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.

[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.

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.

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.

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.

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.

The excess mortality related to cardiovascular diseases and cancer among adults pharmacologically treated for diabetes--the 2001-2006 ENTRED cohort.

AIMS: To compare the 5-year mortality (overall and cause-specific) of a cohort of adults pharmacologically treated for diabetes with that of the rest of the French adult population. METHODS: In 2001, 10 000 adults treated for diabetes were randomly selected from the major French National Health Insurance System database. Vital status and causes of death were successfully extracted from the national registry for 9101 persons. We computed standardized mortality ratios. RESULTS: Over 5 years, 1388 adults pharmacologically treated for diabetes died (15% of the cohort, 32.4/1000 person-years). An excess mortality, which decreased with age, was found for both genders [standardized mortality ratio 1.45 (1.37-1.52)]. Excess mortality was related to: hypertensive disease [2.90 (2.50-3.33)], ischaemic heart disease [2.19 (1.93-2.48)], cerebrovascular disease [1.76 (1.52-2.03)], renal failure [2.14 (1.77-2.56)], hepatic failure [2.17 (1.52-3.00)] in both genders and septicaemia among men [1.56 (1.15-2.09)]. An association was also found with cancer-related mortality: liver cancer in men [3.00 (2.10-4.15)]; pancreatic cancer in women [3.22 (1.94-5.03)]; colon/rectum cancer in both genders [1.66 (1.28-2.12)]. Excess mortality was not observed for breast, lung or stomach cancers. CONCLUSIONS: Adults pharmacologically treated for diabetes had a 45% increased risk of mortality at 5 years, mostly related to cardiovascular complications, emphasizing the need for further prevention. The increased risk of mortality from cancer raises questions about the relationship between cancer and diabetes and prompts the need for improved cancer screening in people with diabetes.

Measuring social inequalities in cause-specific mortality in France: comparison between linked and unlinked approaches.

BACKGROUND: Monitoring the time trends in socioeconomic inequalities in mortality by cause is a key public health issue. The aim of this study was to compare methods to measure social inequalities in cause-specific mortality in the French population aged 25-55 years. More specifically, it compares bias and precision related to the use of occupational class declared at the last census (linked data) to the one declared at the time of death on the death certificate (unlinked data). METHODS: We used a representative sample of 1% of the French population. Causes of death were obtained by direct linkage with the French national death registry. Occupational class was classified into eight categories. Taking professionals and managers as the reference, relative risks of mortality by cause and their 95% confidence intervals were estimated using Poisson models for the 1983-1989, 1991-1997, and 2000-2006 periods. The relative risks were calculated with both linked data and exhaustive unlinked data. RESULTS: Over the 2000-2006 period, occupational classes declared at census and on the death certificate were consistent for half of the deaths. Relative risks for manual workers were found to be similar between the two approaches over the 1983-1989 and 1991-1997 periods, and higher for the unlinked approach over the 2000-2006 period. Over the latter period, the order and magnitude of relative risks varied similarly by occupational class and cause of death for both approaches. Confidence intervals obtained from linked data were wide. CONCLUSION: Occupational class derived from the death certificate must be used with caution as a measure for epidemiological purposes and the available linked data do not allow accurate estimates of social inequalities in cause-specific mortality. Other solutions should be considered in order to improve the follow-up of social inequalities in mortality. This would require the collection of educational level on the death certificate or the linkage of the cause of death database with other exhaustive and informative databases.

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.

Deaths associated with acquired haemophilia in France from 2000 to 2009: multiple cause analysis for best care strategies.

Deaths occurring in the context of acquired haemophilia (AH) may be related to inter-connected causes and mechanisms including bleeding, specific or older patient co-morbidities or iatrogenic complications. However, their magnitude remains unknown. This study aimed to determine the respective weight and frequency of the various causes of death in AH. Multiple-cause analysis based on death certificates data is used in this purpose. Over a 10-year period (2000-2009), 121 deaths with AH as a cause were registered in France. All the deaths were of adults (extremes: 47 and 99 years; mean age: 80.7 years). The average number of causes per death certificate was 4.7. AH was the underlying cause of death (UCD) in 69.4% of the cases, and was more frequent in the older subjects. In contrast, before age of 75 years, AH was more often a contributing cause of death. No postpartum or obvious thromboembolism-related deaths were registered. Haemorrhagic shock was the most frequent direct cause of death (DCD), followed by infectious events, cardiac dysfunction, metabolic and nutritional disorders with muscle wasting and decubitus complications, and cancers (52.9%, 26.4%, 7.5%, 5.8% and 4.1%, respectively). However, when AH was not reported as an UCD, infections become the first DCD (32.4%) followed by bleeding events (16.2%). Best prophylactic and curative strategies for infections are particularly required to improve the prognosis in AH. Moreover, as several of its DCD correspond also to steroids side effects, best tolerated immunosuppressant regimen with steroid-sparing agents adjoining are particularly awaited in AH population.

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.

[Pregnancy and inflammatory bowel disease: experience in 17 patients]. / Enfermedad inflamatoria intestinal y embarazo: experiencia de 16 años.

BACKGROUND: Inflammatory bowel disease (IBD) has a peak incidence between 15 and 25 years of age, thereby affecting women of reproductive age. Fertility rates with inactive IBD are similar to the general population, and drugs currently used, with the exception of methotrexate and thalidomide, have a good safety and efficacy profile during pregnancy. Starting a pregnancy with inactive IBD significantly reduces the potential maternal and fetal complications. AIM: To assess the evolution of pregnancy and the underlying disease in women with IBD. PATIENTS AND METHODS: Retrospective and prospective study of female patients with IBD controlled in our hospital who became pregnant from January 1994 to February, 2011. RESULTS: We followed 17 patients with a total of 19 pregnancies. In two patients the onset of IBD occurred during pregnancy and from the remaining, 11 patients became pregnant during remission of IBD. Most of the patients continued the same treatment during pregnancy and the few flares that occurred were treated satisfactorily. Major complications occurred in three patients, all associated with IBD activity. Fifteen patients had full-term deliveries and the majority of the newborns had normal weight and Apgar score. None had malformations. CONCLUSIONS: Pregnancies among patients with an inactive IBD, have a good evolution. A multidisciplinary approach and patient education are invaluable to achieve these good results.

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.

Non-thermal desorption/ablation of molecular solids induced by ultra-short soft x-ray pulses.

We report the first observation of single-shot soft x-ray laser induced desorption occurring below the ablation threshold in a thin layer of poly (methyl methacrylate)--PMMA. Irradiated by the focused beam from the Free-electron LASer in Hamburg (FLASH) at 21.7 nm, the samples have been investigated by atomic-force microscope (AFM) enabling the visualization of mild surface modifications caused by the desorption. A model describing non-thermal desorption and ablation has been developed and used to analyze single-shot imprints in PMMA. An intermediate regime of materials removal has been found, confirming model predictions. We also report below-threshold multiple-shot desorption of PMMA induced by high-order harmonics (HOH) at 32 nm. Short-time exposure imprints provide sufficient information about transverse beam profile in HOH's tight focus whereas long-time exposed PMMA exhibits radiation-initiated surface ardening making the beam profile measurement infeasible.

n-3 Fatty acid supplementation in burned paediatric patients.

AIM: To determine the effect of dietary supplementation with n-3 fatty acids (FA) in paediatric burned patients who had less than 20% of total body surface affected. METHODS: Burned patients were randomly assigned into two groups, one of them received a supplement of n-3 FA during 5 weeks; the other group was considered as not n-3 supplemented burned group. A third group of no burned patients was selected as control. Blood samples were collected at admission and in burned groups at the final of the study. Plasma and erythrocyte phospholipid FA composition and some biochemical parameters related to the clinical evolution: total plasma proteins and C3 and C4 complement proteins were determined. RESULTS: In the early post-burn patients, there is an increase in saturated and monounsaturated FAs in plasma phospholipids, and a decrease in polyunsaturated FAs compared with control. These alterations are in favour of proinflammatory response to burn injury. In n-3 FA supplemented group, these changes were further reverted, and a favourable response in the amount of total plasma proteins and in C3 and C4 proteins of the complement system was demonstrated. CONCLUSION: Dietary n-3 FA supplementation might be beneficial for patients suffering thermal injury.

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.