Morpho-Anatomy and Mathematical Modelling in Lilium philippinense Baker from Cordillera Central Range, Philippines.

The study presents the morphology, anatomy and mathematical modelling in Benguet lily (Lilium philippinense Baker), a threatened species from the Cordillera Central Range and was often misidentified with the weedy L. formosanum. The plant is an annual herb with linear, spiral leaves; pure white, perfect, funnel-shaped, showy flowers; septicidal elongated capsule; and, brown, light, winged seeds. New findings in the study include the description of the capsule and seeds, biometric measurements of the different plant organs, the significant correlation and regression model of plant height and stem diameter for certain floral measurement, and its diagnostic characteristics vis-à-vis L. formosanum. Interesting findings on the taxon's anatomy show a cross between a typical monocot and a typical dicot anatomy. It has a bifacial leaf structure (a common dicot character) but its spongy layer is not as widely spaced like in dicot leaf. The stem has a distinct cortex and pith (a dicot character) but has a scattered vascular bundles (a monocot character). Lastly, some roots have a narrow pith at the centre of the stele (a monocot character) while some roots have metaxylem elements at the centermost structure (a dicot character). Further studies need to be conducted to determine the ecological significance of these features.

Gamma Knife® stereotactic radiosurgery as a treatment for essential and parkinsonian tremor: long-term experience.

INTRODUCTION: Unilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit. METHODS: We reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months' follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events. RESULTS: Thirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects. CONCLUSIONS: This is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants.

Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: experience at an epilepsy centre.

OBJECTIVE: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. MATERIAL AND METHODS: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. RESULTS: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. CONCLUSION: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.

Gamma Knife® stereotactic radiosurgery as a treatment for essential and parkinsonian tremor: long-term experience. / Radiocirugía estereotáctica con Gamma Knife® como tratamiento del temblor esencial y parkinsoniano: experiencia a largo plazo.

INTRODUCTION: Unilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit. METHODS: We reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months' follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events. RESULTS: Thirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects. CONCLUSIONS: This is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants.

The use of a new collagen matrix to support the regeneration of peri-implant soft tissue laser-assisted: case report.

Several factors compete for both the achievement and the long-term maintenance of osseointegration; among these, of importance is the width and integrity of the peri-implant soft tissue. Many authors already underlined the importance for implant-prosthesis procedures to maintain a good biological seal together with a low bacterial cell surface charge (this is also valid for a natural tooth with an undamaged periodontium). The aim of this work is to present, through a clinical case, a new technique that focuses on the regeneration of soft tissue around a post-extractive implant. For the case reported, a post-extractive implant surgery of an inferior molar of the fourth quadrant with a buccal bone resorption of 3mm in the mesial section of the root, three dimensional collagen matrices (Bioteck) and a blend of equine spongy bone granules (OX Bioteck) were used, combined with aPDT without dye (Rey Protocol). With an easy and not invasive surgery, this technique allows the recreation of new gingiva around the implant.

Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: Experience at an epilepsy centre. / Estereoelectroencefalografía en la evaluación prequirúrgica de epilepsias focales refractarias: experiencia de un centro de epilepsia.

OBJECTIVE: Stereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. MATERIAL AND METHODS: In the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. RESULTS: The median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. CONCLUSION: SEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.

Chromatin three-dimensional interactions mediate genetic effects on gene expression.

Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression, and genetic variants across 317 individuals and two cell types. We show that variability in regulatory activity is structured at the intra- and interchromosomal levels within 12,583 cis-regulatory domains and 30 trans-regulatory hubs that highly reflect the local (that is, topologically associating domains) and global (that is, open and closed chromatin compartments) nuclear chromatin organization. These structures delimit cell type-specific regulatory networks that control gene expression and coexpression and mediate the genetic effects of cis- and trans-acting regulatory variants on genes.

Mortality Analysis of Acute Liver Failure in Uruguay.

BACKGROUND: Acute liver failure (ALF) is a syndrome with high mortality. OBJECTIVE: Describe characteristics and outcomes of patients with ALF in Uruguay, and identify factors associated with mortality. METHODS: A retrospective analysis of 33 patients with ALF was performed between 2009 and 2017. RESULTS: The patients' median age was 43 years, and 64% were women. Average Model for End-Stage Liver Disease (MELD) score at admission was 33. The median referral time to the liver transplant (LT) center was 7 days. The most common etiologies were viral hepatitis (27%), indeterminate (21%), autoimmune (18%), and Wilson disease (15%). Overall mortality was 52% (71% of transplanted and 46% of nontransplanted patients). Dead patients had higher referral time (10 vs 4 days, P = .008), higher MELD scores at admission (37 vs 28) and highest achieved MELD scores (42 vs 29; P < .001), and higher encephalopathy grade III to IV (94% vs 25%, P < .001) than survivors. Patients without LT criteria (n = 4) had lower MELD score at admission (25 vs 34, P = .001) and highest achieved MELD score (27 vs 37, P = .008) compared with the others. Patients with LT criteria but contraindications (n = 7) had higher MELD scores at admission (38 vs 31, P = .02), highest achieved MELD scores (41 vs 34, P = .03), and longer referral time (10 days) than those without contraindications (3.5 days) or those without LT criteria (7.5 days, P = .02). Twenty-two patients were listed; LT was performed in 7, with a median time on waiting list of 6 days. CONCLUSIONS: ALF in Uruguay has high mortality associated with delayed referral to the LT center, MELD score, and encephalopathy. The long waiting times to transplantation might influence mortality.

Risk Factors of Mortality After Liver Transplantation in Uruguay.

INTRODUCTION: Identification of predictive factors of mortality in a liver transplant (LT) program optimizes patient selection and allocation of organs. OBJECTIVE: To determine survival rates and predictive factors of mortality after LT in the National Liver Transplant Program of Uruguay. METHODS: A retrospective study was conducted analyzing data prospectively collected into a multidisciplinary database. All patients transplanted since the beginning of the program on July 2009 to April 2017 were included (n = 148). Twenty-nine factors were analyzed through the univariate Kaplan-Meier model. A Cox regression model was used in the multivariate analysis to identify the independent prognostic factors for survival. RESULTS: Overall survival was 92%, 87%, and 78% at discharge, 1 year, and 3 years, respectively. The Kaplan-Meier survival curves were significantly lower in: recipients aged >60 years, Model for End-Stage Liver Disease score >21, LT due to hepatocellular carcinoma (HCC) and acute liver failure (ALF), donors with comorbidities, intraoperative blood loss beyond the median (>2350 mL), red blood cell transfusion requirement beyond the median (>1254 mL), intraoperative complications, delay of extubation, invasive bacterial, and fungal infection after LT and stay in critical care unit >4 days. The Cox regression model (likelihood ratio test, P = 1.976 e-06) identified the following independent prognostic factors for survival: LT for HCC (hazard ratio [HR] 4.511; P = .001) and ALF (HR 6.346; P = .004), donors with comorbidities (HR 2.354; P = .041), intraoperative complications (HR 2.707; P = .027), and invasive fungal infections (HR 3.281; P = .025). CONCLUSION: The survival rates of LT patients as well as the mortality-associated factors are similar to those reported in the international literature.

[Transmission of death certificates to CepiDc-Inserm related to suspicious deaths, in France, since 2000]. / Transmission des certificats de décès au CépiDc-Inserm en cas de mort suspecte en France, depuis 2000.

BACKGROUND: The purpose of this study is to assess variability in death certificates' transmission related to suspicious deaths. METHODS: The medical part of death certificates of suspicious deaths (violent or sudden deaths, unknown or ill-defined causes of death) were examined. We studied the frequency of suspicious deaths, in France, for deaths aged under 65, from 2000 to 2013, searching for temporal (2000-2013) and spatial correlations between unknown causes of death and other suspicious causes, and report of an autopsy. These results were compared with external data. RESULTS: Standardized proportion of deaths by unknown cause more than doubled during the study period (from 3.4 to 7.5%). The spatial correlation was strongly negative between standardized proportions of unknown causes of death and violent deaths (ICC=-0.80). Report of autopsy varied with cause of suspicious death and estimated zone of the forensic institute. The distribution was consistently distributed with external data, except for homicides. CONCLUSION: Information transmission to CépiDc-Inserm needs to be improved in case of suspicious death, in particularly from forensic institutes. This study emphasizes the urgent need for a complementary form to the death certificate.

Differentiation of Ecuadorian National and CCN-51 cocoa beans and their mixtures by computer vision.

BACKGROUND: Ecuador exports two major types of cocoa beans, the highly regarded and lucrative National, known for its fine aroma, and the CCN-51 clone type, used in bulk for mass chocolate products. In order to discourage exportation of National cocoa adulterated with CCN-51, a fast and objective methodology for distinguishing between the two types of cocoa beans is needed. RESULTS: This study reports a methodology based on computer vision, which makes it possible to recognize these beans and determine the percentage of their mixture. The methodology was challenged with 336 samples of National cocoa and 127 of CCN-51. By excluding the samples with a low fermentation level and white beans, the model discriminated with a precision higher than 98%. The model was also able to identify and quantify adulterations in 75 export batches of National cocoa and separate out poorly fermented beans. CONCLUSION: A scientifically reliable methodology able to discriminate between Ecuadorian National and CCN-51 cocoa beans and their mixtures was successfully developed. © 2017 Society of Chemical Industry.

Compromiso gastrointestinal por Triypanosoma cruzi: ¿cuándo buscar y cuándo tratar? / Digestive involvement by Trypanosoma cruzi: when to look for it and when to treat

Chagas disease is an endemic zoonosis that can cause chronic medical complications in a third of those infected, usually decades after infection. It mainly affects the peripheral nervous system of heart, esophagus and colon. At digestive level, motor dysfunction leads to the development of megaesophagus and megacolon whose predominant symptoms are dysphagia and constipation. It should be suspected in patients with epidemiological history and compatible symptoms. In the chronic phase it is confirmed with the detection of specific antibodies. The etiological treatment is effective in early stages after infection. In the chronic stage the management is symptomatic, medical and/or surgical.

La enfermedad de Chagas es una zoonosis endémica que puede producir complicaciones médicas crónicas en un tercio de los infectados, habitualmente décadas luego de la infección. Afecta principalmente el sistema nervioso periférico de corazón, esófago y colon. A nivel digestivo la disfunción motora lleva a la formación de megaesófago y megacolon cuyos síntomas predominantes son disfagia y constipación. Debe sospecharse en pacientes con antecedentes epidemiológicos y síntomas compatibles. En la fase crónica se confirma con la detección de anticuerpos específicos. El tratamiento etiológico es efectivo en las fases tempranas post-contagio. En la etapa crónica el manejo es sintomático, médico y/o quirúrgico.

Pertinence of electronic death certificates for real-time surveillance and alert, France, 2012-2014.

OBJECTIVES: In France, the early mortality monitoring, conducted by Santé publique France, the French National Public Health agency (SpFrance) (formerly French Institute for public health surveillance-InVS), is based on the administrative data provided by the National Institute for Statistic and Economic Studies (INSEE) and consequently does not allow analyses on medical causes of death. Since 2007, the physicians can certify deaths electronically. In this electronic system (Electronic Death Registration System; EDRS), the medical causes of death, in free-text format, are directly transmitted to SpFrance. In the future, these data could be used in a real-time surveillance system by medical causes of death. The objective of this study was to evaluate the pertinence of e-death certification using the following assessment criteria: timeliness, representativeness, and completeness of sociodemographic and medical information included in the e-death certificates. STUDY DESIGN: This study consisted of a descriptive analysis of the information collected by e-death certificates recorded between January 1, 2012 and July 31, 2014. METHODS: The study quantified the temporal and geographical evolution of the deployment of the EDRS between 2012 and 2014. The timeliness of the system was estimated by calculating the delay between the dates of death and of data availability for analysis. Sociodemographic and death-related characteristics were described. The frequency of missing data was measured for each variable. The number of completed fields per certificate and the number of words per field and per certificate were calculated for the medical causes of death. RESULTS: Between January 2012 and July 2014, 77,776 e-death certificates were collected. A slight increase in the use of the e-death certification was observed during the study period, reaching 6.1% of the total number of deaths in 2014. Good national coverage was noted. Nearly 79% of e-certificates were submitted to SpFrance on the day of the death. We observed a high completeness of the e-certificates. The rate of missing data did not exceed 2.7% for sociodemographic variables. On average, 10 words, distributed in three fields, were used to describe the medical causes of death. CONCLUSIONS: E-death certificates constitute a reactive source of information on medical causes of death. The deployment of EDRS is of major public health interest for the development of a real-time warning surveillance system of mortality by cause.

Oxygen high level laser therapy is efficient in treatment of chronic periodontitis: a clinical and microbiological study using PCR analysis.

In periodontology, lasers have been suggested for the photodynamic therapy (PDT). Such therapy can be defined as the inactivation of cells, microorganisms or molecules induced by light and not by heat. The aim of our study is to assess the effect of Oxygen high-level laser therapy (OHLLT) in removing all bacterial deposits on root or implant surface by means of mechanical instrumentation and laser irradiation. OHLLT has two effects on targeted bacteria and tissues, decontamination and biostimulation. A total of 33 patients were randomly selected with a diagnosis of chronic periodontitis. The patients enrolled were 16 females and 17 males, six smokers and 4 diabetic patients. For each patient a periodontal charting was performed, assessing probing depth, plaque index and bleeding on probing at baseline and after 6 months. Microbiological analysis were performed with PCR Real Time, using paper tips to withdraw gingival fluid in periodontal pockets before and after treatment, at baseline and after 6 months. All patients were treated with OHLLT at baseline, after 1 week, after 2 weeks and every month for 6 months. After 6 months, all periodontal pockets were treated successfully, without complications and no significant differences in results. All clinical parameters showed an improvement, with a decrease both of plaque index (average decrease of 75%), bleeding on probing (average decrease of 62%) and probing depth (average decrease of 1.8 mm). After the treatment, a remarkable decrease in bacteria amount, both for each species and for total bacteria was observed except for Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis demonstrating that this laser protocol is effective on periodontitis treatment. OHLLT is efficient in treatment of chronic periodontitis as demonstrated by clinical and microbiological parameters, going beyond the traditional periodontal therapy.

Effects of laser biostimulation on the epithelial tissue for keratinized layer differentiation: an in vitro study.

Gingival augmentation techniques proposed in the international literature do not exclude a surgical component, which determines consequent post-surgical discomfort and results are not always predictable. In recent years, the introduction of laser biostimulation has led to a less invasive approach, particularly in the treatment of periodontally compromised patients, limiting the surgical phase to seriously compromised cases, with regeneration techniques for the restoration of a correct periodontal tissue anatomy. The aim of this in vitro study is to establish the validity of laser biostimulation in order to develop the epithelial keratinized layer of the tissue by stimulating fibroblasts-keratinocytes organotypic cultures and fibroblasts and keratinocytes mono-cultures. We created two groups (test and control), each one composed of 3 fibroblast cultures, 3 keratinocyte cultures and 3 organotypic cultures. We performed laser irradiation of test group with Wiser Doctor Smile Lambda, Flat Top Handpiece, at 50 J/cm2 of fluency with one application every 40 h for a total of 5 applications. Forty-eight h after the last laser application, we investigated the presence and amount of keratins 5 and 8 with citofluorymetric and western blotting analyses. Analyses showed an increase in keratin synthesis in test group cultures, showing a remarkable increase in production of keratin 8 in co-cultures test. Laser biostimulation can considerably enhance keratin synthesis when applied with high energy doses and repeated applications to keratinocytes-fibroblasts co-cultures.

Resting-state functional connectivity of emotion regulation networks in euthymic and non-euthymic bipolar disorder patients.

BACKGROUND: Previous functional magnetic resonance imaging studies in bipolar disorder (BD) have evidenced changes in functional connectivity (FC) in brain areas associated with emotion processing, but how these changes vary with mood state and specific clinical symptoms is not fully understood. METHODS: We investigated resting-state FC between a priori regions of interest (ROIs) from the default-mode network and key structures for emotion processing and regulation in 27 BD patients and 27 matched healthy controls. We further compared connectivity patterns in subgroups of 15 euthymic and 12 non-euthymic patients and tested for correlations of the connectivity strength with measures of mood, anxiety, and rumination tendency. No correction for multiple comparisons was applied given the small population sample and pre-defined target ROIs. RESULTS: Overall, regardless of mood state, BD patients exhibited increased FC of the left amygdala with left sgACC and PCC, relative to controls. In addition, non-euthymic BD patients showed distinctive decrease in FC between right amygdala and sgACC, whereas euthymic patients showed lower FC between PCC and sgACC. Euthymic patients also displayed increased FC between sgACC and right VLPFC. The sgACC-PCC and sgACC-left amygdala connections were modulated by rumination tendency in non-euthymic patients, whereas the sgACC-VLPFC connection was modulated by both the current mood and tendency to ruminate. CONCLUSION: Our results suggest that sgACC-amygdala coupling is critically affected during mood episodes, and that FC of sgACC play a pivotal role in mood normalization through its interactions with the VLPFC and PCC. However, these preliminary findings require replication with larger samples of patients.

[Death certificate data in France: Production process and main types of analyses]. / Les données des certificats de décès en France : processus de production et principaux types d'analyse.

Mortality data, by the unambiguity of their definition and understanding by all stakeholders, and completeness of registration, are a cornerstone of public health statistics in France and in most industrialized countries. This article describes the data production process, and the main types of possible analyses. Data production is composed of different stages: death certification by a medical doctor on paper or electronic (using a web application) format, data transmission to Inserm, capture and coding of information. The encoding of the information follows the WHO recommendations of the International Classification of Diseases ([ICD], 10th revision used since 2000). It is carried out using an automatic coding software, called Iris, developed in an international consortium. The coding aims, first, at assigning an ICD code to all nosologic entities encountered on the certificate, and then at selecting the underlying cause of death. The latter is the main information used for statistical analyses. Three main types of analysis emerge in the literature: the exploitation of data on the death certificate only, ecological analyses (studies of associations between variables measured across groups) and analysis from data individually linked to other databases. Many public health issues can be addressed with these various analyses. Several developments in the production process are being implemented: the deployment of electronic certification, increased automation of the death certificate information processing and durable and complete record linkage with health insurance and hospitalisation data. They could soon be deeply expanding the scope of possible uses of causes of death data.

Interplay between cellular redox oscillations and circadian clocks.

The circadian clock is a cellular timekeeping mechanism that helps organisms from bacteria to humans to organize their behaviour and physiology around the solar cycle. Current models for circadian timekeeping incorporate transcriptional/translational feedback loop mechanisms in the predominant model systems. However, recent evidence suggests that non-transcriptional oscillations such as metabolic and redox cycles may play a fundamental role in circadian timekeeping. Peroxiredoxins, an antioxidant protein family, undergo rhythmic oxidation on the circadian time scale in a variety of species, including bacteria, insects and mammals, but also in red blood cells, a naturally occurring, non-transcriptional system. The profound interconnectivity between circadian and redox pathways strongly suggests that a conserved timekeeping mechanism based on redox cycles could be integral to generating circadian rhythms.