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Association Between Statin Use and Dry Eye Disease: A Systematic Review and Meta-Analysis.

TOPIC: This systematic review and meta-analysis evaluated the literature-pooled association between statins and dry eye disease (DED). CLINICAL RELEVANCE: Statins, a common treatment modality for dyslipidemia, have been proposed as a potential contributor to DED via their activity in meibomian gland epithelial cells. However, single studies show mixed evidence, and there remains an unmet clinical need to clarify whether statin exposure is associated with DED. METHODS: This review was reported in accordance with the Preferred Reporting Items for Systematic Reviews of Interventions (PRISMA) 2020 statement and was registered a priori on PROSPERO (CRD420251238004). Ovid MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and the reference lists of relevant reviews were searched from inception to November 2025 for studies reporting the association between statin use and DED. Random-effects meta-analysis using inverse-variance weighting was conducted to pool effect estimates as odds ratios with 95% confidence intervals (CIs). Study risk of bias was appraised using the ROBINS-E tool, and the certainty of the evidence was reported using the GRADE framework. RESULTS: Six observational studies were included in the meta-analysis (n = 560,821; 356,012/559,141 [63.7%] statin users). The pooled analysis revealed a significant positive association between statins and DED (odds ratio 1.09, 95% CI 1.05-1.13, P < .001), with an absolute risk difference of 10.2 more DED cases per 1000 (95% CI 5.5 more to 15.2 more). This result was derived from very low-certainty evidence given limitations in study design and serious inconsistency. Subgroup and sensitivity analyses for risk of bias (P = .123), method of outcome ascertainment (P = .737), type of effect estimate (P = .496), and leave-one-out analyses showed no evidence of effect modification and demonstrated consistent direction of association across studies. CONCLUSION: Statin use was associated with a small but statistically significant increase in DED, limited by very low-certainty evidence. Physicians should monitor for and educate patients on ocular surface symptoms in patients using statins with pre-existing DED risk factors. Future studies should use standardized DED diagnostic criteria to investigate the impact of statin dose, type, and duration to better characterize this potential association.

Humans↗

Mutational spectrum of the EPM2A gene in progressive myoclonus epilepsy of Lafora: high degree of allelic heterogeneity and prevalence of deletions.

Progressive myoclonus epilepsy of the Lafora type (Lafora disease) is an autosomal recessive disease characterised by epilepsy, myoclonus, progressive neurological deterioration and the presence of glycogen-like intracellular inclusion bodies (Lafora bodies). We recently cloned the major gene for Lafora disease (EPM2A) and characterised the corresponding product, a putative protein tyrosine phosphatase (LAFPTPase). Here we report the complete coding sequence of the EPM2A gene and the analysis of this gene in 68 Lafora disease chromosomes. We describe 11 novel mutations: three missense (F84L, G240S and P301L), one nonsense (Y86stop), three < 40 bp microdeletions (K90fs, Ex1-32bpdel, Ex1-33bpdel), and two deletions affecting the entire exon 1 (Ex1-del1 and Ex1-del2). In addition, we have identified three patients with a null allele in non-exonic microsatellites EPM2A-3 or EPM2A-4, suggesting the presence of two distinct > 3 kb deletions affecting exon 2 (Ex2-del1 and Ex2-del2). Considering these mutations, a total of 25 mutations, 60% of them generating truncations, have been described thus far in the EPM2A gene. In spite of this remarkable allelic heterogeneity, the R241stop EPM2A mutation was found in approximately 40% of the Lafora disease patients. We also report the characterisation of five new microsatellite markers and one SNP in the EPM2A gene and describe the haplotypic associations of alleles at these sites in normal and EPM2A chromosomes. This analysis suggests that both founder effect and recurrence have contributed to the relatively high prevalence of R241stop mutation in Spain. The data reported here represent the first systematic analysis of the mutational events in the EPM2A gene in Lafora disease patients and provide insight into the origin and evolution of the different EPM2A alleles.

Adolescent↗

Transference neurosis as a waking dream: notes on a clinical enigma.

This paper demonstrates clinically that the interactional features of a transference neurosis are the waking equivalents of a manifest dream. Through analytic investigation of the emerging repetitive extraverbal elements of apparent transference resistance behavior, it is discovered that the systematic analysis of the details of such behavior yields a picture of synthetic construction fundamentally the same as that seen in dreams. By using Freud's technique of systematic dream interpretation, the tightly organized, coded, and camouflaged presence of many key compromise formations determining a neurosis are found to be represented in compact, highly condensed clinical interactions, providing an overall picture of dreamwork in action. The four components of dreamwork are found to be the principal means by which the unconscious genetic and dynamic material is represented in the analytic field.

Adult↗

Reduction and avoidance of lubricant mist demands an integrated assessment approach.

A case study to identify major factors for lubricant mist exposure covered 15 metal machining sites. The investigation included milling, turning, drilling and grinding applications. Systematic analysis considered all relevant data concerning the machine tool, the lubricant and the suction plant. The efficiency of the implemented maintenance program at the installed filter systems was checked by concentration measurements immediately before and after service. All performed measurements of lubricant aerosol and vapor loads upstream and downstream of the installed filter systems were carried out according to VDI 2066 and BIA 3110, respectively. The selection criteria for the sites to be investigated, the systematic nature of the data acquisition and the procedure of the analysis are demonstrated in detail by performing comparisons between selected applications using emulsions and those employing straight oil for lubrication. The results of the study identify recirculation of ventilated air as the major source of workplace exposure to airborne lubricant emissions. More than 60% of the demisters investigated emit air at total lubricant loads (aerosols and vapor) above the limit of 20 mg m-3 at any time of operation; which also means immediately after service. A common reason for exceeded aerosol loads in recirculated air is e.g. the fact that the type of filter system applied is often not suitable for the separation problem. Loads of lubricant vapor are usually higher at the processes which use water emulsions as lubricant. In a quarter of the cases the limits were exceeded solely due to high vapor loads even immediately after service. The exposure can be reduced by replacing the lubricant, installation of a vapor separation plant or avoiding air recirculation. Maintenance time of the demisting system and aerosol separation efficiency of state-of-the-art demisting systems can be expanded by implementation of enhanced preliminary filter stages. This study confirms that appropriate service measures lower both aerosol emissions and lubricant vapor concentrations due to the reduction of exposed oil-wetted surfaces. The performed measurements show no significant relationship between loads of airborne lubricants and the type of machining process. Therefore, investigations at a much more detailed level have to be performed. However, the individual assessment of any workplace due to the complex situation remains essential.

Aerosols↗

Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis.

OBJECTIVE: To systematically review studies of male circumcision and the risk of HIV-1 infection in men in sub-Saharan Africa, and to summarize the findings in a meta-analysis. DESIGN: A meta-analysis of observational studies. METHODS: A systematic literature review was carried out of studies published up to April 1999 that included circumcision as a risk factor for HIV-1 infection among men in sub-Saharan Africa. A random effects meta-analysis was used to calculate a pooled relative risk (RR) and 95% confidence interval (CI) for all studies combined, and stratified by type of study population. Further analyses were conducted among those studies that adjusted for potential confounding factors. RESULTS: Twenty-seven studies were included. Of these, 21 showed a reduced risk of HIV among circumcised men, being approximately half that in uncircumcised men (crude RR = 0.52, CI 0.40-0.68). In 15 studies that adjusted for potential confounding factors, the association was even stronger (adjusted RR = 0.42, CI 0.34-0.54). The association was stronger among men at high risk of HIV (crude RR = 0.27; adjusted RR = 0.29, CI 0.20-0.41) than among men in general populations (crude RR = 0.93; adjusted RR = 0.56, CI 0.44-0.70). CONCLUSION: Male circumcision is associated with a significantly reduced risk of HIV infection among men in sub-Saharan Africa, particularly those at high risk of HIV. These results suggest that consideration should be given to the acceptability and feasibility of providing safe services for male circumcision as an additional HIV prevention strategy in areas of Africa where men are not traditionally circumcised.

Africa South of the Sahara↗

Analysis of symmetry and three-dimensional reconstruction of thin gp32*I crystals.

Thin, multilayered crystals of gp32*I were analyzed by negative stain electron microscopy and image processing. Images of untilted crystals exhibited different projection symmetries and structural motifs. Systematic analysis of these images categorized the projections into four types. Areas producing the type 1 projection were reconstructed in three-dimensions from four tilt series containing 111 images. The three-dimensional data has excellent p121 plane group symmetry and reveals that the gp32*I molecule contains two large domains linked together by a small domain. Computer simulations utilizing projection data suggested that the type 2 and 3 projections arise from superposition of type 1 projections related by a 21 screw axis along the projection axis. The three-dimensional reconstruction was utilized in a final simulation that explained the occurrence of the fourth type of projection. This work provides a firm foundation for future high-resolution analysis of the crystal by electron cryomicroscopy.

Crystallography↗

From Arabidopsis to rice genomics: a survey of French programmes.

During the last ten years, Arabidopsis thaliana has become the most favoured plant system for the study of many aspects of development and adaptation to adverse conditions and diseases. The sequencing of the Arabidopsis thaliana genome is nearly completed with more than 90% of the sequence being released in public databases. This is the first plant genome to be analysed and it has revealed a tremendous amount of information about the nature of the genes it contains and its largely duplicated organisation. French groups have been involved in Arabidopsis genomics at several steps: EST (expressed sequence tags) sequencing, construction and ordering (physical mapping of chromosomes) of a YAC (yeast artificial chromosomes) library, genomic sequencing. In parallel an extensive programme of functional genomics is being undertaken through the systematic analysis of insertional mutants. This information provides a support for analysing other more economically important plant genomes such as the rice genome and constitutes the beginning of a systematic investigation on plant gene functions and will promote new strategies for plant improvement.

Arabidopsis↗

Drug fever: mechanisms, maxims and misconceptions.

Although drug fever is a clinical entity that has received considerable attention in textbooks and review articles, only recently have such writings been subjected to critical analysis. In the present review, mechanisms responsible for drug fever are examined. In addition, published characterizations of the syndrome are compared with the results of a recently published systematic analysis of 148 cases of drug fever. This comparison identified a number of important areas in which descriptions of the clinical entity in textbooks and review articles are at odds with the clinical profile exhibited by actual cases of drug fever.

Body Temperature Regulation↗

[In vivo 1H and 31P NMR spectroscopy of the developing rat brain].

Postnatal development of mammalian brain is characterized by cell proliferation, migration, and differentiation of both neuronal and glial elements. These development process are accompanied by not only morphological changes but also biochemical changes. Nuclear magnetic resonance (NMR) spectroscopy is unique in its capability in obtaining metabolic information. In particular water-suppressed proton (1H) spectroscopy is a powerful tool that can be used to quantify certain intracellular amino acids and lactate. However, to date, no systematic analysis of the metabolic changes associated with brain development utilizing in vivo proton spectroscopy has appeared in the literature. In this study, we performed a non-invasive systematic investigation of the biochemical changes associated with brain maturation in the rat during the first 28 days postnatal in vivo utilizing both 1H and 31P spectroscopy. Phosphocreatine (PCr) was found to increase linearly during this period of development. Phosphomonoester (PME) was high at birth, peaked around the 10th day birth, and declined thereafter. N-acetyl-l-aspartate (NAA) was low at birth, increased in an approximately linear fashion, and reached adult levels by about day 28 postnatal. Choline was high at birth and showed a two step decline, at approximately day seven and day 20 postnatal. Taurine, a sulfur amino acid abundant in fetal brain, was also present in high levels on the first day postnatal.

Amino Acids↗

The substantia innominata and adjacent regions in the human brain: histochemical and biochemical observations.

The substantia innominata was investigated in the adult human brain with particular reference to the cholinergic nature of the nucleus of Meynert. Based on histochemical observations of acetylcholinesterase activity and biochemical estimations of choline acetyltransferase the relations of the Meynert nucleus to adjacent structures in the substantia innominata region were identified precisely. A new dissection procedure is described which permits combined histochemical and histological examination of anatomically complex regions of the human brain, such as the substantia innominata, to be carried out in conjunction with accurate tissue dissection for neurochemical analysis. Using this technique, various acetylcholinesterase-positive and choline acetyltransferase-containing structures are apparent in coronal sections removed from the rostrocaudal length of the substantia innominata. These include, in addition to the prominently stained, putative cholinergic neurons, acetylcholinesterase-positive tracts which contain putative cholinergic projections to the neocortex, and 'islands' of acetylcholinesterase-positive neuropil which presumably reflect a collateral or intrinsic cholinergic innervation in the area. This anatomical complexity of cholinergic structures in the substantia innominata suggests that neurochemical analysis should be conducted on microdissected as opposed to macrodissected tissue samples. Neuropathologically, the present report provides a further basis for optimising quantification of putative cholinergic perikarya. Continued systematic analysis of the nucleus of Meynert at the morphological and biochemical level should thus establish the role of this nucleus in normal brain function and in disease.

Acetylcholinesterase↗

[An approach to use cancer registration to assess cancer risks by occupation and industry].

This study explored how to use cancer registration data to assess cancer risk. Based on the data of the Tianjin Cancer Registry, the occupational and industrial risk for lung cancer were assessed as examples. All cases of cancer aged at least 20 years and reported during 1981-1987 to the TCR formed the basis of the study. A comparison was made using case-case methodology that cases of one cancer site compared with cases of all other sites. Data were re-coded according to 30 occupational and 27 industrial categories. The individuals employed in the interested category were considered as exposed, and subjects employed in all other categories were considered as unexposed. Statistical analysis was conducted by unconditional multiple logistic regression. Regression models included sex, age and year of diagnosis. From our study, the results are constant with previous reports. The systematic analysis of the association between occupation and industry of employment and cancer among men and women registered in the TCR provided confirmation in this population of a number of known or suspected occupational cancer risk factors studied in industrialized countries. The main advantages of this design are 1. To use the data of a cancer registration that are already existed. 2. It is easy, fast and less cost to screening the cancer risk or potential cancer risk. 3. All factors in the database of cancer registration could be evaluated, for example, occupation, industry, education, etc. 4. The way to define cases and exposed groups could decrease the influence of confounding and bias.

Adult↗

Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells.

Classical genetic screens can be limited by the selectivity of mutational targeting, the complexities of anatomically based phenotypic analysis, or difficulties in subsequent gene identification. Focusing on signaling response to the secreted morphogen Hedgehog (Hh), we used RNA interference (RNAi) and a quantitative cultured cell assay to systematically screen functional roles of all kinases and phosphatases, and subsequently 43% of predicted Drosophila genes. Two gene products reported to function in Wingless (Wg) signaling were identified as Hh pathway components: a cell surface protein (Dally-like protein) required for Hh signal reception, and casein kinase 1alpha, a candidate tumor suppressor that regulates basal activities of both Hh and Wg pathways. This type of cultured cell-based functional genomics approach may be useful in the systematic analysis of other biological processes.

Animals↗

Expression and regulation of antimicrobial peptides in articular joints.

Articular joint infection is a surprisingly rare event considering the frequency of joint arthrocentesis and other invasive procedures applied to limb joints. This observation led us to the hypothesis that a local "chemical shield" in the form of antimicrobial proteins provides synovial membrane and articular cartilage with resistance to infection. We subsequently began a systematic analysis of in vitro and in vivo antimicrobially active proteins in healthy articular joints and in disease states such as pyogenic arthritis, rheumatoid arthritis, and osteoarthritis. An anatomical approach with systematic characterization combined with antimicrobial testing revealed expression and production of human antibiotic peptides and proteins. In this review, we focus on the most prominent antimicrobial proteins in articular joints, which we have identified as lysozyme, lactoferrin, secretory phospholipase A2, RNase 7, CAP37, the cathelicidin LL37, and especially the human beta-defensin-2 and -3 (HBD-2/-3). Activation pathways and possible antimicrobial functions are discussed and the involvement in non-antimicrobial processes such as tissue remodelling is also considered.

Cartilage, Articular↗

Overcoming barriers to patient safety.

Creating a culture of patient safety is a critical goal of all patient care unit staff. An analysis of the key barriers to patient safety on a typical inpatient unit in an acute care hospital (unclear unit values), the fear of punishment for errors, the lack of systematic analysis of mistakes, the complexity of the nurses' work, and inadequate teamwork are presented. Nine practices to overcome these barriers and achieve patient safety are discussed.

Attitude of Health Personnel↗

First-pass radionuclide angiographic analysis with two regions of interest to improve left ventricular ejection fraction accuracy.

UNLABELLED: First-pass radionuclide angiographic (FPRNA) analysis, using the standard, single-fixed region of interest (ROI) drawn at end-diastole, often underestimates the left ventricular ejection fraction (LVEF) as determined by other standard techniques. This study examined the hypothesis that correction for the anatomic motion of the aortic valve plane toward the apex during systole, which results in improper inclusion of aortic counts within the single-fixed ROI, using a two-ROI method to compensate for this motion would eliminate this underestimation. METHODS: In 70 patients who underwent FPRNA and planar gated equilibrium radionuclide angiography (GERNA) on the same day, Fourier transform phase and amplitude images were used to generate functional maps of the aorta and the left ventricle on the FPRNA representative cycle. The region of low amplitude between the aorta and left ventricle, which corresponds to the degree of aortic valve plane motion, was used to guide the manual placement of two ROIs. The first was over the left ventricle at the end-diastole including the aortic valve plane area, and the second was a smaller end-systolic ROI drawn over the first ROI, excluding the valve plane area. RESULTS: Both the fixed- and dual-ROI FPRNA methods had excellent correlation with GERNA (r = 0.92 and 0.91, respectively). The mean FPRNA LVEF using a fixed ROI (45% +/- 14%) was significantly lower than GERNA (51% +/- 15%, p < 0.001), but the mean LVEF calculated from the dual-ROI (51% +/- 14%) was essentially identical to those obtained with GERNA. The method of manual placement of the two ROIs had extremely high levels of inter- and intraobserver reproducibility (r = 0.98 and 0.99, respectively). CONCLUSION: Despite good correlation, the standard, fixed-ROI method of FPRNA analysis systematically underestimates the LVEFs of GERNA. This problem can be eliminated by taking into account valve plane motion during the cardiac cycle by using Fourier-guided, dual-ROI analysis on FPRNA. These differences in methods and results should be considered when substituting or comparing LVEFs derived from these techniques.

Female↗

Test-retest repeatability of muscle sympathetic nerve activity: influence of data analysis and head-up tilt.

Total integrated muscle sympathetic nerve activity (MSNA) is composed of bursts that vary in both frequency and amplitude. Various quantifiable indices are currently used to characterize MSNA and its reflex-mediated responses. However, a comprehensive and systematic analysis on the test-retest repeatability of these measures has not been conducted. Therefore, the purpose of this study was to compare the consistency of supine and passive head-up tilt-mediated sympathetic nerve activity using different descriptors of MSNA and a statistical paradigm that included Model II ordinary least products (OLP) regression, Bland-Altman method of differences, and analysis of variance. MSNA (microneurography), stroke volume (SV, Doppler), and arterial blood pressure (ABP, Finapres) were measured during repeated supine and 60 degrees head-up tilt (HUT) conditions separated by a minimum of 3 weeks. MSNA was quantified using; burst frequency (and incidence), burst amplitudes (and total integrated activity) normalized to the largest absolute amplitude within each posture, and calculated percent changes (from supine) in absolute burst amplitude and total integrated activity. Most indices of MSNA showed excellent test-retest repeatability during both postures with neither fixed nor proportional bias. However, MSNA expressed as burst incidence demonstrated both fixed and proportional bias in the supine position, but not during HUT. In addition, HUT-induced percent changes in absolute burst amplitude and total activity displayed a fixed bias with greater increases during the second test (P<0.05). The hemodynamic variables associated with the reflex responses were quite similar between tests (i.e., no bias). It was concluded that, with the exception of burst incidence, the majority of MSNA indices provided reliable markers of sympathetic activity on repeated tests. However, care must be taken when using percent changes in MSNA that incorporate absolute amplitudes.

Adult↗

Proteomics analysis of rat brain protein modulations by grape seed extract.

Dietary supplements such as grape seed extract (GSE) enriched in proanthocyanidins (PA) (oligomeric polyphenols) have been suggested to have multiple health benefits, due to antioxidant and other beneficial activities of the PA. However, a systematic analysis of the molecular basis of these benefits has not been demonstrated. Because the brain is vulnerable to age-related oxidative damage and other insults including inflammation, it was hypothesized that rats ingesting GSE would experience changes in expression or modifications of specific brain proteins that might protect against pathologic events. Normal adult female rats were fed diets supplemented with 5% GSE for 6 weeks. Proteomics analysis (2D electrophoresis and mass spectrometry) of brain homogenates from these animals identified 13 proteins that were altered in amount and/or charge. Because many of these changes were quantitatively in the opposite direction from previous findings for the same proteins in either Alzheimer disease or mouse models of neurodegeneration, the data suggest that these identified proteins may mediate the neuroprotective actions of GSE. This is the first identification and quantitation of specific proteins in mammalian tissues modulated by a dietary supplement, as well as the first to demonstrate links of such proteins with any disease.

Amino Acid Sequence↗

The Daily Point of Light Awards: an analysis of recipients and effects.

During his presidential administration, George Bush used the phrase "points of light" to connote and promote voluntary service. His program to honor those with exemplary service with a Daily Point of Light (DPOL) Award attracted great publicity--but no systematic analysis. Accordingly, this article presents the first comprehensive examination of the DPOL recipients, and the possible effects the Award had for strengthening and publicizing their voluntary activities. The analysis is based on a review of the press releases describing each recipient of the Award and a mail survey of this group administered by the authors.

Awards and Prizes↗