Molecular and physiologic changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first-ever all civilian crew to low Earth orbit, which included the youngest American astronaut (age 29), novel in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables, and immune profiling), ocular alignment measurements, and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiologic, and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

Shaping subcellular tubes through vesicle trafficking: Common and distinct pathways.

Cells with subcellular lumens form some of the most miniature tubes in the tubular organs of animals. These are often crucial components of the system, executing functions at remote body locations. Unlike tubes formed by intercellular or autocellular junctions, the cells with junctionless subcellular lumens face unique challenges in modifying the cell shape and plasma membrane organization to incorporate a membrane-bound tube within, often associated with dramatic cellular growth and extensions. Results in the recent years have shown that membrane dynamics, including both the primary delivery and recycling, is crucial in providing the cell with the flexibility to face these challenges. A significant portion of this information has come from two in vivo invertebrate models; the Drosophila tracheal terminal cells and the C. elegans excretory cell. This review focuses on the data obtained from these systems in the recent past about how trafficking pathways influence subcellular tube and branching morphogenesis. Given that such tubes occur in vertebrate vasculature, these insights are relevant to human health, and we contrast our conclusions with the less understood subcellular tubes of angiogenesis.

The morphometric acclimation to depth explains the long-term resilience of the seagrass Cymodocea nodosa in a shallow tidal lagoon.

Cadiz Bay is a shallow mesotidal lagoon with extensive populations of the seagrass Cymodocea nodosa at intertidal and shallow subtidal elevations. This work aims to understand the mechanisms behind the resilience of this species to gradual sea level rise by studying its acclimation capacity to depth along the shallow littoral, and therefore, to gradual variations in the light environment. To address this objective, these populations have been monitored seasonally over a 10 year period, representing the longest seasonal database available in the literature for this species. The monitoring included populations at 0.4, -0.08 and -0.5 m LAT. The results show that C. nodosa has a strong seasonality for demographic and shoot dynamic properties - with longer shoots and larger growth in summer (high temperature) than in winter (low temperature), but also some losses. Moreover, shoots have different leaf morphometry depending on depth, with small and dense shoots in the intertidal areas (0.4 m) and sparse large shoots in the subtidal ones (-0.08 and 0.5 m). These differences in morphometry and shoot dynamic properties, combined with the differences in shoot density, explain the lack of differences in meadow production balance (i.e. meadow growth - meadow losses) between the intertidal (0.4 m) and the deepest population (-0.5 m), supporting the long term resilience of Cymodocea nodosa in Cadiz Bay. This study contributes to the understanding of the mechanisms behind seagrass stability and resilience, which is particularly important towards predicting the effects of climate change on these key coastal ecosystems, and also highlights the value of continuous long-term monitoring efforts to evaluate seagrass trajectories.

R230C but not - 565C/T variant of the ABCA1 gene is associated with type 2 diabetes in Mexicans through an effect on lowering HDL-cholesterol levels.

PURPOSE: Type 2 diabetes (T2D) and low serum concentration of high-density lipoprotein cholesterol (HDL-c) are common coexisting metabolic disorders. ABCA1 variants have been shown to be associated to these conditions. We sought to test the combined effect of two ABCA1 gene common variants, rs2422493 (- 565C > T) and rs9282541 (R230C) on HDL-c levels and T2D risk. METHODS: Path analysis was conducted in 3,303 Mexican-mestizos to assess the specific contributions of rs2422493 and rs9282541 ABCA1 variants, insulin resistance, waist-to-height ratio (WHtR), and age on HDL-c levels and T2D risk. Participants were classified into four groups according to their ABCA1 variants carrier status: (i) the reference group carried wild type alleles for both ABCA1 variants (-/-), (ii) +/- were carriers of rs2422493 but non-carriers of rs9282541, (iii) -/+ for carriers of rs9282541 but not carriers of rs2422493 and (iv) carriers of minor alleles for both SNPs (+/+). Principal components from two previous genome-wide association studies were used to control for ethnicity. RESULTS: We identified significant indirect effects on T2D risk mediated by HDL-c in groups -/+ and +/+ (ß = 0.04; p = 0.03 and ß = 0.06; p < 0.01, respectively) in comparison to the -/- reference group. Low concentrations of HDL-c were directly and significantly associated with increased T2D risk (ß = -0.70; p < 0.01). WHtR, male gender, age, and insulin resistance were also associated with T2D risk (p < 0.05). There was no significant direct effect for any of the ABCA1 groups on T2D risk: p = 0.99, p = 0.58, and p = 0.91 for groups +/-, -/+, and +/+ respectively. CONCLUSIONS: The ABCA1 rs9282541 (R230C) allele is associated with T2D in Mexicans through its effect on lowering HDL-c levels. This is the first report demonstrating that HDL-c levels act as an intermediate factor between an ABCA1 variant and T2D.

A concise review of opioid-induced esophageal dysfunction: is this a new clinical entity?

Opioids have become the most widely prescribed analgesics in Western countries. Opioid-induced bowel dysfunction is a widely known adverse effect, with constipation the most common manifestation. Most of the opioid-related effects occur in the stomach, small intestine, and colon and have been widely studied. However, the effects related to esophageal motility are less known. Recently published retrospective studies have suggested that long-term use of opioids can cause esophageal motility dysfunction, reflecting symptoms similar to motility disorders, such as achalasia and functional esophagogastric junction outflow obstruction. The most common manometric findings, as reported in the literature, for patients with opioid-induced dysphagia undergoing long-term therapy with these drugs are impaired lower esophageal sphincter relaxation, high amplitude/velocity, and simultaneous esophageal waves, higher integrated relaxation pressure, lower distal latency, and the esophageal contractility can be normal, hypercontractile, or premature. Based on these studies, a new clinical entity known as opioid-induced esophageal dysfunction has been postulated. For these patients, the diagnostic method of choice is high-resolution manometry, although other causes should be ruled out through endoscopy or Computed Tomography (CT). The best therapeutic option for these patients is withdrawal of the opioid; however, this is not always possible, and other options need to be investigated, such as pneumatic dilation and botulinum toxin injection, considering the risks versus the benefits.

A cis-acting element in the promoter of human ether à go-go 1 potassium channel gene mediates repression by calcitriol in human cervical cancer cells.

The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression.

Impact of radical and partial nephrectomy on renal function in patients with renal cancer.

OBJECTIVE: To evaluate renal function in renal cancer patients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) (open or laparoscopic - ORN, OPN, LRN or LPN) and to identify risk factors contributing to renal function loss. METHODS: We analysed 228 consecutive renal cancer patients admitted for OPN, LPN, ORN or LRN. The variables analysed were age, gender, weight, type of surgery (radical versus partial), type of surgical access (open versus laparoscopic), preoperative renal function and history of hypertension, diabetes or malignancy. Absolute renal function was calculated as the difference in glomerular filtration rate (ΔGFR) between the renal function before (GFR0) and 12 months after surgery (GFR12). The relative renal function of patients undergoing PN and RN was evaluated by the change in chronic kidney disease stage. RESULTS: LRN caused the greatest loss in absolute renal function, followed by ORN, LPN and OPN. A GFR of ≥60 ml/min was noted for 90 (68.7%) patients before and 65 (49.6%) patients after RN and for 80 (82.5%) patients before and 74 (76.3%) patients after PN. The chronic kidney disease stage dropped to 4 or 5 in the case of 6 (4.6%) patients who underwent RN and 2 (2.1%) patients who underwent PN. Multivariate analysis revealed that only preoperative weight and type of surgery (radical versus partial) had a significant impact on renal function. CONCLUSION: Renal function significantly decreased in patients undergoing RN, irrespective of the access route. Patients with preoperative poor renal function are at risk of postoperative end-stage renal disease.

Evaluation of Water Sanitation Health Education Programme: Working with the Knowledge of the Basic Sanitation Services in a Developing Community in Rural Haiti after the 2010 Earthquake.

OBJECTIVE: The aim of this study is to measure the knowledge regarding the new sanitation water system being implemented in Dessources, a rural community in the municipality of Croix-des-Bouquets in Haiti after a two-year intervention programme. DESIGN AND METHODS: A cross-sectional epidemiologic design was used to measure the knowledge of the people in the community using a semi-structured questionnaire. Data collection followed a face-to-face interview process in all houses of the community. The instrument content validity was performed by a panel of experts followed by Cronbach's alpha test to establish the reliability of knowledge scale. In addition, association measures were done using Stata 11.0 statistical package. RESULTS: Content validity test were performed with minimum changes and an alpha of 0.74 was obtained for the scale. Response rate was 65.57% (41/60 houses); non-participants were only those who did not meet the inclusion criteria. Most of the participants (77.5%) were 21-49 years old and 85% had been living in the community for more than 20 years. Bivariate analysis showed that the people of Dessources had adequate knowledge. Significant differences, however, were found among the zones that are not in use of the new sanitary systems and among families with more than seven members per house. CONCLUSIONS: Differences found can be explained based on the Rogers theoretical diffusion of innovation model. The evaluation shows that people of Dessources in Haiti have a high knowledge regarding the new water sanitation system and provided evidence of an adequate health education programme intervention.

UAV-borne LiDAR revolutionizing groundwater level mapping.

In hydrogeological research, the systematic and periodic measurement of the piezometric level is fundamental to assess aquifer storage, identify recharge and discharge areas, define flow directions and to infer the balance between inputs and withdrawals. Furthermore, knowledge of this variable and its fluctuations is essential for the efficient management and protection of groundwater resources. In this work, a novel methodology is proposed for the remote acquisition of piezometric information from traditional large-diameter wells, using drone-borne LiDAR observations. The workflow developed consists of different stages, from flight planning and parameter setting, to point cloud generation, data processing and validation and its statistical treatment to extract piezometric information. This methodology has been applied in a small coastal aquifer with numerous wells that have served as monitoring points. The UAV-LiDAR has enabled the straightforward obtention of measurements of the piezometric level with very high vertical accuracies (RMSE of 5 cm) with minimum and maximum residuals of -8.7 and 7.9 cm respectively. Likewise, the method has shown vertical accuracies 3 times better than those inferred from the official DTM of best resolution available in Spain, which is usually used in hydrogeological works. Since the technique provides absolute values of the piezometric level, it eliminates the need for laborious levelling work prior to hydrogeological campaigns. This method has proved to be an effective alternative/complementary technique to traditional measurements of the piezometric level, allowing to monitor extensive or inaccessible areas over short periods of time and to potentially reduce gaps in hydrogeological databases.

Soy protein isoflavones differentially regulate liver X receptor isoforms to modulate lipid metabolism and cholesterol transport in the liver and intestine in mice.

AIMS/HYPOTHESIS: Liver X receptor (LXR)α regulates the genes involved in cholesterol, fatty acid and glucose metabolism. Soy protein (SP) consumption reduces the hepatic accumulation of cholesterol and triacylglycerol, and improves insulin sensitivity. However, it is not known whether these effects are mediated via LXRα. We therefore investigated whether the consumption of SP regulates metabolic changes in cholesterol metabolism and insulin sensitivity via LXRα. METHODS: Wild-type (WT) and Lxrα(-/-) (Lxrα, also known as Nr1h3) mice were fed an SP diet with or without cholesterol for 28 days. The expression of LXRα target genes was measured in liver and intestine, as were hepatic lipid content and faecal bile acid concentration. Oral glucose and insulin tolerance tests were also performed. Hepatocytes were used to study the effect of isoflavones on LXR activity. RESULTS: The livers of WT and Lxrα(-/-) mice fed an SP high-cholesterol diet showed less steatosis than those fed casein. The SP diet increased the expression of the ATP-binding cassette (ABC) sub-family genes Abca1, Abcg5 and Abcg8 in the liver and intestine, as well as increasing total faecal bile acid excretion and insulin sensitivity in WT mice compared with mice fed a casein diet. However, these effects of SP were not observed in Lxrα(-/-) mice. The SP isoflavone, genistein, repressed the activation of LXRα target genes by T0901317, whereas it stimulated the activation of LXRß target genes. The AMP-activated protein kinase inhibitor, compound C, had the opposite effects to those of genistein. CONCLUSIONS/INTERPRETATION: Our results suggest that SP isoflavones stimulate the phosphorylation of LXRα or LXRß, resulting in different biological effects for each LXR isoform.

A randomized controlled trial of internet-based cognitive-behavioural therapy for bulimia nervosa or related disorders in a student population.

BACKGROUND: Bulimic eating disorders are common among female students, yet the majority do not access effective treatment. Internet-based cognitive-behavioural therapy (iCBT) may be able to bridge this gap. METHOD: Seventy-six students with bulimia nervosa (BN) or eating disorder not otherwise specified (EDNOS) were randomly assigned to immediate iCBT with e-mail support over 3 months or to a 3-month waiting list followed by iCBT [waiting list/delayed treatment control (WL/DTC)]. ED outcomes were assessed with the Eating Disorder Examination (EDE) at baseline, 3 months and 6 months. Other outcomes included depression, anxiety and quality of life. RESULTS: Students who had immediate iCBT showed significantly greater improvements at 3 and 6 months than those receiving WL/DTC in ED and other symptoms. CONCLUSIONS: iCBT with e-mail support is efficacious in students with bulimic disorders and has lasting effects.

"A computer isn't gonna judge you": a qualitative study of users' views of an internet-based cognitive behavioural guided self-care treatment package for bulimia nervosa and related disorders.

Little is known about what determines uptake and acceptability of internet-based treatments in eating disorders, and users' experience with such treatments. We investigated these factors in participants of a randomized controlled trial of an internet-based cognitive- behavioural treatment (iCBT) package (Overcoming bulimia online). Nine participants were interviewed using purposive sampling. The content of interviews were analyzed using thematic analysis. Additionally, participants received questionnaires about their impressions of iCBT. Participants talked about their experience of using iCBT, its impact and compared it to other treatments. Questionnaire responses echoed themes identified in the interviews. iCBT was received positively as a way of fitting treatment into busy lives. Comments on the layout of some of the package content and the practitioner support offered were identified as areas that could be modified or improved.

Dosage of anti-PD-1 monoclonal antibodies: a cardinal open question.

Discovery and clinical development of monoclonal antibodies with the ability to interfere in the regulation of the immune response have significantly changed the landscape of oncology in recent years. Among the active agents licensed by the regulatory agencies, nivolumab and pembrolizumab are paradigmatic as the most relevant ones according to the magnitude of available data derived from the extensive preclinical and clinical experience. Although in both cases the respective data sheets indicate well-defined dosage regimens, a review of the literature permits to verify the existence of many issues still unresolved about dosing the two agents, so it must be considered an open question of potentially important consequences, in which to work to improve the effectiveness and efficiency of use.

Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

Outcome of non-variceal acute upper gastrointestinal bleeding in patients with antithrombotic therapy.

AIM: To determine the influence of antithrombotic therapy upon the course of non-variceal upper gastrointestinal bleeding (UGB). METHODS: A cohort study was made of consecutive patients admitted to hospital with non-variceal UGB. Three cohorts were defined: patients receiving vitamin K antagonists (AC); patients with antiplatelet treatment (AP), and patients with neither of these treatments (noACAP) as control group. Outcome was assessed by: (a) number of days in hospital; (b) mortality rate; (c) need for urgent surgery, and (d) rebleeding. The measure of the association between antithrombotic therapy and the course of UGB was adjusted for confounders (age, sex, comorbidity, and the use of NSAIDs and PPIs at the time of UGB presentation). RESULTS: A total of 392 consecutive patients were included: 43 were AC, 107 AP, and 242 noACAP patients. There were no significant differences among groups in terms of rebleeding (AC 11.6%, AP 7.5%, NoACAP 9.1%), the need for urgent surgery (AC 2.3%, AP 1.9%, NoACAP 1.2%) or mortality rate (AC 4.7%, AP 5.6%, NoACAP 5.8%). The number of days in hospital was greater in the AC cohort (4.81 more days; 95% CI 2.83-6.79, p < 0.001). After adjusting for age and comorbidity, the increase in days in hospital among the AC patients was 3.24 days (95% CI 1.22-5.26). CONCLUSIONS: Neither anticoagulation nor antiplatelet treatment exerts an influence upon the course of non-variceal UGB. Nevertheless, anticoagulation is associated with a longer hospital stay. This is partially explained by the older age and increased comorbidity of the patients subjected to such treatment.

Sequence effects in the melting and renaturation of short DNA oligonucleotides: structure and mechanistic pathways.

The renaturation/denaturation of DNA oligonucleotides is characterized in the context of expanded ensemble (EXE) and transition path sampling (TPS) simulations. Free energy profiles have been determined from EXE for DNA sequences of varying composition, chain length, and ionic strength. TPS simulations within a Langevin dynamics formalism have been carried out to obtain further information of the transition state for renaturation. Simulation results reveal that free energy profiles are strikingly similar for the various DNA sequences considered in this work. Taking intact double-stranded DNA to have an extent of reaction ξ = 1.0, the maximum of the free energy profile appears at ξ≈0.15, corresponding to ∼2 base pairs. In terms of chain length, the free energy barrier of longer oligonucleotides (30 versus 15 base pairs) is higher and slightly narrower, due to increased sharpness associated with the transition. Low ionic strength tends to decrease free energy barriers, whereby increasing strand rigidity facilitates reassociation. Two mechanisms for DNA reassociation emerge from our analysis of the transition state ensemble. Repetitive sequences tend to reassociate through a non-specific pathway involving molecular slithering. In contrast, random sequences associate through a more restrictive pathway involving the formation of specific contacts, which then leads to overall molecular zippering. In both random and repetitive sequences, the distribution of contacts suggests that nucleation is favored for sites located within the middle region of the chain. The prevalent extent of reaction for the transition state is ξ≈0.25, and the critical size of the nucleus as obtained from our analysis involves ∼4 base pairs.

First Report of Clover yellow vein virus in Grain Legumes in Spain.

From 1999 to 2002, field surveys were conducted in the legume-growing areas of Spain including Ávila, Badajoz, Cádiz, Córdoba, León, Málaga, Murcia, Salamanca, and Zamora provinces. Leaf tissue from 35 asymptomatic and 224 virus symptomatic plants was sampled and analyzed by indirect-ELISA with a specific monoclonal antibody against the potyvirus group (Adgia, Elkhart, IN). All symptomatic plants of bean (Phaseolus vulgaris L.), broad bean (Vicia faba L.), lentils (Lens culinaris L.), and chickpea (Cicer arietinum L.) were positive for potyvirus infection. Identification as Bean yellow mosaic virus (BYMV) was obtained by double-antibody sandwich (DAS)-ELISA with a polyclonal antiserum (Loewe Biochemica Gmbh, Sauerlach, Germany). To analyze the genetic variability of BYMV Spanish isolates, 33 Spanish isolates were selected at random from our BYMV collection, and extracts from these plants were used with primers 1985 (5'-gagagaatgatacacatactgaa-3') and 1984 (5'-caaggtgagtggacaatgatgg-3') to amplify by immunocapture (IC)-reverse transcription (RT)-PCR a 524-nt fragment of the BYMV genome that includes the C-terminal 417 nt of the coat protein and 107 nt from the 3' untranslated region. The IC-RT-PCR products were cloned into pGEM-T easy vector (Promega, Madison, WI) and a minimum of three clones from each PCR amplification were sequenced. BLAST analysis showed that the sequences of 30 samples were 96 to 98% identical to BYMV, but three samples (GenBank Accession Nos. EU860364-66) from bean, broad bean, and lentils had a high (98%) identity with Clover yellow vein virus (ClYVV). Sequence alignments of the ClYVV Spanish isolates and 14 ClYVV isolates from the GenBank (Accession Nos. AB03308, AB004545, AB011819, AF185959, AF203536, D86044, S77521, D95538-94) were obtained using the Clustal X software. Genetic distances were estimated using the Kimura two-parameter method. Within-population and between-population nucleotide diversities were estimated from the genetic distances (2). ClYVV sequences were phylogenetically separated into two clades: one with the three isolates from Japan (Accession Nos. D89542, D89543, and D89544) and the other with the remaining isolates. Molecular clustering coincides with biology and serological variations of strains 1 and 2 (3). Phylogenetic distances were independent of geographic origin, host, or time of sampling. The nucleotide diversity value among populations (0.18) was higher than within the subpopulations (0.017 and 0.029). dNS/dS in the ClYVV population was 0.031 (<1) and we can conclude that negative selection is occurring in the gene in study and that the population of ClYVV present in Spain is homogenous. In Spain, ClYVV was reported infecting borage (Borago officinalis L.) (1). To our knowledge, this is the first report of natural infection of bean, broad bean, and lentils with ClYVV in Spain. ClYVV might cause important economic losses in grain legumes since it causes an important viral disease of legumes worldwide. References: (1) M. Luis-Arteaga et al. Plant Pathol. 45:38, 1996. (2) M. Nei and T. Gojobori. Mol. Biol. Evol. 3:418, 1986. (3) T. Sasaya et al. Virology 87:1014, 1987.

Health-related quality of life following surgical attenuation of congenital portosystemic shunts versus healthy controls.

OBJECTIVES: To design a health-related quality of life questionnaire for dogs with congenital portosystemic shunts, use it in a cohort of dogs treated with suture attenuation and compare results with those obtained from a healthy control cohort. MATERIALS AND METHODS: Data were collected from the hospital records of dogs treated with suture ligation of an intrahepatic or extrahepatic congenital portosystemic shunt at two referral centres. Owners were asked to complete a questionnaire assessing their dog's health-related quality of life preoperatively (retrospectively) and at the time of follow-up. Owners of control dogs also completed the questionnaire. RESULTS: One hundred and twenty-eight dogs with congenital portosystemic shunts and 131 control dogs were recruited. Median follow-up time was 64 months (range 19.7 to 157.2). The median long-term health-related quality of life score was excellent for both intrahepatic and extrahpatic shunt cases and similar to that of control dogs. The long-term portosystemic shunt clinical sign scores for both intrahepatic and extrahepatic congenital portosystemic shunt dogs were significantly worse than the those of the control group. CLINICAL SIGNIFICANCE: Suture attenuation of congenitial portosystemic shunts is associated with an excellent health-related quality of life score at long-term follow-up.

Cytotoxic Lesions of the Corpus Callosum Caused by Thermogenic Dietary Supplements.

Consumption of over-the-counter dietary supplements to reduce body weight is common among the population. Thermogenics are herbal combinations that claim to produce a fat-burning process through an increase in the cellular metabolic rate and greater cellular energy consumption, having a high risk for patients developing toxic leukoencephalopathy. We present a series of 6 patients with acute neurologic symptoms and MR imaging showing restricted diffusion and decreased apparent diffusion coefficient values (mean value, 400 mm2/s × 10-6) in the entire corpus callosum compatible with a cytotoxic lesion of the corpus callosum. Although patients responded favorably to the product discontinuation with rapid recovery of neurologic symptoms, there was a more prolonged resolution on imaging alterations. Because of the widespread availability and unregulated nature of thermogenic dietary supplements, physicians must be aware of the clinical and radiologic characteristics of these potential complications of their use.

Analysis of heart rate turbulence in advanced heart failure and heart transplantation patients.

OBJECTIVE: The objective of this study was to describe heart rate turbulence (HRT) in advanced heart failure (HF) patients and in a group of patients who underwent heart transplantation (HT). MATERIALS AND METHODS: We performed 24-hour Holter recordings in 20 patients with advanced HF referred to our hospital for HT, including 16 males of overall mean age of 44 +/- 13 years and with a mean ejection fraction (EF) 21 +/- 7%. An additional set of recordings was obtained in a second group of 27 patients who had already undergone HT, including of 21 males of overall mean age of 47 +/- 14 years. We recorded the number of premature ventricular contractions (PVCs), mean heart rate (MHR), and 2 parameters of HRT-turbulence onset (TO) and turbulence slope (TS). RESULTS: Patients with HT showed a low density of premature ventricular complexes, in contrast to patients in the advanced HF group. For this reason, HRT could only be analyzed in 15 of the patients with advanced HF (66%) and in 10 of the patients who underwent HT (37%). MHR was 77 +/- 10 bpm in the advanced HF group and 90 +/- 10 bpm in the HT group. In both groups, TO and TS showed highly attenuated values. CONCLUSIONS: Patients with advanced HF showed a high number of PVCs with attenuated HRT parameters, reflecting increased circulating catecholamine levels and decreased response of the autonomic nervous system. Patients who underwent HT showed elevated MHRs, a small number of PVCs, and attenuated HRT values, as corresponds to a denervated heart.