Midterm outcomes of the Viabahn VBX balloon-expandable covered stent for fenestrations during complex endovascular aortic aneurysm repair.

OBJECTIVES: The optimal bridging stent for fenestrations during complex endovascular aortic aneurysm repair (EVAR) has not been defined. At our institution, the Viabahn VBX is frequently used given its availability and mechanical and heparin-bonding characteristics. This study aimed to assess the performance of the Viabahn VBX vs the iCast balloon-expandable covered stents as bridging stents for fenestrations during complex EVAR. METHODS: A retrospective study of consecutive patients undergoing complex EVAR between 2015 and 2021 was performed. Celiac arteries (CAs), superior mesenteric arteries (SMAs), left renal arteries, and right renal arteries stented with fenestrations were grouped according to the type of bridging stent, VBX vs iCast. Target vessels (TV) stented with a branch or scallop were excluded. The primary end points included primary patency and freedom from TV instability. RESULTS: A total of 292 patients undergoing complex EVAR were treated using VBX or iCast with a mean follow-up of 190 days (interquartile range, 36-384 days) for the VBX cohort and 804 days (interquartile range, 384-1507 days) for the iCast cohort. A total of 677 TVs were stented, including 134 CAs (20%), 175 SMAs (26%), 182 left RAs (27%), 186 right RAs (27%), and 12 additional vessels (2%). Proximal reinforcement was more frequent with VBX than with iCast stent (23% vs 2.4%; P < .0001). There was no difference in primary patency rates at 2 years between VBX and iCast stent for CA (100% vs 96.4%; P = .32), SMA (97.8% vs 100%; P = .14), and the RAs (96.7% vs 99.4%; P = .11). There was no difference between VBX and iCast in the cumulative incidence of type Ic and type IIIc endoleaks (3.2% vs 5.6%; P = .69) or freedom from TV instability at 2 years. CONCLUSIONS: Viabahn VBX stents are a safe and effective option as bridging stents in fenestrations during complex EVAR with comparable midterm outcomes to iCast stents. However, proximal stent reinforcement may be required with VBX stent to ensure adequate sealing at the fenestrations. Longer follow-ups and larger series are required to assess long-term outcomes and durability.

Long-term outcomes of staged iliofemoral endoconduits prior to complex endovascular aortic aneurysm repair.

OBJECTIVE: Adverse iliofemoral anatomy may preclude complex endovascular aortic aneurysm repair (EVAR). In our practice, staged iliofemoral endoconduits (ECs) are planned prior to complex EVAR to improve vascular access and decrease operative time while allowing the stented vessel to heal. This study describes the long-term results of iliofemoral ECs prior to complex EVAR. METHODS: Between 2012 and 2023, 59 patients (44% male; median age, 75 ± 6 years) underwent ECs before complex EVAR using self-expanding covered stents (Viabahn). For common femoral artery (CFA) disease, ECs were delivered percutaneously from contralateral femoral access and extended into the CFA to preserve the future access site for stent graft delivery. Internal iliac artery patency was maintained when feasible. During complex EVAR, the EC extended into the CFA was directly accessed and sequentially dilated until it could accommodate the endograft. Technical success was defined as successful access, closure, and delivery of the endograft during complex EVAR. Endpoints were vascular injury or EC disruption, secondary interventions, and EC patency. RESULTS: Unilateral EC was performed in 45 patients (76%). ECs were extended into the CFA in 21 patients (35%). Median diameters of the native common iliac, external iliac, and CFA were 7 mm (interquartile range [IQR], 6-8 mm), 6 mm (IQR, 5-7 mm), and 6 mm (IQR, 6-7 mm), respectively. Internal iliac artery was inadvertently excluded in 10 patients (17%). Six patients (10%) had an intraoperative vascular injury during the EC procedure, and six patients (10%) had EC disruption during complex EVAR, including five EC collapses requiring re-stenting and one EC fracture requiring open cut-down and reconstruction with patch angioplasty. In 23 patients (39%), 22 Fr OD devices were used; 20 Fr were used in 22 patients (37%), and 18 Fr in 14 patients (24%). Technical success for accessing EC was 89%. There was no difference in major adverse events at 30 days between the iliac ECs and iliofemoral ECs. Primary patency by Kaplan-Meier estimates at 1, 3, and 5 years were 97.5%, 89%, and 82%, respectively. There was no difference in primary patency between iliac and iliofemoral ECs. Six secondary interventions (10%) were required. The mean follow-up was 34 ± 27 months; no limb loss or amputations occurred during the follow-up. CONCLUSIONS: ECs improve vascular access, and their use prior to complex EVAR is associated with low rates of vascular injury, high technical success, and optimal long-term patency. Complex EVAR procedures can be performed percutaneously by accessing the EC directly under ultrasound guidance and using sequential dilation to avoid EC disruption.

Indications, safety, and effectiveness of transcatheter electrosurgical septotomy during endovascular repair of aortic dissections.

OBJECTIVE: Endovascular repair of aortic dissections may be complicated by inadequate sealing zones, persistent false lumen perfusion, and limited space for catheter manipulation and target artery incorporation. The aim of this study was to describe the indications, technical success, and early outcomes of transcatheter electrosurgical septotomy (TES) during endovascular repair of aortic dissections. METHODS: We reviewed the clinical data of consecutive patients treated by endovascular repair of aortic dissections with adjunctive TES in two centers between 2021 and 2023. End points were technical success, defined by successful septotomy without dislodgment of the lamella or target artery occlusion, and 30-day rates of major adverse events (MAEs). RESULTS: Among 197 patients treated by endovascular repair for aortic dissections, 36 patients (18%) (median age, 61.5 years (interquartile range, 55.0-72.5 years; 83% male) underwent adjunctive TES for acute (n = 3 [8%]), subacute (n = 1 [3%]), or chronic postdissection aneurysms (n = 32 [89%]). Indications for TES were severe true lumen (TL) compression (≤16 mm) in 28 patients (78%), target vessel origin from false lumen in 19 (53%), creation of suitable landing zone in 12 (33%), and organ/limb malperfusion in four (11%). Endovascular repair included fenestrated-branched endovascular aortic repair (EVAR) in 18 patients (50%), thoracic EVAR/EVAR/PETTICOAT in 11 (31%), and arch branch repair in 7 (19%). All patients had dissections extending through zones 5 to 7, and 28 patients (78%) underwent TES across the renal-mesenteric segment. Technical success of TES was 92% (33/36) for all patients and 97% (32/33) among those with subacute or chronic postdissection aneurysms. There were three technical failures, including two patients with acute dissections with inadvertent superior mesenteric artery dissection in one patient and distal dislodgement of the dissection lamella in two patients. There were no arterial disruptions. The mean postseptotomy aortic lumen increased from 13.2 ± 4.8 mm to 28.4 ± 6.8 mm (P < .001). All 18 patients treated by fenestrated-branched EVAR had successful incorporation of 78 target arteries. There was one early death (3%) from stroke, and three patients (8%) had major adverse events. After a median follow-up of 8 months (interquartile range, 4.5-13.5 months), 13 patients (36%) had secondary interventions, and two (6%) died from non-aortic-related events. There were no other complications associated with TES. CONCLUSIONS: TES is an adjunctive technique that may optimize sealing zones and luminal aortic diameter during endovascular repair of subacute and chronic postdissection. Although no arterial disruptions or target vessel loss occurred, patients with acute dissections are prone to technical failures related to dislodgement of the lamella.

Early experience with patient-specific unibody bifurcated fenestrated-branched devices for complex endovascular aortic aneurysm repair.

OBJECTIVE: Short distances between the lowest visceral/renal artery and the aortic bifurcation are technically challenging during complex endovascular aortic aneurysm repair (EVAR), particularly after previous infrarenal repair. Traditionally, inverted limb bifurcated devices have been used in addition to fenestrated-branched (FB) endografts, but short overlap, difficult cannulation, and potential crushing of bridging stents are limitations for their use. This study reviews the early experience of patient-specific company manufactured devices (PS-CMDs) with a unibody bifurcated FB design for complex EVAR. METHODS: Consecutive complex EVAR procedures over a 34-month period with unibody bifurcated FB-devices as part of physician-sponsored investigational device exemption studies at two institutions were reviewed. Unibody bifurcated FB designs included FB bifurcated or fenestrated inverted limb devices. End points included technical success, survival, frequency of type I or III endoleaks, limb occlusion, and secondary interventions. RESULTS: Among 168 patients undergoing complex EVAR, 33 patients (19.6%; 78.7% male; mean age, 77 years) received unibody bifurcated FB PS-CMDs. FB bifurcated and fenestrated inverted limb devices were used in 31 (93.9%) and 2 (6.06%) patients, respectively. The median maximum aneurysm diameter was 61 mm (interquartile range [IQR], 55-69 mm). Prior EVAR was reported by 29 patients (87.9%), of whom 2 (6.06%) had suprarenal stents. A short distance between the lowest renal artery and aortic bifurcation was demonstrated in 30 patients (90.9%), with median distance of 47 mm (IQR, 38-54 mm). Preloaded devices were used in 23 patients (69.7%). A total of 128 fenestrations were planned; 22 (17.2%) were preloaded with guidewires and 5 (3.9%) with catheters. The median operative time was 238 minutes (226-300 minutes), with a median fluoroscopy time of 65.5 minutes (IQR, 56.0-77.7 minutes) and a median dose area product of 147 mGy∗cm2 (IQR, 105-194 mGy∗cm2). Exclusive femoral access was used in 14 procedures (42.4%). Technical success was 100%. Target vessel primary patency was 100% at a median follow-up time of 11.7 months (IQR, 3.5-18.6 months). Two patients (6.06%) required reintervention for iliac occlusion; one patient required stenting and the other a femoral-femoral bypass. No aortic-related deaths occurred after the procedure. During follow-up, 11 type II endoleaks (33.3%) and 1 type Ib endoleak (3.03%) were detected; the latter was treated with leg extension. No type Ia or III endoleaks occurred. CONCLUSIONS: Complex EVAR using unibody bifurcated FB-PS-CMDs is a simple, safe, and cost-effective alternative for the treatment of patients with short distances between the renal arteries and the aortic bifurcation. Further studies are required to assess benefits and durability of unibody bifurcated FB devices.

Postdissection aortic aneurysm sac enlargement after fenestrated and branched endovascular aortic aneurysm repair.

OBJECTIVES: Aneurysm sac changes after fenestrated-branched endovascular aneurysm repair (FBEVAR) for postdissection thoracoabdominal aortic aneurysms (PD-TAAs) are poorly understood. Partial thrombosis of the false lumen and endoleaks may impair sac regression. To characterize sac changes after FBEVAR for PD-TAAs, this study examined midterm results and predictors for sac enlargement. METHODS: FBEVARs performed for PD-TAAs in 10 physician-sponsored investigational device exemption studies from 2008 to 2023 were analyzed. The maximum aortic aneurysm diameter was compared between the 30-day computed tomography angiogram and follow-up imaging studies. Aneurysm sac enlargement was defined as an increase in diameter of ≥5 mm. Kaplan-Meier curves and Cox regression were used to evaluate sac enlargement and midterm FBEVAR outcomes. RESULTS: Among 3296 FBEVARs, 290 patients (72.4% male; median age, 68.4 years) were treated for PD-TAAs. Most aneurysms treated were extent II (72%) and III (12%). Mean aneurysm diameter was 66.5 ± 11.2 mm. Mortality at 30 days was 1.4%. At a mean follow-up of 2.9 ± 1.9 years, at least one follow-up imaging study revealed sac enlargement in 43 patients (15%), sac regression in 115 patients (40%), and neither enlargement nor regression in 137 (47%); 5 (2%) demonstrated both expansion and regression during follow-up. Freedom from aneurysm sac enlargement was 93%, 82%, and 80% at 1, 3, and 5 years, respectively. Overall, endoleaks were detected in 27 patients (63%) with sac enlargement and 143 patients (58%) without enlargement (P = .54). Sac enlargement was significantly more frequent among older patients (mean age at the index procedure, 70.2 ± 8.9 years vs 66.5 ± 11 years; P = .04) and those with type II endoleaks at 1 year (74% vs 52%; P = .031). Cox regression revealed age >70 years at baseline (hazard ratio [HR], 2.146; 95% confidence interval [CI], 1.167-3.944; P = .010) and presence of type II endoleak at 1 year (HR, 2.25; 95% CI, 1.07-4.79; P = .032) were independent predictors of sac enlargement. Patient survival was 92%, 81%, and 68% at 1, 3, and 5 years, respectively. Cumulative target vessel instability was 7%, and aneurysm-related mortality was 2% at 5 years. At least 42% of patients required secondary interventions. Sac enlargement did not affect patient survival. CONCLUSIONS: Aneurysm sac enlargement occurs in 15% of patients after FBEVAR for PD-TAAs. Elderly patients (>70 years at baseline) and those with type II endoleaks at 1 year may need closer monitoring and secondary interventions to prevent sac enlargement. Despite sac enlargement in some patients, aneurysm-related mortality at 5 years remains low and overall survival was not associated with sac enlargement.

Single-cell mtDNA heteroplasmy in colorectal cancer.

Human mitochondria can be genetically distinct within the same individual, a phenomenon known as heteroplasmy. In cancer, this phenomenon seems exacerbated, and most mitochondrial mutations seem to be heteroplasmic. How this genetic variation is arranged within and among normal and tumor cells is not well understood. To address this question, here we sequenced single-cell mitochondrial genomes from multiple normal and tumoral locations in four colorectal cancer patients. Our results suggest that single cells, both normal and tumoral, can carry various mitochondrial haplotypes. Remarkably, this intra-cell heteroplasmy can arise before tumor development and be maintained afterward in specific tumoral cell subpopulations. At least in the colorectal patients studied here, the somatic mutations in the single-cells do not seem to have a prominent role in tumorigenesis.

[Chilean clinical guideline for the management of hidradenitis suppurativa - executive summary]. / Guía clínica chilena para el estudio y tratamiento de hidradenitis supurativa. Resumen ejecutivo.

Hidradenitis suppurativa is a chronic inflammatory disease of the hair follicle characterized by recurrent painful and inflamed lesions, predominantly affecting intertriginous regions. Due to its physical sequelae and impact on quality of life, we should be familiarized with this disease to make an appropriate diagnosis and implement an early treatment. This executive summary of the clinical guideline, elaborated by the hidradenitis suppurativa workgroup of the Chilean Society of Dermatology and Venereology (SOCHIDERM), reviews its definition, epidemiology, pathophysiology, risk factors, comorbidities, psycho-emotional impact, clinical presentation, diagnosis, classifications, ultrasonographic evaluation, and its medical and surgical treatments. Finally, a therapeutic approach algorithm is proposed.

Sonographic Comparison of Morphologic Characteristics Between Pilonidal Cysts and Hidradenitis Suppurativa.

OBJECTIVES: To compare the sonographic characteristics of pilonidal cysts and hidradenitis suppurativa. METHODS: A retrospective study of sonographic examinations was performed on 2 groups: 1 with pilonidal cysts and the other with hidradenitis suppurativa. The sonographic characteristics of the pilonidal cyst and hidradenitis suppurativa groups were analyzed, compared, and correlated, including an analysis of the histologic findings. For the pilonidal cyst group, the distribution, morphologic characteristics, location, shape, diameter, axis, vascularity, and scarring were also described. Statistical analyses included Spearman, Wilcoxon, Kruskall-Wallis, χ2 , and Fisher tests. RESULTS: The sonographic examinations of 84 patients were reviewed: 43 with pilonidal cysts and 41 with hidradenitis suppurativa. The comparison of the morphologic characteristics of the key lesions between the pilonidal cyst and hidradenitis suppurativa groups showed no statistically significant differences (P < .05). Both groups had similar dermal and hypodermal saclike and bandlike structures that communicated with the widened base of the hair follicles. Retained fragments of hair tracts within the lesions were sonographically detected in both pilonidal cysts (100%) and hidradenitis suppurativa (83%) and also found on histologic specimens; however, the density of hair tracts per structure was higher in pilonidal cysts. Sonographic signs of scarring were absent in 63% of pilonidal cysts. Only 2% of pilonidal cysts showed communicating bandlike structures. CONCLUSIONS: Key lesions of pilonidal cysts and hidradenitis suppurativa have similar sonographic morphologic characteristics, which suggests that a pilonidal cyst may be a variant or localized form of hidradenitis suppurativa. The retained fragments of hair tracts frequently detected in both entities may be caused by ectopic production of hair and not by embedding. Common therapeutic strategies and research can be designed for both entities.

Color Doppler ultrasound assessment of morphology and types of fistulous tracts in hidradenitis suppurativa (HS).

BACKGROUND: Fistulous tracts in hidradenitis suppurativa (HS) are key signs of severity and their clinical evaluation alone may be limited for assessing their presence and morphology. There is also a need to determine the factors that allow reversibility of the anatomic changes in HS. OBJECTIVE: We sought to categorize fistulous tracts in HS. METHODS: A retrospective study of color Doppler ultrasound images of cases with positive clinical and sonographic criteria of HS with fistulous tracts was performed. The sonographic staging of HS, location, and anatomic characteristics of the tracts were registered and graded. Statistical analysis for correlating variables was performed using bivariate and multivariate studies. RESULTS: In all, 52 patients presenting 96 fistulous tracts met the criteria. Morphology was defined and a sonographic classification into 3 types of fistulae was developed. Type 3 concentrated 71% of the cases presenting communicating tracts, and type 2, 29%. Types 2 and 3 represented 63% of patients with multiple fistulous tracts. Fistulous tracts types 2 and 3 were significantly correlated with age 35 years or older and groin location. LIMITATIONS: Ultrasound cannot detect lesions less than 0.1 mm. CONCLUSION: Fistulous tracts in HS can be categorized using ultrasound, which may support earlier and more precise management.

Allelic diversity for neutral markers retains a higher adaptive potential for quantitative traits than expected heterozygosity.

The adaptive potential of a population depends on the amount of additive genetic variance for quantitative traits of evolutionary importance. This variance is a direct function of the expected frequency of heterozygotes for the loci which affect the trait (QTL). It has been argued, but not demonstrated experimentally, that long-term response to selection is more dependent on QTL allelic diversity than on QTL heterozygosity. Conservation programmes, aimed at preserving this variation, usually rely on neutral markers rather than on quantitative traits for making decisions on management. Here, we address, both through simulation analyses and experimental studies with Drosophila melanogaster, the question of whether allelic diversity for neutral markers is a better indicator of a high adaptive potential than expected heterozygosity. In both experimental and simulation studies, we established synthetic populations for which either heterozygosity or allelic diversity was maximized using information from QTL (simulations) or unlinked neutral markers (simulations and experiment). The synthetic populations were selected for the quantitative trait to evaluate the evolutionary potential provided by the two optimization methods. Our results show that maximizing the number of alleles of a low number of markers implies higher responses to selection than maximizing their heterozygosity.

Up and over staged endoconduit technique for endovascular aortic aneurysm repair.

Adverse iliofemoral anatomy can preclude complex endovascular aortic aneurysm repair. This study aims to describe the "up-and-over" staged endoconduit technique to improve access and avoid vascular injury before complex endovascular aneurysm repair. A staged procedure for complex endovascular aortic aneurysm repair is performed using an endoconduit (W.L. Gore & Associates). After obtaining contralateral femoral access, the extension of iliofemoral disease is assessed using angiography. The endoconduit is advanced "up and over" the aortic bifurcation and delivered percutaneously into the common femoral artery to treat a diseased access site and maintain intact the ipsilateral femoral access for future stent graft deployment. Internal iliac artery patency is maintained when feasible. During complex aneurysm repair, the endoconduit is accessed directly under ultrasound guidance using sequential dilation to avoid vascular injury. PerClose sutures (Abbott Vascular) are used to close the endoconduit femoral access site. This study found that staged "up and over" endoconduit creation is a useful technique before complex endovascular aneurysm repair in patients with adverse iliofemoral anatomy. Avoiding accessing the main femoral access site during the first stage prevents vascular or access site injuries and allows for both iliac and femoral disease to be addressed.

Early results of transcatheter electrosurgical aortic septotomy for endovascular repair of chronic dissecting aortoiliac aneurysms.

Objective: Endovascular repair of chronic dissecting aortoiliac aneurysms is challenging given the rigid septum, compressed true lumen (TL), and target vessels frequently originating in the false lumen. We have used transcatheter electrosurgical aortic septotomy (TEAS) before stent graft implantation under intravascular ultrasound (IVUS) and fusion guidance. The purpose of this study is to assess the outcomes of TEAS during complex endovascular repair of dissecting aneurysms. Methods: From 2021 to 2023, 17 patients underwent TEAS. The primary end point was technical success, with secondary end points of proximal and distal seals, target vessel instability, aortic and iliac TL and cross-sectional area (CSA) expansion, and aortic-related death. During the procedure, the aortic septum is crossed through a pre-existing entry or via electrocautery-activated 0.018-in. Astato XS20 wire (Asahi-Intecc) under IVUS and fusion guidance. The penetrated wire is then snared in the false lumen and pulled through the ipsilateral femoral access. A 1-cm length of the middle of the Astato wire coating is kinked in a three-sided polygonal configuration, denuded the inner surface of the wire using a no. 15 blade, and positioned at the apex of the septum. Both ends of the Astato wire are insulated with 0.018-in. microcatheters, and the back end of the wire is denuded and connected to cautery. Gentle traction is applied to the wire, and short bursts of electrocautery cutting are applied at 60 to 80 W. Results: The technical success of the septotomy was 100%. No incidence of visceral or lower extremity malperfusion, vascular injury, or distal embolization occurred. Of the 17 patients, 4 underwent thoracic endovascular aneurysm repair, 2 underwent endovascular aortic repair, and 11 underwent fenestrated/branched endovascular aneurysm repair after septotomy. All target vessels were successfully stented. A distal landing zone seal with exclusion of the false lumen was achieved in 16 of the 17 patients (94.1%). One patient required embolization of the false lumen of the celiac artery after septotomy. The TL mean diameter and CSA of the descending thoracic aorta after septotomy was expanded by 7.01 ± 1.9 mm (relative mean diameter expansion, 42.3%; P < .0001) and 2.71 ± 0.4 cm2 (relative mean CSA expansion, 57.3%, P<.0001). For patients who required septotomy through the common iliac arteries, the mean TL was expanded by 8.1 ± 3.7 mm (relative mean diameter expansion, 76%; P < .0001) and 1.76 ± 0.91 cm2 (relative mean CSA expansion, 209%; P < .0001). The 1-year freedom from target vessel instability was 91%. Conclusions: The use of IVUS and fusion-guided TEAS offers a promising technique to facilitate TL expansion and false lumen exclusion in chronic dissecting aortic aneurysms before repair. The durability and long-term outcomes of this technique in a larger cohort remain to be elucidated.

Effects of Chronic Obstructive Pulmonary Disease on the Outcomes of Fenestrated-Branched Endovascular Aortic Aneurysm Repair.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is common in patients with aortic aneurysms. Severe COPD is associated with an increased risk of aneurysm rupture and perioperative complications. This study assesses the outcomes of COPD and non-COPD patients after fenestrated-branched endovascular aortic aneurysm repair (FBEVAR). MATERIALS AND METHODS: A single institution, retrospective study of FBEVAR patients between 2011 and 2020 compared outcomes between COPD and non-COPD patients. COPD patients were stratified by Global Initiative for Chronic Obstructive Lung Disease criteria and oxygen dependence. Outcome measures included 30-day mortality, pulmonary complications, major adverse events (MAE), and mid-term survival. RESULTS: 387 patients (71% male, age 72 years, interquartile range [68-79]) underwent FBEVAR. 181 patients (47%) had COPD. Smoking history was more frequent in COPD patients (P = .022). Among COPD patients, 20.4% were oxygen-dependent. Technical success, defined as successful delivery of the main aortic endograft and all intended side branches, was 98.4%. 30-day mortality (P = .83) and MAE rates (P = .87) were similar between groups. While not statistically significant, COPD patients had more frequent pulmonary complications (6.1% vs. 2.4%, P = .13) and were more frequently discharged on oxygen (P = .002). There were no differences in intensive care unit or hospital length of stay between groups (P = .29; P = .85, respectively). 5-year survival was similar between groups (P = .10). Oxygen-dependent COPD and severe-very severe COPD were associated with decreased mid-term survival (Hazard Ratio 2.39, P = .048). CONCLUSIONS: FBEVAR is safe and effective for treating complex aortic pathology in COPD patients, including oxygen-dependent patients. Patients with more severe COPD were more frequently discharged on oxygen. Mid-term survival was slightly reduced in patients with oxygen-dependent and severe-very severe COPD. LEVEL OF EVIDENCE: Level 3, non-randomized controlled cohort/follow-up study.

Methylation changes associated with early maturation stages in the Atlantic salmon.

BACKGROUND: Early maturation in the Atlantic salmon is an interesting subject for numerous research lines. Prior to sea migration, parr can reach sexual maturation and successfully fertilize adult female eggs during the reproductive season. These individuals are known as precocious parr, mature parr or "sneakers". Reasons for early maturation are unknown and this transitory stage is usually considered to be a threshold trait. Here, we compare methylation patterns between mature and immature salmon parr from two different rivers in order to infer if such methylation differences may be related to their maturation condition. First we analyzed genetic differences between rivers by means of AFLPs. Then, we compared the DNA methylation differences between mature and immature parrs, using a Methylation-Sensitive Amplified Polymorphism (MSAP), which is a modification of the AFLPs method by making use of the differential sensitivity of a pair of restriction enzymes isoschizomeres to cytosine methylation. The tissues essayed included brain, liver and gonads. RESULTS: AFLPs statistical analysis showed that there was no significant differentiation between rivers or a significant differentiation between maturation states in each river. MSAP statistical analysis showed that among the three tissues sampled, the gonads had the highest number of significant single-locus variation among populations with 74 loci followed by brain with 70 and finally liver with only 12. Principal components analysis (PCA) of the MSAP profiles revealed different profiles among different tissues (liver, brain and testis) clearly separating maturation states in the testis tissue when compared to the liver. CONCLUSIONS: Our results reveal that genetically-similar mature and immature salmon parr present high levels of DNA methylation variation in two of the three analyzed tissues. We hypothesize that early maturation may be mostly mediated by epigenetic processes rather than by genetic differences between parrs. To our knowledge this is the first study that attempt to link phenotypic plasticity in salmonids and epigenetic changes.

Postprandial changes of amino acid and acylcarnitine concentrations in dried blood samples.

Blood sampling for newborn screening cannot be standardized as for example blood collection in adults after an overnight fast. Therefore the influence of postprandial changes and individual variation is valuable information for the assessment of sensitivity and specificity of newborn screening for certain disorders. We have analyzed 92 pairs of dried blood samples taken pre- and one hour postprandially, respectively. We have determined the mean increase in metabolite concentration and calculated its significance. Individual variation after an overnight fast in healthy adults (n = 3) was between 12 and 32% (SD). Postprandial increases of acylcarnitines were mostly not significant and not exceeding 10%. Postprandial increase of amino acids was highly significant for most proteinogenic amino acids, but not for all. With the collected data we were able to estimate that mainly decreased levels of methionine and, to a lesser extent, of free carnitine could be "masked" by postprandial increases of the respective metabolites, and could therefore lead to false negative results for the detection of disorders of cobalamin metabolism and carnitine transporter deficiency.

Eruptive disseminated Spitz nevi - Case report.

Spitz nevus is a benign melanocytic lesion, which presents in several ways: solitary, agminated, or disseminated. The disseminated variant is uncommon; it may have a rapid evolution (the eruptive form) and be difficult to manage. This report presents the case of a 24-year-old patient with multiple papules on his limbs, which had appeared four years previously. On physical examination, 120 pink and skin-colored papules were seen, which under dermoscopy were observed to be homogeneous, pink vascular lesions. Histopathologic study revealed epithelioid cells arranged in groups or singly in the dermis and dermo-epidermal junction. They were HMB-45 positive in the superficial dermis, and Ki-67<1%. Given these findings, a diagnosis of eruptive disseminated Spitz nevi was made.

Profile and entrepreneurial intention of nursing students: a comparison between Brazil and Chile.

OBJECTIVE: to identify and compare factors associated with profile, intentions, motivations, and barriers to entrepreneurial behavior of nursing students from Brazil and Chile. METHODS: this cross-sectional study was carried out between March and September 2018 including 889 nursing students. A form was used to assess the socio-demographic profile, professional claims, entrepreneurial intentions and motivations. Statistical analysis used Chi-Square and Fisher's Exact tests, with a 5% significance level, and a simple logistic regression model. RESULTS: there are significant differences between countries in the profile of students and in the motivations studied, but not in professional pretensions and entrepreneurial intentions. Lack of education on the subject reveals itself as an important barrier to entrepreneurship. CONCLUSION: given the lack of teaching entrepreneurship in undergraduate nursing courses and the characteristics inherent to students, education must be appropriate to different cultures to prepare future professionals for other areas of practice.

metapop2: Re-implementation of software for the analysis and management of subdivided populations using gene and allelic diversity.

Management programmes often have to make decisions based on the analysis of the genetic properties and diversity of populations. Expected heterozygosity (or gene diversity) and population structure parameters are often used to make recommendations for conservation, such as avoidance of inbreeding or migration across subpopulations. Allelic diversity, however, can also provide complementary and useful information for conservation programmes, as it is highly sensitive to population bottlenecks, and is more related to long-term selection response than heterozygosity. Here we present a completely revised and updated re-implementation of the software metapop for the analysis of diversity in subdivided populations, as well as a tool for the management and dynamic estimation of optimal contributions in conservation programmes. This new update includes computation of allelic diversity for population analysis and management, as well as a simulation mode to forecast the consequences of taking different management strategies over time. Furthermore, the new implementation in C++ includes code optimization and improved memory usage, allowing for fast analysis of large data sets including single nucleotide polymorphism markers, as well as enhanced cross-software and cross-platform compatibility.

Emission and dispersal of antibiotic resistance genes through bioaerosols generated during the treatment of municipal sewage.

Wastewater treatment plants act as socio-ecological couplers through the concentration, treatment, and subsequent environmental release of sewage collected from surrounding communities and are often considered hotspots for antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). While studies have identified the release of ARB/ARGs in treated liquid sewage, little is known about potential dispersal through wastewater bioaerosol emissions. The aim of this study was to better define the contribution of WWTP bioaerosols to potential environmental distribution of ARB/ARGs. Bioaerosols were collected immediately upwind and downwind from the aeration tanks of a municipal wastewater treatment plant and liquid sludge samples were obtained from the aeration tanks. From the bioaerosol and liquid samples, qPCR assays identified 44 ARGs that confer resistance to a wide range of antibiotics. Comparison of the ARG profiles across samples showed that the downwind bioaerosol profile was 68% similar to the profile found in liquid sludge samples. Community 16S rRNA gene sequencing also showed that downwind bioaerosols had similar taxonomic profiles as those generated from liquid sludge while the upwind profiles showed a distinct difference. Preliminary ARG dispersion modeling estimated an ARG emission rate of ~10,620 genes per hour from the liquid sludge and indicated that the bioaerosols have the potential to be carried kilometers away from the WWTP source based on wind speed. The overall results from this study suggest that bioaerosols generated during WWTP processes can aid in the emission and dispersal of bacteria and ARGs, resulting in a possible route of human exposure and deposition into surrounding environments.

Optimal Management of Genetic Diversity in Subdivided Populations.

One of the main objectives of conservation programs is the maintenance of genetic diversity because this provides the adaptive potential of populations to face new environmental challenges. Genetic diversity is generally assessed by means of neutral molecular markers, and it is usually quantified by the expected heterozygosity under Hardy-Weinberg equilibrium and the number of alleles per locus or allelic diversity. These two measures of genetic diversity are complementary because whereas the former is directly related to genetic variance for quantitative traits and, therefore, to the short-term response to selection and adaptation, the latter is more sensitive to population bottlenecks and relates more strongly to the long-term capacity of adaptation of populations. In the context of structured populations undergoing conservation programs, it is important to decide the optimum management strategy to preserve as much genetic diversity as possible while avoiding inbreeding. Here we examine, through computer simulations, the consequences of choosing a conservation strategy based on maximizing either heterozygosity or allelic diversity of single-nucleotide polymorphism haplotypes in a subdivided population. Our results suggest that maximization of allelic diversity can be more efficient in maintaining the genetic diversity of subdivided populations than maximization of expected heterozygosity because the former maintains a larger number of alleles while making a better control of inbreeding. Thus, maximization of allelic diversity should be a recommended strategy in conservation programs for structured populations.