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Satellite DNAs are arrays of tandem repeats found in the eukaryotic genome. They are mainly found in pericentromeric heterochromatin and have been believed to be mostly inert, leading satellite DNAs to be erroneously regarded as junk. Recent studies have started to elucidate the function of satellite DNA, yet little is known about the peculiar case where satellite DNA is found within the introns of protein coding genes, resulting in incredibly large introns, a phenomenon termed intron gigantism. Studies in Drosophila demonstrated that satellite DNA-containing introns are transcribed with the gene and require specialized mechanisms to overcome the burdens imposed by the extremely long stretches of repetitive DNA. Whether intron gigantism confers any benefit or serves any functional purpose for cells and/or organisms remains elusive. Here we review our current understanding of intron gigantism: where it is found, the challenges it imposes, how it is regulated and what purpose it may serve.

Resume Introduction Le taux d’infection du site operatoire profond (ISOP) apres une chirurgie conservatrice pour l’echinococcose kystique du foie (EKF) varie de 12 a 26 % avec un taux de mortalite postoperatoire compris entre 0 et 7,5 %. Cette revue systematique avec meta-analyse visait a determiner si l’omentoplastie (OP) associee a une chirurgie conservatrice pour une EKF entraine une diminution des taux de morbidite et de mortalite par rapport au drainage externe par tube (DET). Patients et methodes Nous avons identifie 4540 articles par une recherche dans les bases de donnees. Apres avoir verifie les criteres d’inclusion et d’exclusion, nous avons retenu huit etudes pour l’analyse finale: deux essais controles randomises (ECR), une etude comparative prospective et cinq etudes comparatives retrospectives. Le critere de jugement principal etait la morbidite au niveau du site operatoire qui etait limitee a «l’infection du site operatoire profond (ISOP) avec ou sans re-operation». Resultats Huit etudes ont rapporte des resultats pour l’ISOP [6/374 (OP) et 60/403 (DET), respectivement]. L’ISOP etait statistiquement moins importante avec l’OP (par rapport au DET) OR = 0,17 IC95 % [0,05,0,62] (p = 0,007). Une meta-regression, incluant les huit etudes, a montre une interaction en faveur de l’OP. On a egalement constate une diminution statistiquement significative des fuites biliaires ± fistule et de la morbidite globale dans le groupe OP par rapport au DET. D’autre part, aucune difference statistiquement significative n’a ete constatee entre ces deux groupes en ce qui concerne les saignements profonds, la mortalite et la recidive. Conclusion Cette meta-analyse avec meta-regression a montre qu’il y avait moins d’ISOP, de fuites biliaires ± fistules et de morbidite globale d’une facon statistiquement significative dans le groupe OP par rapport au groupe DET.

Resume Objectif Le leiomyome est la tumeur benigne la plus frequente de l’œsophage. L’enucleation extramuqueuse est le traitement de choix. Nous avons evalue la faisabilite et les resultats de la chirurgie mini-invasive (CMI) a l’aide de la chirurgie thoracoscopique video-assistee (TSVA) ou de la chirurgie laparoscopique (LSVA) pour l’enucleation du leiomyome de l’œsophage. Population et methodes Il s’agit d’une etude retrospective des patients traites par TSVA ou LSVA pour leiomyome de l’œsophage a l’hopital Viet Duc de Hanoi entre 2010 et 2017 par le meme operateur. L’approche operatoire, la taille de tumeur, les complications et les resultats postoperatoires ont ete enregistres. Resultats Soixante-quinze patients ont ete inclus. L’âge moyen des patients etait de 41,9 ans (extremes 20 a 68 ans). Le rapport hommes/femmes etait de 2,1:1. Cinquante-cinq patients (73,3 %) ont eu des symptomes cliniques. Les tumeurs etaient localisees au tiers superieur (12 %), au tiers moyen (51 %) ou au tiers inferieur (37 %) de l’œsophage. La taille moyenne de la tumeur a ete de 3,7 (2–11) cm. L’enucleation par LSVA a ete realisee chez 23 patients qui avaient un leiomyome situe pres du cardia (jonction œsogastrique ou œsophage abdominal). Les 52 patients restants ont subi une TSVA droite (n = 42) ou gauche (n = 10). Lorsqu’une plaie de la muqueuse de l’œsophage est survenue (5 patients (6,7 %)) pendant la dissection, elle a toujours pu etre reparee par MIS sans entrainer de morbidite tardive. Une mini-incision supplementaire (2 mini-laparotomies et 1 thoracotomie) a ete necessaire chez trois patients (4 %) en raison de la grande taille de la tumeur ou des plaies de la muqueuse œsophagienne. La duree moyenne de l’intervention a ete de 105 minutes par TSVA et de 174 minutes par LSVA. Aucune complication perioperatoire majeure chirurgicale ou medicale n’a ete observee. La duree moyenne du sejour a l’hopital a ete de 7,2 (5 a 12) jours. Conclusions L’enucleation par CMI du leiomyome de l’œsophage est techniquement sure et associee a un taux eleve de succes, avec une morbidite medicochirurgicale basse. La TSVA pourrait etre appliquee a presque tous les leiomyomes de l’œsophage. Cependant, la LSVA a ete preferee pour des tumeurs situees pres de la jonction œsogastrique afin de realiser une valve antireflux apres enucleation.

The electrostatic interaction of RNA with its aqueous environment is most relevant for defining macromolecular structure and biological function. The attractive interaction of phosphate groups in the RNA backbone with ions in the water environment leads to the accumulation of positively charged ions in the first few hydration layers around RNA. Electrostatics of this ion atmosphere and the resulting ion concentration profiles have been described by solutions of the nonlinear Poisson-Boltzmann equation and atomistic molecular dynamics (MD) simulations. Much less is known on contact pairs of RNA phosphate groups with ions at the RNA surface, regarding their abundance, molecular geometry, and role in defining RNA structure. Here, we present a combined theoretical and experimental study of interactions of a short RNA duplex with magnesium (Mg2+) ions. MD simulations covering a microsecond time range give detailed hydration geometries as well as electrostatics and spatial arrangements of phosphate-Mg2+ pairs, including both pairs in direct contact and separated by a single water layer. The theoretical predictions are benchmarked by linear infrared absorption and nonlinear two-dimensional infrared (2D-IR) spectra of the asymmetric phosphate stretch vibration which probes both local interaction geometries and electric fields. Contact pairs of phosphate groups and Mg2+ ions are identified via their impact on the vibrational frequency position and line shape. A quantitative analysis of infrared spectra for a range of Mg2+ excess concentrations and comparison with fluorescence titration measurements shows that on average 20 to 30% of the Mg2+ ions interacting with the RNA duplex form contact pairs. The experimental and MD results are in good agreement. In contrast, calculations based on the nonlinear Poisson-Boltzmann equation fail in describing the ion arrangement, molecular electrostatic potential and local electric field strengths correctly. Our results underline the importance of local electric field mapping and molecular-level simulations to correctly account for the electrostatics at the RNA-water interface.

Background One cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) has shown superiority in recurrence-free survival over retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I non-seminomatous germ cell tumours (NSGCTs) of the testis in the setting of a phase III trial. We report the recurrences and late toxicities of this study after 13 years of follow-up. Methods Questionnaires from 382 patients with CS I NSGCT treated with 1 cycle of adjuvant BEP (arm A) or RPLND + two cycles of adjuvant BEP in cases of pathological stage II disease (arm B) were evaluated regarding recurrences and late toxicity. Overall, information on recurrence status was available in 337 patients, and 170 questionnaires were evaluable for toxicity (arm A: 95; arm B: 75). Results With a median follow-up of 13.8 years (0–22), 3 patients (1.6%) in arm A and 16 patients (8.4%) in arm B experienced recurrence. The 15-year PFS in arm A/B was 99% (CI 96–100%)/92% (CI 89–99%) (p = 0.0049). The 15-year OS in arm A/B was 93% (CI 87–97%)/93% (CI 86–97%) (p = 0.83). Eight patients (4.2%) in arm A and four patients (2.1%) in arm B showed metachronous secondary testicular cancer (p = 0.26). Five patients (2.6%) in arm A and four patients (2.1%) in arm B developed other malignancies. Toxicities were not significantly different apart from retrograde ejaculation, which occurred more frequently after RPLND (10% versus 24%, p = 0.01). Conclusions With long-term observation, one cycle of BEP remains superior to RPLND in preventing recurrence and was tolerated without any clinically relevant long-term toxicities.

In light of today's role of minimally access surgery in colorectal oncologic treatment, we analyzed the impact of laparoscopic cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in selected patients with peritoneal metastases (PM) originating from colorectal and appendiceal cancer (CRAC).Postoperative and oncologic outcomes were compared between patients with CRAC-PM treated by CRS/HIPEC undergoing laparoscopic (L-CRS/HIPEC) or open (O-CRS/HIPEC) procedures according to data collected from our tertiary referral hospital prospective database from April 2016 to April 2021. We excluded patients who did not undergo operation with curative intent. L-CRS was performed in patients who had no multifocal mesenteric lesions, no large abdominal mass, nor massive adhesions. Patients were matched by propensity scores 1:1 for peritoneal cancer index, completeness of cytoreduction score, concomitant resectable distal metastasis, primary tumor location, RAS mutation status and American Society of Anesthesiologists (ASA) classification.Of 106 eligible patients, 68 were matched (34 L-CRS/HIPEC; 34 O-CRS/HIPEC) by propensity scores. Compared with the open approach, L-CRS/HIPEC was associated with less overall surgical morbidities (14.7% vs. 38.2%; p = 0.028), shorter median hospital stay (10 [5-15] vs. 12 [8-33] days; p 0.001) and reduced median waiting time before adjuvant chemotherapy (4.7 [3.0-13.2] vs. 5.7 [4.1-24.1] weeks; p = 0.047). No statistically significant difference was found in operative time or major morbidity rates between the two groups. After a median follow-up of 33.2 months, the rate of early peritoneal loco-regional recurrence, location of initial recurrence or 3-year survival outcomes were not statistically significantly related to the type of access (L-CRS/HIPEC vs. O-CRS/HIPEC).Laparoscopy for CRS/HIPEC is technically feasible and oncologically safe to treat selected patients with CRAC-PM. Further randomized control trials are required to confirm the benefits of minimal access surgery for the management of PM.

Kirkwood-Buff integration (KBI) is implemented into the massively-parallel molecular simulation tool ms2 and assessed by molecular dynamics simulations of binary liquid mixtures. The formalism of Kruger et al. (P. Kruger et al., J. Phys. Chem. Lett. 4: 235–238, 2013) that adopts NVT ensemble data to the μVT ensemble is employed throughout. Taking advantage of its linear scaling with inverse system size, the extrapolation to the thermodynamic limit is analyzed. KBI are calculated with standard radial distribution functions (RDF) and two corrected RDF forms. Simulations in the NVT ensemble are carried out in the entire composition range for four Lennard-Jones mixtures, studying system size dependence by varying N = 4000, 8000 and 16000 molecules. Moreover, four mixtures of “real” components are considered with N = 4000. Thermodynamic factor, partial molar volumes and isothermal compressibility are calculated from KBI and compared with benchmark data from NpT ensemble simulations. The assessment shows that the formalism of Kruger et al. greatly improves KBI and that extrapolation is important, particularly for smaller systems.

Vibrational relaxation and energy redistribution of Zundel cations H5O2+ in acetonitrile and neat water are studied by femtosecond infrared pump-probe spectroscopy with resonant excitation of the 1200 cm−1 proton transfer mode. Transient spectra in a range from 1000 to 2200 cm−1 reveal intermode anharmonic couplings and a sub-100 fs decay of the proton transfer mode, followed by femtosecond vibrational redistribution within the cations’ vibrational manifold and picosecond energy transfer to the solvent. Energy transfer to an aqueous environment occurs on the same time scale as within neat water, demonstrating the strong coupling of cations and water solvation shell.

The recognition of the role of the environment in contributing to the obesity epidemic has led to increasing efforts to address obesity through environmental or place-based approaches in the past decade. This has challenged the use of the quasi-experimental design for evaluating community interventions. The objective of this study is to describe the development of an index of dose of exposure to community interventions that impact early childhood obesity. The goal is to provide an alternative means for evaluating the impact of multiple intervention strategies that target the same community at the same time. Two workgroups developed domains, constructs and protocols for estimating a "community intervention dose index" (CIDI). Information used to develop the protocol came from multiple sources including databases and reports of major funding organizations on obesity-related interventions implemented in Los Angeles County from 2005 to 2015, key informant interviews, and published literature. The workgroups identified five domains relevant to the consideration of dose of exposure to interventions: physical resources, social resources, context, capacity development, and programs and policies; developed a system for classifying programs and policies into macro- and micro-level intervention strategies; and sought ratings of strategy effectiveness from a panel of 13 experts using the Delphi technique, to develop an algorithm for calculating CIDI that considers intervention strength, reach and fidelity. This CIDI can be estimated for each community and used to evaluate the impact of multiple programs that use a myriad of intervention strategies for addressing a defined health outcome.

Dietary iodine requirements are high during pregnancy, lactation, and infancy, making women and infants vulnerable to iodine deficiency. Universal salt iodization (USI) has been remarkably successful for preventing iodine deficiency in the general population, but it is uncertain if USI provides adequate iodine intakes during the first 1000 d.We set out to assess if USI provides sufficient dietary iodine to meet the iodine requirements and achieve adequate iodine nutrition in all vulnerable population groups.We conducted an international, cross-sectional, multicenter study in 3 study sites with mandatory USI legislation. We enrolled 5860 participants from 6 population groups (school-age children, nonpregnant nonlactating women of reproductive age, pregnant women, lactating women, 0-6-mo-old infants, and 7-24-mo-old infants) and assessed iodine status [urinary iodine concentration (UIC)] and thyroid function in Linfen, China (n = 2408), Tuguegarao, the Philippines (n = 2512), and Zagreb, Croatia (n = 940). We analyzed the iodine concentration in household salt, breast milk, drinking water, and cow's milk.The salt iodine concentration was low (15 mg/kg) in 2.7%, 33.6%, and 3.1%, adequate (15-40 mg/kg) in 96.3%, 48.4%, and 96.4%, and high (40 mg/kg) in 1.0%, 18.0%, and 0.5% of household salt samples in Linfen (n = 402), Tuguegarao (n = 1003), and Zagreb (n = 195), respectively. The median UIC showed adequate iodine nutrition in all population groups, except for excessive iodine intake in school-age children in the Philippines and borderline low intake in pregnant women in Croatia.Salt iodization at ∼25 mg/kg that covers a high proportion of the total amount of salt consumed supplies sufficient dietary iodine to ensure adequate iodine nutrition in all population groups, although intakes may be borderline low during pregnancy. Large variations in salt iodine concentrations increase the risk for both low and high iodine intakes. Strict monitoring of the national salt iodization program is therefore essential for optimal iodine nutrition. This trial was registered at clinicaltrials.gov as NCT02196337.

Light induced bond cleavage is an ubiquitous process in large molecules, yet its quantum nature is not fully understood. We present a comprehensive description of the ultrafast light induced C Cl bond cleavage in diarylmethyl chlorides combining femtosecond transient absorption measurements with ab initio calculations. We observe a delayed appearance of radicals (80 fs) and cations (125 fs). The excited state wavepacket moves initially toward two conical intersections and the passing through these intersections determines the partitioning into the differing product channels. Different locations of the conical intersections explain the observed delay times.

Background In 2005, the International Study Group of Pancreatic Fistula developed a definition and grading of postoperative pancreatic fistula that has been accepted universally. Eleven years later, because postoperative pancreatic fistula remains one of the most relevant and harmful complications of pancreatic operation, the International Study Group of Pancreatic Fistula classification has become the gold standard in defining postoperative pancreatic fistula in clinical practice. The aim of the present report is to verify the value of the International Study Group of Pancreatic Fistula definition and grading of postoperative pancreatic fistula and to update the International Study Group of Pancreatic Fistula classification in light of recent evidence that has emerged, as well as to address the lingering controversies about the original definition and grading of postoperative pancreatic fistula. Methods The International Study Group of Pancreatic Fistula reconvened as the International Study Group in Pancreatic Surgery in order to perform a review of the recent literature and consequently to update and revise the grading system of postoperative pancreatic fistula. Results Based on the literature since 2005 investigating the validity and clinical use of the original International Study Group of Pancreatic Fistula classification, a clinically relevant postoperative pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula. Consequently, the former “grade A postoperative pancreatic fistula” is now redefined and called a “biochemical leak,” because it has no clinical importance and is no longer referred to a true pancreatic fistula. Postoperative pancreatic fistula grades B and C are confirmed but defined more strictly. In particular, grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. Conclusion This new definition and grading system of postoperative pancreatic fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula. Use of this updated classification will also allow for more precise comparisons of surgical quality between surgeons and units who perform pancreatic surgery.

Background Increased incorporation of minimally invasive pancreatic resections (MIPR) has emerged into hepato-pancreato-biliary practice, however, no standardization exists for its safe adoption. Novel strategies are presented for dissemination of safe MIPR. Methods An international State-of-the-Art conference evaluating multiple aspects of MIPR was conducted by a panel of pancreas experts in Sao Paulo, Brazil on April 20, 2016. Training and education issues were discussed regarding the introduction of novel strategies for safe dissemination of MIPR. Results The low volume of pancreatic resections per institution poses a challenge for surgeons to overcome their MIPR learning curve without deliberate training. A mastery-based simulation and biotissue curriculum can improve technical proficiency and allow for training of surgeons before the operating room. Video-based platforms allow for performance reporting and feedback necessary for coaching and surgical quality improvement. Centers of excellence with training involving a standardized approach and proctorship are important concepts that can be utilized in various formats internationally. Discussion Surgical volume is not sufficient to ensure quality and patient safety in MIPR. Safe adoption of these complex procedures should consider innovative mastery-based training outside of the operating room, novel video based coaching techniques and prospective reporting of patient data and outcomes using standardized definitions.

Background Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. Methods The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. Results Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. Conclusion This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication.