Reticulate Skin Lesions: Practical Color-Based Algorithm for Initial Clinical Assessment. / Lesiones cutáneas reticulares: algoritmo clínico práctico basado en el color de la lesión para el abordaje inicial.

Reticular patterns are observed in a great variety of skin diseases. While these morphologic patterns are often highly distinctive, they are seldom discussed or studied in clinical contexts or recognized as a diagnostic category in their own right. Diseases presenting with reticulate skin lesions have multiple etiologies (tumors, infections, vascular disorders, inflammatory conditions, and metabolic or genetic alterations) and can range from relatively benign conditions to life-threatening ones. We review a selection of these diseases and propose a clinical diagnostic algorithm based on predominant coloring and clinical features to aid in their initial assessment.

[Translated article] Reticulate Skin Lesions: Practical Color-Based Algorithm for Initial Clinical Assessment.

Reticular patterns are observed in a great variety of skin diseases. While these morphologic patterns are often highly distinctive, they are seldom discussed or studied in clinical contexts or recognized as a diagnostic category in their own right. Diseases presenting with reticulate skin lesions have multiple etiologies (tumors, infections, vascular disorders, inflammatory conditions, and metabolic or genetic alterations) and can range from relatively benign conditions to life-threatening ones. We review a selection of these diseases and propose a clinical diagnostic algorithm based on predominant coloring and clinical features to aid in their initial assessment.

Determining of risk areas due to exposure to heavy metals in the Toluca Valley using epiphytic mosses as a biomonitor.

The work aim is to identify the risk areas by exposure to Cr, Cu, Pb and Zn in the Metropolitan Zone of Toluca Valley (MZTV) using the mosses Fabriona cilaris and Leskea angustata as a biomonitors, geostatistical interpolation and multi-criteria evaluation by analytical hierarchy process. The results from the estimation of the enrichment factors (EF) showed that Pb is the heavy metal with the highest values, followed by the Zn, Cu and Cr. The EF obtained for all heavy metals show that there is a moderate to high anthropogenic enrichment. The above indicates that in the MZTV there are emission sources that contribute (significantly) in the amount of Cr, Cu, Pb and Zn accumulated in the biomonitor. Combustion processes, vehicle emissions, biomass burning, brick kiln emissions, agricultural and livestock activities, manufacturing industry and re-deposition by the action of the wind, were identified as the main heavy metals sources in the MZTV. Risk maps showed the high and medium risk areas are located in sites with poor urban vegetation coverage and close to highways and industrial parks. Low risk areas are located in sites with high urban vegetation coverage. The method used for identifying risk areas is a rapid and low-cost evaluation tool can allow local government environmental agencies to define public policies on air pollution control.

Community-based screening of hepatitis C with a one-step RNA detection algorithm from dried-blood spots: Analysis of key populations in Barcelona, Spain.

Alternative strategies are required to enhance the diagnosis of silent hepatitis C virus (HCV) infections in key populations at risk. Among them, HCV prevalence and bio-behavioural data are scarce for HIV-negative men who have sex with men (MSM) and men and trans-women sex workers. We sought to describe and assess the potential benefits of a community-based one-step HCV screening and confirmatory strategy for these populations in Barcelona. The screening strategy based on a real-time RT-PCR assay for HCV-RNA detection in dried-blood spots (DBS) was validated and implemented in addition to an antibody point-of-care test in a community centre. HCV prevalence was assessed, and bio-behavioural data were collected. The molecular assay was precise, reproducible, sensitive and specific. Four HIV-negative MSM reported being currently infected (0.75% HCV self-reported prevalence). Implementation of DBS testing was easy, and acceptability was >95%, but no silent HCV case was diagnosed (N = 580). High-risk sexual practices and drug use for sex were reported frequently. HIV prevalence was 4.7% in MSM and 10% in sex workers. Self-reported prevalence of other STIs ranged from 11.3% to 36.2%. In conclusion, HCV-RNA testing in DBS showed a good performance, but the assessed one-step strategy does not seem beneficial in this setting. Although no silent HCV infections were detected, the observed high-risk behaviours and prevalence of other STIs suggest that HCV spread should be periodically monitored among these populations in Barcelona by means of behavioural surveillance, rapid antibody testing and molecular confirmation in DBS.

mRNA profiling identifies low levels of phosphatases dual­specific phosphatase­7 (DUSP7) and cell division cycle­25B (CDC25B) in patients with early arthritis.

Phosphotyrosine phosphatases (PTPs) control phosphorylation levels and, consequently, regulate the output of intracellular signalling networks in health and disease. Despite the high number of PTPs expressed in CD4 T cells and their involvement in autoimmunity, information about the expression profile of PTPs in these cells has not been obtained in patients diagnosed with autoimmune diseases. Here, we compare the expression profile of PTPs in CD4 T cells of healthy volunteers and patients submitted to an early arthritis clinic, due to suspicion of rheumatoid arthritis, an autoimmune disease mediated by CD4 T cells. We found lower transcript levels of the mitogen-activated protein kinase (MAPK) phosphatase dual-specific phosphatase-7 (DUSP7) and the cell division cycle-25B (CDC25B) in T cells of patients. While the low expression level of DUSP7 was restricted to patients with positive rheumatoid factor and anti-citrullinated protein antibodies, the altered expression of CDC25B correlated with the activity of the disease. Low levels of CDC25B might contribute to the progression of the autoimmune arthritis and/or might be consequence of the inflammatory environment in the active disease. The possible role of DUSP7 and CDC25B as biomarkers of the disease in clinical protocols is discussed.

Daytime restricted feeding modifies the daily regulation of fatty acid ß-oxidation and the lipoprotein profile in rats.

Daytime restricted feeding (2 h of food access from 12.00 to 14.00 hours for 3 weeks) is an experimental protocol that modifies the relationship between metabolic networks and the circadian molecular clock. The precise anatomical locus that controls the biochemical and physiological adaptations to optimise nutrient use is unknown. We explored the changes in liver oxidative lipid handling, such as ß-oxidation and its regulation, as well as adaptations in the lipoprotein profile. It was found that daytime restricted feeding promoted an elevation of circulating ketone bodies before mealtime, an altered hepatic daily rhythmicity of 14CO2 production from radioactive palmitic acid, and an up-regulation of the fatty acid oxidation activators, the α-subunit of AMP-activated protein kinase (AMPK), the deacetylase silent mating type information regulation homolog 1, and the transcriptional factor PPARγ-1α coactivator. An increased localisation of phosphorylated α-subunit of AMPK in the periportal hepatocytes was also observed. Liver hepatic lipase C, important for lipoprotein transformation, showed a change of daily phase with a peak at the time of food access. In serum, there was an increase of LDL, which was responsible for a net elevation of circulating cholesterol. We conclude that our results indicate an enhanced fasting response in the liver during daily synchronisation to food access, which involves altered metabolic and cellular control of fatty acid oxidation as well a significant elevation of serum LDL. These adaptations could be part of the metabolic input that underlies the expression of the food-entrained oscillator.

Bioactivation of Phytoestrogens: Intestinal Bacteria and Health.

Phytoestrogens are polyphenols similar to human estrogens found in plants or derived from plant precursors. Phytoestrogens are found in high concentration in soya, flaxseed and other seeds, fruits, vegetables, cereals, tea, chocolate, etc. They comprise several classes of chemical compounds (stilbenes, coumestans, isoflavones, ellagitannins, and lignans) which are structurally similar to endogenous estrogens but which can have both estrogenic and antiestrogenic effects. Although epidemiological and experimental evidence indicates that intake of phytoestrogens in foods may be protective against certain chronic diseases, discrepancies have been observed between in vivo and in vitro experiments. The microbial transformations have not been reported so far in stilbenes and coumestans. However, isoflavones, ellagitanins, and lignans are metabolized by intestinal bacteria to produce equol, urolithins, and enterolignans, respectively. Equol, urolithin, and enterolignans are more bioavailable, and have more estrogenic/antiestrogenic and antioxidant activity than their precursors. Moreover, equol, urolithins and enterolignans have anti-inflammatory effects and induce antiproliferative and apoptosis-inducing activities. The transformation of isoflavones, ellagitanins, and lignans by intestinal microbiota is essential to be protective against certain chronic diseases, as cancer, cardiovascular disease, osteoporosis, and menopausal symptoms. Bioavailability, bioactivity, and health effects of dietary phytoestrogens are strongly determined by the intestinal bacteria of each individual.

Pharmacokinetics, efficacy prediction indexes, and residue depletion of ribavirin in Atlantic salmon's (Salmo salar) muscle after oral administration in feed.

Ribavirin is an antiviral used in human medicine, but it has not been authorized for use in veterinary medicine although it is effective against infectious salmon anemia (ISA) virus, between others. In this study, we present a pharmacokinetic profile of ribavirin in Atlantic salmon (Salmo salar), efficacy prediction indexes, and the measure of its withdrawal time. To determine the pharmacokinetic profile, fishes were orally administered with a single ribavirin dose of 1.6 mg/kg bw, and then, plasma concentrations were measured at different times. From the time-vs.-concentration curve, Cmax = 413.57 ng/mL, Tmax  = 6.96 h, AUC = 21394.01 µg·h/mL, t1/2  = 81.61 h, and K10  = 0.0421/h were obtained. Ribavirin reached adequate concentrations during the pharmacokinetic study, with prediction indexes of Cmax /IC50  = 20.7, AUC/IC50  = 1069.7, and T>IC50  = 71 h, where IC is the inhibitory concentration 50%. For ribavirin depletion study, fishes were orally administered with a dairy dose of 1.6 mg/kg bw during 10 days. Concentrations were measured on edible tissue on different days post-treatment. A linear regression of the time vs. concentration was conducted, obtaining a withdrawal time of 1966 °C days. Results obtained reveal that the dose of 1.6 mg/kg bw orally administered is effective for ISA virus, originating a reasonable withdrawal period within the productive schedules of Atlantic salmon.

Metformin and cancer: Between the bioenergetic disturbances and the antifolate activity.

For decades, metformin has been the first-line drug for the treatment of type II diabetes mellitus, and it thus is the most widely prescribed antihyperglycemic drug. Retrospective studies associate the use of metformin with a reduction in cancer incidence and cancer-related death. However, despite extensive research about the molecular effects of metformin in cancer cells, its mode of action remains controversial. In this review, we summarize the current molecular evidence in an effort to elucidate metformin's mode of action against cancer cells. Some authors describe that metformin acts directly on mitochondria, inhibiting complex I and restricting the cell's ability to cope with energetic stress. Furthermore, as the drug interrupts the tricarboxylic acid cycle, metformin-induced alteration of mitochondrial function leads to a compensatory increase in lactate and glycolytic ATP. It has also been reported that cell cycle arrest, autophagy, apoptosis and cell death induction is mediated by the activation of AMPK and Redd1 proteins, thus inhibiting the mTOR pathway. Additionally, unbiased metabolomics studies have provided strong evidence to support that metformin alters the methionine and folate cycles, with a concomitant decrease in nucleotide synthesis. Indeed, purines such as thymidine or hypoxanthine restore the proliferation of tumor cells treated with metformin in vitro. Consequently, some authors prefer to refer to metformin as an "antimetabolite drug" rather than a "mitochondrial toxin". Finally, we also review the current controversy concerning the relationship between the experimental conditions of in vitro-reported effects and the plasma concentrations achieved by chronic treatment with metformin.

Antifungal prophylaxis with anidulafungin to minimize drug interactions with an antiepileptic treatment in a hematopoietic stem cell transplant recipient.

WHAT IS KNOWN AND OBJECTIVE: Invasive fungal infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). This provides a clear rationale for antifungal prophylaxis in this population. A concern is the potential for drug interactions, given that most of antifungals are metabolized through the P450 cytochrome system. CASE SUMMARY: We present a case of a 33-year-old woman, with a past history of high-risk epilepsy, who underwent allogeneic HSCT for a myelodysplastic syndrome. Anidulafungin was successfully used as antifungal prophylaxis to minimize drug interactions with her antiepileptic treatment. WHAT IS NEW AND CONCLUSION: This is the first reported case of antifungal prophylaxis with this echinocandin in HSCT. Anidulafungin may be an option in transplant recipients with multiple risk factors for drug interactions.

Metabolic impact of an NADH-producing glucose-6-phosphate dehydrogenase in Escherichia coli.

In Escherichia coli, the oxidative branch of the pentose phosphate pathway (oxPPP) is one of the major sources of NADPH when glucose is the sole carbon nutrient. However, unbalanced NADPH production causes growth impairment as observed in a strain lacking phosphoglucoisomerase (Δpgi). In this work, we studied the metabolic response of this bacterium to the replacement of its glucose-6-phosphate dehydrogenase (G6PDH) by an NADH-producing variant. The homologous enzyme from Leuconostoc mesenteroides was studied by molecular dynamics and site-directed mutagenesis to obtain the NAD-preferring LmG6PDH(R46E,Q47E). Through homologous recombination, the zwf loci (encoding G6PDH) in the chromosomes of WT and Δpgi E. coli strains were replaced by DNA encoding LmG6PDH(R46E,Q47E). Contrary to some predictions performed with flux balance analysis, the replacements caused a substantial effect on the growth rates, increasing 59 % in the Δpgi strain, while falling 44 % in the WT. Quantitative PCR (qPCR) analysis of the zwf locus showed that the expression level of the mutant enzyme was similar to the native enzyme and the expression of genes encoding key enzymes of the central pathways also showed moderate changes among the studied strains. The phenotypic and qPCR data were integrated into in silico modelling, showing an operative G6PDH flux contributing to the NADH pool. Our results indicated that, in vivo, the generation of NADH by G6PDH is beneficial or disadvantageous for growth depending on the operation of the upper Embden-Meyerhof pathway. Interestingly, a genomic database search suggested that in bacteria lacking phosphofructokinase, the G6PDHs tend to have similar preferences for NAD and NADP. The importance of the generation of NADPH in a pathway such as the oxPPP is discussed.

Production and characterization of a tributyrin esterase from Lactobacillus plantarum suitable for cheese lipolysis.

Lactobacillus plantarum is a lactic acid bacterium that can be found during cheese ripening. Lipolysis of milk triacylglycerols to free fatty acids during cheese ripening has fundamental consequences on cheese flavor. In the present study, the gene lp_1760, encoding a putative esterase or lipase, was cloned and expressed in Escherichia coli BL21 (DE3) and the overproduced Lp_1760 protein was biochemically characterized. Lp_1760 hydrolyzed p-nitrophenyl esters of fatty acids from C2 to C16, with a preference for p-nitrophenyl butyrate. On triglycerides, Lp_1760 showed higher activity on tributyrin than on triacetin. Although optimal conditions for activity were 45°C and pH 7, Lp_1760 retains activity under conditions commonly found during cheese making and ripening. The Lp_1760 showed more than 50% activity at 5°C and exhibited thermal stability at high temperatures. Enzymatic activity was strongly inhibited by sodium dodecyl sulfate and phenylmethylsulfonyl fluoride. The Lp_1760 tributyrin esterase showed high activity in the presence of NaCl, lactic acid, and calcium chloride. The results suggest that Lp_1760 might be a useful tributyrin esterase to be used in cheese manufacturing.

Evaluating odour control technologies using reliability and sustainability criteria--a case study for water treatment plants.

Technologies for odour control have been widely reviewed and their optimal range of application and performance has been clearly established. Selection criteria, mainly driven by process economics, are usually based on the air flow volume, the inlet concentrations and the required removal efficiency. However, these criteria are shifting with social and environmental issues becoming as important as process economics. A methodology is illustrated to quantify sustainability and robustness of odour control technology in the context of odour control at wastewater treatment or water recycling plants. The most commonly used odour abatement techniques (biofiltration, biotrickling filtration, activated carbon adsorption, chemical scrubbing, activated sludge diffusion and biotrickling filtration coupled with activated carbon adsorption) are evaluated in terms of: (1) sustainability, with quantification of process economics, environmental performance and social impact using the sustainability metrics of the Institution of Chemical Engineers; (2) sensitivity towards design and operating parameters like utility prices (energy and labour), inlet odour concentration (H2S) and design safety (gas contact time); (3) robustness, quantifications of operating reliability, with recommendations to improve reliability during their lifespan of operations. The results show that the odour treatment technologies with the highest investments presented the lowest operating costs, which means that the net present value (NPV) should be used as a selection criterion rather than investment costs. Economies of scale are more important in biotechniques (biofiltration and biotrickling filtration) as, at increased airflows, their reduction in overall costs over 20 years (NPV20) is more extreme when compared to the physical/chemical technologies (chemical scrubbing and activated carbon filtration). Due to their low NPV and their low environmental impact, activated sludge diffusion and biotrickling filtration are in general the most cost-effective, and probably the technologies to be considered first for odour treatment in a wastewater treatment or water recycling plant. When, in an economical and risk evaluation, the reliability is counted to be as relevant as the overall costs, a hybrid technology (biotrickling filtration with activated carbon polishing) would be comparable to biotrickling filtration and activated sludge diffusion as the most preferred technologies, when all technologies are designed to have a 99% reduction of H2S and a 95% reduction of the odour concentration.

[Common bile duct stricture caused by vascular ring: a case report]. / Estenosis crítica de conducto hepático común por anillo vascular: reporte de un caso.

INTRODUCTION: The most common congenital malformations of the bile duct are biliary atresia and choledochal cyst. In addition, the most common liver anatomical variation is the right hepatic artery aberration. The goal of this study is to characterize a patient with this disease and propose the hepatoduodenal anastomosis as surgical treatment. CASE REPORT: One-month-old patient with suspected congenital biliary atresia due to progressive jaundice and acholia since birth. Liver tests consistent with a cholestatic pattern and brain MRI scan consistent with biliary atresia. Periods of decreased bilirubin and sporadic slight pigmentation of depositions were described. The surgical finding was a bile duct stricture due to a vascular ring caused by aberrant right hepatic artery. Resection of bile duct and hepatic-duodenal bypass were performed. The patient evolved satisfactorily from this condition. CONCLUSION: There are few reports of biliary obstruction due to vascular malformations. It is important to keep in mind that not all neonatal jaundice episodes are caused by biliary atresia or choledochal cyst. The clinical course, laboratory tests and imaging should be considered and in the case of suspicion, further exploration should take place.

The fundamental role of pH in CH4 bioconversion into polyhydroxybutyrate in mixed methanotrophic cultures.

Climate change and plastic pollution are likely the most relevant challenges for the environment in the 21st century. Developing cost-effective technologies for the bioconversion of methane (CH4) into polyhydroxyalkanoates (PHAs) could simultaneously mitigate CH4 emissions and boost the commercialization of biodegradable polymers. Despite the fact that the role of temperature, nitrogen deprivation, CH4:O2 ratio or micronutrients availability on the PHA accumulation capacity of methanotrophs has been carefully explored, there is still a need for optimization of the CH4-to-PHA bioconversion process prior to becoming a feasible platform in future biorefineries. In this study, the influence of different cultivation broth pH values (5.5, 7, 8.5 and 10) on bacterial biomass growth, CH4 bioconversion rate, PHA accumulation capacity and bacterial community structure was investigated in a stirred tank bioreactor under nitrogen deprivation conditions. Higher CH4 elimination rates were obtained at increasing pH, with a maximum value of 50.4 ± 2.7 g CH4·m-3·h-1 observed at pH 8.5. This was likely mediated by an increased ionic strength in the mineral medium, which enhanced the gas-liquid mass transfer. Interestingly, higher PHB accumulations were observed at decreasing pH, with the highest PHB contents recorded at a pH 5.5 (43.7 ± 3.4 %w·w-1). The strong selective pressure of low pH towards the growth of Type II methanotrophic bacteria could explain this finding. The genus Methylocystis increased its abundance from 34 % up to 85 and 90 % at pH 5.5 and 7, respectively. On the contrary, Methylocystis was less abundant in the community enriched at pH 8.5 (14 %). The accumulation of intracellular PHB as energy and carbon storage material allowed the maintenance of high CH4 biodegradation rates during 48 h after complete nitrogen deprivation. The results here obtained demonstrated for the first time a crucial and multifactorial role of pH on the bioconversion performance of CH4 into PHA.

A comparative assessment of treatment methods to release ferulic and p-cumaric acids from Brewer's Spent Grains.

Brewers' spent grain (BSG) is the main byproduct from the brewing industry, which accounts for 85 % of the total waste generated during beer production. This lignocellulosic material is traditionally used as livestock feed and sold at a low price. However, BSG can be used as a low-cost feedstock for the production of bioactive molecules and chemicals precursors, upgrading the value of this byproduct. In this context, BSG is a promising feedstock for the extraction of antioxidants like ferulic acid (FA) and p-coumaric acid (p-Cu). The effectiveness of three hydrolysis treatments were evaluated for the extraction of FA and p-Cu from BSG, namely enzymatic (based on the synergistic cooperation between a feruloyl esterase and an endo-1,4-ß-xylanase), alkaline and hydrothermal. The hydrothermal treatment produced the highest extraction yields (7.2 g/kgBSG and 1.4 g/kgBSG for FA and p-Cu, respectively) in a short extraction time (an hour). On the other hand, enzymatic hydrolysis extracted 4.3 g/kgBSG for FA and negligible yields for p-Cu in 4 h of incubation at 25 °C. Yields of 5.5 g/kgBSG for FA and 0.6 g/kgBSG for p-Cu were obtained in more than 5 h of alkaline treatment at 120 °C. The mass and energy balances revealed the high dependence of the operating costs on the concentration of BSG used during the extraction process, with costs of 34.5 €, 6607 € and 205.5 € per kg of FA for the chemical, enzymatic and hydrothermal extraction methods at 100 kg BSG/m3.

Efficient gene expression from integration-deficient lentiviral vectors in the spinal cord.

Gene transfer to spinal cord cells may be crucial for therapy in spinal muscular atrophy, amyotrophic lateral sclerosis and spinal cord injury. Lentiviral vectors are efficient for transduction of a variety of cells, but like all integrating vectors they pose a risk of insertional mutagenesis. Integration-deficient lentiviral vectors (IDLVs) remain episomal but retain the transduction efficiency of standard integrating lentiviral vectors, particularly when the episomes are not diluted out through repeated cell division. We have now applied IDLVs for transduction of spinal cord in vitro, in explants and in vivo. Our results demonstrate similar efficiency of eGFP expression from integrating lentiviral vectors and IDLVs in most cell types analyzed, including motor neurons, interneurons, dorsal root ganglia (DRG) neurons and astroglia. IDLV-mediated expression of pro-glial-cell-derived neurotrophic factor (Gdnf) rescues motor neuron cultures from death caused by removal of exogenous trophic support. IDLVs also mediate efficient RNA interference in DRG neuron cultures. After intraparenchymal injection in the rat and mouse cervical and lumbar regions in vivo, transduction is mainly neuronal, with both motor neurons and interneurons being efficiently targeted. These results suggest that IDLVs could be efficient and safer tools for spinal cord transduction in future therapeutic strategies.

Experimental demonstration of an OpenFlow based software-defined optical network employing packet, fixed and flexible DWDM grid technologies on an international multi-domain testbed.

Software defined networking (SDN) and flexible grid optical transport technology are two key technologies that allow network operators to customize their infrastructure based on application requirements and therefore minimizing the extra capital and operational costs required for hosting new applications. In this paper, for the first time we report on design, implementation & demonstration of a novel OpenFlow based SDN unified control plane allowing seamless operation across heterogeneous state-of-the-art optical and packet transport domains. We verify and experimentally evaluate OpenFlow protocol extensions for flexible DWDM grid transport technology along with its integration with fixed DWDM grid and layer-2 packet switching.

An amperometric affinity penicillin-binding protein magnetosensor for the detection of ß-lactam antibiotics in milk.

The preparation, characterization and performance evaluation of an amperometric affinity disposable magnetosensor, based on the use of a recombinant penicillin-binding protein (PBP) and screen-printed carbon electrodes (SPCEs), for the specific detection and quantification of ß-lactam antibiotic residues in milk are reported. The PBP was immobilized onto His-Tag-Isolation-modified magnetic beads (His-Tag-Isolation-MBs), and a direct competitive assay using a tracer with horseradish peroxidase (HRP) for the enzymatic labeling was performed. The amperometric response obtained at -0.20 V vs. the Ag pseudo-reference electrode of the SPCE after the addition of H2O2 in the presence of hydroquinone (HQ) was used as the transduction signal. The developed methodology showed very low detection limits (in the low ppb level) for the 6 antibiotics tested in untreated milk samples, and a good selectivity against other antibiotic residues frequently detected in milk and dairy products. Due to the bioreceptor employed, this methodology was able to detect only the active form of ß-lactam antibiotics with high affinities for both penicillins and cephalosporins. Moreover, the analysis took only 30 min.

Regularity in daily mood stabilizer dosage taken by patients with bipolar disorder.

OBJECTIVE: The aim of this study was to investigate regularity in the daily mood stabilizer dosage taken by patients with bipolar disorder, and identify factors associated with irregularity. METHODS: Self-reported daily mood and medication data were available from 206 patients who took the same mood stabilizer for ≥100 days. Approximate entropy (ApEn) was used to measure serial regularity in daily mood stabilizer dosage. Generalized estimating equations (GEE) were used to estimate if demographic or clinical variables were associated with ApEn. RESULTS: There was a wide range of regularity in the daily mood stabilizer dosage. The mean percent of days of missing doses was 13.6%. The number of psychotropic medications (p=0.007), pill burden (p=0.004) and percent of days with depressed mood (p=0.013) were associated with more irregularity, while the percent of days euthymic (p=0.014) was associated with less irregularity. The percent of days missing doses was not associated with the number of medications, pill burden or mood ratings. DISCUSSION: Patients may have irregularity in daily dosage in spite of a low percent of days missing doses. Psychotropic medication regimen complexity and depression are associated with increased dosage irregularity. Research is needed on how irregularity in daily dosage impacts the continuity of drug action of mood stabilizers.