio. In this survey the various gastric preneoplastic modifications, subdivided in precancerous conditions and lesions are examined and guidelines are proposed in order to offer quick and easily applicable solutions.

Gastroscopy↗
PubMed2002

A new generation of scanners for DNA chips.

Today, most of the DNA chips are used with fluorescent markers. Associated with fluorescence confocal scanners, this technology achieves remarkable performances in terms of sensitivity and accuracy. The main technical issues related to these scanners have already been reviewed. However, these scanners are costly, especially when high density chips are used. In this case, a mechanical precision of 1 microm or less is required to achieve the measurement precision required. This cost level prevents the spread of this technology in the diagnostic market. We will present a new concept for scanners with equivalent or superior performances, with a cost cut of 5-10. This concept is inspired from the field of optical disk and reader. Basically, an optical format is added to the chip, before DNA deposition. This format contains tracks which are superimposed to the DNA features. These tracks define the path that an optical head of a CD player must follow in order to scan the surface of the DNA chip. Such a head is a very cheap component, and has a precision of less than 100 nm thanks to real-time focus and tracking. These functions are fulfilled by electromagnetic actuators mounted on the support of the frontal lens. We show here that it is possible to use such a head to build a fluorescence confocal scanner with equivalent or even better performances than conventional scanners.

Equipment Design↗
PubMed2004

The role of dental hygienists in oral health prevention.

Most dental diseases are preventable. This indicates that the main concept of dentistry could be changed to a situation in which the dental hygienist becomes the principal oral care professional. The competencies of dental hygienists focus on disease prevention and oral health promotion; thus referral to a dentist would only become necessary in the event of a failure in the preventive program where disease cannot be controlled. Future oral health care personnel need to be better educated to encourage people to implement healthy lifestyles rather than to treat teeth. In addition, the connection between oral health, general health and health-related quality of life will necessitate a multidisciplinary approach to prevention and oral health promotion. To focus strictly on oral health would too narrowly define the role of the dental hygienist in comprehensive prevention and health promotion. There is no precise boundary between the oral cavity and the rest of the body. Dietary advice to prevent dental caries and smoking cessation counseling to prevent periodontal disease and oral cancer also promote general health. Consequently the focus on prevention and health promotion makes the dental hygienist a very important person in the dental team of the future.

Counseling↗
PubMed2003

Gastric secretion.

PURPOSE OF REVIEW: Gastric acid facilitates the digestion of protein and the absorption of iron, calcium, and vitamin B12. It also protects against bacterial overgrowth and enteric infection, including prion disease. When homeostatic mechanisms malfunction, the volume and concentration of acid may overwhelm mucosal defense mechanisms, leading to duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. This article reviews recent knowledge contributing to understanding of the regulation of gastric acid secretion at the central, peripheral, and intracellular levels. RECENT FINDINGS: The vagus nerve contains afferent fibers that transmit sensory information from the stomach to the nucleus of the solitary tract. Input from the nucleus of the solitary tract is relayed to vagal efferent neurons that originate from two brain stem nuclei: the nucleus ambiguus and the dorsal motor nucleus of the vagus. The latter is also influenced by thyrotropin-releasing hormone neurons that act centrally to stimulate acid secretion. The main peripheral stimulants of acid secretion are the hormone gastrin and the paracrine amine histamine. Gastrin stimulates acid secretion directly and, more importantly, indirectly by releasing histamine from fundic enterochromaffin-like cells. Gastrin also exerts trophic effects on various tissues, including the gastric and intestinal mucosa. The main inhibitor of acid secretion is somatostatin. Somatostatin, acting via ssTR2 receptors, exerts a tonic paracrine inhibitory influence on the secretion of gastrin, histamine, and acid secretion. Calcitonin gene-related peptide, adrenomedullin, amylin, atrial natriuretic peptide, and pituitary adenylate cyclase-activating polypeptide all stimulate somatostatin secretion and thus inhibit acid secretion. HK-ATPase, the proton pump of the parietal cell, is stored within cytoplasmic tubulovesicles during the resting state, but during stimulation, it is shuttled to the canalicular membrane by a poorly understood mechanism that probably involves soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins. The proton pump inhibitor, pantoprazole, is unique in that it binds cysteine 822, located deep within the membrane domain of the alpha-subunit. The difficulty that reducing agents, such as glutathione, have in reaching cysteine 822 may be responsible for the longer half-time for acid recovery observed with pantoprazole. Hypergastrinemia, induced by proton pump inhibitors, enhances expression of cyclooxygenase-2 and hence prostaglandins within parietal cells, a feedback pathway that may protect the stomach against acid-induced damage. SUMMARY: In the past year, significant advances have been made in understanding of the regulation of gastric acid secretion. Ultimately, these advances should lead to improved therapies to prevent and treat acid-related disorders. Gastric acid secretion must be precisely controlled at a variety of levels to prevent disease caused by hyperchlorhydria and hypochlorhydria. The mechanisms include neural (central and peripheral), hormonal, paracrine, and intracellular pathways that operate in concert to switch acid secretion on during ingestion of a meal and off during the interdigestive period. A better understanding of the physiology of acid secretion in health and disease should eventually lead to improved therapies to prevent and treat acid-related disorders.

Journal Article↗
PubMed2002

Tinted spectacles and visually sensitive migraine.

A double-masked randomized controlled study with cross-over design compared the effectiveness of precision ophthalmic tints in the prevention of headache in migraine sufferers. Seventeen patients chose the colour of light that optimally reduced perceptual distortion of text and maximized clarity and comfort. They were later given glasses with spectral filters providing optimal colour under conventional white lighting ('optimal' tint) or glasses that provided a slightly different colour ('control' tint). The tints were supplied in random order, each for 6 weeks, separated by an interval of at least 2 weeks with no tints. Headache diaries showed that the frequency of headaches was marginally lower when the 'optimal' tint was worn, compared with the 'control'. The trial extends to adults with migraine, the results of a previous double-masked study demonstrating, in children with reading difficulty, beneficial effects of precision tints in reducing symptom frequency. In the present study, however, the effects are suggestive rather than conclusive.

Adolescent↗
PubMed2006

Chemoprevention: risk reduction with medical therapy of inflammatory bowel disease.

The ideal chemopreventative agent, in addition to being efficacious in the prevention of cancer, must be easily administered, affordable, safe, and well tolerated, with minimal side effects. In the past decade, a growing body of literature has emerged on the prevention of CRC in patients with long-standing CD and UC. The data are not definitive and consist almost exclusively of retrospective case-control and cohort studies rather than the more rigorous prospective RCTs. 5-ASA compounds have been most thoroughly studied, and most of the existing data support the use of 5-ASA in the prevention of CRC. Although the precise dose and duration are unclear, studies suggest that chronic systemic administration of 5-ASA at a dose of at least 1.2 g/d is most likely to be effective. A beneficial effect of folate, albeit not statistically significant, has been consistently shown in every study performed for this purpose. Folate supplementation, which is safe and affordable, should also be recommended for all patients with IBD, especially those taking sulfasalazine. UDCA has been shown to exert a protective effect in most studies on patients with UC and concomitant PSC. Because this patient population is at particularly high risk for CRC, it is advisable to consider UDCA in all patients with colitis complicated by PSC. For patients without PSC, sufficient data do not exist to recommend it for the purpose of cancer prevention. Five of the six corticosteroid studies have found a beneficial effect of systemic steroids, although most did not reach statistical significance. Regardless, given the frequent and serious adverse effects associated with chronic steroid use, systemic corticosteroids should not be prescribed for this indication. Budesonide, an oral corticosteroid with minimal systemic absorption, is a potential alternative, although it has not yet been studied as a chemopreventative agent. Similarly, until the long-term safety of chronic NSAID use can be demonstrated in patients with IBD, the role of NSAIDs in chemoprevention remains undefined. Although the data are conflicting, immune-modulating medications, such as AZA, do not seem to confer any reduction in the risk of dysplasia or CRC. The data on calcium supplementation and statin use are still too limited to endorse their use for the prevention of colitis-related CRC. Chemoprevention is an area that holds great promise in the reduction of morbidity and mortality associated with IBD. Further studies, including prospective trials when possible and cost-effectiveness analyses, need to be performed to develop an optimal strategy for the reduction of cancer risk in patients with IBD.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Prevention of atherosclerosis among 11-year-old schoolchildren in two Moscow administrative districts.

A total of 4,213 boys and girls 11 years of age were screened in two Moscow administrative districts. Preventive measures were conducted in one district and were directed at excess body mass, systolic blood pressure, blood lipids (only among boys), cigarette smoking, and physical inactivity. A reference group of peers, who did not receive advice on prevention, was selected from another district. The intervention was targeted to three groups--schoolchildren, their parents, and teaching staff. It included round-table discussions, lectures, and the distribution of health-education materials relating to dietary habits and smoking. Over a 3-year period, these measures resulted in nonsignificant decline in the age-specific increase in body mass compared to the reference group. The intervention group had smaller subscapular skinfold thickness measurements than the reference group. These differences were significant. Mean systolic blood pressure increased with age in both groups. The increase was less in the intervention group than in the reference group and affected boys less than girls. A significant decrease in lipids (cholesterol and triglycerides) was observed in the intervention district. We conclude that additional study is needed to evaluate more precisely the effectiveness of such prevention efforts.

Arteriosclerosis↗
PubMed1997

Mechanical effect of the Angelchik prosthesis on the competency of the gastric cardia: pathophysiologic implications and surgical perspectives.

The Angelchik prosthesis appears to be effective in preventing gastroesophageal reflux, although its precise mechanism of action remains controversial. In a unique in vitro model, 10 freshly harvested canine esophagogastric specimens were tested for their ability to remain competent against challenges of intragastric pressure under controlled conditions of intra-abdominal pressure, longitudinal esophageal tension, lower esophageal sphincter pressure and overall length and circumference of the cardia (measure of gastric dilatation). Competency of the specimen was assessed by stepwise variation in the overall length of the sphincter, while keeping constant intraabdominal pressure (20 cm H2O), intragastric pressure (20 cm H2O), esophageal tension (physiologic), lower esophageal sphincter pressure (15 cm H2O) and degree of gastric dilatation (3 cm). With each specimen serving as its own control, the effect produced by the application of an Angelchik prosthesis was evaluated. Results consistently demonstrated that at any lower esophageal sphincter length the percent of competency was increased when the prosthesis was applied (P < 0.01). The findings indicate that the Angelchik prosthesis controls reflux by preventing unfolding of the lower esophageal sphincter when challenged by intragastric pressure.

Animals↗
PubMed2002

Butyrate reduces colonic paracellular permeability by enhancing PPARgamma activation.

Butyrate may have a role in preventing ulcerative colitis, but its precise mechanism is unknown. Also, PPARgamma (peroxisome proliferator-activated receptor gamma) is expressed at high levels both in the colonic epithelium and colon cancer cell lines, but no report was shown on the relationship between PPARgamma activation and the effect of butyrate. We investigated the effects of butyrate and PPARgamma agonist on paracellular permeability. To discover whether PPARgamma expressed in the cell lines treated with butyrate was functional or not, we transfected HT-29 cells with an acyl-CoA oxidase promoter-luciferase reporter plasmid containing a PPRE (peroxisome proliferator responsive element) and analyzed the luciferase activity. Butyrate and PPARgamma agonist significantly reduced paracellular permeability of the colon cell line (p<0.05) and this effect indicated that butyrate and PPARgamma agonist decreased HT-29 cell growth and increased differentiation (p<0.01). PPRE activation treated with butyrate was approximately four and a half times that in untreated cells (p<0.01). These findings suggest that the effect of butyrate on paracellular permeability has apparently taken place through PPARgamma activation and this effect attributes to preventing inflammation of the colon.

Butyrates↗
PubMed1991

Genetics of colon cancer.

Strikingly rapid advances in the identification of genetic events that are important in colonic carcinogenesis have been made in the past several years. Specific inherited (adenomatous polyposis coli gene) and acquired (ras gene point mutations; c-myc gene amplification; allelic deletion at specific sites on chromosomes 5, 17, and 18) genetic abnormalities appear to be capable of mediating steps in the progression from normal to malignant colonic mucosa. Understanding these genetic factors and how they influence cellular function will have a profound effect on medical practice. High-risk populations will be (and are being) identified by genetic markers, thus allowing prevention and screening to be more precisely targeted to the population at risk; intervention strategies will be designed on the basis of the known cellular defects of neoplastic colonic mucosa; and new molecular preventive and therapeutic approaches can be developed.

Adenomatous Polyposis Coli↗
PubMed2001

Soy isoflavone supplementation in healthy men prevents NF-kappa B activation by TNF-alpha in blood lymphocytes.

Dietary intake of soy has been associated with a decreased risk of cancer. Soy isoflavones have been postulated to be the protective compounds in soybeans; however, the precise mechanism by which soy isoflavones prevent human cancer is not known. The major soy isoflavones, genistein and daidzein, are antioxidant compounds, therefore one possible mechanism of action is through their antioxidant effect. We have previously demonstrated that the soy isoflavone, genistein, inhibits the activation of the redox-sensitive transcription factor, NF-kappa B, in prostate cancer cells in vitro. In this study, we have demonstrated that genistein, but not daidzein, inhibits TNF-alpha-induced NF-kappa B activation in cultured human lymphocytes. Additionally, we investigated the in vivo effect of soy isoflavone supplementation on NF-kappa B activation induced by TNF-alpha in vitro in peripheral blood lymphocytes of six healthy men. We show that healthy male subjects receiving 50 mg isoflavone mixture (Novasoy) twice daily for 3 weeks are protected from TNF-alpha induced NF-kappa B activation. Additionally, we observed a reduction of 5-hydroxymethyl-2'-deoxyuridine (5-OHmdU), a marker for oxidative DNA damage, following isoflavone supplementation. The inhibitory effect of soy isoflavones was no longer present 3 months after the supplementation. This preliminary study demonstrates that soy isoflavone supplementation may protect cells from oxidative stress-inducing agents by inhibiting NF-kappa B activation and decreasing DNA adduct levels.

Adult↗
PubMed1991

The current unsatisfactory state of relapse prevention in schizophrenic psychoses--suggestions for improvement.

The current state of relapse prevention in schizophrenic psychoses is very unsatisfactory. Although in the form of neuroleptics a very efficient means of relapse prevention has been available for almost 40 years, approximately 50% of the schizophrenic patients still suffer a relapse within the first year after their most recent episode. Seventy percent of the hospitalized schizophrenic patients are readmissions, and the noncompliance rate for neuroleptic relapse prevention is 75%. An important factor contributing to these high rates of noncompliance and relapse seems to be the fact that, 40 years after the introduction of neuroleptics, there is still no consensus on how these drugs are to be used in relapse prevention. An inquiry among Austrian and German psychiatrists revealed unacceptably high discrepancies concerning their recommendations for indication and duration of neuroleptic relapse prevention. To overcome this unsatisfactory situation, an international consensus meeting on guidelines for neuroleptic relapse prevention was organized by the author in April 1989. Precise guidelines on indication, duration, and dosage of neuroleptic for relapse prevention that resulted from that meeting are presented.

Antipsychotic Agents↗
PubMed1993

Etiology of melanoma.

Although the precise etiology of melanoma remains unknown, much data link sunlight to melanoma. The imperfect evidence associating sun exposure (particularly UVB radiation) with melanoma emerges from human data, obviating problems inherent in extrapolation from animal and other models. However, the mechanism by which sunlight might possibly initiate or promote melanoma remains obscure. Some clarification should emerge from the potential isolation of genes that carry susceptibility to melanoma in families prone to the disease; such work could serve as a basis to distinguish genetic and environmental influences in melanoma [167]. Continued studies of faulty DNA repair in XP patients may elucidate the steps in mutagenesis and carcinogenesis. Future case-control studies must address the limits on the accuracy of recall and the limits on statistical methods to separate the cluster of phenotypic risk needed in determining biologically effective dose. Animal and in vitro studies must contribute more insight. Further research in the South American opossum models appears promising [72]. Although ozone depletion has been documented, there has been little definitive evidence of subsequent increase of UVB at the Earth's surface. Nevertheless, the threat posed by ozone depletion deserves continued environmental action and public education. The role of precursor lesions, particularly dysplastic nevi/atypical moles, must be clarified with future research. The distribution of melanoma among various work forces suggests that occupational risk factors may play an important role in the etiology of this disease [168-170]. The consistent reports of excess melanoma among accountants, clerical workers, professional workers, and teachers deserve further study. Furthermore, evidence of excesses in printing and press, petrochemical, and the telecommunications industries require follow-up. Carefully planned studies that account for nonoccupational risk factors are recommended. Research over the last four decades has brought much information about melanoma etiology. More work is needed to learn the precise cause and ultimately to prevent avoidable mortality from malignant melanoma.

Animals↗