Loeffler's Endocarditis- A cause of endomyocardial fibrosis in a patient of juvenile idiopathic arthritis: A Case Report.

Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated, it carries a very high morbidity and mortality rate. The case of a 20 years old girl, a known case of polyarticular juvenile idiopathic arthritis since the age of 13 years was reported at Federal Government Polyclinic Hospital, Islamabad on 14th May 2022. She presented with an acute history of shortness of breath and cough for two weeks. Her initial echocardiogram showed suspicion of Loeffler's Endocarditis, which is attributed to be an adverse effect of etanercept- a tumour necrosis factor (TNF) inhibitor, which she had been prescribed for her arthritis. The patient is currently being managed with high doses of steroids, therapeutic anticoagulation with rivaroxaban, carvedilol for tachycardia and mycophenolate mofetil as an immunosuppressant.

Massive genome reduction predates the divergence of Symbiodiniaceae dinoflagellates.

Dinoflagellates in the family Symbiodiniaceae are taxonomically diverse, predominantly symbiotic lineages that are well-known for their association with corals. The ancestor of these taxa is believed to have been free-living. The establishment of symbiosis (i.e. symbiogenesis) is hypothesized to have occurred multiple times during Symbiodiniaceae evolution, but its impact on genome evolution of these taxa is largely unknown. Among Symbiodiniaceae, the genus Effrenium is a free-living lineage that is phylogenetically positioned between two robustly supported groups of genera within which symbiotic taxa have emerged. The apparent lack of symbiogenesis in Effrenium suggests that the ancestral features of Symbiodiniaceae may have been retained in this lineage. Here, we present de novo assembled genomes (1.2-1.9 Gbp in size) and transcriptome data from three isolates of Effrenium voratum and conduct a comparative analysis that includes 16 Symbiodiniaceae taxa and the other dinoflagellates. Surprisingly, we find that genome reduction, which is often associated with a symbiotic lifestyle, predates the origin of Symbiodiniaceae. The free-living lifestyle distinguishes Effrenium from symbiotic Symbiodiniaceae vis-à-vis their longer introns, more-extensive mRNA editing, fewer (~30%) lineage-specific gene sets, and lower (~10%) level of pseudogenization. These results demonstrate how genome reduction and the adaptation to distinct lifestyles intersect to drive diversification and genome evolution of Symbiodiniaceae.

Fatigue Assessment Using FACIT-F Scale in Spondyloarthropathy Patients and its Correlation with BASDAI and BASFI Scores.

OBJECTIVE: To measure fatigue in axial spondyloarthropathy patients and find its correlation with the disease activity measures. STUDY DESIGN: Cross-sectional, descriptive study. Place and Duration of the Study: Rheumatology Unit, Federal Government Polyclinic Hospital, from November 2021 to May 2022. METHODOLOGY: This study included 45 patients fulfilling the ASAS criteria for spondyloarthropathy. Bathankylosing spondylitis disease activity (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and functional assessment of chronic illness therapy- fatigue (FACIT-F) scores were measured for each patient. RESULTS: In this study, there were 9 (20%) female patients and 36 (80%) male patients. There were 39 (86.7%) patients who had ankylosing spondylitis, 4 (8.9%) had axial spondyloarthropathy with peripheral arthritis and 2 (4.4%) had enthesitis-related juvenile idiopathic arthritis. The mean duration of the disease was 5.45 ± 4.19 years. Active disease with a BASDAI score of ≥4 was found in 16 (35.6%) patients while 29 (64.4%) had a BASDAI score <4. Severe fatigue with a FACIT-F score of <30 was found in 31 (68.9%) of the patients while less fatigue with FACIT-F score >30 was found in 14 (31.1%). The mean BASFI score of the cohort was 3.23 ± 2.01. Spearman's rho correlation analysis showed a significant strong correlation between the FACIT-F score, BASDAI and BASFI scores (p<0.001). CONCLUSION: Patients with active disease and higher BASFI scores had a lower FACIT-F score suggesting more fatigue, thus correlating with the disease activity. KEY WORDS: Bath ankylosing spondylitis disease activity (BASDAI), Functional assessment of chronic illness therapy-fatigue (FACIT-F), Ankylosing spondylitis (AS), Bath ankylosing spondylitis functional index (BASFI), Assessment in ankylosing spondylitis (ASAS).

Multi-omics analysis reveals the molecular response to heat stress in a "red tide" dinoflagellate.

BACKGROUND: "Red tides" are harmful algal blooms caused by dinoflagellate microalgae that accumulate toxins lethal to other organisms, including humans via consumption of contaminated seafood. These algal blooms are driven by a combination of environmental factors including nutrient enrichment, particularly in warm waters, and are increasingly frequent. The molecular, regulatory, and evolutionary mechanisms that underlie the heat stress response in these harmful bloom-forming algal species remain little understood, due in part to the limited genomic resources from dinoflagellates, complicated by the large sizes of genomes, exhibiting features atypical of eukaryotes. RESULTS: We present the de novo assembled genome (~ 4.75 Gbp with 85,849 protein-coding genes), transcriptome, proteome, and metabolome from Prorocentrum cordatum, a globally abundant, bloom-forming dinoflagellate. Using axenic algal cultures, we study the molecular mechanisms that underpin the algal response to heat stress, which is relevant to current ocean warming trends. We present the first evidence of a complementary interplay between RNA editing and exon usage that regulates the expression and functional diversity of biomolecules, reflected by reduction in photosynthesis, central metabolism, and protein synthesis. These results reveal genomic signatures and post-transcriptional regulation for the first time in a pelagic dinoflagellate. CONCLUSIONS: Our multi-omics analyses uncover the molecular response to heat stress in an important bloom-forming algal species, which is driven by complex gene structures in a large, high-G+C genome, combined with multi-level transcriptional regulation. The dynamics and interplay of molecular regulatory mechanisms may explain in part how dinoflagellates diversified to become some of the most ecologically successful organisms on Earth.

Gene duplication is the primary driver of intraspecific genomic divergence in coral algal symbionts.

Dinoflagellates in the order Suessiales include the family Symbiodiniaceae, which have essential roles as photosymbionts in corals, and their cold-adapted sister group, Polarella glacialis. These diverse taxa exhibit extensive genomic divergence, although their genomes are relatively small (haploid size < 3 Gbp) when compared with most other free-living dinoflagellates. Different strains of Symbiodiniaceae form symbiosis with distinct hosts and exhibit different regimes of gene expression, but intraspecific whole-genome divergence is poorly understood. Focusing on three Symbiodiniaceae species (the free-living Effrenium voratum and the symbiotic Symbiodinium microadriaticum and Durusdinium trenchii) and the free-living outgroup P. glacialis, for which whole-genome data from multiple isolates are available, we assessed intraspecific genomic divergence with respect to sequence and structure. Our analysis, based on alignment and alignment-free methods, revealed a greater extent of intraspecific sequence divergence in Symbiodiniaceae than in P. glacialis. Our results underscore the role of gene duplication in generating functional innovation, with a greater prevalence of tandemly duplicated single-exon genes observed in the genomes of free-living species than in symbionts. These results demonstrate the remarkable intraspecific genomic divergence in dinoflagellates under the constraint of reduced genome sizes, shaped by genetic duplications and symbiogenesis events during the diversification of Symbiodiniaceae.

Carotid Intimomedial Thickness (CIMT) in Patients with Rheumatoid Arthritis; the Need for More Aggressive Cardiovascular Screening in RA.

OBJECTIVE: To use carotid intimal medial thickness as a marker of early atherosclerosis in patients with rheumatoid arthritis. STUDY DESIGN: Cross-sectional descriptive study. Place and Duration of the Study: Rheumatology Unit of Federal Government Polyclinic Hospital, Islamabad, from 1st June 2019 till 30th January 2022. METHODOLOGY: The study included 190 patients divided equally into cases of rheumatoid arthritis and healthy control groups. Carotid intimal medial thickness was measured using the carotid doppler ultrasound. The mean values of both the study groups were evaluated using the independent sample t-tests. Different statistical tests for correlation were also used where appropriate. RESULTS: This study included a total of 190 patients, 95 each in case and control groups. There were 15 (15.8%) males and 80 (84.2%) females with mean age of 43.5±12.8 years among cases, while 27 (28.4%) males and 68 (71.6%) females with mean age of 43.1±10.1 years in the control group. A significantly higher number of cases had a carotid intima-media thickness of more than 0.6 mm as compared to controls (43.2% vs. 25.3%, p=0.009). Cases with seropositive status were 1.98 times more likely to have higher carotid intima-medial thickness compared with controls. CONCLUSION: Carotid intima-media thickness measurement is important as a surrogate marker of atherosclerotic process in patients with rheumatoid arthritis. KEY WORDS: Rheumatoid arthritis (RA), Carotid intimal medial thickness (CIMT), Atherosclerosis, Cardiovascular disease (CVD).

Effect of integrated medicines management on the quality of drug treatment in hospitalised multimorbid patients - a secondary endpoint analysis of a randomised controlled trial.

OBJECTIVES: To investigate the effect of integrated medicines management provided to hospitalised multimorbid patients on the quality of drug treatment at discharge measured as the mean number of potential prescribing omissions and potentially inappropriate medicines. METHODS: Multimorbid patients ≥18 years, using a minimum of four regular drugs from a minimum of two therapeutic drug classes, were recruited from the Internal Medicine ward, Oslo University Hospital, Norway, from August 2014 to March 2016 and randomly assigned, 1:1, to the intervention or control group. Intervention patients received integrated medicines management throughout the hospital stay. Control patients received standard care. This paper reports the results of a pre-specified secondary endpoint analysis of a randomised controlled trial; the difference between the intervention and control group at discharge in the mean number of potential prescribing omissions and potentially inappropriate medicines, measured with START-2 and STOPP-2 criteria, respectively. The difference between the groups was calculated using rank analysis. KEY FINDINGS: In total, 386 patients were analysed. Integrated medicines management reduced the mean number of potential prescribing omissions at discharge, compared to the control group, 1.34 versus 1.57, respectively (mean difference 0.23, 95% CI 0.07-0.38, P = 0.005, adjusted for values at admission). There was no difference in the mean number of potentially inappropriate medicines at discharge (1.84 versus 1.88, respectively; mean difference 0.03, 95% CI -0.18 to 0.25, P = 0.762, adjusted for values at admission). CONCLUSIONS: Integrated medicines management delivered to multimorbid patients during a hospital stay led to an improvement in undertreatment. No effect on deprescribing of inappropriate treatment was seen.

Improved Cladocopium goreaui Genome Assembly Reveals Features of a Facultative Coral Symbiont and the Complex Evolutionary History of Dinoflagellate Genes.

Dinoflagellates of the family Symbiodiniaceae are crucial photosymbionts in corals and other marine organisms. Of these, Cladocopium goreaui is one of the most dominant symbiont species in the Indo-Pacific. Here, we present an improved genome assembly of C. goreaui combining new long-read sequence data with previously generated short-read data. Incorporating new full-length transcripts to guide gene prediction, the C. goreaui genome (1.2 Gb) exhibits a high extent of completeness (82.4% based on BUSCO protein recovery) and better resolution of repetitive sequence regions; 45,322 gene models were predicted, and 327 putative, topologically associated domains of the chromosomes were identified. Comparison with other Symbiodiniaceae genomes revealed a prevalence of repeats and duplicated genes in C. goreaui, and lineage-specific genes indicating functional innovation. Incorporating 2,841,408 protein sequences from 96 taxonomically diverse eukaryotes and representative prokaryotes in a phylogenomic approach, we assessed the evolutionary history of C. goreaui genes. Of the 5246 phylogenetic trees inferred from homologous protein sets containing two or more phyla, 35-36% have putatively originated via horizontal gene transfer (HGT), predominantly (19-23%) via an ancestral Archaeplastida lineage implicated in the endosymbiotic origin of plastids: 10-11% are of green algal origin, including genes encoding photosynthetic functions. Our results demonstrate the utility of long-read sequence data in resolving structural features of a dinoflagellate genome, and highlight how genetic transfer has shaped genome evolution of a facultative symbiont, and more broadly of dinoflagellates.

Genome-Guided Analysis of Seven Weed Species Reveals Conserved Sequence and Structural Features of Key Gene Targets for Herbicide Development.

Herbicides are commonly deployed as the front-line treatment to control infestations of weeds in native ecosystems and among crop plants in agriculture. However, the prevalence of herbicide resistance in many species is a major global challenge. The specificity and effectiveness of herbicides acting on diverse weed species are tightly linked to targeted proteins. The conservation and variance at these sites among different weed species remain largely unexplored. Using novel genome data in a genome-guided approach, 12 common herbicide-target genes and their coded proteins were identified from seven species of Weeds of National Significance in Australia: Alternanthera philoxeroides (alligator weed), Lycium ferocissimum (African boxthorn), Senecio madagascariensis (fireweed), Lantana camara (lantana), Parthenium hysterophorus (parthenium), Cryptostegia grandiflora (rubber vine), and Eichhornia crassipes (water hyacinth). Gene and protein sequences targeted by the acetolactate synthase (ALS) inhibitors and glyphosate were recovered. Compared to structurally resolved homologous proteins as reference, high sequence conservation was observed at the herbicide-target sites in the ALS (target for ALS inhibitors), and in 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (target for glyphosate). Although the sequences are largely conserved in the seven phylogenetically diverse species, mutations observed in the ALS proteins of fireweed and parthenium suggest resistance of these weeds to ALS-inhibiting and other herbicides. These protein sites remain as attractive targets for the development of novel inhibitors and herbicides. This notion is reinforced by the results from the phylogenetic analysis of the 12 proteins, which reveal a largely consistent vertical inheritance in their evolutionary histories. These results demonstrate the utility of high-throughput genome sequencing to rapidly identify and characterize gene targets by computational methods, bypassing the experimental characterization of individual genes. Data generated from this study provide a useful reference for future investigations in herbicide discovery and development.

Alignment-Free Analysis of Whole-Genome Sequences From Symbiodiniaceae Reveals Different Phylogenetic Signals in Distinct Regions.

Dinoflagellates of the family Symbiodiniaceae are predominantly essential symbionts of corals and other marine organisms. Recent research reveals extensive genome sequence divergence among Symbiodiniaceae taxa and high phylogenetic diversity hidden behind subtly different cell morphologies. Using an alignment-free phylogenetic approach based on sub-sequences of fixed length k (i.e. k-mers), we assessed the phylogenetic signal among whole-genome sequences from 16 Symbiodiniaceae taxa (including the genera of Symbiodinium, Breviolum, Cladocopium, Durusdinium and Fugacium) and two strains of Polarella glacialis as outgroup. Based on phylogenetic trees inferred from k-mers in distinct genomic regions (i.e. repeat-masked genome sequences, protein-coding sequences, introns and repeats) and in protein sequences, the phylogenetic signal associated with protein-coding DNA and the encoded amino acids is largely consistent with the Symbiodiniaceae phylogeny based on established markers, such as large subunit rRNA. The other genome sequences (introns and repeats) exhibit distinct phylogenetic signals, supporting the expected differential evolutionary pressure acting on these regions. Our analysis of conserved core k-mers revealed the prevalence of conserved k-mers (>95% core 23-mers among all 18 genomes) in annotated repeats and non-genic regions of the genomes. We observed 180 distinct repeat types that are significantly enriched in genomes of the symbiotic versus free-living Symbiodinium taxa, suggesting an enhanced activity of transposable elements linked to the symbiotic lifestyle. We provide evidence that representation of alignment-free phylogenies as dynamic networks enhances the ability to generate new hypotheses about genome evolution in Symbiodiniaceae. These results demonstrate the potential of alignment-free phylogenetic methods as a scalable approach for inferring comprehensive, unbiased whole-genome phylogenies of dinoflagellates and more broadly of microbial eukaryotes.

Genome-powered classification of microbial eukaryotes: focus on coral algal symbionts.

Modern microbial taxonomy generally relies on the use of single marker genes or sets of concatenated genes to generate a framework for the delineation and classification of organisms at different taxonomic levels. However, given that DNA is the 'blueprint of life', and hence the ultimate arbiter of taxonomy, classification systems should attempt to use as much of the blueprint as possible to capture a comprehensive phylogenetic signal. Recent analysis of whole-genome sequences from coral reef symbionts (dinoflagellates of the family Symbiodiniaceae) and other microalgal groups has uncovered extensive divergence not recognised by current algal taxonomic approaches. In the era of 'sequence everything', we argue that whole-genome data are pivotal to guide informed taxonomic inference, particularly for microbial eukaryotes.

Black and white or shades of grey: Religious approaches and Muslim marital conflict.

While the diversity of diasporic Muslim public experiences has been examined, the social contours of religious approach have received less attention. Moreover, the ways in which religion shapes marital relations remains understudied. This article, which features data from a larger research project, highlights two divergent trends in Muslim approaches to religion: exclusivity, which frames only one approach to Islam as correct, and inclusivity, which frames multiple approaches as correct. This divergence plays a role in shaping definitions of 'good Muslim', as exclusivist Muslims focus on ritual acts (outward observance), while inclusivist Muslims prioritize good manners (inward observance). The author demonstrates how these inward and outward definitions of Muslimness in turn inform how participants evaluate their spouses' religiosity and, thus, the potential for conflict over religiosity with their spouses.

Alors que la diversité des expériences publiques des musulmans de la diaspora a été largement analysée, les contours sociaux de l'approche religieuse ont reçu moins d'attention. Par ailleurs, la manière dont la religion façonne les relations conjugales reste un sujet peu étudié. Cet article, qui présente les données d'un projet de recherche plus vaste, met en évidence deux tendances divergentes dans les approches musulmanes de la religion: l'exclusivité, qui considère qu'une seule approche de l'islam est acceptable, et l'inclusivité, qui considère que plusieurs approches sont acceptables. Cette contradiction joue un rôle dans la manière de définir le « bon musulman ¼, car les musulmans exclusivistes se concentrent sur les actes rituels (observance extérieure), alors que les musulmans inclusivistes privilégient les bonnes manières (observance intérieure). L'auteur démontre comment ces définitions « intérieures ¼ et « extérieures ¼ de la condition musulmane influencent à leur tour la façon dont les participants évaluent la religiosité de leur conjoint et, par conséquent, les possibilités de conflit avec leur conjoint en matière de religiosité.

Microalgal nanocellulose - opportunities for a circular bioeconomy.

Over 3 billion years, photosynthetic algae have evolved complex uses for cellulose, the most abundant polymer worldwide. A major cell-wall component of lignocellulosic plants, seaweeds, microalgae, and bacteria, cellulose can be processed to nanocellulose, a promising nanomaterial with novel properties. The structural diversity of macro- and microalgal nanocelluloses opens opportunities to couple low-impact biomass production with novel, green-chemistry processing to yield valuable, sustainable nanomaterials for a multitude of applications ranging from novel wound dressings to organic solar cells. We review the origins of algal cellulose and the applications and uses of nanocellulose, and highlight the potential for microalgae as a nanocellulose source. Given the limited state of current knowledge, we identify research challenges and strategies to help to realise this potential.

Comparison of 15 dinoflagellate genomes reveals extensive sequence and structural divergence in family Symbiodiniaceae and genus Symbiodinium.

BACKGROUND: Dinoflagellates in the family Symbiodiniaceae are important photosynthetic symbionts in cnidarians (such as corals) and other coral reef organisms. Breakdown of the coral-dinoflagellate symbiosis due to environmental stress (i.e. coral bleaching) can lead to coral death and the potential collapse of reef ecosystems. However, evolution of Symbiodiniaceae genomes, and its implications for the coral, is little understood. Genome sequences of Symbiodiniaceae remain scarce due in part to their large genome sizes (1-5 Gbp) and idiosyncratic genome features. RESULTS: Here, we present de novo genome assemblies of seven members of the genus Symbiodinium, of which two are free-living, one is an opportunistic symbiont, and the remainder are mutualistic symbionts. Integrating other available data, we compare 15 dinoflagellate genomes revealing high sequence and structural divergence. Divergence among some Symbiodinium isolates is comparable to that among distinct genera of Symbiodiniaceae. We also recovered hundreds of gene families specific to each lineage, many of which encode unknown functions. An in-depth comparison between the genomes of the symbiotic Symbiodinium tridacnidorum (isolated from a coral) and the free-living Symbiodinium natans reveals a greater prevalence of transposable elements, genetic duplication, structural rearrangements, and pseudogenisation in the symbiotic species. CONCLUSIONS: Our results underscore the potential impact of lifestyle on lineage-specific gene-function innovation, genome divergence, and the diversification of Symbiodinium and Symbiodiniaceae. The divergent features we report, and their putative causes, may also apply to other microbial eukaryotes that have undergone symbiotic phases in their evolutionary history.

Sex in Symbiodiniaceae dinoflagellates: genomic evidence for independent loss of the canonical synaptonemal complex.

Dinoflagellates of the Symbiodiniaceae family encompass diverse symbionts that are critical to corals and other species living in coral reefs. It is well known that sexual reproduction enhances adaptive evolution in changing environments. Although genes related to meiotic functions were reported in Symbiodiniaceae, cytological evidence of meiosis and fertilisation are however yet to be observed in these taxa. Using transcriptome and genome data from 21 Symbiodiniaceae isolates, we studied genes that encode proteins associated with distinct stages of meiosis and syngamy. We report the absence of genes that encode main components of the synaptonemal complex (SC), a protein structure that mediates homologous chromosomal pairing and class I crossovers. This result suggests an independent loss of canonical SCs in the alveolates, that also includes the SC-lacking ciliates. We hypothesise that this loss was due in part to permanently condensed chromosomes and repeat-rich sequences in Symbiodiniaceae (and other dinoflagellates) which favoured the SC-independent class II crossover pathway. Our results reveal novel insights into evolution of the meiotic molecular machinery in the ecologically important Symbiodiniaceae and in other eukaryotes.

Use of Plackett-Burman design for enhanced phytase production by Williopsis saturnus NCIM 3298 for applications in animal feed and ethanol production.

Distiller-dried grain solid (DDGS), a co-product of alcohol production, contains cereal grain residues, proteins, and yeast metabolites, which make it suitable in poultry feeding. However, high phytate content of DDGS limits its applicability in poultry feed. In this study, Plackett-Burman design was used to improve cell-bound phytase production by Williopsis saturnus NCIM 3298, and we achieved an enzyme activity of 269 IU/g of dry-wet biomass. The effect of this enhanced phytase-displaying yeast strain on hydrolysis of corn phytate and subsequently on ethanol production and DDGS quality was then investigated. Results of saccharification in the presence of phytase showed that reducing sugar content of liquefied mash increased by 11%, which subsequently improved the ethanol production by 18% (w/v) (p < 0.01) compared with the control. Notably, phytase treatment decreased the phytate content of corn by 70% (p < 0.01) compared with the control, thereby improving the availability of free phosphate in fermentation broth and DDGS. Thus, the results obtained suggest that the addition of W. saturnus NCIM 3298 strain has the potential of providing a new source of phytase that would be useful in the feed and ethanol industries.

Blastocystis Mitochondrial Genomes Appear to Show Multiple Independent Gains and Losses of Start and Stop Codons.

Complete mitochondrion-related organelle (MRO) genomes of several subtypes (STs) of the unicellular stramenopile Blastocystis are presented. Complete conservation of gene content and synteny in gene order is observed across all MRO genomes, comprising 27 protein coding genes, 2 ribosomal RNA genes, and 16 transfer RNA (tRNA) genes. Despite the synteny, differences in the degree of overlap between genes were observed between subtypes and also between isolates within the same subtype. Other notable features include unusual base-pairing mismatches in the predicted secondary structures of some tRNAs. Intriguingly, the rps4 gene in some MRO genomes is missing a start codon and, based on phylogenetic relationships among STs, this loss has happened twice independently. One unidentified open reading frame (orf160) is present in all MRO genomes. However, with the exception of ST4 where the feature has been lost secondarily, orf160 contains variously one or two in-frame stop codons. The overall evidence suggests that both the orf160 and rps4 genes are functional in all STs, but how they are expressed remains unclear.

In vitro microleakage of a fissure sealant polymerized by either a quartz tungsten halogen curing light or a plasma arc curing light.

BACKGROUND: The benefits of using plasma arc curing lights with their shorter curing times in the management of children are potentially great, provided there are no adverse effects. OBJECTIVE: The aim of this study was to investigate whether the microleakage of a resin-based sealant is influenced by polymerization with either a conventional quartz tungsten halogen or a plasma arc curing light. DESIGN: This study took the form of an in vitro randomized control trial. Seventy extracted human first and second permanent premolars and molars were randomly allocated into two groups. Their occlusal surfaces were sealed with a light-cured fissure sealant using either a quartz tungsten halogen curing light or a plasma arc curing light. The teeth were then sectioned, resulting in four surfaces per tooth, which were examined for microleakage under x 15 magnification with a light microscope. The principal unit of analysis was the tooth (worst section score) and not the section microleakage score. RESULTS: No statistical significant difference in microleakage scoring between the two groups was demonstrated. CONCLUSION: This study found no difference in the degree of microleakage of fissure sealants polymerized by either light source.

Low-dose spironolactone in the management of resistant hypertension: a surveillance study.

METHODS: We have conducted an open observational study of the use of spironolactone 25-50 mg in the management of patients with resistant hypertension. This drug was recommended in 133 patients who were already receiving an angiotensin-blocking drug in addition to other therapies. RESULTS: Of these, three defaulted from follow-up and 11 could not tolerate spironolactone. We therefore have outcome data on 119 patients. The addition of spironolactone (median dose 25 mg) was associated with a mean (SD) fall in systolic blood pressure of 21.7 mmHg (24.0; P < 0.001) and diastolic blood pressure of 8.5 mmHg (14.9; P < 0.001). In two patients spironolactone had to be discontinued on account of a rise of serum potassium to above 6.0 mmol/l, whereas overall the mean increase in serum potassium was 0.3 mmol/l. CONCLUSION: With careful monitoring of plasma electrolytes, spironolactone at a low dose is an effective add-in drug in patients with hypertension resistant to a regime that includes an angiotensin-blocking agent.

A mouse model of breast cancer metastasis to the choroid of the eye.

Transformed mouse mammary epithelial cells, r3T, injected into the arterial circulation form bone metastases with high frequency. Here we report that metastases to the choroid of the eye also occur in these mice with a penetrance of at least 50%. The tumors can occupy as much as half the volume of the eye, and pigmented cells become incorporated into and distributed throughout the tumors. Pigmentation is also observed in the brains and optic nerves of mice with choroidal tumors, suggesting that the tumor cells stimulate migration of pigmented cells along the optic nerve into the brain. To our knowledge, this is the first mouse model of breast cancer choroidal metastasis, and should be useful in the study of this disease.